Trial Outcomes & Findings for A Phase 1b/2 Study of Safety and Efficacy of Rociletinib in Combination With MPDL3280A in Patients With Advanced or Metastatic EGFR-mutant NSCLC (NCT NCT02630186)

Last Updated: 2019-07-05

Results Overview

The safety analyses will be performed using the safety population. Safety data analysis will be conducted on all patients receiving at least one dose of rociletinib or MPDL3280A.

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

3 participants

Primary outcome timeframe

Continuously, up to approximately 18.5 months

Results posted on

2019-07-05

Participant Flow

Three patients were enrolled at a single center in the United States.

The Dose Finding Phase included a 7 day Run in Period of rociletinib monotherapy, at the Dosing Cohort-defined dose level, prior to the initiation of combination treatment.

Participant milestones

Participant milestones
Measure	Single Arm Rociletinib and MPDL3280A in Combination Rociletinib (CO-1686), a novel, potent, covalent (irreversible) small molecule, tyrosine kinase inhibitor (TKI) administered orally (PO) to patients with EGFRm NSCLC in combination with MPDL3280A, a human IgG1 monoclonal antibody administered intravenously (IV).
Overall Study STARTED	3
Overall Study COMPLETED	2
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Single Arm Rociletinib and MPDL3280A in Combination Rociletinib (CO-1686), a novel, potent, covalent (irreversible) small molecule, tyrosine kinase inhibitor (TKI) administered orally (PO) to patients with EGFRm NSCLC in combination with MPDL3280A, a human IgG1 monoclonal antibody administered intravenously (IV).
Overall Study Withdrawal by Subject	1

Baseline Characteristics

A Phase 1b/2 Study of Safety and Efficacy of Rociletinib in Combination With MPDL3280A in Patients With Advanced or Metastatic EGFR-mutant NSCLC

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Single Arm Rociletinib and MPDL3280A in Combination n=3 Participants Rociletinib (CO-1686), a novel, potent, covalent (irreversible) small molecule, tyrosine kinase inhibitor (TKI) administered orally (PO) to patients with EGFRm NSCLC in combination with MPDL3280A, a human IgG1 monoclonal antibody administered intravenously (IV).
Age, Categorical <=18 years	0 Participants n=99 Participants
Age, Categorical Between 18 and 65 years	1 Participants n=99 Participants
Age, Categorical >=65 years	2 Participants n=99 Participants
Age, Continuous	66 years n=99 Participants
Sex: Female, Male Female	3 Participants n=99 Participants
Sex: Female, Male Male	0 Participants n=99 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants
Race (NIH/OMB) Asian	1 Participants n=99 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants
Race (NIH/OMB) Black or African American	0 Participants n=99 Participants
Race (NIH/OMB) White	2 Participants n=99 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants
Region of Enrollment United States	3 participants n=99 Participants

PRIMARY outcome

Timeframe: Continuously, up to approximately 18.5 months

Population: All patients enrolled in the study.

The safety analyses will be performed using the safety population. Safety data analysis will be conducted on all patients receiving at least one dose of rociletinib or MPDL3280A.

Outcome measures

Outcome measures
Measure	Single Arm Rociletinib and MPDL3280A in Combination n=3 Participants Rociletinib (CO-1686), a novel, potent, covalent (irreversible) small molecule, tyrosine kinase inhibitor (TKI) administered orally (PO) to patients with EGFRm NSCLC in combination with MPDL3280A, a human IgG1 monoclonal antibody administered intravenously (IV).
Number of Treatment-emergent Adverse Events, as Assessed by NCI CTCAE v4.03	31 Treatment emergent adverse events

PRIMARY outcome

Timeframe: Treatment Day 1 and Day 15

Population: Due to the small number of patients enrolled and small number of PK samples collected as a result of early termination of the study, these analyses were not conducted.

Blood sampling for PK analyses of both rociletinib and MPDL3280A will be conducted in all patients treated with rociletinib and MPDL3280A. Cmax will be estimated for rociletinib, using non-compartmental models. Comparisons across dose levels will be made to assess proportionality.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Treatment Day 1 and Day 15

Population: Due to the small number of patients enrolled and small number of PK samples collected as a result of early termination of the study, these analyses were not conducted.

Blood sampling for PK analyses of both rociletinib and MPDL3280A will be conducted in all patients treated with rociletinib and MPDL3280A. Tmax will be estimated for rociletinib, using non-compartmental models. Comparisons across dose levels will be made to assess proportionality.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Approximately every 6 weeks up to 24 months

Population: Due to the small number of patients enrolled and small number of PK samples collected as a result of early termination of the study, these analyses were not conducted.

Blood sampling for PK analyses of both rociletinib and MPDL3280A will be conducted in all patients treated with rociletinib and MPDL3280A. Cmin will be estimated for rociletinib, using non-compartmental models. Comparisons across dose levels will be made to assess proportionality.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Treatment Day 1 and Day 8

Population: Due to the small number of patients enrolled and small number of PK sample collected as a result of early termination of the study, these analyses were not conducted.

Blood sampling for PK analyses of both rociletinib and MPDL3280A will be conducted in all patients treated with rociletinib and MPDL3280A. AUC0 24 will be estimated for rociletinib, using non-compartmental models. Comparisons across dose levels will be made to assess proportionality.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Cycle 1 Day 1

Population: Due to the small number of patients enrolled and small number of PK samples collected as a result of early termination of the study, these analyses were not conducted.

Blood sampling for PK analyses of both rociletinib and MPDL3280A will be conducted in all patients treated with rociletinib and MPDL3280A. Cmax, for MPDL3280A will be assessed using non-compartmental models. Comparisons across dose levels will be made to assess proportionality.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Approximately every 6 weeks up to 24 months

Population: Due to the small number of patients enrolled and small number of PK samples collected as a result of early termination of the study, these analyses were not conducted.

Blood sampling for PK analyses of both rociletinib and MPDL3280A will be conducted in all patients treated with rociletinib and MPDL3280A. Cmin for MPDL3280A will be assessed using non-compartmental models. Comparisons across dose levels will be made to assess proportionality.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Approximately every 6-9 weeks

Population: Given the early termination of the study and that no patients were enrolled in Phase 2 of the study, no conclusions can be drawn.

To determine the efficacy of the combination of rociletinib and MPDL3280A based on overall response rate per RECIST v1.1 in the following groups of patients: * Group A: Patients with EGFRm advanced or metastatic NSCLC who have not previously received an EGFR TKI or chemotherapy. * Group B: Patients with EGFRm advanced or metastatic NSCLC who have progressed on a prior EGFR TKI.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Approximately every 6-9 weeks, up to 24 months

Population: Given the early termination of the study and that no patients were enrolled in Phase 2 of the study, no conclusions can be drawn.

Conventional response criteria may not be adequate to characterize the antitumor activity of immunotherapeutic agents like MPDL3280A, which can produce delayed responses that may be preceded by initial apparent radiological progression, including the appearance of new lesions. Therefore, modified response criteria have been developed that account for the possible appearance of new lesions and allow radiological progression to be confirmed at a subsequent assessment. In this protocol, patients will be permitted to continue study treatment even after modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria for progressive disease are met if the benefit-risk ratio is judged to be favorable. These modified criteria are derived from RECIST version 1.1 (v1.1) conventions and immune related response criteria (irRC).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Approximately every 6-9 weeks, up to 24 months

Population: Given the early termination of the study and that no patients were enrolled in Phase 2 of the study, no conclusions can be drawn.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Approximately every 6-9 weeks, up to 24 months

Population: Given the early termination of the study and that no patients were enrolled in Phase 2 of the study, no conclusions can be drawn.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to approximately 18.5 months

Population: Count of the number of enrolled patients alive at study termination.

Patients who received the combination of rociletinib and MPDL3280A alive at the termination of this study.

Outcome measures

Outcome measures
Measure	Single Arm Rociletinib and MPDL3280A in Combination n=2 Participants Rociletinib (CO-1686), a novel, potent, covalent (irreversible) small molecule, tyrosine kinase inhibitor (TKI) administered orally (PO) to patients with EGFRm NSCLC in combination with MPDL3280A, a human IgG1 monoclonal antibody administered intravenously (IV).
Number of Patients Alive at Study Termination	2 participants

SECONDARY outcome

Timeframe: Blood samples will be collected from each patient approximately every 3 weeks, up to 24 months

Population: Due to the small number of patients enrolled and small number of samples collected as a result of early termination of the study, these analyses were not conducted.

Tumor tissue, plasma, and blood specimens will be used for pharmacodynamic assessment of rociletinib and/or MPDL3280A activity, to evaluate the concordance of mutant EGFR detection between tissue and plasma, and to explore biomarkers that may be predictive of response or resistance to rociletinib and/or MPDL3280A. Biomarkers and changes in biomarker status will be investigated for associations with rociletinib and/or MPDL3280A exposure, safety, and clinical activity. Given the limited sample size, no formal statistical analysis is planned.

Outcome measures

Outcome data not reported

Adverse Events

Single Arm Rociletinib and MPDL3280A in Combination

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Single Arm Rociletinib and MPDL3280A in Combination n=3 participants at risk Rociletinib (CO-1686), a novel, potent, covalent (irreversible) small molecule, tyrosine kinase inhibitor (TKI) administered orally (PO) to patients with EGFRm NSCLC in combination with MPDL3280A, a human IgG1 monoclonal antibody administered intravenously (IV).
Gastrointestinal disorders Pancreatitis	33.3% 1/3 • Number of events 1 • Adverse events were reported from the date of first dose of study drug and until 28 days after the last dose of study drug. One patient withdrew consent during the washout period having only received rociletinib. This patient did not receive MPDL3280A.

Other adverse events

Other adverse events
Measure	Single Arm Rociletinib and MPDL3280A in Combination n=3 participants at risk Rociletinib (CO-1686), a novel, potent, covalent (irreversible) small molecule, tyrosine kinase inhibitor (TKI) administered orally (PO) to patients with EGFRm NSCLC in combination with MPDL3280A, a human IgG1 monoclonal antibody administered intravenously (IV).
Gastrointestinal disorders Nausea	66.7% 2/3 • Number of events 2 • Adverse events were reported from the date of first dose of study drug and until 28 days after the last dose of study drug. One patient withdrew consent during the washout period having only received rociletinib. This patient did not receive MPDL3280A.
Metabolism and nutrition disorders Hyperglycemia	33.3% 1/3 • Number of events 3 • Adverse events were reported from the date of first dose of study drug and until 28 days after the last dose of study drug. One patient withdrew consent during the washout period having only received rociletinib. This patient did not receive MPDL3280A.
Gastrointestinal disorders Diarrhea	100.0% 3/3 • Number of events 3 • Adverse events were reported from the date of first dose of study drug and until 28 days after the last dose of study drug. One patient withdrew consent during the washout period having only received rociletinib. This patient did not receive MPDL3280A.
Investigations Increased Blood Sugar	33.3% 1/3 • Number of events 1 • Adverse events were reported from the date of first dose of study drug and until 28 days after the last dose of study drug. One patient withdrew consent during the washout period having only received rociletinib. This patient did not receive MPDL3280A.
Gastrointestinal disorders Gastroesophageal reflux disease	33.3% 1/3 • Number of events 1 • Adverse events were reported from the date of first dose of study drug and until 28 days after the last dose of study drug. One patient withdrew consent during the washout period having only received rociletinib. This patient did not receive MPDL3280A.
Blood and lymphatic system disorders Anemia	33.3% 1/3 • Number of events 1 • Adverse events were reported from the date of first dose of study drug and until 28 days after the last dose of study drug. One patient withdrew consent during the washout period having only received rociletinib. This patient did not receive MPDL3280A.
Metabolism and nutrition disorders Hyponatremia	33.3% 1/3 • Number of events 1 • Adverse events were reported from the date of first dose of study drug and until 28 days after the last dose of study drug. One patient withdrew consent during the washout period having only received rociletinib. This patient did not receive MPDL3280A.
General disorders Fatigue	33.3% 1/3 • Number of events 1 • Adverse events were reported from the date of first dose of study drug and until 28 days after the last dose of study drug. One patient withdrew consent during the washout period having only received rociletinib. This patient did not receive MPDL3280A.
Investigations Stomach Pain	33.3% 1/3 • Number of events 1 • Adverse events were reported from the date of first dose of study drug and until 28 days after the last dose of study drug. One patient withdrew consent during the washout period having only received rociletinib. This patient did not receive MPDL3280A.
Musculoskeletal and connective tissue disorders Muscle Cramps	66.7% 2/3 • Number of events 2 • Adverse events were reported from the date of first dose of study drug and until 28 days after the last dose of study drug. One patient withdrew consent during the washout period having only received rociletinib. This patient did not receive MPDL3280A.
Investigations Weight decreased	33.3% 1/3 • Number of events 1 • Adverse events were reported from the date of first dose of study drug and until 28 days after the last dose of study drug. One patient withdrew consent during the washout period having only received rociletinib. This patient did not receive MPDL3280A.
Investigations Prolonged QTc interval	33.3% 1/3 • Number of events 2 • Adverse events were reported from the date of first dose of study drug and until 28 days after the last dose of study drug. One patient withdrew consent during the washout period having only received rociletinib. This patient did not receive MPDL3280A.
Infections and infestations Cellulitis	33.3% 1/3 • Number of events 1 • Adverse events were reported from the date of first dose of study drug and until 28 days after the last dose of study drug. One patient withdrew consent during the washout period having only received rociletinib. This patient did not receive MPDL3280A.
Investigations Intermittent epigastric discomfort	33.3% 1/3 • Number of events 1 • Adverse events were reported from the date of first dose of study drug and until 28 days after the last dose of study drug. One patient withdrew consent during the washout period having only received rociletinib. This patient did not receive MPDL3280A.
Gastrointestinal disorders Stomach Pain	33.3% 1/3 • Number of events 2 • Adverse events were reported from the date of first dose of study drug and until 28 days after the last dose of study drug. One patient withdrew consent during the washout period having only received rociletinib. This patient did not receive MPDL3280A.
Metabolism and nutrition disorders Anorexia	33.3% 1/3 • Number of events 1 • Adverse events were reported from the date of first dose of study drug and until 28 days after the last dose of study drug. One patient withdrew consent during the washout period having only received rociletinib. This patient did not receive MPDL3280A.
Skin and subcutaneous tissue disorders Ecchymosis	33.3% 1/3 • Number of events 1 • Adverse events were reported from the date of first dose of study drug and until 28 days after the last dose of study drug. One patient withdrew consent during the washout period having only received rociletinib. This patient did not receive MPDL3280A.
Gastrointestinal disorders Epigastric pain	33.3% 1/3 • Number of events 1 • Adverse events were reported from the date of first dose of study drug and until 28 days after the last dose of study drug. One patient withdrew consent during the washout period having only received rociletinib. This patient did not receive MPDL3280A.
Ear and labyrinth disorders Eustachian tube dysfunction	33.3% 1/3 • Number of events 1 • Adverse events were reported from the date of first dose of study drug and until 28 days after the last dose of study drug. One patient withdrew consent during the washout period having only received rociletinib. This patient did not receive MPDL3280A.
Ear and labyrinth disorders Bilateral hearing loss	33.3% 1/3 • Number of events 1 • Adverse events were reported from the date of first dose of study drug and until 28 days after the last dose of study drug. One patient withdrew consent during the washout period having only received rociletinib. This patient did not receive MPDL3280A.
Infections and infestations Urinary tract infection	33.3% 1/3 • Number of events 2 • Adverse events were reported from the date of first dose of study drug and until 28 days after the last dose of study drug. One patient withdrew consent during the washout period having only received rociletinib. This patient did not receive MPDL3280A.
Renal and urinary disorders Dysuria	33.3% 1/3 • Number of events 1 • Adverse events were reported from the date of first dose of study drug and until 28 days after the last dose of study drug. One patient withdrew consent during the washout period having only received rociletinib. This patient did not receive MPDL3280A.
Skin and subcutaneous tissue disorders Firm raised lesion, dorsum of left foot	33.3% 1/3 • Number of events 1 • Adverse events were reported from the date of first dose of study drug and until 28 days after the last dose of study drug. One patient withdrew consent during the washout period having only received rociletinib. This patient did not receive MPDL3280A.
Eye disorders Cataracts	33.3% 1/3 • Number of events 1 • Adverse events were reported from the date of first dose of study drug and until 28 days after the last dose of study drug. One patient withdrew consent during the washout period having only received rociletinib. This patient did not receive MPDL3280A.
Nervous system disorders Headache	33.3% 1/3 • Number of events 2 • Adverse events were reported from the date of first dose of study drug and until 28 days after the last dose of study drug. One patient withdrew consent during the washout period having only received rociletinib. This patient did not receive MPDL3280A.
General disorders Swelling finger	33.3% 1/3 • Number of events 1 • Adverse events were reported from the date of first dose of study drug and until 28 days after the last dose of study drug. One patient withdrew consent during the washout period having only received rociletinib. This patient did not receive MPDL3280A.
Investigations Elevated aspartate aminotransferase	33.3% 1/3 • Number of events 1 • Adverse events were reported from the date of first dose of study drug and until 28 days after the last dose of study drug. One patient withdrew consent during the washout period having only received rociletinib. This patient did not receive MPDL3280A.
Investigations Elevated alanine aminotransferase	33.3% 1/3 • Number of events 1 • Adverse events were reported from the date of first dose of study drug and until 28 days after the last dose of study drug. One patient withdrew consent during the washout period having only received rociletinib. This patient did not receive MPDL3280A.
Investigations Elevated blood alkaline phosphatase	33.3% 1/3 • Number of events 1 • Adverse events were reported from the date of first dose of study drug and until 28 days after the last dose of study drug. One patient withdrew consent during the washout period having only received rociletinib. This patient did not receive MPDL3280A.
Infections and infestations Herpes virus reactivation	33.3% 1/3 • Number of events 1 • Adverse events were reported from the date of first dose of study drug and until 28 days after the last dose of study drug. One patient withdrew consent during the washout period having only received rociletinib. This patient did not receive MPDL3280A.

Additional Information

Elizabeth Bradley

Clovis Oncology, Inc.

Phone: 1-415-409-5495

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place