Phase I Multicenter, Open-Label, First-in-Human Study of BMS-986497 (ORM-6151) as a Monotherapy, in Double Combination With Azacitidine and in Triple Combination With Azacitidine and Venetoclax in Subjects With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome
Overview
- Phase
- Phase 1
- Intervention
- BMS-986497
- Conditions
- Acute Myeloid Leukemia
- Sponsor
- Bristol-Myers Squibb
- Enrollment
- 105
- Locations
- 15
- Primary Endpoint
- Incidence of treatment-emergent adverse events (TEAEs)
- Status
- Recruiting
- Last Updated
- 6 months ago
Overview
Brief Summary
The purpose of this study is to assess the safety, tolerability, drug levels, drug efficacy and determine the recommended dose of BMS-986497 as a monotherapy, in double combination with Azacitidine and in triple combination with Azacitidine and Venetoclax in participants with relapsed or refractory acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Adults with primary or secondary relapsed and/or refractory acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS).
- •Detectable levels of cluster of differentiation 33 (CD33) expression.
- •Failed alternative therapies with established benefit.
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤2 and adequate organ function.
Exclusion Criteria
- •Acute Promyelocytic Leukemia.
- •Clinically active central nervous system leukemia.
- •Active malignant solid tumor.
- •Pregnant or breastfeeding.
- •Other protocol-defined inclusion/exclusion criteria apply.
Arms & Interventions
Part 1: Dose Escalation BMS-986497 (Monotherapy)
Intervention: BMS-986497
Part 2, Cohort A: Dose Expansion BMS-986497 (Combination Therapy)
Intervention: BMS-986497
Part 2, Cohort A: Dose Expansion BMS-986497 (Combination Therapy)
Intervention: Azacitidine
Part 2, Cohort B: Dose Expansion BMS-986497 (Triple Combination Therapy)
Intervention: BMS-986497
Part 2, Cohort B: Dose Expansion BMS-986497 (Triple Combination Therapy)
Intervention: Azacitidine
Part 2, Cohort B: Dose Expansion BMS-986497 (Triple Combination Therapy)
Intervention: Venetoclax
Outcomes
Primary Outcomes
Incidence of treatment-emergent adverse events (TEAEs)
Time Frame: Up to 2 years
Determine the Recommended Phase 2 Dose (RP2D) of BMS-986497 as Monotherapy
Time Frame: Up to 2 years
RP2D of BMS-986497 as Combination Therapy
Time Frame: Up to 2 years
The combination therapy included BMS-986497 and Azacitidine
RP2D of BMS-986497 as Triple Combination Therapy
Time Frame: Up to 2 years
The triple combination therapy included BMS-986497, Azacitidine and Venetoclax.
Incidence of dose-limiting toxicities (DLTs)
Time Frame: Up to 21 days
Secondary Outcomes
- Best overall response (BOR)(Up to 4 years)
- Complete remission (CR)(Up to 4 years)
- Time to reach Cmax (Tmax)(Up to 2 years)
- Area under the curve from time 0 to last quantifiable concentration (AUC0-last)(Up to 2 years)
- Complete remission with incomplete hematologic recovery (Cri)(Up to 4 years)
- Event-free survival (EFS)(Up to 4 years)
- Transition rate to allogeneic hematopoietic stem cell transplantation (HSCT)(Up to 4 years)
- Maximum concentration (Cmax)(Up to 2 years)
- Overall response rate (ORR)(Up to 4 years)
- Duration of response (DoR)(Up to 4 years)
- Complete remission with partial hematologic recovery (CRh) rate(Up to 4 years)
- Incidence of Anti-drug antibody (ADA) against BMS-986497(Up to 2 years)