A Study of CC-99712, a BCMA Antibody-Drug Conjugate, in Participants With Relapsed and Refractory Multiple Myeloma

A Phase 1, Multicenter, Open-label, Dose Finding Study of CC-99712, a BCMA Antibody-Drug Conjugate, in Subjects With Relapsed and Refractory Multiple Myeloma

Study CC-99712-MM-001 is an open-label, Phase 1, dose escalation (Part A) and expansion (Part B), First-in-Human (FIH) clinical study of CC-99712 in monotherapy or combination with BMS-986405 in participants with relapsed and refractory multiple myeloma (MM). The dose escalation part (Part A) of the study will evaluate the safety and tolerability of escalating doses of CC-99712, administered intravenously (IV) in monotherapy (Arm 1) or combination with BMS-986405 (Arm 2), to determine the maximum tolerated dose (MTD) of CC-99712 guided by a Bayesian logistic regression model (BLRM). A modified accelerated titration design will also be used for Arm 1 and Arm 2. The MTD may be established separately for CC-99712 administered at Q3W and/ or Q4W schedules. The expansion part (Part B) will further evaluate the safety and efficacy of CC-99712 in monotherapy (Arm 1) or combination (Arm 2) administered at or below the MTD in selected expansion cohorts in order to determine the RP2D. One or more doses or dosing regimens may be selected for cohort expansion. All participants will be treated until confirmed disease progression per IMWG criteria, unacceptable toxicity, or participants//Investigator decision to withdraw.

Study Overview

• Status: Terminated
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: CC-99712; Drug: BMS-986405

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Local Institution - 202
  • Quebec
    • Montreal, Quebec, Canada, H1T 2M4
      • Local Institution - 201
• France
  • Marseille Cedex 9, France, 13273
    • Institut Paoli Calmettes
  • Montpellier CEDEX 5, France, 34295
    • CHU Montpellier - Hôpital Saint Eloi
  • Paris, France, 75571
    • Hôpital Saint Antoine
  • Pierre Bénite, France, 69495
    • Local Institution - 305
• Italy
  • Bologna, Italy, 40138
    • Local Institution - 501
• Spain
  • Barcelona, Spain, 08036
    • Local Institution - 405
  • Madrid, Spain, 28041
    • Local Institution - 401
  • Malaga, Spain, 29010
    • Local Institution - 0505
  • Salamanca, Spain, 37007
    • Local Institution - 402
  • Sevillla, Spain, 41013
    • Local Institution - 404
  • Valencia, Spain, 46026
    • Local Institution - 403
• United States
  • California
    • La Jolla, California, United States, 92093
      • Local Institution - 107
  • Florida
    • Sarasota, Florida, United States, 34232
      • Local Institution - 105
  • New York
    • Buffalo, New York, United States, 14263
      • Local Institution - 103
    • New York, New York, United States, 10029
      • Local Institution - 106
  • Oregon
    • Portland, Oregon, United States, 97239
      • Local Institution - 101
  • Texas
    • Dallas, Texas, United States, 75390
      • Local Institution - 104
  • Washington
    • Seattle, Washington, United States, 98104
      • Local Institution - 102

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Participants must satisfy the following criteria to be enrolled in the study:

Inclusion

• Participant is ≥ 18 years of age at the time of signing the ICF.
• Participant has a history of multiple myeloma (MM) with relapsed and/or refractory disease
• Participant must have measurable disease.
• Participant has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.

Exclusion Criteria

• Participant has symptomatic central nervous system involvement of MM.
• Participant had a prior autologous stem cell transplant ≤ 3 months prior to starting CC-99712.
• Participant had a prior allogeneic stem cell transplant with either standard or reduced intensity conditioning ≤ 6 months prior to starting CC-99712 or is on systemic immunosuppression for graft-versus host disease.
• Subject is a pregnant or lactating female.
• Subject has known human immunodeficiency virus (HIV) infection.
• Subject has active hepatitis B or C (HBV/HCV) infection.

Other protocol-defined inclusion/exclusion criteria apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1 (CC-99712 monotherapy); CC-99712 will be administered via intravenous (IV) infusion.	Drug: CC-99712; CC-99712
Experimental: Arm 2 (CC-99712 and BMS-986405 combination); CC-99712 will be administered via IV infusion. BMS-986405 will be administered orally.	Drug: CC-99712; CC-99712; Drug: BMS-986405; BMS-986405; Other Names: GSI (Gamma secretase inhibitor)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events (AEs)	Number of participants with adverse event	From enrollment until at least 42 days after completion of study treatment
Maximum Tolerated Dose (MTD) in participants with relapsed and refractory MM	Is defined as the highest dose that causes DLTs in no more than 33% of patient population during the first cycle of treatment.	Up to 28 days
Dose Limiting Toxicity (DLT) in participants with relapsed and refractory MM	Is defined as any of the following toxicities occurring within the DLT assessment window	Up to 28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR)	Is defined as the proportion of participants who achieve a partial response or better (eg, Partial response (PR), Very good partial response (VGPR), Complete response (CR) or sCR), according to IMWG response criteria.	Up to 3 years
Time to Response	Is defined as the time from the first CC-99712 dose date to the date of first documented response (PR or better).	Up to 3 years
Duration of Response	Is defined as the time from the earliest date of documented response (≥ PR) to the first documented disease progression or death, whichever occurs first.	Up to 3 years
Progression-free Survival (PFS)	Is defined as the time from the first dose of CC-99712 to progressive disease (PD) or death from any cause, whichever occurs first.	Up to 3 years
Overall Survival (OS)	Is defined as the time from the first dose of CC-99712 to death from any cause.	Up to 3 years
Pharmacokinetics- Cmax	Maximum plasma concentration of drug	Up to 3 years
Pharmacokinetics- Tmax	Time to peak (maximum) serum concentration	Up to 3 years
Pharmacokinetics- AUC(TAU)	Area under the serum concentration time-curve	Up to 3 years
Pharmacokinetics- CLT	Total body clearance of the drug from the serum	Up to 3 years
Pharmacokinetics- Ctrough	Lowest concentration of drug immediately prior to administration of the next dose	Up to 3 years
Presence and frequency of ADA using a validated bridging immunoassay with electrochemiluminescence detection	Anti-CC-99712 antibodies	Up to 3 years

Collaborators and Investigators

• Sponsor: Celgene
• Investigators: Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): August 26, 2019
• Primary Completion (Actual): July 8, 2024
• Study Completion (Actual): August 19, 2024

Study Registration Dates

• First Submitted: July 25, 2019
• First Submitted That Met QC Criteria: July 25, 2019
• First Posted (Actual): July 29, 2019

Study Record Updates

• Last Update Posted (Actual): August 30, 2024
• Last Update Submitted That Met QC Criteria: August 28, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Multiple Myeloma; BCMA; Antibody drug conjugate; Relapsed and refractory; CC-99712; BMS-986405
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gamma Secretase Inhibitors and Modulators
• Other Study ID Numbers: CC-99712-MM-001; U1111-1231-9404 (Other Identifier: WHO); 2020-004514-35 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Information relating to our policy on data sharing and the process for requesting data can be found at the following link:

https://www.celgene.com/research-development/clinical-trials/clinical-trials-data-sharing/

• IPD Sharing Time Frame: See Plan Description
• IPD Sharing Access Criteria: See Plan Description
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No