Trial Outcomes & Findings for Pembrolizumab and XL888 in Patients With Advanced Gastrointestinal Cancer (NCT NCT03095781)
NCT ID: NCT03095781
Last Updated: 2026-05-22
Results Overview
Summary statistics will be presented. Toxicities will be presented as worst toxicity per patient.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
47 participants
Primary outcome timeframe
Cycle length 21 days. Outcome determined on day 22 (after completion of cycle 1)
Results posted on
2026-05-22
Participant Flow
Participant milestones
| Measure |
Dose Expansion Pancreatic Cancer (Arm A)
In the dose expansion phase, Arm A will be open for 16 patients with pancreatic adenocarcinoma. Patients must have histologic diagnosis and either locally advanced unresectable or metastatic disease that has failed at least one standard regimen. Eight patients will participate in the paired biopsy studies. Patient selected for biopsy must have a primary or metastatic non-bone site that is amenable to safe biopsy.
Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
XL888: Given PO
Pembrolizumab: Given IV
|
Dose Expansion Colorectal Cancer (Arm B)
In the dose expansion phase, Arm B will be open for 16 patients with colorectal adenocarcinoma. Patients must have histologic diagnosis and either locally advanced unresectable or metastatic disease and have previously received oxaliplatin, irinotecan, and a fluoropyrimidine. Eight patients will participate in the paired biopsy studies. Patient selected for biopsy must have a primary or metastatic non-bone site that is amenable to safe biopsy.
XL888: Given PO
Pembrolizumab: Given IV
|
Dose Escalation 45 mg PO Twice Weekly
In the dose escalation phase, the trial will be open for patients with stage IV or locally advanced unresectable gastrointestinal adenocarcinomas (gastric, GEJ, cholangiocarcinoma, hepatocellular, pancreas, small intestinal tumors) who have failed at least one prior therapy. Patients with colorectal cancer must have previously received oxaliplatin, irinotecan, and a fluoropyrimidine.
Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
XL888: Given PO
Pembrolizumab: Given IV
|
Dose Escalation 60 mg PO Twice Weekly
In the dose escalation phase, the trial will be open for patients with stage IV or locally advanced unresectable gastrointestinal adenocarcinomas (gastric, GEJ, cholangiocarcinoma, hepatocellular, pancreas, small intestinal tumors) who have failed at least one prior therapy. Patients with colorectal cancer must have previously received oxaliplatin, irinotecan, and a fluoropyrimidine.
Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
XL888: Given PO
Pembrolizumab: Given IV
|
Dose Escalation 90 mg PO Twice Weekly
In the dose escalation phase, the trial will be open for patients with stage IV or locally advanced unresectable gastrointestinal adenocarcinomas (gastric, GEJ, cholangiocarcinoma, hepatocellular, pancreas, small intestinal tumors) who have failed at least one prior therapy. Patients with colorectal cancer must have previously received oxaliplatin, irinotecan, and a fluoropyrimidine.
Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
XL888: Given PO
Pembrolizumab: Given IV
|
|---|---|---|---|---|---|
|
Overall Study
STARTED
|
17
|
16
|
3
|
3
|
8
|
|
Overall Study
COMPLETED
|
17
|
16
|
3
|
3
|
8
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Pembrolizumab and XL888 in Patients With Advanced Gastrointestinal Cancer
Baseline characteristics by cohort
| Measure |
Dose Expansion Pancreatic Cancer (Arm A)
n=17 Participants
In the dose expansion phase, Arm A will be open for 16 patients with pancreatic adenocarcinoma. Patients must have histologic diagnosis and either locally advanced unresectable or metastatic disease that has failed at least one standard regimen. Eight patients will participate in the paired biopsy studies. Patient selected for biopsy must have a primary or metastatic non-bone site that is amenable to safe biopsy.
Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
XL888: Given PO
Pembrolizumab: Given IV
|
Dose Expansion Colorectal Cancer (Arm B)
n=16 Participants
In the dose expansion phase, Arm B will be open for 16 patients with colorectal adenocarcinoma. Patients must have histologic diagnosis and either locally advanced unresectable or metastatic disease and have previously received oxaliplatin, irinotecan, and a fluoropyrimidine. Eight patients will participate in the paired biopsy studies. Patient selected for biopsy must have a primary or metastatic non-bone site that is amenable to safe biopsy.
XL888: Given PO
Pembrolizumab: Given IV
|
Dose Escalation 45 mg PO Twice Weekly
n=3 Participants
In the dose escalation phase, the trial will be open for patients with stage IV or locally advanced unresectable gastrointestinal adenocarcinomas (gastric, GEJ, cholangiocarcinoma, hepatocellular, pancreas, small intestinal tumors) who have failed at least one prior therapy. Patients with colorectal cancer must have previously received oxaliplatin, irinotecan, and a fluoropyrimidine.
Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
XL888: Given PO
Pembrolizumab: Given IV
|
Dose Escalation 60 mg PO Twice Weekly
n=3 Participants
In the dose escalation phase, the trial will be open for patients with stage IV or locally advanced unresectable gastrointestinal adenocarcinomas (gastric, GEJ, cholangiocarcinoma, hepatocellular, pancreas, small intestinal tumors) who have failed at least one prior therapy. Patients with colorectal cancer must have previously received oxaliplatin, irinotecan, and a fluoropyrimidine.
Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
XL888: Given PO
Pembrolizumab: Given IV
|
Dose Escalation 90 mg PO Twice Weekly
n=8 Participants
In the dose escalation phase, the trial will be open for patients with stage IV or locally advanced unresectable gastrointestinal adenocarcinomas (gastric, GEJ, cholangiocarcinoma, hepatocellular, pancreas, small intestinal tumors) who have failed at least one prior therapy. Patients with colorectal cancer must have previously received oxaliplatin, irinotecan, and a fluoropyrimidine.
Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
XL888: Given PO
Pembrolizumab: Given IV
|
Total
n=47 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=2 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=6 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=28 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
7 Participants
n=2 Participants
|
14 Participants
n=4 Participants
|
0 Participants
n=6 Participants
|
0 Participants
n=8 Participants
|
3 Participants
n=8 Participants
|
24 Participants
n=28 Participants
|
|
Age, Categorical
>=65 years
|
10 Participants
n=2 Participants
|
2 Participants
n=4 Participants
|
3 Participants
n=6 Participants
|
3 Participants
n=8 Participants
|
5 Participants
n=8 Participants
|
23 Participants
n=28 Participants
|
|
Age, Continuous
|
68.0 Years
n=2 Participants
|
56.5 Years
n=4 Participants
|
68 Years
n=6 Participants
|
55 Years
n=8 Participants
|
67 Years
n=8 Participants
|
63 Years
n=28 Participants
|
|
Sex: Female, Male
Female
|
9 Participants
n=2 Participants
|
9 Participants
n=4 Participants
|
2 Participants
n=6 Participants
|
1 Participants
n=8 Participants
|
2 Participants
n=8 Participants
|
23 Participants
n=28 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=2 Participants
|
7 Participants
n=4 Participants
|
1 Participants
n=6 Participants
|
2 Participants
n=8 Participants
|
6 Participants
n=8 Participants
|
24 Participants
n=28 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=2 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=6 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=28 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=2 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=6 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=28 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=2 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=6 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=28 Participants
|
|
Race (NIH/OMB)
Black or African American
|
3 Participants
n=2 Participants
|
3 Participants
n=4 Participants
|
0 Participants
n=6 Participants
|
0 Participants
n=8 Participants
|
1 Participants
n=8 Participants
|
7 Participants
n=28 Participants
|
|
Race (NIH/OMB)
White
|
12 Participants
n=2 Participants
|
13 Participants
n=4 Participants
|
3 Participants
n=6 Participants
|
3 Participants
n=8 Participants
|
7 Participants
n=8 Participants
|
38 Participants
n=28 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=2 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=6 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=28 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=2 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=6 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
2 Participants
n=28 Participants
|
|
Region of Enrollment
United States
|
17 participants
n=2 Participants
|
16 participants
n=4 Participants
|
3 participants
n=6 Participants
|
3 participants
n=8 Participants
|
8 participants
n=8 Participants
|
47 participants
n=28 Participants
|
PRIMARY outcome
Timeframe: Cycle length 21 days. Outcome determined on day 22 (after completion of cycle 1)Summary statistics will be presented. Toxicities will be presented as worst toxicity per patient.
Outcome measures
| Measure |
Dose Expansion Pancreatic Cancer (Arm A)
n=17 Participants
In the dose expansion phase, Arm A will be open for 16 patients with pancreatic adenocarcinoma. Patients must have histologic diagnosis and either locally advanced unresectable or metastatic disease that has failed at least one standard regimen. Eight patients will participate in the paired biopsy studies. Patient selected for biopsy must have a primary or metastatic non-bone site that is amenable to safe biopsy.
Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
XL888: Given PO
Pembrolizumab: Given IV
|
Dose Expansion Colorectal Cancer (Arm B)
n=16 Participants
In the dose expansion phase, Arm B will be open for 16 patients with colorectal adenocarcinoma. Patients must have histologic diagnosis and either locally advanced unresectable or metastatic disease and have previously received oxaliplatin, irinotecan, and a fluoropyrimidine. Eight patients will participate in the paired biopsy studies. Patient selected for biopsy must have a primary or metastatic non-bone site that is amenable to safe biopsy.
XL888: Given PO
Pembrolizumab: Given IV
|
Dose Escalation 45 mg PO Twice Weekly
n=3 Participants
In the dose escalation phase, the trial will be open for patients with stage IV or locally advanced unresectable gastrointestinal adenocarcinomas (gastric, GEJ, cholangiocarcinoma, hepatocellular, pancreas, small intestinal tumors) who have failed at least one prior therapy. Patients with colorectal cancer must have previously received oxaliplatin, irinotecan, and a fluoropyrimidine.
Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
XL888: Given PO
Pembrolizumab: Given IV
|
Dose Escalation 60 mg PO Twice Weekly
n=3 Participants
In the dose escalation phase, the trial will be open for patients with stage IV or locally advanced unresectable gastrointestinal adenocarcinomas (gastric, GEJ, cholangiocarcinoma, hepatocellular, pancreas, small intestinal tumors) who have failed at least one prior therapy. Patients with colorectal cancer must have previously received oxaliplatin, irinotecan, and a fluoropyrimidine.
Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
XL888: Given PO
Pembrolizumab: Given IV
|
Dose Escalation 90 mg PO Twice Weekly
n=8 Participants
In the dose escalation phase, the trial will be open for patients with stage IV or locally advanced unresectable gastrointestinal adenocarcinomas (gastric, GEJ, cholangiocarcinoma, hepatocellular, pancreas, small intestinal tumors) who have failed at least one prior therapy. Patients with colorectal cancer must have previously received oxaliplatin, irinotecan, and a fluoropyrimidine.
Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
XL888: Given PO
Pembrolizumab: Given IV
|
|---|---|---|---|---|---|
|
Recommended Phase II Dose of the Combination of XL888 and Pembrolizumab as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
Injury, poisoning and procedural complications
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Recommended Phase II Dose of the Combination of XL888 and Pembrolizumab as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
Investigations
|
9 Participants
|
5 Participants
|
0 Participants
|
0 Participants
|
2 Participants
|
|
Recommended Phase II Dose of the Combination of XL888 and Pembrolizumab as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
Metabolism and nutrition disorders
|
10 Participants
|
8 Participants
|
1 Participants
|
1 Participants
|
1 Participants
|
|
Recommended Phase II Dose of the Combination of XL888 and Pembrolizumab as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
Musculoskeletal and connective tissue disorders
|
2 Participants
|
7 Participants
|
1 Participants
|
0 Participants
|
1 Participants
|
|
Recommended Phase II Dose of the Combination of XL888 and Pembrolizumab as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
Nervous system disorders
|
8 Participants
|
5 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Recommended Phase II Dose of the Combination of XL888 and Pembrolizumab as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
Psychiatric disorders
|
6 Participants
|
1 Participants
|
0 Participants
|
1 Participants
|
1 Participants
|
|
Recommended Phase II Dose of the Combination of XL888 and Pembrolizumab as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
Renal and urinary disorders
|
4 Participants
|
4 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Recommended Phase II Dose of the Combination of XL888 and Pembrolizumab as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
Respiratory, thoracic and mediastinal disorders
|
1 Participants
|
7 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Recommended Phase II Dose of the Combination of XL888 and Pembrolizumab as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
Skin and subcutaneous tissue disorders
|
2 Participants
|
2 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Recommended Phase II Dose of the Combination of XL888 and Pembrolizumab as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
Any
|
14 Participants
|
16 Participants
|
3 Participants
|
3 Participants
|
5 Participants
|
|
Recommended Phase II Dose of the Combination of XL888 and Pembrolizumab as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
Blood and lymphatic system disorders
|
10 Participants
|
6 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Recommended Phase II Dose of the Combination of XL888 and Pembrolizumab as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
Cardiac disorders
|
3 Participants
|
3 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Recommended Phase II Dose of the Combination of XL888 and Pembrolizumab as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
Ear and labyrinth disorders
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Recommended Phase II Dose of the Combination of XL888 and Pembrolizumab as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
Endocrine disorders
|
1 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Recommended Phase II Dose of the Combination of XL888 and Pembrolizumab as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
Eye disorders
|
3 Participants
|
5 Participants
|
0 Participants
|
0 Participants
|
2 Participants
|
|
Recommended Phase II Dose of the Combination of XL888 and Pembrolizumab as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
Gastrointestinal disorders
|
10 Participants
|
14 Participants
|
3 Participants
|
2 Participants
|
2 Participants
|
|
Recommended Phase II Dose of the Combination of XL888 and Pembrolizumab as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
General disorders and administration site conditions
|
12 Participants
|
13 Participants
|
1 Participants
|
2 Participants
|
1 Participants
|
|
Recommended Phase II Dose of the Combination of XL888 and Pembrolizumab as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
Hepatobiliary disorders
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Recommended Phase II Dose of the Combination of XL888 and Pembrolizumab as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
Immune system disorders
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Recommended Phase II Dose of the Combination of XL888 and Pembrolizumab as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
Infections and infestations
|
0 Participants
|
4 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Recommended Phase II Dose of the Combination of XL888 and Pembrolizumab as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
Social circumstances
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Recommended Phase II Dose of the Combination of XL888 and Pembrolizumab as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
Vascular disorders
|
2 Participants
|
2 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to 2 years after cycle 1, day 1. Cycle length is 21 days.RECIST version 1.1 will be used in this study for assessment of tumor response. While either CT or MRI may be utilized, as per RECIST 1.1, CT is the preferred imaging technique in this study.
Outcome measures
| Measure |
Dose Expansion Pancreatic Cancer (Arm A)
n=17 Participants
In the dose expansion phase, Arm A will be open for 16 patients with pancreatic adenocarcinoma. Patients must have histologic diagnosis and either locally advanced unresectable or metastatic disease that has failed at least one standard regimen. Eight patients will participate in the paired biopsy studies. Patient selected for biopsy must have a primary or metastatic non-bone site that is amenable to safe biopsy.
Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
XL888: Given PO
Pembrolizumab: Given IV
|
Dose Expansion Colorectal Cancer (Arm B)
n=16 Participants
In the dose expansion phase, Arm B will be open for 16 patients with colorectal adenocarcinoma. Patients must have histologic diagnosis and either locally advanced unresectable or metastatic disease and have previously received oxaliplatin, irinotecan, and a fluoropyrimidine. Eight patients will participate in the paired biopsy studies. Patient selected for biopsy must have a primary or metastatic non-bone site that is amenable to safe biopsy.
XL888: Given PO
Pembrolizumab: Given IV
|
Dose Escalation 45 mg PO Twice Weekly
n=3 Participants
In the dose escalation phase, the trial will be open for patients with stage IV or locally advanced unresectable gastrointestinal adenocarcinomas (gastric, GEJ, cholangiocarcinoma, hepatocellular, pancreas, small intestinal tumors) who have failed at least one prior therapy. Patients with colorectal cancer must have previously received oxaliplatin, irinotecan, and a fluoropyrimidine.
Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
XL888: Given PO
Pembrolizumab: Given IV
|
Dose Escalation 60 mg PO Twice Weekly
n=3 Participants
In the dose escalation phase, the trial will be open for patients with stage IV or locally advanced unresectable gastrointestinal adenocarcinomas (gastric, GEJ, cholangiocarcinoma, hepatocellular, pancreas, small intestinal tumors) who have failed at least one prior therapy. Patients with colorectal cancer must have previously received oxaliplatin, irinotecan, and a fluoropyrimidine.
Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
XL888: Given PO
Pembrolizumab: Given IV
|
Dose Escalation 90 mg PO Twice Weekly
n=4 Participants
In the dose escalation phase, the trial will be open for patients with stage IV or locally advanced unresectable gastrointestinal adenocarcinomas (gastric, GEJ, cholangiocarcinoma, hepatocellular, pancreas, small intestinal tumors) who have failed at least one prior therapy. Patients with colorectal cancer must have previously received oxaliplatin, irinotecan, and a fluoropyrimidine.
Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
XL888: Given PO
Pembrolizumab: Given IV
|
|---|---|---|---|---|---|
|
Overall Response Rate as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
|
0 Percentage of participants
|
0 Percentage of participants
|
0 Percentage of participants
|
0 Percentage of participants
|
0 Percentage of participants
|
SECONDARY outcome
Timeframe: Up to 1 year after cycle 1, day 1. Each cycle is 21 days.Once a subject experiences confirmed disease progression or starts a new anti-cancer therapy, the subject moves into the survival follow-up phase and should be contacted by telephone every 12 weeks to assess for survival status until death, withdrawal of consent, or the end of the study, whichever occurs first.
Outcome measures
| Measure |
Dose Expansion Pancreatic Cancer (Arm A)
n=17 Participants
In the dose expansion phase, Arm A will be open for 16 patients with pancreatic adenocarcinoma. Patients must have histologic diagnosis and either locally advanced unresectable or metastatic disease that has failed at least one standard regimen. Eight patients will participate in the paired biopsy studies. Patient selected for biopsy must have a primary or metastatic non-bone site that is amenable to safe biopsy.
Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
XL888: Given PO
Pembrolizumab: Given IV
|
Dose Expansion Colorectal Cancer (Arm B)
n=16 Participants
In the dose expansion phase, Arm B will be open for 16 patients with colorectal adenocarcinoma. Patients must have histologic diagnosis and either locally advanced unresectable or metastatic disease and have previously received oxaliplatin, irinotecan, and a fluoropyrimidine. Eight patients will participate in the paired biopsy studies. Patient selected for biopsy must have a primary or metastatic non-bone site that is amenable to safe biopsy.
XL888: Given PO
Pembrolizumab: Given IV
|
Dose Escalation 45 mg PO Twice Weekly
n=3 Participants
In the dose escalation phase, the trial will be open for patients with stage IV or locally advanced unresectable gastrointestinal adenocarcinomas (gastric, GEJ, cholangiocarcinoma, hepatocellular, pancreas, small intestinal tumors) who have failed at least one prior therapy. Patients with colorectal cancer must have previously received oxaliplatin, irinotecan, and a fluoropyrimidine.
Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
XL888: Given PO
Pembrolizumab: Given IV
|
Dose Escalation 60 mg PO Twice Weekly
n=3 Participants
In the dose escalation phase, the trial will be open for patients with stage IV or locally advanced unresectable gastrointestinal adenocarcinomas (gastric, GEJ, cholangiocarcinoma, hepatocellular, pancreas, small intestinal tumors) who have failed at least one prior therapy. Patients with colorectal cancer must have previously received oxaliplatin, irinotecan, and a fluoropyrimidine.
Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
XL888: Given PO
Pembrolizumab: Given IV
|
Dose Escalation 90 mg PO Twice Weekly
n=8 Participants
In the dose escalation phase, the trial will be open for patients with stage IV or locally advanced unresectable gastrointestinal adenocarcinomas (gastric, GEJ, cholangiocarcinoma, hepatocellular, pancreas, small intestinal tumors) who have failed at least one prior therapy. Patients with colorectal cancer must have previously received oxaliplatin, irinotecan, and a fluoropyrimidine.
Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
XL888: Given PO
Pembrolizumab: Given IV
|
|---|---|---|---|---|---|
|
Overall Survival
|
4.4 Months
Interval 2.3 to 6.9
|
5.5 Months
Interval 3.0 to 9.9
|
6.3 Months
Interval 3.4 to
Insufficient number of participants with events, boundary couldn't be calculated
|
9.5 Months
Interval 7.0 to
Insufficient number of participants with events, boundary couldn't be calculated
|
3.5 Months
Interval 1.3 to 10.2
|
SECONDARY outcome
Timeframe: Up to 6 months after cycle 1, day 1. Each cycle is 21 daysSummary statistics will be presented. Progression is defined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1 .0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Outcome measures
| Measure |
Dose Expansion Pancreatic Cancer (Arm A)
n=17 Participants
In the dose expansion phase, Arm A will be open for 16 patients with pancreatic adenocarcinoma. Patients must have histologic diagnosis and either locally advanced unresectable or metastatic disease that has failed at least one standard regimen. Eight patients will participate in the paired biopsy studies. Patient selected for biopsy must have a primary or metastatic non-bone site that is amenable to safe biopsy.
Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
XL888: Given PO
Pembrolizumab: Given IV
|
Dose Expansion Colorectal Cancer (Arm B)
n=16 Participants
In the dose expansion phase, Arm B will be open for 16 patients with colorectal adenocarcinoma. Patients must have histologic diagnosis and either locally advanced unresectable or metastatic disease and have previously received oxaliplatin, irinotecan, and a fluoropyrimidine. Eight patients will participate in the paired biopsy studies. Patient selected for biopsy must have a primary or metastatic non-bone site that is amenable to safe biopsy.
XL888: Given PO
Pembrolizumab: Given IV
|
Dose Escalation 45 mg PO Twice Weekly
n=3 Participants
In the dose escalation phase, the trial will be open for patients with stage IV or locally advanced unresectable gastrointestinal adenocarcinomas (gastric, GEJ, cholangiocarcinoma, hepatocellular, pancreas, small intestinal tumors) who have failed at least one prior therapy. Patients with colorectal cancer must have previously received oxaliplatin, irinotecan, and a fluoropyrimidine.
Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
XL888: Given PO
Pembrolizumab: Given IV
|
Dose Escalation 60 mg PO Twice Weekly
n=3 Participants
In the dose escalation phase, the trial will be open for patients with stage IV or locally advanced unresectable gastrointestinal adenocarcinomas (gastric, GEJ, cholangiocarcinoma, hepatocellular, pancreas, small intestinal tumors) who have failed at least one prior therapy. Patients with colorectal cancer must have previously received oxaliplatin, irinotecan, and a fluoropyrimidine.
Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
XL888: Given PO
Pembrolizumab: Given IV
|
Dose Escalation 90 mg PO Twice Weekly
n=8 Participants
In the dose escalation phase, the trial will be open for patients with stage IV or locally advanced unresectable gastrointestinal adenocarcinomas (gastric, GEJ, cholangiocarcinoma, hepatocellular, pancreas, small intestinal tumors) who have failed at least one prior therapy. Patients with colorectal cancer must have previously received oxaliplatin, irinotecan, and a fluoropyrimidine.
Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
XL888: Given PO
Pembrolizumab: Given IV
|
|---|---|---|---|---|---|
|
Progression Free Survival
|
2.0 Months
Interval 1.9 to 2.0
|
1.9 Months
Interval 1.3 to 2.0
|
2 Months
Interval 1.9 to
Insufficient sample size of participants and number of events.
|
2.1 Months
Interval 2.1 to
Insufficient sample size of participants and number of events.
|
2.2 Months
Interval 1.3 to 5.8
|
SECONDARY outcome
Timeframe: Up to 2 years after cycle 1, day 1. Each cycle is 21 days.Summary statistics will be presented. Progression is defined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1 .0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Outcome measures
| Measure |
Dose Expansion Pancreatic Cancer (Arm A)
n=17 Participants
In the dose expansion phase, Arm A will be open for 16 patients with pancreatic adenocarcinoma. Patients must have histologic diagnosis and either locally advanced unresectable or metastatic disease that has failed at least one standard regimen. Eight patients will participate in the paired biopsy studies. Patient selected for biopsy must have a primary or metastatic non-bone site that is amenable to safe biopsy.
Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
XL888: Given PO
Pembrolizumab: Given IV
|
Dose Expansion Colorectal Cancer (Arm B)
n=16 Participants
In the dose expansion phase, Arm B will be open for 16 patients with colorectal adenocarcinoma. Patients must have histologic diagnosis and either locally advanced unresectable or metastatic disease and have previously received oxaliplatin, irinotecan, and a fluoropyrimidine. Eight patients will participate in the paired biopsy studies. Patient selected for biopsy must have a primary or metastatic non-bone site that is amenable to safe biopsy.
XL888: Given PO
Pembrolizumab: Given IV
|
Dose Escalation 45 mg PO Twice Weekly
n=3 Participants
In the dose escalation phase, the trial will be open for patients with stage IV or locally advanced unresectable gastrointestinal adenocarcinomas (gastric, GEJ, cholangiocarcinoma, hepatocellular, pancreas, small intestinal tumors) who have failed at least one prior therapy. Patients with colorectal cancer must have previously received oxaliplatin, irinotecan, and a fluoropyrimidine.
Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
XL888: Given PO
Pembrolizumab: Given IV
|
Dose Escalation 60 mg PO Twice Weekly
n=3 Participants
In the dose escalation phase, the trial will be open for patients with stage IV or locally advanced unresectable gastrointestinal adenocarcinomas (gastric, GEJ, cholangiocarcinoma, hepatocellular, pancreas, small intestinal tumors) who have failed at least one prior therapy. Patients with colorectal cancer must have previously received oxaliplatin, irinotecan, and a fluoropyrimidine.
Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
XL888: Given PO
Pembrolizumab: Given IV
|
Dose Escalation 90 mg PO Twice Weekly
n=8 Participants
In the dose escalation phase, the trial will be open for patients with stage IV or locally advanced unresectable gastrointestinal adenocarcinomas (gastric, GEJ, cholangiocarcinoma, hepatocellular, pancreas, small intestinal tumors) who have failed at least one prior therapy. Patients with colorectal cancer must have previously received oxaliplatin, irinotecan, and a fluoropyrimidine.
Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
XL888: Given PO
Pembrolizumab: Given IV
|
|---|---|---|---|---|---|
|
Response Duration as Assessed by RECIST 1.1
|
0 Months
No patients had a response (i.e. CR or PR) so 0 months for DOR
|
0 Months
No patients had a response (i.e. CR or PR) so 0 months for DOR
|
0 Months
No patients had a response (i.e. CR or PR) so 0 months for DOR
|
0 Months
No patients had a response (i.e. CR or PR) so 0 months for DOR
|
0 Months
No patients had a response (i.e. CR or PR) so 0 months for DOR
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Up to 2 years after cycle 1, day 1. Each cycle is 21 days.Population: Blood samples failed quality control during testing therefore the specimen for the missing patients were not testable.
Change in cytokine and chemokine concentrations from Cycle 1 Day 1 (baseline) to Cycle 1 Day 15, calculated as the within-subject difference (Day 15 minus Day 1). Immune mediators assessed included Eotaxin, Fractalkine, G-CSF, GM-CSF, IL-1RA, IL-4, IL-6, IL-9, IL-13, IL-15, IP-10, MCP-1, MCP-3, M-CSF, and MDC. Positive values indicate an increase from baseline, and negative values indicate a decrease from baseline.
Outcome measures
| Measure |
Dose Expansion Pancreatic Cancer (Arm A)
n=17 Participants
In the dose expansion phase, Arm A will be open for 16 patients with pancreatic adenocarcinoma. Patients must have histologic diagnosis and either locally advanced unresectable or metastatic disease that has failed at least one standard regimen. Eight patients will participate in the paired biopsy studies. Patient selected for biopsy must have a primary or metastatic non-bone site that is amenable to safe biopsy.
Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
XL888: Given PO
Pembrolizumab: Given IV
|
Dose Expansion Colorectal Cancer (Arm B)
n=16 Participants
In the dose expansion phase, Arm B will be open for 16 patients with colorectal adenocarcinoma. Patients must have histologic diagnosis and either locally advanced unresectable or metastatic disease and have previously received oxaliplatin, irinotecan, and a fluoropyrimidine. Eight patients will participate in the paired biopsy studies. Patient selected for biopsy must have a primary or metastatic non-bone site that is amenable to safe biopsy.
XL888: Given PO
Pembrolizumab: Given IV
|
Dose Escalation 45 mg PO Twice Weekly
n=3 Participants
In the dose escalation phase, the trial will be open for patients with stage IV or locally advanced unresectable gastrointestinal adenocarcinomas (gastric, GEJ, cholangiocarcinoma, hepatocellular, pancreas, small intestinal tumors) who have failed at least one prior therapy. Patients with colorectal cancer must have previously received oxaliplatin, irinotecan, and a fluoropyrimidine.
Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
XL888: Given PO
Pembrolizumab: Given IV
|
Dose Escalation 60 mg PO Twice Weekly
n=3 Participants
In the dose escalation phase, the trial will be open for patients with stage IV or locally advanced unresectable gastrointestinal adenocarcinomas (gastric, GEJ, cholangiocarcinoma, hepatocellular, pancreas, small intestinal tumors) who have failed at least one prior therapy. Patients with colorectal cancer must have previously received oxaliplatin, irinotecan, and a fluoropyrimidine.
Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
XL888: Given PO
Pembrolizumab: Given IV
|
Dose Escalation 90 mg PO Twice Weekly
n=8 Participants
In the dose escalation phase, the trial will be open for patients with stage IV or locally advanced unresectable gastrointestinal adenocarcinomas (gastric, GEJ, cholangiocarcinoma, hepatocellular, pancreas, small intestinal tumors) who have failed at least one prior therapy. Patients with colorectal cancer must have previously received oxaliplatin, irinotecan, and a fluoropyrimidine.
Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
XL888: Given PO
Pembrolizumab: Given IV
|
|---|---|---|---|---|---|
|
Change in Cytokine and Chemokine Concentrations From Cycle 1 Day 1 to Cycle 1 Day 15
IL_6
|
4.47 pg/mL
Standard Deviation 6.76
|
3.56 pg/mL
Standard Deviation 4.93
|
7.69 pg/mL
Standard Deviation 3.7
|
-2.64 pg/mL
Standard Deviation 5.64
|
52.17 pg/mL
Standard Deviation 100.33
|
|
Change in Cytokine and Chemokine Concentrations From Cycle 1 Day 1 to Cycle 1 Day 15
EOTAXIN
|
8.76 pg/mL
Standard Deviation 13.69
|
1.47 pg/mL
Standard Deviation 7.2
|
4.73 pg/mL
Standard Deviation 6.86
|
-1.44 pg/mL
Standard Deviation 10.06
|
2.55 pg/mL
Standard Deviation 15.49
|
|
Change in Cytokine and Chemokine Concentrations From Cycle 1 Day 1 to Cycle 1 Day 15
FRACTALKINE
|
24.65 pg/mL
Standard Deviation 35.47
|
22.27 pg/mL
Standard Deviation 30.46
|
24.04 pg/mL
Standard Deviation 12.34
|
1.13 pg/mL
Standard Deviation 32.08
|
33.04 pg/mL
Standard Deviation 265.21
|
|
Change in Cytokine and Chemokine Concentrations From Cycle 1 Day 1 to Cycle 1 Day 15
G_CSF
|
-5.91 pg/mL
Standard Deviation 16.64
|
-8.94 pg/mL
Standard Deviation 41.19
|
.92 pg/mL
Standard Deviation NA
One patient has this data so standard deviation couldn't be calculated
|
—
|
477.7 pg/mL
Standard Deviation 576.95
|
|
Change in Cytokine and Chemokine Concentrations From Cycle 1 Day 1 to Cycle 1 Day 15
GM_CSF
|
1.38 pg/mL
Standard Deviation 13.22
|
8.18 pg/mL
Standard Deviation 7.55
|
-31.38 pg/mL
Standard Deviation 50.46
|
103.73 pg/mL
Standard Deviation 183.4
|
118.14 pg/mL
Standard Deviation 218.33
|
|
Change in Cytokine and Chemokine Concentrations From Cycle 1 Day 1 to Cycle 1 Day 15
IL_1RA
|
84.07 pg/mL
Standard Deviation 178.41
|
21.95 pg/mL
Standard Deviation 60.83
|
-4.95 pg/mL
Standard Deviation 8.72
|
26.74 pg/mL
Standard Deviation 39.1
|
306.24 pg/mL
Standard Deviation 672.22
|
|
Change in Cytokine and Chemokine Concentrations From Cycle 1 Day 1 to Cycle 1 Day 15
IL_4
|
0.89 pg/mL
Standard Deviation 2.13
|
0.49 pg/mL
Standard Deviation 0.66
|
0.14 pg/mL
Standard Deviation 0.24
|
-1.77 pg/mL
Standard Deviation NA
Insufficient sample size of biomarker data to calculate estimate(s)
|
9.22 pg/mL
Standard Deviation 17.52
|
|
Change in Cytokine and Chemokine Concentrations From Cycle 1 Day 1 to Cycle 1 Day 15
IL_9
|
0.42 pg/mL
Standard Deviation 4.08
|
-1.3 pg/mL
Standard Deviation 3.49
|
0.53 pg/mL
Standard Deviation NA
Insufficient sample size of biomarker data to calculate estimate(s)
|
-2.1 pg/mL
Standard Deviation NA
Insufficient sample size of biomarker data to calculate estimate(s)
|
7.65 pg/mL
Standard Deviation 20.7
|
|
Change in Cytokine and Chemokine Concentrations From Cycle 1 Day 1 to Cycle 1 Day 15
IL_13
|
11.33 pg/mL
Standard Deviation 20.35
|
-6.9 pg/mL
Standard Deviation 55.13
|
6.13 pg/mL
Standard Deviation 11.42
|
27.54 pg/mL
Standard Deviation NA
Insufficient sample size of biomarker data to calculate estimate(s)
|
79.6 pg/mL
Standard Deviation 186.56
|
|
Change in Cytokine and Chemokine Concentrations From Cycle 1 Day 1 to Cycle 1 Day 15
IL_15
|
2.38 pg/mL
Standard Deviation 5.96
|
3.02 pg/mL
Standard Deviation 5.51
|
2.07 pg/mL
Standard Deviation 4.4
|
-0.33 pg/mL
Standard Deviation 4.09
|
47.61 pg/mL
Standard Deviation 91.75
|
|
Change in Cytokine and Chemokine Concentrations From Cycle 1 Day 1 to Cycle 1 Day 15
IP_10
|
223.66 pg/mL
Standard Deviation 253.46
|
73.22 pg/mL
Standard Deviation 84.76
|
1175.68 pg/mL
Standard Deviation 1586.94
|
239.49 pg/mL
Standard Deviation 274.64
|
132.48 pg/mL
Standard Deviation 100.36
|
|
Change in Cytokine and Chemokine Concentrations From Cycle 1 Day 1 to Cycle 1 Day 15
MCP_1
|
30.2 pg/mL
Standard Deviation 64.74
|
39.38 pg/mL
Standard Deviation 57.61
|
-17.79 pg/mL
Standard Deviation 153.31
|
40.78 pg/mL
Standard Deviation 120.34
|
201.79 pg/mL
Standard Deviation 451.94
|
|
Change in Cytokine and Chemokine Concentrations From Cycle 1 Day 1 to Cycle 1 Day 15
MCP_3
|
2.83 pg/mL
Standard Deviation 4.32
|
2.17 pg/mL
Standard Deviation 3.21
|
1.96 pg/mL
Standard Deviation 1.13
|
-4.32 pg/mL
Standard Deviation 3.02
|
36 pg/mL
Standard Deviation 80.33
|
|
Change in Cytokine and Chemokine Concentrations From Cycle 1 Day 1 to Cycle 1 Day 15
M_CSF
|
24.85 pg/mL
Standard Deviation 63.97
|
0.65 pg/mL
Standard Deviation 59.02
|
32.91 pg/mL
Standard Deviation 40.45
|
—
|
6.92 pg/mL
Standard Deviation 115.1
|
|
Change in Cytokine and Chemokine Concentrations From Cycle 1 Day 1 to Cycle 1 Day 15
MDC
|
137.89 pg/mL
Standard Deviation 246.27
|
38.67 pg/mL
Standard Deviation 188.94
|
-2.49 pg/mL
Standard Deviation 583.2
|
240.73 pg/mL
Standard Deviation 264.68
|
253.38 pg/mL
Standard Deviation 337.61
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Up to 2 years after cycle 1, day 1. Each cycle is 21 days.Population: Blood samples failed quality control during testing therefore the specimen for the missing patients were not testable.
Change in peripheral blood immune cell subset percentages from Cycle 1 Day 1 (baseline) to Cycle 1 Day 15, calculated as the within-subject difference (Day 15 minus Day 1). Immune cell subsets were assessed using the Maxpar Direct Immune Profiling Assay (MDIPA) and included lymphocyte, T-cell, B-cell, natural killer (NK) cell, monocyte, and dendritic cell populations, including naïve, central memory, effector memory, terminal effector, regulatory T-cell, helper T-cell polarization, γδ T-cell, and MAIT/NKT-like subsets. Positive values indicate an increase from baseline, and negative values indicate a decrease from baseline.
Outcome measures
| Measure |
Dose Expansion Pancreatic Cancer (Arm A)
n=17 Participants
In the dose expansion phase, Arm A will be open for 16 patients with pancreatic adenocarcinoma. Patients must have histologic diagnosis and either locally advanced unresectable or metastatic disease that has failed at least one standard regimen. Eight patients will participate in the paired biopsy studies. Patient selected for biopsy must have a primary or metastatic non-bone site that is amenable to safe biopsy.
Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
XL888: Given PO
Pembrolizumab: Given IV
|
Dose Expansion Colorectal Cancer (Arm B)
n=16 Participants
In the dose expansion phase, Arm B will be open for 16 patients with colorectal adenocarcinoma. Patients must have histologic diagnosis and either locally advanced unresectable or metastatic disease and have previously received oxaliplatin, irinotecan, and a fluoropyrimidine. Eight patients will participate in the paired biopsy studies. Patient selected for biopsy must have a primary or metastatic non-bone site that is amenable to safe biopsy.
XL888: Given PO
Pembrolizumab: Given IV
|
Dose Escalation 45 mg PO Twice Weekly
n=3 Participants
In the dose escalation phase, the trial will be open for patients with stage IV or locally advanced unresectable gastrointestinal adenocarcinomas (gastric, GEJ, cholangiocarcinoma, hepatocellular, pancreas, small intestinal tumors) who have failed at least one prior therapy. Patients with colorectal cancer must have previously received oxaliplatin, irinotecan, and a fluoropyrimidine.
Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
XL888: Given PO
Pembrolizumab: Given IV
|
Dose Escalation 60 mg PO Twice Weekly
n=3 Participants
In the dose escalation phase, the trial will be open for patients with stage IV or locally advanced unresectable gastrointestinal adenocarcinomas (gastric, GEJ, cholangiocarcinoma, hepatocellular, pancreas, small intestinal tumors) who have failed at least one prior therapy. Patients with colorectal cancer must have previously received oxaliplatin, irinotecan, and a fluoropyrimidine.
Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
XL888: Given PO
Pembrolizumab: Given IV
|
Dose Escalation 90 mg PO Twice Weekly
n=8 Participants
In the dose escalation phase, the trial will be open for patients with stage IV or locally advanced unresectable gastrointestinal adenocarcinomas (gastric, GEJ, cholangiocarcinoma, hepatocellular, pancreas, small intestinal tumors) who have failed at least one prior therapy. Patients with colorectal cancer must have previously received oxaliplatin, irinotecan, and a fluoropyrimidine.
Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
XL888: Given PO
Pembrolizumab: Given IV
|
|---|---|---|---|---|---|
|
Change in Peripheral Blood Immune Cell Subsets From Cycle 1 Day 1 to Cycle 1 Day 15
CD4_T_CELLS_CD3
|
-0.37 Percentage points
Standard Deviation 3.83
|
-0.67 Percentage points
Standard Deviation 3.55
|
-2.9 Percentage points
Standard Deviation 8.23
|
-3.7 Percentage points
Standard Deviation 6.1
|
2.5 Percentage points
Standard Deviation 5.36
|
|
Change in Peripheral Blood Immune Cell Subsets From Cycle 1 Day 1 to Cycle 1 Day 15
TREG_CD4
|
0.41 Percentage points
Standard Deviation 0.73
|
0.95 Percentage points
Standard Deviation 1.36
|
2.46 Percentage points
Standard Deviation 1.86
|
0.51 Percentage points
Standard Deviation 1.14
|
-0.33 Percentage points
Standard Deviation 1.25
|
|
Change in Peripheral Blood Immune Cell Subsets From Cycle 1 Day 1 to Cycle 1 Day 15
GAMMA_DELTA_T_CELLS_LIVE
|
0.23 Percentage points
Standard Deviation 0.81
|
0.26 Percentage points
Standard Deviation 0.69
|
0.08 Percentage points
Standard Deviation 0.94
|
-0.01 Percentage points
Standard Deviation 0.62
|
-0.45 Percentage points
Standard Deviation 1.39
|
|
Change in Peripheral Blood Immune Cell Subsets From Cycle 1 Day 1 to Cycle 1 Day 15
GAMMA_DELTA_T_CELLS_CD3
|
-0.43 Percentage points
Standard Deviation 2.24
|
1.03 Percentage points
Standard Deviation 1.47
|
0.67 Percentage points
Standard Deviation 2.84
|
0.44 Percentage points
Standard Deviation 1.46
|
0.08 Percentage points
Standard Deviation 1.57
|
|
Change in Peripheral Blood Immune Cell Subsets From Cycle 1 Day 1 to Cycle 1 Day 15
MAIT_NKT_CD4_CELLS__LIVE
|
-0.21 Percentage points
Standard Deviation 0.32
|
-0.13 Percentage points
Standard Deviation 0.32
|
-0.15 Percentage points
Standard Deviation 0.29
|
-0.28 Percentage points
Standard Deviation 0.26
|
-0.04 Percentage points
Standard Deviation 0.22
|
|
Change in Peripheral Blood Immune Cell Subsets From Cycle 1 Day 1 to Cycle 1 Day 15
LYMPHOCYTES_LIVE
|
0.99 Percentage points
Standard Deviation 10.22
|
-4.81 Percentage points
Standard Deviation 8.72
|
-9.37 Percentage points
Standard Deviation 2.58
|
-9.31 Percentage points
Standard Deviation 12.39
|
-1.4 Percentage points
Standard Deviation 5.52
|
|
Change in Peripheral Blood Immune Cell Subsets From Cycle 1 Day 1 to Cycle 1 Day 15
CD3_T_CELLS_LIVE
|
1.48 Percentage points
Standard Deviation 8.69
|
-4.73 Percentage points
Standard Deviation 6.58
|
-11.01 Percentage points
Standard Deviation 0.96
|
-8.76 Percentage points
Standard Deviation 13.04
|
-5.51 Percentage points
Standard Deviation 5.83
|
|
Change in Peripheral Blood Immune Cell Subsets From Cycle 1 Day 1 to Cycle 1 Day 15
CD3_T_CELLS_LYMPHOCYTES
|
0.88 Percentage points
Standard Deviation 3.55
|
-1.98 Percentage points
Standard Deviation 4.62
|
-10.9 Percentage points
Standard Deviation 7.57
|
-3.48 Percentage points
Standard Deviation 6.21
|
-7.18 Percentage points
Standard Deviation 4.18
|
|
Change in Peripheral Blood Immune Cell Subsets From Cycle 1 Day 1 to Cycle 1 Day 15
CD8_T_CELLS_LIVE
|
0.86 Percentage points
Standard Deviation 2.94
|
-1.61 Percentage points
Standard Deviation 3.33
|
-1.35 Percentage points
Standard Deviation 2.2
|
-1.24 Percentage points
Standard Deviation 2.12
|
-3.14 Percentage points
Standard Deviation 4.12
|
|
Change in Peripheral Blood Immune Cell Subsets From Cycle 1 Day 1 to Cycle 1 Day 15
CD8_T_CELLS_CD3
|
1.54 Percentage points
Standard Deviation 3.55
|
-0.09 Percentage points
Standard Deviation 2.54
|
2.17 Percentage points
Standard Deviation 5.74
|
3.76 Percentage points
Standard Deviation 4.98
|
-2.73 Percentage points
Standard Deviation 4.09
|
|
Change in Peripheral Blood Immune Cell Subsets From Cycle 1 Day 1 to Cycle 1 Day 15
CD8_NA_VE_LIVE
|
-0.08 Percentage points
Standard Deviation 1.06
|
-0.81 Percentage points
Standard Deviation 1.18
|
-0.52 Percentage points
Standard Deviation 0.53
|
-2.32 Percentage points
Standard Deviation 2.06
|
-0.24 Percentage points
Standard Deviation 0.79
|
|
Change in Peripheral Blood Immune Cell Subsets From Cycle 1 Day 1 to Cycle 1 Day 15
CD8_NA_VE_CD8
|
-2.5 Percentage points
Standard Deviation 6.32
|
-3.15 Percentage points
Standard Deviation 8.45
|
-1.75 Percentage points
Standard Deviation 7.56
|
-14.6 Percentage points
Standard Deviation 17.7
|
2.02 Percentage points
Standard Deviation 7.49
|
|
Change in Peripheral Blood Immune Cell Subsets From Cycle 1 Day 1 to Cycle 1 Day 15
CD8_CM_LIVE
|
-0.03 Percentage points
Standard Deviation 0.29
|
-0.21 Percentage points
Standard Deviation 0.43
|
-0.43 Percentage points
Standard Deviation 0.16
|
-0.69 Percentage points
Standard Deviation 0.57
|
-0.38 Percentage points
Standard Deviation 0.67
|
|
Change in Peripheral Blood Immune Cell Subsets From Cycle 1 Day 1 to Cycle 1 Day 15
CD8_CM_CD8
|
-0.94 Percentage points
Standard Deviation 2.45
|
-0.12 Percentage points
Standard Deviation 1.68
|
-3.07 Percentage points
Standard Deviation 2.07
|
-3.82 Percentage points
Standard Deviation 2.58
|
-1.3 Percentage points
Standard Deviation 2.5
|
|
Change in Peripheral Blood Immune Cell Subsets From Cycle 1 Day 1 to Cycle 1 Day 15
CD8_EM_LIVE
|
0.37 Percentage points
Standard Deviation 1.24
|
-0.53 Percentage points
Standard Deviation 1.2
|
-0.26 Percentage points
Standard Deviation 0.63
|
0.31 Percentage points
Standard Deviation 1.31
|
-1.24 Percentage points
Standard Deviation 2.13
|
|
Change in Peripheral Blood Immune Cell Subsets From Cycle 1 Day 1 to Cycle 1 Day 15
CD8_EM_CD8
|
1.99 Percentage points
Standard Deviation 7.35
|
-0.1 Percentage points
Standard Deviation 7.9
|
0.47 Percentage points
Standard Deviation 0.95
|
3.69 Percentage points
Standard Deviation 6.5
|
-3.49 Percentage points
Standard Deviation 9.74
|
|
Change in Peripheral Blood Immune Cell Subsets From Cycle 1 Day 1 to Cycle 1 Day 15
CD8_TE_LIVE
|
0.58 Percentage points
Standard Deviation 1.42
|
-0.06 Percentage points
Standard Deviation 3.38
|
-0.14 Percentage points
Standard Deviation 1.79
|
1.25 Percentage points
Standard Deviation 1.53
|
-1.32 Percentage points
Standard Deviation 2.68
|
|
Change in Peripheral Blood Immune Cell Subsets From Cycle 1 Day 1 to Cycle 1 Day 15
CD8_TE_CD8
|
1.33 Percentage points
Standard Deviation 5.28
|
3.59 Percentage points
Standard Deviation 10.76
|
4.35 Percentage points
Standard Deviation 9.11
|
10.26 Percentage points
Standard Deviation 16.32
|
2.5 Percentage points
Standard Deviation 5.47
|
|
Change in Peripheral Blood Immune Cell Subsets From Cycle 1 Day 1 to Cycle 1 Day 15
CD4_T_CELLS_LIVE
|
0.6 Percentage points
Standard Deviation 5.56
|
-3.26 Percentage points
Standard Deviation 3.67
|
-9.59 Percentage points
Standard Deviation 3.6
|
-7.24 Percentage points
Standard Deviation 10.88
|
-1.88 Percentage points
Standard Deviation 2.11
|
|
Change in Peripheral Blood Immune Cell Subsets From Cycle 1 Day 1 to Cycle 1 Day 15
CD4_NA_VE_LIVE
|
1.06 Percentage points
Standard Deviation 2.74
|
-1.34 Percentage points
Standard Deviation 2.71
|
-1.96 Percentage points
Standard Deviation 3.56
|
-1.59 Percentage points
Standard Deviation 3.39
|
-0.11 Percentage points
Standard Deviation 2.59
|
|
Change in Peripheral Blood Immune Cell Subsets From Cycle 1 Day 1 to Cycle 1 Day 15
CD4_NA_VE_CD4
|
1.01 Percentage points
Standard Deviation 4.6
|
-0.67 Percentage points
Standard Deviation 9.19
|
-1.47 Percentage points
Standard Deviation 5.79
|
1.47 Percentage points
Standard Deviation 4.32
|
2.74 Percentage points
Standard Deviation 9.32
|
|
Change in Peripheral Blood Immune Cell Subsets From Cycle 1 Day 1 to Cycle 1 Day 15
CD4_CM_LIVE
|
-0.84 Percentage points
Standard Deviation 1.99
|
-1.55 Percentage points
Standard Deviation 2.35
|
-2.96 Percentage points
Standard Deviation 1.94
|
-3.52 Percentage points
Standard Deviation 6.21
|
0.52 Percentage points
Standard Deviation 1.9
|
|
Change in Peripheral Blood Immune Cell Subsets From Cycle 1 Day 1 to Cycle 1 Day 15
CD4_CM_CD4
|
-2.35 Percentage points
Standard Deviation 3.08
|
-3.09 Percentage points
Standard Deviation 7.65
|
-2.82 Percentage points
Standard Deviation 2.27
|
-3 Percentage points
Standard Deviation 5.56
|
3.48 Percentage points
Standard Deviation 6.14
|
|
Change in Peripheral Blood Immune Cell Subsets From Cycle 1 Day 1 to Cycle 1 Day 15
CD4_EM_LIVE
|
0.36 Percentage points
Standard Deviation 1.49
|
-0.64 Percentage points
Standard Deviation 1.55
|
-2.33 Percentage points
Standard Deviation 2.31
|
-1.67 Percentage points
Standard Deviation 0.96
|
-1.85 Percentage points
Standard Deviation 2.27
|
|
Change in Peripheral Blood Immune Cell Subsets From Cycle 1 Day 1 to Cycle 1 Day 15
CD4_EM_CD4
|
2.18 Percentage points
Standard Deviation 5.51
|
1.02 Percentage points
Standard Deviation 5.58
|
-1.2 Percentage points
Standard Deviation 2.95
|
-0.8 Percentage points
Standard Deviation 4.61
|
-4.61 Percentage points
Standard Deviation 5.14
|
|
Change in Peripheral Blood Immune Cell Subsets From Cycle 1 Day 1 to Cycle 1 Day 15
CD4_TE_LIVE
|
0.12 Percentage points
Standard Deviation 1.03
|
0.07 Percentage points
Standard Deviation 2.74
|
-2.34 Percentage points
Standard Deviation 4.41
|
-0.46 Percentage points
Standard Deviation 0.55
|
0.25 Percentage points
Standard Deviation 1.49
|
|
Change in Peripheral Blood Immune Cell Subsets From Cycle 1 Day 1 to Cycle 1 Day 15
CD4_TE_CD4
|
0.8 Percentage points
Standard Deviation 3.14
|
2.75 Percentage points
Standard Deviation 8.46
|
5.5 Percentage points
Standard Deviation 10.08
|
2.33 Percentage points
Standard Deviation 4.61
|
1.92 Percentage points
Standard Deviation 3.84
|
|
Change in Peripheral Blood Immune Cell Subsets From Cycle 1 Day 1 to Cycle 1 Day 15
TREG_LIVE
|
0.13 Percentage points
Standard Deviation 0.29
|
0.08 Percentage points
Standard Deviation 0.25
|
-0.13 Percentage points
Standard Deviation 0.48
|
-.011 Percentage points
Standard Deviation 0.14
|
-0.13 Percentage points
Standard Deviation 0.32
|
|
Change in Peripheral Blood Immune Cell Subsets From Cycle 1 Day 1 to Cycle 1 Day 15
TH1_LIKE_LIVE
|
-0.15 Percentage points
Standard Deviation 0.24
|
-0.08 Percentage points
Standard Deviation 0.21
|
-0.54 Percentage points
Standard Deviation 0.77
|
0.01 Percentage points
Standard Deviation 0.1
|
-0.06 Percentage points
Standard Deviation 0.23
|
|
Change in Peripheral Blood Immune Cell Subsets From Cycle 1 Day 1 to Cycle 1 Day 15
TH1_LIKE_CD4
|
-0.56 Percentage points
Standard Deviation 0.86
|
-0.22 Percentage points
Standard Deviation 0.58
|
-0.92 Percentage points
Standard Deviation 1.92
|
0.37 Percentage points
Standard Deviation 0.72
|
-0.42 Percentage points
Standard Deviation 1.14
|
|
Change in Peripheral Blood Immune Cell Subsets From Cycle 1 Day 1 to Cycle 1 Day 15
TH2_LIKE_LIVE
|
0.28 Percentage points
Standard Deviation 2.25
|
-1.05 Percentage points
Standard Deviation 1.71
|
-2.82 Percentage points
Standard Deviation 2.01
|
-2.17 Percentage points
Standard Deviation 2.4
|
0.19 Percentage points
Standard Deviation 1.15
|
|
Change in Peripheral Blood Immune Cell Subsets From Cycle 1 Day 1 to Cycle 1 Day 15
TH2_LIKE_CD4
|
0.89 Percentage points
Standard Deviation 4.66
|
-0.1 Percentage points
Standard Deviation 6.09
|
2.25 Percentage points
Standard Deviation 8.91
|
1.53 Percentage points
Standard Deviation 10.28
|
3.32 Percentage points
Standard Deviation 7.17
|
|
Change in Peripheral Blood Immune Cell Subsets From Cycle 1 Day 1 to Cycle 1 Day 15
TH17_LIKE_LIVE
|
-0.46 Percentage points
Standard Deviation 0.87
|
-0.23 Percentage points
Standard Deviation 0.79
|
-0.92 Percentage points
Standard Deviation 0.91
|
-1.25 Percentage points
Standard Deviation 1.39
|
-0.89 Percentage points
Standard Deviation 0.79
|
|
Change in Peripheral Blood Immune Cell Subsets From Cycle 1 Day 1 to Cycle 1 Day 15
TH17_LIKE_CD4
|
-1.22 Percentage points
Standard Deviation 3.35
|
-0.06 Percentage points
Standard Deviation 2.39
|
-2.16 Percentage points
Standard Deviation 4.29
|
-3.1 Percentage points
Standard Deviation 3.33
|
-3.41 Percentage points
Standard Deviation 3.76
|
|
Change in Peripheral Blood Immune Cell Subsets From Cycle 1 Day 1 to Cycle 1 Day 15
MAIT_NKT_CD4__CELLS_CD3
|
-0.75 Percentage points
Standard Deviation 0.53
|
-0.08 Percentage points
Standard Deviation 0.94
|
0.06 Percentage points
Standard Deviation 0.71
|
-0.49 Percentage points
Standard Deviation 0.69
|
0.15 Percentage points
Standard Deviation 0.46
|
|
Change in Peripheral Blood Immune Cell Subsets From Cycle 1 Day 1 to Cycle 1 Day 15
B_CELLS_LIVE
|
-0.59 Percentage points
Standard Deviation 1.35
|
-0.46 Percentage points
Standard Deviation 2.02
|
0 Percentage points
Standard Deviation 0.58
|
-2.77 Percentage points
Standard Deviation 1.28
|
1.35 Percentage points
Standard Deviation 3.07
|
|
Change in Peripheral Blood Immune Cell Subsets From Cycle 1 Day 1 to Cycle 1 Day 15
B_CELLS_LYMPHOCYTES
|
-0.77 Percentage points
Standard Deviation 1.62
|
0.04 Percentage points
Standard Deviation 2.74
|
1.59 Percentage points
Standard Deviation 1.25
|
-3.58 Percentage points
Standard Deviation 0.68
|
2.55 Percentage points
Standard Deviation 5.58
|
|
Change in Peripheral Blood Immune Cell Subsets From Cycle 1 Day 1 to Cycle 1 Day 15
B_CELLS_NA_VE_LIVE
|
-0.36 Percentage points
Standard Deviation 1.31
|
-0.4 Percentage points
Standard Deviation 1.91
|
0.15 Percentage points
Standard Deviation 0.61
|
-2.61 Percentage points
Standard Deviation 1.3
|
1.16 Percentage points
Standard Deviation 2.95
|
|
Change in Peripheral Blood Immune Cell Subsets From Cycle 1 Day 1 to Cycle 1 Day 15
B_CELLS_NA_VE_B_CELLS
|
9.63 Percentage points
Standard Deviation 11.61
|
1.04 Percentage points
Standard Deviation 2.53
|
10.76 Percentage points
Standard Deviation 13.49
|
-0.08 Percentage points
Standard Deviation 3.45
|
3 Percentage points
Standard Deviation 10.78
|
|
Change in Peripheral Blood Immune Cell Subsets From Cycle 1 Day 1 to Cycle 1 Day 15
B_CELLS_MEM_LIVE
|
-0.13 Percentage points
Standard Deviation 0.24
|
-0.08 Percentage points
Standard Deviation 0.14
|
-0.05 Percentage points
Standard Deviation 0.02
|
-0.24 Percentage points
Standard Deviation 0
|
0.23 Percentage points
Standard Deviation 0.3
|
|
Change in Peripheral Blood Immune Cell Subsets From Cycle 1 Day 1 to Cycle 1 Day 15
B_CELLS_MEM_B_CELLS
|
-5.09 Percentage points
Standard Deviation 5.76
|
-1.87 Percentage points
Standard Deviation 2.41
|
-3.07 Percentage points
Standard Deviation 0.24
|
-1.07 Percentage points
Standard Deviation 3.49
|
-2.16 Percentage points
Standard Deviation 7.38
|
|
Change in Peripheral Blood Immune Cell Subsets From Cycle 1 Day 1 to Cycle 1 Day 15
PLASMABLASTS__LIVE
|
-0.17 Percentage points
Standard Deviation 0.33
|
-0.06 Percentage points
Standard Deviation 0.08
|
-0.12 Percentage points
Standard Deviation 0.18
|
—
|
—
|
|
Change in Peripheral Blood Immune Cell Subsets From Cycle 1 Day 1 to Cycle 1 Day 15
PLASMABLASTS_B_CELLS
|
-5.95 Percentage points
Standard Deviation 9.68
|
-0.26 Percentage points
Standard Deviation 0.11
|
-11.94 Percentage points
Standard Deviation 15.76
|
—
|
—
|
|
Change in Peripheral Blood Immune Cell Subsets From Cycle 1 Day 1 to Cycle 1 Day 15
NK_CELLS_LIVE
|
0.1 Percentage points
Standard Deviation 1.27
|
0.4 Percentage points
Standard Deviation 3.88
|
1.64 Percentage points
Standard Deviation 2.51
|
2.22 Percentage points
Standard Deviation 1.91
|
2.76 Percentage points
Standard Deviation 2.75
|
|
Change in Peripheral Blood Immune Cell Subsets From Cycle 1 Day 1 to Cycle 1 Day 15
NK_CELLS_LYMPHOCYTES
|
-0.11 Percentage points
Standard Deviation 3.69
|
1.93 Percentage points
Standard Deviation 4.76
|
9.31 Percentage points
Standard Deviation 6.38
|
7.05 Percentage points
Standard Deviation 6.82
|
4.63 Percentage points
Standard Deviation 4.39
|
|
Change in Peripheral Blood Immune Cell Subsets From Cycle 1 Day 1 to Cycle 1 Day 15
MONOCYTES_LIVE
|
-2.08 Percentage points
Standard Deviation 11.48
|
4.61 Percentage points
Standard Deviation 10.02
|
10.02 Percentage points
Standard Deviation 8.84
|
8.85 Percentage points
Standard Deviation 8.92
|
0.51 Percentage points
Standard Deviation 6.16
|
|
Change in Peripheral Blood Immune Cell Subsets From Cycle 1 Day 1 to Cycle 1 Day 15
DENDRITIC_CELLS_LIVE
|
-0.22 Percentage points
Standard Deviation 0.42
|
-0.08 Percentage points
Standard Deviation 0.32
|
-0.56 Percentage points
Standard Deviation 0.88
|
-0.14 Percentage points
Standard Deviation 0.95
|
-0.48 Percentage points
Standard Deviation 0.14
|
Adverse Events
Dose Expansion Pancreatic Cancer (Arm A)
Serious events: 5 serious events
Other events: 0 other events
Deaths: 1 deaths
Dose Expansion Pancreatic Cancer (Arm B)
Serious events: 7 serious events
Other events: 1 other events
Deaths: 1 deaths
Dose Escalation 45 mg PO Twice Weekly
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Dose Escalation 60 mg PO Twice Weekly
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Dose Escalation 90 mg PO Twice Weekly
Serious events: 2 serious events
Other events: 1 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Dose Expansion Pancreatic Cancer (Arm A)
n=17 participants at risk
In the dose expansion phase, Arm A will be open for 16 patients with pancreatic adenocarcinoma. Patients must have histologic diagnosis and either locally advanced unresectable or metastatic disease that has failed at least one standard regimen. Eight patients will participate in the paired biopsy studies. Patient selected for biopsy must have a primary or metastatic non-bone site that is amenable to safe biopsy.
Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
XL888: Given PO
Pembrolizumab: Given IV
|
Dose Expansion Pancreatic Cancer (Arm B)
n=16 participants at risk
In the dose expansion phase, Arm B will be open for 16 patients with colorectal adenocarcinoma. Patients must have histologic diagnosis and either locally advanced unresectable or metastatic disease and have previously received oxaliplatin, irinotecan, and a fluoropyrimidine. Eight patients will participate in the paired biopsy studies. Patient selected for biopsy must have a primary or metastatic non-bone site that is amenable to safe biopsy.
XL888: Given PO
Pembrolizumab: Given IV
|
Dose Escalation 45 mg PO Twice Weekly
n=3 participants at risk
In the dose escalation phase, the trial will be open for patients with stage IV or locally advanced unresectable gastrointestinal adenocarcinomas (gastric, GEJ, cholangiocarcinoma, hepatocellular, pancreas, small intestinal tumors) who have failed at least one prior therapy. Patients with colorectal cancer must have previously received oxaliplatin, irinotecan, and a fluoropyrimidine.
Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
XL888: Given PO
Pembrolizumab: Given IV
|
Dose Escalation 60 mg PO Twice Weekly
n=3 participants at risk
In the dose escalation phase, the trial will be open for patients with stage IV or locally advanced unresectable gastrointestinal adenocarcinomas (gastric, GEJ, cholangiocarcinoma, hepatocellular, pancreas, small intestinal tumors) who have failed at least one prior therapy. Patients with colorectal cancer must have previously received oxaliplatin, irinotecan, and a fluoropyrimidine.
Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
XL888: Given PO
Pembrolizumab: Given IV
|
Dose Escalation 90 mg PO Twice Weekly
n=8 participants at risk
In the dose escalation phase, the trial will be open for patients with stage IV or locally advanced unresectable gastrointestinal adenocarcinomas (gastric, GEJ, cholangiocarcinoma, hepatocellular, pancreas, small intestinal tumors) who have failed at least one prior therapy. Patients with colorectal cancer must have previously received oxaliplatin, irinotecan, and a fluoropyrimidine.
Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
XL888: Given PO
Pembrolizumab: Given IV
|
|---|---|---|---|---|---|
|
Metabolism and nutrition disorders
Dehydration
|
29.4%
5/17 • Up to 1 year after cycle 1, day 1
|
0.00%
0/16 • Up to 1 year after cycle 1, day 1
|
0.00%
0/3 • Up to 1 year after cycle 1, day 1
|
0.00%
0/3 • Up to 1 year after cycle 1, day 1
|
0.00%
0/8 • Up to 1 year after cycle 1, day 1
|
|
General disorders
Fever
|
0.00%
0/17 • Up to 1 year after cycle 1, day 1
|
43.8%
7/16 • Up to 1 year after cycle 1, day 1
|
0.00%
0/3 • Up to 1 year after cycle 1, day 1
|
0.00%
0/3 • Up to 1 year after cycle 1, day 1
|
0.00%
0/8 • Up to 1 year after cycle 1, day 1
|
|
General disorders
Chills
|
0.00%
0/17 • Up to 1 year after cycle 1, day 1
|
43.8%
7/16 • Up to 1 year after cycle 1, day 1
|
0.00%
0/3 • Up to 1 year after cycle 1, day 1
|
0.00%
0/3 • Up to 1 year after cycle 1, day 1
|
0.00%
0/8 • Up to 1 year after cycle 1, day 1
|
|
Infections and infestations
Pelvic infection
|
0.00%
0/17 • Up to 1 year after cycle 1, day 1
|
43.8%
7/16 • Up to 1 year after cycle 1, day 1
|
0.00%
0/3 • Up to 1 year after cycle 1, day 1
|
0.00%
0/3 • Up to 1 year after cycle 1, day 1
|
0.00%
0/8 • Up to 1 year after cycle 1, day 1
|
|
Vascular disorders
Hypertension
|
0.00%
0/17 • Up to 1 year after cycle 1, day 1
|
43.8%
7/16 • Up to 1 year after cycle 1, day 1
|
0.00%
0/3 • Up to 1 year after cycle 1, day 1
|
0.00%
0/3 • Up to 1 year after cycle 1, day 1
|
0.00%
0/8 • Up to 1 year after cycle 1, day 1
|
|
General disorders
General disorders and administration site conditions - Other, specify
|
29.4%
5/17 • Up to 1 year after cycle 1, day 1
|
0.00%
0/16 • Up to 1 year after cycle 1, day 1
|
0.00%
0/3 • Up to 1 year after cycle 1, day 1
|
0.00%
0/3 • Up to 1 year after cycle 1, day 1
|
25.0%
2/8 • Up to 1 year after cycle 1, day 1
|
|
Nervous system disorders
Stroke
|
29.4%
5/17 • Up to 1 year after cycle 1, day 1
|
0.00%
0/16 • Up to 1 year after cycle 1, day 1
|
0.00%
0/3 • Up to 1 year after cycle 1, day 1
|
0.00%
0/3 • Up to 1 year after cycle 1, day 1
|
0.00%
0/8 • Up to 1 year after cycle 1, day 1
|
|
Gastrointestinal disorders
Dyspepsia
|
29.4%
5/17 • Up to 1 year after cycle 1, day 1
|
0.00%
0/16 • Up to 1 year after cycle 1, day 1
|
0.00%
0/3 • Up to 1 year after cycle 1, day 1
|
0.00%
0/3 • Up to 1 year after cycle 1, day 1
|
0.00%
0/8 • Up to 1 year after cycle 1, day 1
|
|
Eye disorders
Periorbital edema
|
29.4%
5/17 • Up to 1 year after cycle 1, day 1
|
0.00%
0/16 • Up to 1 year after cycle 1, day 1
|
0.00%
0/3 • Up to 1 year after cycle 1, day 1
|
0.00%
0/3 • Up to 1 year after cycle 1, day 1
|
0.00%
0/8 • Up to 1 year after cycle 1, day 1
|
|
Gastrointestinal disorders
Diarrhea
|
29.4%
5/17 • Up to 1 year after cycle 1, day 1
|
0.00%
0/16 • Up to 1 year after cycle 1, day 1
|
0.00%
0/3 • Up to 1 year after cycle 1, day 1
|
0.00%
0/3 • Up to 1 year after cycle 1, day 1
|
0.00%
0/8 • Up to 1 year after cycle 1, day 1
|
|
Gastrointestinal disorders
Constipation
|
29.4%
5/17 • Up to 1 year after cycle 1, day 1
|
0.00%
0/16 • Up to 1 year after cycle 1, day 1
|
0.00%
0/3 • Up to 1 year after cycle 1, day 1
|
0.00%
0/3 • Up to 1 year after cycle 1, day 1
|
0.00%
0/8 • Up to 1 year after cycle 1, day 1
|
|
Gastrointestinal disorders
Nausea
|
29.4%
5/17 • Up to 1 year after cycle 1, day 1
|
0.00%
0/16 • Up to 1 year after cycle 1, day 1
|
0.00%
0/3 • Up to 1 year after cycle 1, day 1
|
0.00%
0/3 • Up to 1 year after cycle 1, day 1
|
0.00%
0/8 • Up to 1 year after cycle 1, day 1
|
|
Gastrointestinal disorders
Vomiting
|
29.4%
5/17 • Up to 1 year after cycle 1, day 1
|
0.00%
0/16 • Up to 1 year after cycle 1, day 1
|
0.00%
0/3 • Up to 1 year after cycle 1, day 1
|
0.00%
0/3 • Up to 1 year after cycle 1, day 1
|
0.00%
0/8 • Up to 1 year after cycle 1, day 1
|
|
Blood and lymphatic system disorders
Blood and lymphatic system disorders - Other, specify
|
0.00%
0/17 • Up to 1 year after cycle 1, day 1
|
43.8%
7/16 • Up to 1 year after cycle 1, day 1
|
0.00%
0/3 • Up to 1 year after cycle 1, day 1
|
0.00%
0/3 • Up to 1 year after cycle 1, day 1
|
0.00%
0/8 • Up to 1 year after cycle 1, day 1
|
|
Infections and infestations
Tooth infection
|
0.00%
0/17 • Up to 1 year after cycle 1, day 1
|
43.8%
7/16 • Up to 1 year after cycle 1, day 1
|
0.00%
0/3 • Up to 1 year after cycle 1, day 1
|
0.00%
0/3 • Up to 1 year after cycle 1, day 1
|
0.00%
0/8 • Up to 1 year after cycle 1, day 1
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/17 • Up to 1 year after cycle 1, day 1
|
43.8%
7/16 • Up to 1 year after cycle 1, day 1
|
0.00%
0/3 • Up to 1 year after cycle 1, day 1
|
0.00%
0/3 • Up to 1 year after cycle 1, day 1
|
0.00%
0/8 • Up to 1 year after cycle 1, day 1
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
0.00%
0/17 • Up to 1 year after cycle 1, day 1
|
43.8%
7/16 • Up to 1 year after cycle 1, day 1
|
0.00%
0/3 • Up to 1 year after cycle 1, day 1
|
0.00%
0/3 • Up to 1 year after cycle 1, day 1
|
0.00%
0/8 • Up to 1 year after cycle 1, day 1
|
|
Nervous system disorders
Paresthesia
|
0.00%
0/17 • Up to 1 year after cycle 1, day 1
|
43.8%
7/16 • Up to 1 year after cycle 1, day 1
|
0.00%
0/3 • Up to 1 year after cycle 1, day 1
|
0.00%
0/3 • Up to 1 year after cycle 1, day 1
|
0.00%
0/8 • Up to 1 year after cycle 1, day 1
|
|
Eye disorders
Retinopathy
|
0.00%
0/17 • Up to 1 year after cycle 1, day 1
|
0.00%
0/16 • Up to 1 year after cycle 1, day 1
|
0.00%
0/3 • Up to 1 year after cycle 1, day 1
|
0.00%
0/3 • Up to 1 year after cycle 1, day 1
|
25.0%
2/8 • Up to 1 year after cycle 1, day 1
|
|
Immune system disorders
Autoimmune disorder
|
0.00%
0/17 • Up to 1 year after cycle 1, day 1
|
0.00%
0/16 • Up to 1 year after cycle 1, day 1
|
0.00%
0/3 • Up to 1 year after cycle 1, day 1
|
0.00%
0/3 • Up to 1 year after cycle 1, day 1
|
25.0%
2/8 • Up to 1 year after cycle 1, day 1
|
Other adverse events
| Measure |
Dose Expansion Pancreatic Cancer (Arm A)
n=17 participants at risk
In the dose expansion phase, Arm A will be open for 16 patients with pancreatic adenocarcinoma. Patients must have histologic diagnosis and either locally advanced unresectable or metastatic disease that has failed at least one standard regimen. Eight patients will participate in the paired biopsy studies. Patient selected for biopsy must have a primary or metastatic non-bone site that is amenable to safe biopsy.
Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
XL888: Given PO
Pembrolizumab: Given IV
|
Dose Expansion Pancreatic Cancer (Arm B)
n=16 participants at risk
In the dose expansion phase, Arm B will be open for 16 patients with colorectal adenocarcinoma. Patients must have histologic diagnosis and either locally advanced unresectable or metastatic disease and have previously received oxaliplatin, irinotecan, and a fluoropyrimidine. Eight patients will participate in the paired biopsy studies. Patient selected for biopsy must have a primary or metastatic non-bone site that is amenable to safe biopsy.
XL888: Given PO
Pembrolizumab: Given IV
|
Dose Escalation 45 mg PO Twice Weekly
n=3 participants at risk
In the dose escalation phase, the trial will be open for patients with stage IV or locally advanced unresectable gastrointestinal adenocarcinomas (gastric, GEJ, cholangiocarcinoma, hepatocellular, pancreas, small intestinal tumors) who have failed at least one prior therapy. Patients with colorectal cancer must have previously received oxaliplatin, irinotecan, and a fluoropyrimidine.
Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
XL888: Given PO
Pembrolizumab: Given IV
|
Dose Escalation 60 mg PO Twice Weekly
n=3 participants at risk
In the dose escalation phase, the trial will be open for patients with stage IV or locally advanced unresectable gastrointestinal adenocarcinomas (gastric, GEJ, cholangiocarcinoma, hepatocellular, pancreas, small intestinal tumors) who have failed at least one prior therapy. Patients with colorectal cancer must have previously received oxaliplatin, irinotecan, and a fluoropyrimidine.
Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
XL888: Given PO
Pembrolizumab: Given IV
|
Dose Escalation 90 mg PO Twice Weekly
n=8 participants at risk
In the dose escalation phase, the trial will be open for patients with stage IV or locally advanced unresectable gastrointestinal adenocarcinomas (gastric, GEJ, cholangiocarcinoma, hepatocellular, pancreas, small intestinal tumors) who have failed at least one prior therapy. Patients with colorectal cancer must have previously received oxaliplatin, irinotecan, and a fluoropyrimidine.
Patients receive pembrolizumab IV over 30 minutes on day 1 and XL888 PO on days 1, 4, 8, 11, 15, and 18. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
XL888: Given PO
Pembrolizumab: Given IV
|
|---|---|---|---|---|---|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/17 • Up to 1 year after cycle 1, day 1
|
6.2%
1/16 • Up to 1 year after cycle 1, day 1
|
0.00%
0/3 • Up to 1 year after cycle 1, day 1
|
0.00%
0/3 • Up to 1 year after cycle 1, day 1
|
0.00%
0/8 • Up to 1 year after cycle 1, day 1
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/17 • Up to 1 year after cycle 1, day 1
|
6.2%
1/16 • Up to 1 year after cycle 1, day 1
|
0.00%
0/3 • Up to 1 year after cycle 1, day 1
|
0.00%
0/3 • Up to 1 year after cycle 1, day 1
|
0.00%
0/8 • Up to 1 year after cycle 1, day 1
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/17 • Up to 1 year after cycle 1, day 1
|
0.00%
0/16 • Up to 1 year after cycle 1, day 1
|
0.00%
0/3 • Up to 1 year after cycle 1, day 1
|
0.00%
0/3 • Up to 1 year after cycle 1, day 1
|
12.5%
1/8 • Up to 1 year after cycle 1, day 1
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/17 • Up to 1 year after cycle 1, day 1
|
0.00%
0/16 • Up to 1 year after cycle 1, day 1
|
0.00%
0/3 • Up to 1 year after cycle 1, day 1
|
0.00%
0/3 • Up to 1 year after cycle 1, day 1
|
12.5%
1/8 • Up to 1 year after cycle 1, day 1
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place