A Study to Assess BMS-986453 in Participants With Relapsed and/or Refractory Multiple Myeloma

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to assess BMS-986453 in participants with relapsed and/or refractory multiple myeloma (RRMM).

Official Title
-----------------
A Phase 1, Open-Label, Dose-Finding Study of BMS-986453, Dual Targeting BCMAxGPRC5D Chimeric Antigen Receptor T Cells, in Participants With Relapsed and/or Refractory Multiple Myeloma

Conditions
-----------------
Relapsed and/or Refractory Multiple Myeloma

Intervention / Treatment
-----------------
* Drug: BMS-986453
* Drug: Fludarabine
* Drug: Cyclophosphamide


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Participants must have a diagnosis of multiple myeloma with relapsed and/or refractory disease. Participants must have confirmed progressive disease on or within 12 months (measured from the last dose) of completing treatment with the last anti-myeloma treatment regimen before study entry. Participants in Part A and Part B Cohort 1 must have received at least 3 prior anti-myeloma treatment regimens, including a proteasome inhibitor and immunomodulatory agent. Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Participants must have adequate organ function. Exclusion Criteria: Participants must not have any known active or history of central nervous system (CNS) involvement of multiple myeloma. Participants must not have active or history of plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes) syndrome, or clinically significant amyloidosis. Participants must not have a history or presence of clinically significant CNS pathology such as seizure disorder, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, or cerebellar disease, or presence of clinically active psychosis. Other protocol-defined inclusion/exclusion criteria apply

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Administration of BMS-986453<br> | Drug: BMS-986453<br>* Specified dose on specified days<br>Drug: Fludarabine<br>* Specified dose on specified days<br>Drug: Cyclophosphamide<br>* Specified dose on specified days<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-emergent adverse events (AEs) |  | Up to 2 years | 
| Number of participants with serious adverse events (SAEs) |  | Up to 2 years | 
| Number of participants with AEs leading to discontinuation |  | Up to 2 years | 
| Number of participants with AEs leading to death |  | Up to 2 years | 
| Number of participants with dose-limiting toxicities (DLTs) |  | Up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum observed concentration (Cmax) |  | Up to 2 years | 
| Time of maximum observed concentration (Tmax) |  | Up to 2 years | 
| Area under the blood concentration-time curve from time zero to 28 days after dosing (AUC(0-28D)) |  | Up to 2 years | 
| Overall response rate (ORR) |  | Up to 2 years | 
| Complete response rate (CRR) |  | Up to 2 years | 
| Number of participants with very good partial response (VGPR) or better |  | Up to 2 years | 
| Progression-free survival (PFS) |  | Up to 2 years | 
| Overall survival (OS) |  | Up to 2 years | 
| Time to response (TTR) |  | Up to 2 years | 
| Time to complete response (TTCR) |  | Up to 2 years | 
| Duration of response (DOR) |  | Up to 2 years | 
| Duration of complete response (DOCR) |  | Up to 2 years | 
| Persistence of BMS-986453 in peripheral blood | Defined as a transgene count greater than or equal to the lower limit of detection (LLOD) | Up to 2 years | 
| Expansion rate | Defined as Cmax divided by Tmax | Up to 2 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Dual Targeting, BCMAxGPRC5D, GPRC5DxBCMA, BMS-986453, CAR T, CART, Multiple Myeloma, Relapsed and/or Refractory