Trial Outcomes & Findings for A Phase 1B Study to Investigate the Safety and Preliminary Efficacy for the Combination of Dasatinib Plus Nivolumab in Patients With Chronic Myeloid Leukemia (NCT NCT02011945)

NCT ID: NCT02011945

Last Updated: 2020-03-18

Results Overview

DLT will be determined based on the incidence and intensity of drug related adverse events (AEs). The following drug-related AEs (whether related to one or both agents) occurring during the first 6 weeks of combined treatment with both dasatinib plus nivolumab (ie, Weeks 3 to 8, inclusive) would be considered DLTs: * Grade 4 hematologic AE lasting \> 7 days despite appropriate medical intervention, except as noted below; * Grade 3 or Grade 4 nonhematologic AE irrespective of duration; * Grade 2 nonhematologic AE lasting \> 7 days despite appropriate medical intervention (exception: asymptomatic laboratory values of Grade 2 which do not require medical intervention); * Any toxicity managed by discontinuation of nivolumab; * Grade ≥ 2 AE not controlled by medical intervention and requiring dasatinib treatment interruption for \> 28 consecutive days; * Grade ≥ 2 AE not controlled by medical intervention and requiring missing 2 consecutive doses of nivolumab.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

35 participants

Primary outcome timeframe

Week 3 to week 6

Results posted on

2020-03-18

Participant Flow

35 Participants enrolled; 31 participants randomized. Reasons not randomized: 1 participant withdrew consent, 3 participants no longer met the study criteria.

Participant milestones

Participant milestones
Measure	Dasatinib Only dasatinib 100 mg QD(CP) or 140 mg QD (AP)	Dose Level 1 Nivolumab 1 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)	Dose Level 2 Nivolumab 3 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)
Overall Study STARTED	2	13	16
Overall Study COMPLETED	0	3	6
Overall Study NOT COMPLETED	2	10	10

Reasons for withdrawal

Reasons for withdrawal
Measure	Dasatinib Only dasatinib 100 mg QD(CP) or 140 mg QD (AP)	Dose Level 1 Nivolumab 1 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)	Dose Level 2 Nivolumab 3 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)
Overall Study Participant requested to Discontinue	0	1	1
Overall Study Adverse Event unrelated to Drug	0	2	1
Overall Study Study Drug Toxicity	0	0	1
Overall Study Treatment Failure	0	7	6
Overall Study No Longer Meets Study Criteria	1	0	0
Overall Study Proceeded to stem cell transplant	0	0	1
Overall Study Sub-Optimal Response to dasatinib	1	0	0

Baseline Characteristics

A Phase 1B Study to Investigate the Safety and Preliminary Efficacy for the Combination of Dasatinib Plus Nivolumab in Patients With Chronic Myeloid Leukemia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dasatinib Only n=2 Participants dasatinib 100 mg QD(CP) or 140 mg QD (AP)	Dose Level 1 n=13 Participants Nivolumab 1 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)	Dose Level 2 n=16 Participants Nivolumab 3 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)	Total n=31 Participants Total of all reporting groups
Age, Continuous	48.5 Years STANDARD_DEVIATION 13.4 • n=5 Participants	61.2 Years STANDARD_DEVIATION 12.4 • n=7 Participants	47.1 Years STANDARD_DEVIATION 13.6 • n=5 Participants	53.1 Years STANDARD_DEVIATION 14.5 • n=4 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	7 Participants n=7 Participants	5 Participants n=5 Participants	13 Participants n=4 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	6 Participants n=7 Participants	11 Participants n=5 Participants	18 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	0 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants	12 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	9 Participants n=7 Participants	7 Participants n=5 Participants	18 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	4 Participants n=4 Participants
Race (NIH/OMB) White	2 Participants n=5 Participants	11 Participants n=7 Participants	13 Participants n=5 Participants	26 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants

PRIMARY outcome

Timeframe: Week 3 to week 6

Population: All Treated Participants

Outcome measures

Outcome measures
Measure	Dasatinib Only n=2 Participants dasatinib 100 mg QD(CP) or 140 mg QD (AP)	Dose Level 1 n=13 Participants Nivolumab 1 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)	Dose Level 2 n=16 Participants Nivolumab 3 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)
Incidence of Dose Limiting Toxicities (DLT)	0 Number of Incidence	0 Number of Incidence	0 Number of Incidence

PRIMARY outcome

Timeframe: Initiation of study drug to discontinuation of nivolumab stop date + 100 days or discontinuation of dasatinib + 30 days

Population: All Treated Participants

Any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation subject administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of investigational product, whether or not considered related to the investigational product.

Outcome measures

Outcome measures
Measure	Dasatinib Only n=2 Participants dasatinib 100 mg QD(CP) or 140 mg QD (AP)	Dose Level 1 n=13 Participants Nivolumab 1 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)	Dose Level 2 n=16 Participants Nivolumab 3 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)
Incidence of Adverse Events (AEs) CML-CP, No Prior dasatinib treatment	—	1 Number of Adverse Events	2 Number of Adverse Events
Incidence of Adverse Events (AEs) CML-CP, Prior dasatinib treatment	1 Number of Adverse Events	8 Number of Adverse Events	11 Number of Adverse Events
Incidence of Adverse Events (AEs) CML-AP participants	—	4 Number of Adverse Events	3 Number of Adverse Events

PRIMARY outcome

Timeframe: Initiation of study drug to within 100 days of discontinuation of nivolumab dosing and 30 days of dasatinib dosing

Population: All Treated Participants

Any untoward medical occurrence that at any dose: results in death, is life threatening, requires in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is a important medical event.Requires inpatient hospitalization or causes prolongation of existing hospitalization, results.

Outcome measures

Outcome measures
Measure	Dasatinib Only n=2 Participants dasatinib 100 mg QD(CP) or 140 mg QD (AP)	Dose Level 1 n=13 Participants Nivolumab 1 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)	Dose Level 2 n=16 Participants Nivolumab 3 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)
Incidence of Serious Adverse Events (SAEs) CML-CP, No Prior dasatinib treatment	—	0 Number of Adverse Events	2 Number of Adverse Events
Incidence of Serious Adverse Events (SAEs) CML-CP, Prior dasatinib treatment	0 Number of Adverse Events	3 Number of Adverse Events	4 Number of Adverse Events
Incidence of Serious Adverse Events (SAEs) CML-AP participants	—	4 Number of Adverse Events	2 Number of Adverse Events

PRIMARY outcome

Timeframe: Up to 40 Months

Population: All Treated Participants

The number of participants with a shift in laboratory test results from baseline to Grade 3-4 in hematology

Outcome measures

Outcome measures
Measure	Dasatinib Only n=2 Participants dasatinib 100 mg QD(CP) or 140 mg QD (AP)	Dose Level 1 n=13 Participants Nivolumab 1 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)	Dose Level 2 n=16 Participants Nivolumab 3 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)
Incidence of Change From Baseline in Clinical Laboratory Tests: Hematology Hemoglobin	0 Participants	2 Participants	4 Participants
Incidence of Change From Baseline in Clinical Laboratory Tests: Hematology Platelets	0 Participants	5 Participants	4 Participants
Incidence of Change From Baseline in Clinical Laboratory Tests: Hematology Absolute Neutrophil Count (ANC)	0 Participants	5 Participants	3 Participants
Incidence of Change From Baseline in Clinical Laboratory Tests: Hematology White Blood Cell (WBC)	0 Participants	1 Participants	3 Participants

PRIMARY outcome

Timeframe: Up to 40 Months

Population: All Treated Participants with at least one treatment measure

The number of participants with an abnormal Liver function test. Aspartate aminotransferase (AST) Alanine aminotransferase (ALT) Upper Limit of Normal (ULN)

Outcome measures

Outcome measures
Measure	Dasatinib Only n=2 Participants dasatinib 100 mg QD(CP) or 140 mg QD (AP)	Dose Level 1 n=13 Participants Nivolumab 1 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)	Dose Level 2 n=16 Participants Nivolumab 3 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)
Incidence of Abnormalities in Clinical Laboratory Tests: Liver Tests ALT or AST > 3xULN	0 Participants	1 Participants	1 Participants
Incidence of Abnormalities in Clinical Laboratory Tests: Liver Tests ALT or AST > 5xULN	0 Participants	0 Participants	0 Participants
Incidence of Abnormalities in Clinical Laboratory Tests: Liver Tests ALT or AST > 10xULN	0 Participants	0 Participants	0 Participants
Incidence of Abnormalities in Clinical Laboratory Tests: Liver Tests ALT or AST > 20xULN	0 Participants	0 Participants	0 Participants
Incidence of Abnormalities in Clinical Laboratory Tests: Liver Tests Total Bilirubin (Tbili) > 2xULN	0 Participants	1 Participants	1 Participants
Incidence of Abnormalities in Clinical Laboratory Tests: Liver Tests ALT or AST > 3xULN w/ Tbili > 2xULN within 1 day	0 Participants	1 Participants	0 Participants
Incidence of Abnormalities in Clinical Laboratory Tests: Liver Tests ALT or AST > 3xULN w/ Tbili > 2xULN within 30 days	0 Participants	1 Participants	0 Participants

PRIMARY outcome

Timeframe: Up to 40 Months

Population: All Treated Participants

Free T3 (FT3) Free T4 (FT4) Lower Limit of Normal (LLN)

Outcome measures

Outcome measures
Measure	Dasatinib Only n=2 Participants dasatinib 100 mg QD(CP) or 140 mg QD (AP)	Dose Level 1 n=13 Participants Nivolumab 1 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)	Dose Level 2 n=16 Participants Nivolumab 3 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)
Incidence of Laboratory Abnormalities in Specific Thyroid Tests TSH > ULN	0 Number of Incidences	4 Number of Incidences	4 Number of Incidences
Incidence of Laboratory Abnormalities in Specific Thyroid Tests TSH > ULN: WITH TSH ≤ ULN AT BASELINE	0 Number of Incidences	3 Number of Incidences	3 Number of Incidences
Incidence of Laboratory Abnormalities in Specific Thyroid Tests TSH > ULN: WITH AT LEAST ONE FT3/FT4 TEST < LLN	0 Number of Incidences	2 Number of Incidences	1 Number of Incidences
Incidence of Laboratory Abnormalities in Specific Thyroid Tests TSH > ULN: WITH ALL OTHER FT3/FT4 TEST ≥ LLN	0 Number of Incidences	1 Number of Incidences	1 Number of Incidences
Incidence of Laboratory Abnormalities in Specific Thyroid Tests TSH > ULN: WITH FT3/FT4 TEST MISSING	0 Number of Incidences	1 Number of Incidences	2 Number of Incidences
Incidence of Laboratory Abnormalities in Specific Thyroid Tests TSH > 2*ULN	0 Number of Incidences	2 Number of Incidences	1 Number of Incidences
Incidence of Laboratory Abnormalities in Specific Thyroid Tests TSH > 2*ULN: WITH TSH <= ULN AT BASELINE	0 Number of Incidences	1 Number of Incidences	0 Number of Incidences
Incidence of Laboratory Abnormalities in Specific Thyroid Tests TSH > 2*ULN: WITH AT LEAST ONE FT3/FT4 TEST < LLN	0 Number of Incidences	2 Number of Incidences	1 Number of Incidences
Incidence of Laboratory Abnormalities in Specific Thyroid Tests TSH > 2*ULN: WITH ALL OTHER FT3/FT4 TEST ≥ LLN	0 Number of Incidences	0 Number of Incidences	0 Number of Incidences
Incidence of Laboratory Abnormalities in Specific Thyroid Tests TSH > 2*ULN: WITH FT3/FT4 TEST MISSING	0 Number of Incidences	0 Number of Incidences	0 Number of Incidences
Incidence of Laboratory Abnormalities in Specific Thyroid Tests TSH < LLN	0 Number of Incidences	3 Number of Incidences	1 Number of Incidences
Incidence of Laboratory Abnormalities in Specific Thyroid Tests TSH < LLN: WITH TSH >= LLN AT BASELINE	0 Number of Incidences	3 Number of Incidences	1 Number of Incidences
Incidence of Laboratory Abnormalities in Specific Thyroid Tests TSH < LLN: WITH AT LEAST ONE FT3/FT4 TEST > ULN	0 Number of Incidences	0 Number of Incidences	1 Number of Incidences
Incidence of Laboratory Abnormalities in Specific Thyroid Tests TSH < LLN: WITH ALL OTHER FT3/FT4 TEST ≤ ULN	0 Number of Incidences	1 Number of Incidences	0 Number of Incidences
Incidence of Laboratory Abnormalities in Specific Thyroid Tests TSH < LLN: WITH FT3/FT4 TEST MISSING	0 Number of Incidences	2 Number of Incidences	0 Number of Incidences

SECONDARY outcome

Timeframe: upto 36 Months

Population: All treated Participants, CML-CP no prior Dasatinib participants

Molecular response was assessed using BCR-ABL transcript levels measurement by real-time quantitative polymerase chain reaction (RQ-PCR). MMR is defined as ≥ 3-log reduction in BCR-ABL transcripts or a ratio of ≤ 0.1% on the International Scale (IS).

Outcome measures

Outcome measures
Measure	Dasatinib Only dasatinib 100 mg QD(CP) or 140 mg QD (AP)	Dose Level 1 n=1 Participants Nivolumab 1 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)	Dose Level 2 n=2 Participants Nivolumab 3 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)
Rate of Major Molecular Response (MMR) : Chronic Myelogenous Leukemia - Chronic Phase (CML-CP), No Prior Dasatinib Participants MMR Rate by 6 Months	—	100 Percentage of Participants Interval 2.5 to 100.0	0 Percentage of Participants Interval 0.0 to 84.2
Rate of Major Molecular Response (MMR) : Chronic Myelogenous Leukemia - Chronic Phase (CML-CP), No Prior Dasatinib Participants MMR Rate by 12 Months	—	100 Percentage of Participants Interval 2.5 to 100.0	0 Percentage of Participants Interval 0.0 to 84.2
Rate of Major Molecular Response (MMR) : Chronic Myelogenous Leukemia - Chronic Phase (CML-CP), No Prior Dasatinib Participants MMR Rate by 24 Months	—	100 Percentage of Participants Interval 2.5 to 100.0	0 Percentage of Participants Interval 0.0 to 84.2
Rate of Major Molecular Response (MMR) : Chronic Myelogenous Leukemia - Chronic Phase (CML-CP), No Prior Dasatinib Participants MMR Rate by 36 Months	—	100 Percentage of Participants Interval 2.5 to 100.0	0 Percentage of Participants Interval 0.0 to 84.2

SECONDARY outcome

Timeframe: upto 36 Months

Population: All treated Participants, CML-CP prior Dasatinib participants

Outcome measures

Outcome measures
Measure	Dasatinib Only n=2 Participants dasatinib 100 mg QD(CP) or 140 mg QD (AP)	Dose Level 1 n=8 Participants Nivolumab 1 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)	Dose Level 2 n=11 Participants Nivolumab 3 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)
Rate of Major Molecular Response (MMR) : Chronic Myelogenous Leukemia - Chronic Phase (CML-CP), Prior Dasatinib Participants MMR Rate by 12 Months	0 Percentage Interval 0.0 to 84.2	25 Percentage Interval 3.2 to 65.1	27.3 Percentage Interval 6.0 to 61.0
Rate of Major Molecular Response (MMR) : Chronic Myelogenous Leukemia - Chronic Phase (CML-CP), Prior Dasatinib Participants MMR Rate by 24 Months	0 Percentage Interval 0.0 to 84.2	25 Percentage Interval 3.2 to 65.1	36.4 Percentage Interval 10.9 to 69.2
Rate of Major Molecular Response (MMR) : Chronic Myelogenous Leukemia - Chronic Phase (CML-CP), Prior Dasatinib Participants MMR Rate by 36 Months	0 Percentage Interval 0.0 to 84.2	25.0 Percentage Interval 3.2 to 65.1	45.5 Percentage Interval 16.7 to 76.6
Rate of Major Molecular Response (MMR) : Chronic Myelogenous Leukemia - Chronic Phase (CML-CP), Prior Dasatinib Participants MMR Rate by 6 Months	0 Percentage Interval 0.0 to 84.2	25 Percentage Interval 3.2 to 65.1	18.2 Percentage Interval 2.3 to 51.8

SECONDARY outcome

Timeframe: upto 36 Months

Population: All treated Participants, CML-AP Participants

Outcome measures

Outcome measures
Measure	Dasatinib Only dasatinib 100 mg QD(CP) or 140 mg QD (AP)	Dose Level 1 n=4 Participants Nivolumab 1 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)	Dose Level 2 n=3 Participants Nivolumab 3 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)
Rate of Major Molecular Response (MMR) : Chronic Myelogenous Leukemia - Advanced Phase (CML-AP) Participants MMR Rate by 6 Months	—	0 Percentage Interval 0.0 to 60.2	33.3 Percentage Interval 0.8 to 90.6
Rate of Major Molecular Response (MMR) : Chronic Myelogenous Leukemia - Advanced Phase (CML-AP) Participants MMR Rate by 12 Months	—	0 Percentage Interval 0.0 to 60.2	66.7 Percentage Interval 9.4 to 99.2
Rate of Major Molecular Response (MMR) : Chronic Myelogenous Leukemia - Advanced Phase (CML-AP) Participants MMR Rate by 24 Months	—	0 Percentage Interval 0.0 to 60.2	66.7 Percentage Interval 9.4 to 99.2
Rate of Major Molecular Response (MMR) : Chronic Myelogenous Leukemia - Advanced Phase (CML-AP) Participants MMR Rate by 36 Months	—	0 Percentage Interval 0.0 to 60.2	66.7 Percentage Interval 9.4 to 99.2

SECONDARY outcome

Timeframe: upto 36 Months

Population: All treated Participants, CML-CP no prior Dasatinib participants

Molecular response was assessed using BCR-ABL transcript levels measurement by real-time quantitative polymerase chain reaction (RQ-PCR). A molecular response 4.5 (MR4.5) was defined as ≥ 4.5-log reduction in BCR-ABL transcripts or a ratio of ≤ 0.00316% on the International Scale (IS).

Outcome measures

Outcome measures
Measure	Dasatinib Only dasatinib 100 mg QD(CP) or 140 mg QD (AP)	Dose Level 1 n=1 Participants Nivolumab 1 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)	Dose Level 2 n=2 Participants Nivolumab 3 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)
Rate of Molecular Response 4.5 (MR4.5) : Chronic Myelogenous Leukemia - Chronic Phase (CML-CP), No Prior Dasatinib Participants MR4.5 Rate by 6 Months	—	0.0 Percentage Interval 0.0 to 97.5	0.0 Percentage Interval 0.0 to 84.2
Rate of Molecular Response 4.5 (MR4.5) : Chronic Myelogenous Leukemia - Chronic Phase (CML-CP), No Prior Dasatinib Participants MR4.5 Rate by 12 Months	—	0.0 Percentage Interval 0.0 to 97.5	0.0 Percentage Interval 0.0 to 84.2
Rate of Molecular Response 4.5 (MR4.5) : Chronic Myelogenous Leukemia - Chronic Phase (CML-CP), No Prior Dasatinib Participants MR4.5 Rate by 24 Months	—	0.0 Percentage Interval 0.0 to 97.5	0.0 Percentage Interval 0.0 to 84.2
Rate of Molecular Response 4.5 (MR4.5) : Chronic Myelogenous Leukemia - Chronic Phase (CML-CP), No Prior Dasatinib Participants MR4.5 Rate by 36 Months	—	100 Percentage Interval 2.5 to 100.0	0.0 Percentage Interval 0.0 to 84.2

SECONDARY outcome

Timeframe: upto 36 Months

Population: All treated Participants, CML-CP prior Dasatinib participants

Outcome measures

Outcome measures
Measure	Dasatinib Only n=2 Participants dasatinib 100 mg QD(CP) or 140 mg QD (AP)	Dose Level 1 n=8 Participants Nivolumab 1 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)	Dose Level 2 n=11 Participants Nivolumab 3 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)
Rate of Molecular Response 4.5 (MR4.5) : Chronic Myelogenous Leukemia - Chronic Phase (CML-CP), Prior Dasatinib Participants MR4.5 Rate by 6 Months	0 Percentage Interval 0.0 to 84.2	0.0 Percentage Interval 0.0 to 36.9	0.0 Percentage Interval 0.0 to 28.5
Rate of Molecular Response 4.5 (MR4.5) : Chronic Myelogenous Leukemia - Chronic Phase (CML-CP), Prior Dasatinib Participants MR4.5 Rate by 12 Months	0 Percentage Interval 0.0 to 84.2	0.0 Percentage Interval 0.0 to 36.9	0.0 Percentage Interval 0.0 to 28.5
Rate of Molecular Response 4.5 (MR4.5) : Chronic Myelogenous Leukemia - Chronic Phase (CML-CP), Prior Dasatinib Participants MR4.5 Rate by 24 Months	0 Percentage Interval 0.0 to 84.2	0.0 Percentage Interval 0.0 to 36.9	0.0 Percentage Interval 0.0 to 28.5
Rate of Molecular Response 4.5 (MR4.5) : Chronic Myelogenous Leukemia - Chronic Phase (CML-CP), Prior Dasatinib Participants MR4.5 Rate by 36 Months	0 Percentage Interval 0.0 to 84.2	0.0 Percentage Interval 0.0 to 36.9	0.0 Percentage Interval 0.0 to 28.5

SECONDARY outcome

Timeframe: upto 36 Months

Population: All treated Participants, CML-AP Participants

Outcome measures

Outcome measures
Measure	Dasatinib Only dasatinib 100 mg QD(CP) or 140 mg QD (AP)	Dose Level 1 n=4 Participants Nivolumab 1 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)	Dose Level 2 n=3 Participants Nivolumab 3 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)
Rate of Molecular Response 4.5 (MR4.5) : Chronic Myelogenous Leukemia - Advanced Phase (CML-AP) Participants MR4.5 Rate by 6 Months	—	0.0 Percentage Interval 0.0 to 60.2	0.0 Percentage Interval 0.0 to 70.8
Rate of Molecular Response 4.5 (MR4.5) : Chronic Myelogenous Leukemia - Advanced Phase (CML-AP) Participants MR4.5 Rate by 12 Months	—	0.0 Percentage Interval 0.0 to 60.2	0.0 Percentage Interval 0.0 to 70.8
Rate of Molecular Response 4.5 (MR4.5) : Chronic Myelogenous Leukemia - Advanced Phase (CML-AP) Participants MR4.5 Rate by 24 Months	—	0.0 Percentage Interval 0.0 to 60.2	0.0 Percentage Interval 0.0 to 70.8
Rate of Molecular Response 4.5 (MR4.5) : Chronic Myelogenous Leukemia - Advanced Phase (CML-AP) Participants MR4.5 Rate by 36 Months	—	0.0 Percentage Interval 0.0 to 60.2	0.0 Percentage Interval 0.0 to 70.8

SECONDARY outcome

Timeframe: Up to 36 Months

Population: CML-CP No Prior Dasatinib Subjects

measured from the date of first dosing until measurement criteria are first met for MMR. The participants who do not respond will be censored on the date of their last molecular assessment. It is defined for all treated participants.

Outcome measures

Outcome measures
Measure	Dasatinib Only dasatinib 100 mg QD(CP) or 140 mg QD (AP)	Dose Level 1 n=1 Participants Nivolumab 1 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)	Dose Level 2 n=2 Participants Nivolumab 3 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)
Time to Major Molecular Response (MMR) - CML-CP No Prior Dasatinib Participants	—	0.53 Months Insufficient number of participants with events	NA Months Insufficient number of participants with events

SECONDARY outcome

Timeframe: Up to 36 Months

Population: CML-CP Prior Dasatinib participants

Outcome measures

Outcome measures
Measure	Dasatinib Only n=2 Participants dasatinib 100 mg QD(CP) or 140 mg QD (AP)	Dose Level 1 n=8 Participants Nivolumab 1 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)	Dose Level 2 n=11 Participants Nivolumab 3 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)
Time to Major Molecular Response (MMR) - CML-CP Prior Dasatinib Participants	NA Months Insufficient number of participants with events	NA Months Interval 0.56 to Insufficient number of participants with events	35.45 Months Interval 0.95 to Insufficient number of participants with events

SECONDARY outcome

Timeframe: Up to 36 Months

Population: CML-AP Participants

Outcome measures

Outcome measures
Measure	Dasatinib Only dasatinib 100 mg QD(CP) or 140 mg QD (AP)	Dose Level 1 n=4 Participants Nivolumab 1 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)	Dose Level 2 n=3 Participants Nivolumab 3 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)
Time to Major Molecular Response (MMR) - CML-AP Participants	—	NA Months Median and Confidence limits not estimable	5.54 Months Interval 1.84 to 9.23

SECONDARY outcome

Timeframe: Up to 36 Months

Population: CML-CP No Prior Dasatinib participants

will be computed for participants who have achieved MMR. It will be defined as the time from the first assessment in which MMR, is documented until the first assessment at which disease progression (or confirmed loss of MMR) is documented. Participants who neither progress nor die will be censored on the date of their last molecular assessment

Outcome measures

Outcome measures
Measure	Dasatinib Only dasatinib 100 mg QD(CP) or 140 mg QD (AP)	Dose Level 1 n=1 Participants Nivolumab 1 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)	Dose Level 2 Nivolumab 3 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)
Duration of Major Molecular Response (MMR) - CML-CP No Prior Dasatinib Participants	—	NA Months Insufficient number of participants with events	—

SECONDARY outcome

Timeframe: Up to 36 Months

Population: CML-CP Prior Dasatinib Participants

Outcome measures

Outcome measures
Measure	Dasatinib Only dasatinib 100 mg QD(CP) or 140 mg QD (AP)	Dose Level 1 n=2 Participants Nivolumab 1 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)	Dose Level 2 n=5 Participants Nivolumab 3 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)
Duration of Major Molecular Response (MMR) - CML-CP Prior Dasatinib Participants	—	NA Months Interval 23.49 to Insufficient number of participants with events	NA Months Insufficient number of participants with events

SECONDARY outcome

Timeframe: Up to 36 Months

Population: CML-AP Participants

Outcome measures

Outcome measures
Measure	Dasatinib Only dasatinib 100 mg QD(CP) or 140 mg QD (AP)	Dose Level 1 Nivolumab 1 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)	Dose Level 2 n=2 Participants Nivolumab 3 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)
Duration of Major Molecular Response (MMR) - CML-AP Participants	—	—	NA Months Insufficient number of participants with events

SECONDARY outcome

Timeframe: Up to 36 Months

Population: CML-CP No Prior Dasatinib Participants

measured from the date of first dosing until measurement criteria are first met for MR4.5. The participants who do not respond will be censored on the date of their last molecular assessment. It is defined for all treated participants.

Outcome measures

Outcome measures
Measure	Dasatinib Only dasatinib 100 mg QD(CP) or 140 mg QD (AP)	Dose Level 1 n=1 Participants Nivolumab 1 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)	Dose Level 2 n=2 Participants Nivolumab 3 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)
Time to Molecular Response 4.5(MR4.5) - CML-CP No Prior Dasatinib Participants	—	35.25 Months Insufficient number of participants with events	NA Months Insufficient number of participants with events

SECONDARY outcome

Timeframe: Up to 36 Months

Population: CML-CP Prior Dasatinib Participants

Outcome measures

Outcome measures
Measure	Dasatinib Only n=2 Participants dasatinib 100 mg QD(CP) or 140 mg QD (AP)	Dose Level 1 n=8 Participants Nivolumab 1 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)	Dose Level 2 n=11 Participants Nivolumab 3 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)
Time to Molecular Response 4.5(MR4.5) - CML-CP Prior Dasatinib Participants	NA Months Insufficient number of participants with events	NA Months Insufficient number of participants with events	NA Months Insufficient number of participants with events

SECONDARY outcome

Timeframe: Up to 36 Months

Population: CML-AP Participants

Outcome measures

Outcome measures
Measure	Dasatinib Only dasatinib 100 mg QD(CP) or 140 mg QD (AP)	Dose Level 1 n=4 Participants Nivolumab 1 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)	Dose Level 2 n=3 Participants Nivolumab 3 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)
Time to Molecular Response 4.5(MR4.5) - CML-AP Participants	—	NA Months Insufficient number of participants with events	NA Months Insufficient number of participants with events

SECONDARY outcome

Timeframe: Up to 36 Months

Population: CML-CP No Prior Dasatinib Participants

will be computed for participants who have achieved MR4.5. It will be defined as the time from the first assessment in which MR4.5, is documented until the first assessment at which disease progression (or confirmed loss of MR4.5 documented. Participants who neither progress nor die will be censored on the date of their last molecular assessment

Outcome measures

Outcome measures
Measure	Dasatinib Only dasatinib 100 mg QD(CP) or 140 mg QD (AP)	Dose Level 1 n=1 Participants Nivolumab 1 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)	Dose Level 2 Nivolumab 3 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)
Duration of Molecular Response 4.5 (MR4.5) - CML-CP No Prior Dasatinib Participants	—	NA Months Insufficient number of participants with events	—

SECONDARY outcome

Timeframe: Up to 36 Months

Population: CML-CP Prior Dasatinib Participants

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 36 Months

Population: CML-AP Participants

Outcome measures

Outcome data not reported

Adverse Events

Dasatinib Only

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Dose Level 1

Serious events: 7 serious events

Other events: 13 other events

Deaths: 2 deaths

Dose Level 2

Serious events: 8 serious events

Other events: 16 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Bristol-Myers Squibb Study Director

Bristol-Myers squibb

Phone: Please Email

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	Dasatinib Only n=2 participants at risk dasatinib 100 mg QD(CP) or 140 mg QD (AP)	Dose Level 1 n=13 participants at risk Nivolumab 1 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)	Dose Level 2 n=16 participants at risk Nivolumab 3 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/2 • Initiation of study drug to within 100 days of discontinuation of nivolumab dosing and 30 days of dasatinib dosing	7.7% 1/13 • Initiation of study drug to within 100 days of discontinuation of nivolumab dosing and 30 days of dasatinib dosing	6.2% 1/16 • Initiation of study drug to within 100 days of discontinuation of nivolumab dosing and 30 days of dasatinib dosing
Gastrointestinal disorders Abdominal pain upper	0.00% 0/2 • Initiation of study drug to within 100 days of discontinuation of nivolumab dosing and 30 days of dasatinib dosing	0.00% 0/13 • Initiation of study drug to within 100 days of discontinuation of nivolumab dosing and 30 days of dasatinib dosing	6.2% 1/16 • Initiation of study drug to within 100 days of discontinuation of nivolumab dosing and 30 days of dasatinib dosing
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/2 • Initiation of study drug to within 100 days of discontinuation of nivolumab dosing and 30 days of dasatinib dosing	7.7% 1/13 • Initiation of study drug to within 100 days of discontinuation of nivolumab dosing and 30 days of dasatinib dosing	0.00% 0/16 • Initiation of study drug to within 100 days of discontinuation of nivolumab dosing and 30 days of dasatinib dosing
Gastrointestinal disorders Nausea	0.00% 0/2 • Initiation of study drug to within 100 days of discontinuation of nivolumab dosing and 30 days of dasatinib dosing	0.00% 0/13 • Initiation of study drug to within 100 days of discontinuation of nivolumab dosing and 30 days of dasatinib dosing	6.2% 1/16 • Initiation of study drug to within 100 days of discontinuation of nivolumab dosing and 30 days of dasatinib dosing
General disorders Device related thrombosis	0.00% 0/2 • Initiation of study drug to within 100 days of discontinuation of nivolumab dosing and 30 days of dasatinib dosing	0.00% 0/13 • Initiation of study drug to within 100 days of discontinuation of nivolumab dosing and 30 days of dasatinib dosing	6.2% 1/16 • Initiation of study drug to within 100 days of discontinuation of nivolumab dosing and 30 days of dasatinib dosing
General disorders Influenza like illness	0.00% 0/2 • Initiation of study drug to within 100 days of discontinuation of nivolumab dosing and 30 days of dasatinib dosing	7.7% 1/13 • Initiation of study drug to within 100 days of discontinuation of nivolumab dosing and 30 days of dasatinib dosing	0.00% 0/16 • Initiation of study drug to within 100 days of discontinuation of nivolumab dosing and 30 days of dasatinib dosing
Hepatobiliary disorders Cholelithiasis	0.00% 0/2 • Initiation of study drug to within 100 days of discontinuation of nivolumab dosing and 30 days of dasatinib dosing	0.00% 0/13 • Initiation of study drug to within 100 days of discontinuation of nivolumab dosing and 30 days of dasatinib dosing	6.2% 1/16 • Initiation of study drug to within 100 days of discontinuation of nivolumab dosing and 30 days of dasatinib dosing
Infections and infestations Bronchiolitis	0.00% 0/2 • Initiation of study drug to within 100 days of discontinuation of nivolumab dosing and 30 days of dasatinib dosing	7.7% 1/13 • Initiation of study drug to within 100 days of discontinuation of nivolumab dosing and 30 days of dasatinib dosing	0.00% 0/16 • Initiation of study drug to within 100 days of discontinuation of nivolumab dosing and 30 days of dasatinib dosing
Infections and infestations Epiglottitis	0.00% 0/2 • Initiation of study drug to within 100 days of discontinuation of nivolumab dosing and 30 days of dasatinib dosing	7.7% 1/13 • Initiation of study drug to within 100 days of discontinuation of nivolumab dosing and 30 days of dasatinib dosing	0.00% 0/16 • Initiation of study drug to within 100 days of discontinuation of nivolumab dosing and 30 days of dasatinib dosing
Infections and infestations Septic shock	0.00% 0/2 • Initiation of study drug to within 100 days of discontinuation of nivolumab dosing and 30 days of dasatinib dosing	7.7% 1/13 • Initiation of study drug to within 100 days of discontinuation of nivolumab dosing and 30 days of dasatinib dosing	0.00% 0/16 • Initiation of study drug to within 100 days of discontinuation of nivolumab dosing and 30 days of dasatinib dosing
Injury, poisoning and procedural complications Subdural haematoma	0.00% 0/2 • Initiation of study drug to within 100 days of discontinuation of nivolumab dosing and 30 days of dasatinib dosing	0.00% 0/13 • Initiation of study drug to within 100 days of discontinuation of nivolumab dosing and 30 days of dasatinib dosing	6.2% 1/16 • Initiation of study drug to within 100 days of discontinuation of nivolumab dosing and 30 days of dasatinib dosing
Investigations Lipase increased	0.00% 0/2 • Initiation of study drug to within 100 days of discontinuation of nivolumab dosing and 30 days of dasatinib dosing	7.7% 1/13 • Initiation of study drug to within 100 days of discontinuation of nivolumab dosing and 30 days of dasatinib dosing	0.00% 0/16 • Initiation of study drug to within 100 days of discontinuation of nivolumab dosing and 30 days of dasatinib dosing
Investigations White blood cell count increased	0.00% 0/2 • Initiation of study drug to within 100 days of discontinuation of nivolumab dosing and 30 days of dasatinib dosing	7.7% 1/13 • Initiation of study drug to within 100 days of discontinuation of nivolumab dosing and 30 days of dasatinib dosing	0.00% 0/16 • Initiation of study drug to within 100 days of discontinuation of nivolumab dosing and 30 days of dasatinib dosing
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Acute myeloid leukaemia	0.00% 0/2 • Initiation of study drug to within 100 days of discontinuation of nivolumab dosing and 30 days of dasatinib dosing	0.00% 0/13 • Initiation of study drug to within 100 days of discontinuation of nivolumab dosing and 30 days of dasatinib dosing	6.2% 1/16 • Initiation of study drug to within 100 days of discontinuation of nivolumab dosing and 30 days of dasatinib dosing
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma of colon	0.00% 0/2 • Initiation of study drug to within 100 days of discontinuation of nivolumab dosing and 30 days of dasatinib dosing	0.00% 0/13 • Initiation of study drug to within 100 days of discontinuation of nivolumab dosing and 30 days of dasatinib dosing	6.2% 1/16 • Initiation of study drug to within 100 days of discontinuation of nivolumab dosing and 30 days of dasatinib dosing
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Blast crisis in myelogenous leukaemia	0.00% 0/2 • Initiation of study drug to within 100 days of discontinuation of nivolumab dosing and 30 days of dasatinib dosing	7.7% 1/13 • Initiation of study drug to within 100 days of discontinuation of nivolumab dosing and 30 days of dasatinib dosing	6.2% 1/16 • Initiation of study drug to within 100 days of discontinuation of nivolumab dosing and 30 days of dasatinib dosing
Nervous system disorders Cerebral ischaemia	0.00% 0/2 • Initiation of study drug to within 100 days of discontinuation of nivolumab dosing and 30 days of dasatinib dosing	0.00% 0/13 • Initiation of study drug to within 100 days of discontinuation of nivolumab dosing and 30 days of dasatinib dosing	6.2% 1/16 • Initiation of study drug to within 100 days of discontinuation of nivolumab dosing and 30 days of dasatinib dosing
Nervous system disorders Facial paralysis	0.00% 0/2 • Initiation of study drug to within 100 days of discontinuation of nivolumab dosing and 30 days of dasatinib dosing	0.00% 0/13 • Initiation of study drug to within 100 days of discontinuation of nivolumab dosing and 30 days of dasatinib dosing	6.2% 1/16 • Initiation of study drug to within 100 days of discontinuation of nivolumab dosing and 30 days of dasatinib dosing
Nervous system disorders Syncope	0.00% 0/2 • Initiation of study drug to within 100 days of discontinuation of nivolumab dosing and 30 days of dasatinib dosing	0.00% 0/13 • Initiation of study drug to within 100 days of discontinuation of nivolumab dosing and 30 days of dasatinib dosing	6.2% 1/16 • Initiation of study drug to within 100 days of discontinuation of nivolumab dosing and 30 days of dasatinib dosing
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/2 • Initiation of study drug to within 100 days of discontinuation of nivolumab dosing and 30 days of dasatinib dosing	7.7% 1/13 • Initiation of study drug to within 100 days of discontinuation of nivolumab dosing and 30 days of dasatinib dosing	0.00% 0/16 • Initiation of study drug to within 100 days of discontinuation of nivolumab dosing and 30 days of dasatinib dosing