Trial Outcomes & Findings for Insulin-like Growth Factor 1 Receptor (IGF-1R) Antibody AMG479 (Ganitumab) in Combination With the Src Family Kinase (SFK) Inhibitor Dasatinib in People With Embryonal and Alveolar Rhabdomyosarcoma (NCT NCT03041701)

Last Updated: 2022-04-14

Results Overview

The safe dose or maximum tolerated dose (MTD) is defined as the dose level at which no more than 1 of up to 3-6 participants experience a dose-limiting toxicity (DLT) during the first cycle of treatment, and the dose below that at which at least 2 (of ≤6) participants have DLT as a result of the drug. A DLT is any toxicity of grade 3 or higher, with the specific exception of grade 3 nausea and vomiting of \< 5 days duration, grade 3 fever or infection \< 5 days duration, and grade 3 neutropenia or thrombocytopenia, for example.

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

14 participants

Primary outcome timeframe

First 35 days of treatment

Results posted on

2022-04-14

Participant Flow

Participant milestones

Participant milestones
Measure	Phase 1 Dose Level 1 Dose Escalation Dasatinib 60 mg/m^2 Every Day (QD)/Ganitumab 18 mg/kg Phase 1 Dose Level 1 Dose Escalation: Dasatinib 60mg/m\^2 by mouth (PO) every day (QD) at Day-7. Ganitumab 18mg/kg intravenous (IV) every two weeks starting at Day 0. Cycle 1 is Day -7 to 27; all other cycles are Day 0 to 27	Phase 1 Dose Level 2 Dose Escalation Dasatinib 60 mg/m^2 Twice Daily (BID)/Ganitumab 18 mg/kg Phase 1 Dose Level 2 Dose Escalation: Dasatinib 60mg/m\^2 by mouth (PO) twice a day (BID) at Day-7. Ganitumab 18mg/kg intravenous (IV) every two weeks starting at Day 0. Cycle 1 is Day -7 to 27; all other cycles are Day 0 to 27	Phase 2 Dose Level 1 Maximum Tolerated Dose Dasatinib 60 mg/m^2 Every Day (QD)/ Ganitumab 18 mg/kg Phase 2 Dose Level 1 Maximum Tolerated Dose: Dasatinib 60mg/m\^2 by mouth (PO) every day (QD) at Day-7. Ganitumab 18mg/kg intravenous (IV) every two weeks starting at Day 0. Cycle 1 is Day -7 to 27; all other cycles are Day 0 to 27
Ph I: Dose Level 1 and 2 Dose Escalation STARTED	7	6	0
Ph I: Dose Level 1 and 2 Dose Escalation COMPLETED	6	5	0
Ph I: Dose Level 1 and 2 Dose Escalation NOT COMPLETED	1	1	0
Ph 2:Dose Level 1 Maximum Tolerated Dose STARTED	0	0	1
Ph 2:Dose Level 1 Maximum Tolerated Dose COMPLETED	0	0	0
Ph 2:Dose Level 1 Maximum Tolerated Dose NOT COMPLETED	0	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Phase 1 Dose Level 1 Dose Escalation Dasatinib 60 mg/m^2 Every Day (QD)/Ganitumab 18 mg/kg Phase 1 Dose Level 1 Dose Escalation: Dasatinib 60mg/m\^2 by mouth (PO) every day (QD) at Day-7. Ganitumab 18mg/kg intravenous (IV) every two weeks starting at Day 0. Cycle 1 is Day -7 to 27; all other cycles are Day 0 to 27	Phase 1 Dose Level 2 Dose Escalation Dasatinib 60 mg/m^2 Twice Daily (BID)/Ganitumab 18 mg/kg Phase 1 Dose Level 2 Dose Escalation: Dasatinib 60mg/m\^2 by mouth (PO) twice a day (BID) at Day-7. Ganitumab 18mg/kg intravenous (IV) every two weeks starting at Day 0. Cycle 1 is Day -7 to 27; all other cycles are Day 0 to 27	Phase 2 Dose Level 1 Maximum Tolerated Dose Dasatinib 60 mg/m^2 Every Day (QD)/ Ganitumab 18 mg/kg Phase 2 Dose Level 1 Maximum Tolerated Dose: Dasatinib 60mg/m\^2 by mouth (PO) every day (QD) at Day-7. Ganitumab 18mg/kg intravenous (IV) every two weeks starting at Day 0. Cycle 1 is Day -7 to 27; all other cycles are Day 0 to 27
Ph I: Dose Level 1 and 2 Dose Escalation Not evaluable for toxicity	1	1	0
Ph 2:Dose Level 1 Maximum Tolerated Dose Unacceptable further treatment	0	0	1

Baseline Characteristics

Insulin-like Growth Factor 1 Receptor (IGF-1R) Antibody AMG479 (Ganitumab) in Combination With the Src Family Kinase (SFK) Inhibitor Dasatinib in People With Embryonal and Alveolar Rhabdomyosarcoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Phase 1 Dose Level 1 Dose Escalation Dasatinib 60 mg/m^2 Every Day (QD)/Ganitumab 18 mg/kg n=7 Participants Phase 1 Dose Level 1 Dose Escalation: Dasatinib 60mg/m\^2 by mouth (PO) every day (QD) at Day-7. Ganitumab 18mg/kg intravenous (IV) every two weeks starting at Day 0. Cycle 1 is Day -7 to 27; all other cycles are Day 0 to 27	Phase 1 Dose Level 2 Dose Escalation Dasatinib 60 mg/m^2 Twice Daily (BID)/Ganitumab 18 mg/kg n=6 Participants Phase 1 Dose Level 2 Dose Escalation: Dasatinib 60mg/m\^2 by mouth (PO) twice a day (BID) at Day-7. Ganitumab 18mg/kg intravenous (IV) every two weeks starting at Day 0. Cycle 1 is Day -7 to 27; all other cycles are Day 0 to 27	Phase 2 Dose Level 1 Maximum Tolerated Dose Dasatinib 60 mg/m^2 Every Day (QD)/ Ganitumab 18 mg/kg n=1 Participants Phase 2 Dose Level 1 Maximum Tolerated Dose: Dasatinib 60mg/m\^2 by mouth (PO) every day (QD) at Day-7. Ganitumab 18mg/kg intravenous (IV) every two weeks starting at Day 0. Cycle 1 is Day -7 to 27; all other cycles are Day 0 to 27	Total n=14 Participants Total of all reporting groups
Age, Categorical <=18 years	4 Participants n=99 Participants	2 Participants n=107 Participants	1 Participants n=206 Participants	7 Participants n=7 Participants
Age, Categorical Between 18 and 65 years	3 Participants n=99 Participants	4 Participants n=107 Participants	0 Participants n=206 Participants	7 Participants n=7 Participants
Age, Categorical >=65 years	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Age, Continuous	13.71 years STANDARD_DEVIATION 5.15 • n=99 Participants	20.17 years STANDARD_DEVIATION 8.18 • n=107 Participants	5 years STANDARD_DEVIATION 0 • n=206 Participants	15.86 years STANDARD_DEVIATION 7.62 • n=7 Participants
Sex: Female, Male Female	6 Participants n=99 Participants	1 Participants n=107 Participants	0 Participants n=206 Participants	7 Participants n=7 Participants
Sex: Female, Male Male	1 Participants n=99 Participants	5 Participants n=107 Participants	1 Participants n=206 Participants	7 Participants n=7 Participants
Race/Ethnicity, Customized Hispanic	0 Participants n=99 Participants	1 Participants n=107 Participants	0 Participants n=206 Participants	1 Participants n=7 Participants
Race/Ethnicity, Customized Not Hispanic	5 Participants n=99 Participants	4 Participants n=107 Participants	1 Participants n=206 Participants	10 Participants n=7 Participants
Race/Ethnicity, Customized Ethnicity unknown	2 Participants n=99 Participants	1 Participants n=107 Participants	0 Participants n=206 Participants	3 Participants n=7 Participants
Race/Ethnicity, Customized Black	0 Participants n=99 Participants	1 Participants n=107 Participants	0 Participants n=206 Participants	1 Participants n=7 Participants
Race/Ethnicity, Customized White	6 Participants n=99 Participants	2 Participants n=107 Participants	1 Participants n=206 Participants	9 Participants n=7 Participants
Race/Ethnicity, Customized Asian	0 Participants n=99 Participants	2 Participants n=107 Participants	0 Participants n=206 Participants	2 Participants n=7 Participants
Race/Ethnicity, Customized Race unknown	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Race/Ethnicity, Customized White + Unknown	1 Participants n=99 Participants	1 Participants n=107 Participants	0 Participants n=206 Participants	2 Participants n=7 Participants
Region of Enrollment United States	7 participants n=99 Participants	6 participants n=107 Participants	1 participants n=206 Participants	14 participants n=7 Participants

PRIMARY outcome

Timeframe: First 35 days of treatment

Population: Dasatinib MTD schedule is daily.

Outcome measures

Outcome measures
Measure	All Participants n=13 Participants All participants on: Phase 1 Dose Level 1 and Phase 1 Dose Level 2.	Phase 2 Dose Level 1 Maximum Tolerated Dose Dasatinib 60 mg/m^2 Every Day (QD)/ Ganitumab 18 mg/kg Phase 2 Dose Level 1 Maximum Tolerated Dose: Dasatinib 60mg/m\^2 by mouth (PO) every day (QD) at Day-7. Ganitumab 18mg/kg intravenous (IV) every two weeks starting at Day 0. Cycle 1 is Day -7 to 27; all other cycles are Day 0 to 27	Phase 2 Dose Level 1 Maximum Tolerated Dose Dasatinib 60 mg/m^2 Every Day (QD)/ Ganitumab 18 mg/kg Phase 2 Dose Level 1 Maximum Tolerated Dose: Dasatinib 60mg/m\^2 by mouth (PO) every day (QD) at Day-7. Ganitumab 18mg/kg intravenous (IV) every two weeks starting at Day 0. Cycle 1 is Day -7 to 27; all other cycles are Day 0 to 27
Phase I: Safe Dose of Dasatinib When Given With Ganitumab in Participants With Relapsed or Refractory Embryonal or Alveolar Rhabdomyosarcoma (RMS)	60 mg/m^2	—	—

PRIMARY outcome

Timeframe: Participants were followed for the duration of their treatment which ranged from 0-6 cycles (each cycle is 28 days) and averaged approximately 2 months.

Population: Per protocol, participants (pts) who receive dasatinib at the maximum tolerated (MTD) dose+ganitumab during phase(ph) I will be included in the evaluation of ph II objectives, if evaluable. 5/7 pts on the Ph 1 at the MTD are evaluable and were analyzed with RECIST (versus 0/7 analyzed) since all evaluable pts underwent disease response analysis. Same applies to ph 2 (1/1 evaluable/analyzed). Pts treated at dose level 2 were not analyzed for this objective because dose level 2 was not the MTD.

Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response is disappearance of all target lesions. Partial response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters.

Outcome measures

Outcome measures
Measure	All Participants n=5 Participants All participants on: Phase 1 Dose Level 1 and Phase 1 Dose Level 2.	Phase 2 Dose Level 1 Maximum Tolerated Dose Dasatinib 60 mg/m^2 Every Day (QD)/ Ganitumab 18 mg/kg n=1 Participants Phase 2 Dose Level 1 Maximum Tolerated Dose: Dasatinib 60mg/m\^2 by mouth (PO) every day (QD) at Day-7. Ganitumab 18mg/kg intravenous (IV) every two weeks starting at Day 0. Cycle 1 is Day -7 to 27; all other cycles are Day 0 to 27	Phase 2 Dose Level 1 Maximum Tolerated Dose Dasatinib 60 mg/m^2 Every Day (QD)/ Ganitumab 18 mg/kg Phase 2 Dose Level 1 Maximum Tolerated Dose: Dasatinib 60mg/m\^2 by mouth (PO) every day (QD) at Day-7. Ganitumab 18mg/kg intravenous (IV) every two weeks starting at Day 0. Cycle 1 is Day -7 to 27; all other cycles are Day 0 to 27
Phase II: Number of Participants Who Experience an Objective Clinical Response (CR or PR) When Treated With Ganitumab Plus Dasatinib Complete Response	0 Participants	0 Participants	—
Phase II: Number of Participants Who Experience an Objective Clinical Response (CR or PR) When Treated With Ganitumab Plus Dasatinib Partial Response	0 Participants	0 Participants	—

PRIMARY outcome

Timeframe: At 4 months

Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Progressive disease is least a 20% increase in the sum of the diameters of target lesions) taking as reference the smallest sum of diameters while on study.

Outcome measures

Outcome measures
Measure	All Participants n=5 Participants All participants on: Phase 1 Dose Level 1 and Phase 1 Dose Level 2.	Phase 2 Dose Level 1 Maximum Tolerated Dose Dasatinib 60 mg/m^2 Every Day (QD)/ Ganitumab 18 mg/kg n=1 Participants Phase 2 Dose Level 1 Maximum Tolerated Dose: Dasatinib 60mg/m\^2 by mouth (PO) every day (QD) at Day-7. Ganitumab 18mg/kg intravenous (IV) every two weeks starting at Day 0. Cycle 1 is Day -7 to 27; all other cycles are Day 0 to 27	Phase 2 Dose Level 1 Maximum Tolerated Dose Dasatinib 60 mg/m^2 Every Day (QD)/ Ganitumab 18 mg/kg Phase 2 Dose Level 1 Maximum Tolerated Dose: Dasatinib 60mg/m\^2 by mouth (PO) every day (QD) at Day-7. Ganitumab 18mg/kg intravenous (IV) every two weeks starting at Day 0. Cycle 1 is Day -7 to 27; all other cycles are Day 0 to 27
Phase II: Number of Participants That is Without Progression at 4 Months	1 Participants	0 Participants	—

SECONDARY outcome

Timeframe: Participants were followed for the duration of their treatment which ranged from 0-6 cycles (each cycle is 28 days) and averaged approximately 2 months.

PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. Progression was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Progressive disease is at least a 20% increase in the sum of the diameters of target lesions) taking as reference the smallest sum of diameters while on study.

Outcome measures

Outcome measures
Measure	All Participants n=5 Participants All participants on: Phase 1 Dose Level 1 and Phase 1 Dose Level 2.	Phase 2 Dose Level 1 Maximum Tolerated Dose Dasatinib 60 mg/m^2 Every Day (QD)/ Ganitumab 18 mg/kg n=1 Participants Phase 2 Dose Level 1 Maximum Tolerated Dose: Dasatinib 60mg/m\^2 by mouth (PO) every day (QD) at Day-7. Ganitumab 18mg/kg intravenous (IV) every two weeks starting at Day 0. Cycle 1 is Day -7 to 27; all other cycles are Day 0 to 27	Phase 2 Dose Level 1 Maximum Tolerated Dose Dasatinib 60 mg/m^2 Every Day (QD)/ Ganitumab 18 mg/kg Phase 2 Dose Level 1 Maximum Tolerated Dose: Dasatinib 60mg/m\^2 by mouth (PO) every day (QD) at Day-7. Ganitumab 18mg/kg intravenous (IV) every two weeks starting at Day 0. Cycle 1 is Day -7 to 27; all other cycles are Day 0 to 27
Phase II: Progression Free Survival (PFS) in Participants Receiving Insulin-like Growth Factor 1 Receptor (IGF-1R) Antibody AMG479 (Ganitumab) in Combination With the Src Family Kinase (SFK) Inhibitor Dasatinib	1.93 Months Interval 1.67 to 5.83	0.88 Months Full range cannot be determined for one participant.	—

SECONDARY outcome

Timeframe: 6 months

Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Stable disease is neither sufficient shrinkage to qualify for partial response (i.e., at least a 30% decrease in the sum of the diameters of target lesions) nor sufficient increase to qualify for progressive disease (i.e., at least a 20% increase in the sum of the diameters of target lesions) taking as reference the smallest sum of diameters while on study.

Outcome measures

Outcome measures
Measure	All Participants n=5 Participants All participants on: Phase 1 Dose Level 1 and Phase 1 Dose Level 2.	Phase 2 Dose Level 1 Maximum Tolerated Dose Dasatinib 60 mg/m^2 Every Day (QD)/ Ganitumab 18 mg/kg n=1 Participants Phase 2 Dose Level 1 Maximum Tolerated Dose: Dasatinib 60mg/m\^2 by mouth (PO) every day (QD) at Day-7. Ganitumab 18mg/kg intravenous (IV) every two weeks starting at Day 0. Cycle 1 is Day -7 to 27; all other cycles are Day 0 to 27	Phase 2 Dose Level 1 Maximum Tolerated Dose Dasatinib 60 mg/m^2 Every Day (QD)/ Ganitumab 18 mg/kg Phase 2 Dose Level 1 Maximum Tolerated Dose: Dasatinib 60mg/m\^2 by mouth (PO) every day (QD) at Day-7. Ganitumab 18mg/kg intravenous (IV) every two weeks starting at Day 0. Cycle 1 is Day -7 to 27; all other cycles are Day 0 to 27
Phase II: Number of Participants With Stable Disease >= 6 Months as Defined by the Response Evaluation Criteria in Solid Tumors (RECIST) in Participants Receiving Ganitumab With Dasatinib	1 Participants	0 Participants	—

SECONDARY outcome

Timeframe: Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.

Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Grade 3 is severe. Grade 4 is life-threatening. Grade 5 is death related to adverse event.

Outcome measures

Outcome measures
Measure	All Participants n=7 Participants All participants on: Phase 1 Dose Level 1 and Phase 1 Dose Level 2.	Phase 2 Dose Level 1 Maximum Tolerated Dose Dasatinib 60 mg/m^2 Every Day (QD)/ Ganitumab 18 mg/kg n=6 Participants Phase 2 Dose Level 1 Maximum Tolerated Dose: Dasatinib 60mg/m\^2 by mouth (PO) every day (QD) at Day-7. Ganitumab 18mg/kg intravenous (IV) every two weeks starting at Day 0. Cycle 1 is Day -7 to 27; all other cycles are Day 0 to 27	Phase 2 Dose Level 1 Maximum Tolerated Dose Dasatinib 60 mg/m^2 Every Day (QD)/ Ganitumab 18 mg/kg Phase 2 Dose Level 1 Maximum Tolerated Dose: Dasatinib 60mg/m\^2 by mouth (PO) every day (QD) at Day-7. Ganitumab 18mg/kg intravenous (IV) every two weeks starting at Day 0. Cycle 1 is Day -7 to 27; all other cycles are Day 0 to 27
Phase I: Number of Participants With Grade ≥3 Adverse Events Related to Treatment With Ganitumab and Dasatinib Grade 3 related to ganitumab	1 Participants	3 Participants	—
Phase I: Number of Participants With Grade ≥3 Adverse Events Related to Treatment With Ganitumab and Dasatinib Grade 4 related to ganitumab	0 Participants	0 Participants	—
Phase I: Number of Participants With Grade ≥3 Adverse Events Related to Treatment With Ganitumab and Dasatinib Grade 5 related to ganitumab	0 Participants	0 Participants	—
Phase I: Number of Participants With Grade ≥3 Adverse Events Related to Treatment With Ganitumab and Dasatinib Grade 3 related to dasatinib	3 Participants	4 Participants	—
Phase I: Number of Participants With Grade ≥3 Adverse Events Related to Treatment With Ganitumab and Dasatinib Grade 4 related to dasatinib	1 Participants	0 Participants	—
Phase I: Number of Participants With Grade ≥3 Adverse Events Related to Treatment With Ganitumab and Dasatinib Grade 5 related to dasatinib	0 Participants	0 Participants	—

SECONDARY outcome

Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Grade 3 is severe. Grade 4 is life-threatening. Grade 5 is death related to adverse event.

Outcome measures

Outcome measures
Measure	All Participants n=1 Participants All participants on: Phase 1 Dose Level 1 and Phase 1 Dose Level 2.	Phase 2 Dose Level 1 Maximum Tolerated Dose Dasatinib 60 mg/m^2 Every Day (QD)/ Ganitumab 18 mg/kg Phase 2 Dose Level 1 Maximum Tolerated Dose: Dasatinib 60mg/m\^2 by mouth (PO) every day (QD) at Day-7. Ganitumab 18mg/kg intravenous (IV) every two weeks starting at Day 0. Cycle 1 is Day -7 to 27; all other cycles are Day 0 to 27	Phase 2 Dose Level 1 Maximum Tolerated Dose Dasatinib 60 mg/m^2 Every Day (QD)/ Ganitumab 18 mg/kg Phase 2 Dose Level 1 Maximum Tolerated Dose: Dasatinib 60mg/m\^2 by mouth (PO) every day (QD) at Day-7. Ganitumab 18mg/kg intravenous (IV) every two weeks starting at Day 0. Cycle 1 is Day -7 to 27; all other cycles are Day 0 to 27
Phase II: Number of Participants With Grade ≥3 Adverse Events Related to Treatment With Ganitumab and Dasatinib Grade 3 related to ganitumab	0 Participants	—	—
Phase II: Number of Participants With Grade ≥3 Adverse Events Related to Treatment With Ganitumab and Dasatinib Grade 4 related to ganitumab	0 Participants	—	—
Phase II: Number of Participants With Grade ≥3 Adverse Events Related to Treatment With Ganitumab and Dasatinib Grade 5 related to ganitumab	0 Participants	—	—
Phase II: Number of Participants With Grade ≥3 Adverse Events Related to Treatment With Ganitumab and Dasatinib Grade 3 related to dasatinib	0 Participants	—	—
Phase II: Number of Participants With Grade ≥3 Adverse Events Related to Treatment With Ganitumab and Dasatinib Grade 4 related to dasatinib	0 Participants	—	—
Phase II: Number of Participants With Grade ≥3 Adverse Events Related to Treatment With Ganitumab and Dasatinib Grade 5 related to dasatinib	0 Participants	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: First 35 days of treatment

A DLT is any toxicity of grade 3 or higher, with the specific exception of grade 3 nausea and vomiting of \< 5 days duration, grade 3 fever or infection \< 5 days duration, and grade 3 neutropenia or thrombocytopenia, for example.

Outcome measures

Outcome measures
Measure	All Participants n=7 Participants All participants on: Phase 1 Dose Level 1 and Phase 1 Dose Level 2.	Phase 2 Dose Level 1 Maximum Tolerated Dose Dasatinib 60 mg/m^2 Every Day (QD)/ Ganitumab 18 mg/kg n=6 Participants Phase 2 Dose Level 1 Maximum Tolerated Dose: Dasatinib 60mg/m\^2 by mouth (PO) every day (QD) at Day-7. Ganitumab 18mg/kg intravenous (IV) every two weeks starting at Day 0. Cycle 1 is Day -7 to 27; all other cycles are Day 0 to 27	Phase 2 Dose Level 1 Maximum Tolerated Dose Dasatinib 60 mg/m^2 Every Day (QD)/ Ganitumab 18 mg/kg Phase 2 Dose Level 1 Maximum Tolerated Dose: Dasatinib 60mg/m\^2 by mouth (PO) every day (QD) at Day-7. Ganitumab 18mg/kg intravenous (IV) every two weeks starting at Day 0. Cycle 1 is Day -7 to 27; all other cycles are Day 0 to 27
Phase I: Number of Participants With a Dose-Limiting Toxicity (DLT)	1 Participants	2 Participants	—

OTHER_PRE_SPECIFIED outcome

Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Outcome measures

Outcome measures
Measure	All Participants n=7 Participants All participants on: Phase 1 Dose Level 1 and Phase 1 Dose Level 2.	Phase 2 Dose Level 1 Maximum Tolerated Dose Dasatinib 60 mg/m^2 Every Day (QD)/ Ganitumab 18 mg/kg n=6 Participants Phase 2 Dose Level 1 Maximum Tolerated Dose: Dasatinib 60mg/m\^2 by mouth (PO) every day (QD) at Day-7. Ganitumab 18mg/kg intravenous (IV) every two weeks starting at Day 0. Cycle 1 is Day -7 to 27; all other cycles are Day 0 to 27	Phase 2 Dose Level 1 Maximum Tolerated Dose Dasatinib 60 mg/m^2 Every Day (QD)/ Ganitumab 18 mg/kg n=1 Participants Phase 2 Dose Level 1 Maximum Tolerated Dose: Dasatinib 60mg/m\^2 by mouth (PO) every day (QD) at Day-7. Ganitumab 18mg/kg intravenous (IV) every two weeks starting at Day 0. Cycle 1 is Day -7 to 27; all other cycles are Day 0 to 27
Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)	7 Participants	6 Participants	1 Participants

Adverse Events

Phase 1 Dose Level 1 Dose Escalation Dasatinib 60 mg/m^2 Every Day (QD)/Ganitumab 18 mg/kg

Serious events: 4 serious events

Other events: 7 other events

Deaths: 2 deaths

Phase 1 Dose Level 2 Dose Escalation Dasatinib 60 mg/m^2 Twice Daily (BID)/Ganitumab 18 mg/kg

Serious events: 5 serious events

Other events: 6 other events

Deaths: 1 deaths

Phase 2 Dose Level 1 Maximum Tolerated Dose Dasatinib 60 mg/m^2 Every Day (QD)/ Ganitumab 18 mg/kg

Serious events: 1 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Dr. Christine Heske

National Cancer Institute

Phone: 240-760-6197

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Phase 1 Dose Level 1 Dose Escalation Dasatinib 60 mg/m^2 Every Day (QD)/Ganitumab 18 mg/kg n=7 participants at risk Phase 1 Dose Level 1 Dose Escalation: Dasatinib 60mg/m\^2 by mouth (PO) every day (QD) at Day-7. Ganitumab 18mg/kg intravenous (IV) every two weeks starting at Day 0. Cycle 1 is Day -7 to 27; all other cycles are Day 0 to 27	Phase 1 Dose Level 2 Dose Escalation Dasatinib 60 mg/m^2 Twice Daily (BID)/Ganitumab 18 mg/kg n=6 participants at risk Phase 1 Dose Level 2 Dose Escalation: Dasatinib 60mg/m\^2 by mouth (PO) twice a day (BID) at Day-7. Ganitumab 18mg/kg intravenous (IV) every two weeks starting at Day 0. Cycle 1 is Day -7 to 27; all other cycles are Day 0 to 27	Phase 2 Dose Level 1 Maximum Tolerated Dose Dasatinib 60 mg/m^2 Every Day (QD)/ Ganitumab 18 mg/kg n=1 participants at risk Phase 2 Dose Level 1 Maximum Tolerated Dose: Dasatinib 60mg/m\^2 by mouth (PO) every day (QD) at Day-7. Ganitumab 18mg/kg intravenous (IV) every two weeks starting at Day 0. Cycle 1 is Day -7 to 27; all other cycles are Day 0 to 27
Gastrointestinal disorders Abdominal pain	14.3% 1/7 • Number of events 1 • Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.
Gastrointestinal disorders Ascites	0.00% 0/7 • Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.
Musculoskeletal and connective tissue disorders Back pain	14.3% 1/7 • Number of events 1 • Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.
Respiratory, thoracic and mediastinal disorders Bronchopulmonary hemorrhage	0.00% 0/7 • Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.
Metabolism and nutrition disorders Dehydration	0.00% 0/7 • Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.
General disorders Fatigue	0.00% 0/7 • Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.
General disorders Fever	28.6% 2/7 • Number of events 2 • Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.	0.00% 0/6 • Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.
Renal and urinary disorders Hematuria	14.3% 1/7 • Number of events 1 • Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.
Metabolism and nutrition disorders Hypocalcemia	14.3% 1/7 • Number of events 1 • Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.	0.00% 0/6 • Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.
Metabolism and nutrition disorders Hyponatremia	0.00% 0/7 • Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.
Respiratory, thoracic and mediastinal disorders Hypoxia	14.3% 1/7 • Number of events 1 • Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.
Infections and infestations Infections and infestations - Other, Blood culture positive for Klebsiella pneumonia	14.3% 1/7 • Number of events 1 • Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.	0.00% 0/6 • Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.
Infections and infestations Kidney infection	14.3% 1/7 • Number of events 1 • Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.	0.00% 0/6 • Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.
Metabolism and nutrition disorders Metabolism and nutrition disorders - Other, Hyponatremia	0.00% 0/7 • Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.
Gastrointestinal disorders Nausea	0.00% 0/7 • Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, tumor hemorrhage	0.00% 0/7 • Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.	0.00% 0/6 • Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.	100.0% 1/1 • Number of events 1 • Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.
Gastrointestinal disorders Oral hemorrhage	0.00% 0/7 • Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.
Cardiac disorders Pericardial effusion	0.00% 0/7 • Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.
Respiratory, thoracic and mediastinal disorders Pleuritic pain	14.3% 1/7 • Number of events 1 • Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.	0.00% 0/6 • Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/7 • Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.
Respiratory, thoracic and mediastinal disorders Respiratory failure	28.6% 2/7 • Number of events 2 • Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.
Infections and infestations Urinary tract infection	14.3% 1/7 • Number of events 1 • Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.	0.00% 0/6 • Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.
Gastrointestinal disorders Vomiting	0.00% 0/7 • Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.	33.3% 2/6 • Number of events 2 • Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.	0.00% 0/1 • Date treatment consent signed to date off study, approximately 14 months and 18 days for phase 1 dose level 1, 27 months and 2 days for phase 1 dose level 2, and 1 month and 24 days for phase 2 dose level 1.