Clinical trial NCT06419634: Study of BMS-986497 (ORM-6151) as a Monotherapy, in Double and Triple Combination With Azacitidine and Venetoclax in Participants With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Acute Myeloid Leukemia
Myelodysplastic Syndrome
Keywords: BMS-986497
First-in-Human
ORM-6151
Acute myeloid leukemia (AML)
Myelodysplastic syndrome (MDS)
Cluster of differentiation 33 (CD33)
G1 to S phase transition 1 (GSPT1)
Open label study
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2024-05-17
Enrollment: 105
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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).


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.

Primary outcomes:
measure: Incidence of dose-limiting toxicities (DLTs)
timeFrame: Up to 21 days
measure: Incidence of treatment-emergent adverse events (TEAEs)
timeFrame: Up to 2 years
measure: Determine the Recommended Phase 2 Dose (RP2D) of BMS-986497 as Monotherapy
timeFrame: Up to 2 years
measure: RP2D of BMS-986497 as Combination Therapy
timeFrame: Up to 2 years
measure: RP2D of BMS-986497 as Triple Combination Therapy
timeFrame: Up to 2 years
Secondary outcomes:
measure: Maximum concentration (Cmax)
timeFrame: Up to 2 years
measure: Time to reach Cmax (Tmax)
timeFrame: Up to 2 years
measure: Area under the curve from time 0 to last quantifiable concentration (AUC0-last)
timeFrame: Up to 2 years
measure: Overall response rate (ORR)
timeFrame: Up to 4 years
measure: Duration of response (DoR)
timeFrame: Up to 4 years
measure: Best overall response (BOR)
timeFrame: Up to 4 years
measure: Complete remission (CR)
timeFrame: Up to 4 years
measure: Complete remission with incomplete hematologic recovery (Cri)
timeFrame: Up to 4 years
measure: Complete remission with partial hematologic recovery (CRh) rate
timeFrame: Up to 4 years
measure: Event-free survival (EFS)
timeFrame: Up to 4 years
measure: Transition rate to allogeneic hematopoietic stem cell transplantation (HSCT)
timeFrame: Up to 4 years
measure: Incidence of Anti-drug antibody (ADA) against BMS-986497
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale-New Haven Hospital
state: Connecticut
city: Chicago
country: United States
facility: Local Institution - 0010
state: Illinois
city: Boston
country: United States
facility: Local Institution - 0007
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University School of Medicine, Siteman Cancer Center
state: Missouri
city: Hackensack
country: United States
facility: John Theurer Cancer Center at Hackensack University Medical Center
state: New Jersey
city: New York
country: United States
facility: Columbia University Irving Medical Center
state: New York
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: Fairfax
country: United States
facility: Local Institution - 0009
state: Virginia
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Quebec
city: Marseille
country: France
facility: Local Institution - 0017
state: Bouches-du-Rhône
city: Paris
country: France
facility: Local Institution - 0018
city: Toulouse
country: France
facility: Local Institution - 0022
city: Barcelona
country: Spain
facility: Local Institution - 0020
state: Catalunya [Cataluña]
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: