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

• ClinicalTrials.gov Identifier: NCT04036461
• Recruitment Status: Recruiting
• First Posted: July 29, 2019
• Last Update Posted: May 10, 2023
• Sponsor: Celgene
• Information provided by (Responsible Party): Celgene

Tracking Information

• First Submitted Date: July 25, 2019
• First Posted Date: July 29, 2019
• Last Update Posted Date: May 10, 2023
• Actual Study Start Date: August 26, 2019
• Estimated Primary Completion Date: December 27, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 17, 2021)

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

Original Primary Outcome Measures (submitted: July 25, 2019)

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

Current Secondary Outcome Measures (submitted: October 24, 2022)

• Overall Response Rate (ORR) [ Time Frame: Up to 3 years ]
  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.
• Time to Response [ Time Frame: Up to 3 years ]
  Is defined as the time from the first CC-99712 dose date to the date of first documented response (PR or better).
• Duration of Response [ Time Frame: Up to 3 years ]
  Is defined as the time from the earliest date of documented response (≥ PR) to the first documented disease progression or death, whichever occurs first.
• Progression-free Survival (PFS) [ Time Frame: Up to 3 years ]
  Is defined as the time from the first dose of CC-99712 to progressive disease (PD) or death from any cause, whichever occurs first.
• Overall Survival (OS) [ Time Frame: Up to 3 years ]
  Is defined as the time from the first dose of CC-99712 to death from any cause.
• Pharmacokinetics- Cmax [ Time Frame: Up to 3 years ]
  Maximum plasma concentration of drug
• Pharmacokinetics- Tmax [ Time Frame: Up to 3 years ]
  Time to peak (maximum) serum concentration
• Pharmacokinetics- AUC(TAU) [ Time Frame: Up to 3 years ]
  Area under the serum concentration time-curve
• Pharmacokinetics- CLT [ Time Frame: Up to 3 years ]
  Total body clearance of the drug from the serum
• Pharmacokinetics- Ctrough [ Time Frame: Up to 3 years ]
  Lowest concentration of drug immediately prior to administration of the next dose
• Presence and frequency of ADA using a validated bridging immunoassay with electrochemiluminescence detection [ Time Frame: Up to 3 years ]
  Anti-CC-99712 antibodies

Original Secondary Outcome Measures (submitted: July 25, 2019)

• Overall Response Rate (ORR) [ Time Frame: Up to 3 years ]
  Is defined as the proportion of subjects 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.
• Time to Response [ Time Frame: Up to 3 years ]
  Is defined as the time from the first CC-99712 dose date to the date of first documented response (PR or better).
• Duration of Response [ Time Frame: Up to 3 years ]
  Is defined as the time from the earliest date of documented response (≥ PR) to the first documented disease progression or death, whichever occurs first.
• Progression-free Survival (PFS) [ Time Frame: Up to 3 years ]
  Is defined as the time from the first dose of CC-99712 to progressive disease (PD) or death from any cause, whichever occurs first.
• Overall Survival (OS) [ Time Frame: Up to 3 years ]
  Is defined as the time from the first dose of CC-99712 to death from any cause.
• Pharmacokinetics- Cmax [ Time Frame: Up to 3 years ]
  Maximum plasma concentration of drug
• Pharmacokinetics- Cmin [ Time Frame: Up to 3 years ]
  Minimum plasma concentration of drug
• Pharmacokinetics- AUC [ Time Frame: Up to 3 years ]
  Area under the curve
• Pharmacokinetics- tmax [ Time Frame: Up to 3 years ]
  Time to peak (maximum) serum concentration
• Pharmacokinetics- t1/2 [ Time Frame: Up to 3 years ]
  Half-life
• Pharmacokinetics- CL [ Time Frame: Up to 3 years ]
  Clearance
• Pharmacokinetics- Vss [ Time Frame: Up to 3 years ]
  Volume of Distribution
• Presence and frequency of ADA using a validated bridging immunoassay with electrochemiluminescence detection [ Time Frame: Up to 3 years ]
  Anti-CC-99712 antibodies

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of CC-99712, a BCMA Antibody-Drug Conjugate, in Participants With Relapsed and Refractory Multiple Myeloma
• Official Title: 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
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Multiple Myeloma

Intervention

• Drug: CC-99712
  CC-99712
• Drug: BMS-986405
  BMS-986405
  Other Name: GSI (Gamma secretase inhibitor)

Study Arms

• Experimental: Arm 1 (CC-99712 monotherapy)
  CC-99712 will be administered via intravenous (IV) infusion.
  Intervention: Drug: 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.
  Interventions:

  • Drug: CC-99712
  • Drug: BMS-986405

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: August 17, 2021): 160
• Original Estimated Enrollment (submitted: July 25, 2019): 120
• Estimated Study Completion Date: May 26, 2025
• Estimated Primary Completion Date: December 27, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: BMS Study Connect Contact Center www.BMSStudyConnect.com; 855-907-3286; Clinical.Trials@bms.com

Contact: First line of the email MUST contain NCT # and Site #.

• Listed Location Countries: Canada, France, Italy, Spain, United States

Administrative Information

• NCT Number: NCT04036461
• Other Study ID Numbers: CC-99712-MM-001; U1111-1231-9404 ( Other Identifier: WHO ); 2020-004514-35 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes

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/

• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Supporting Materials: Clinical Study Report (CSR)
• Supporting Materials: Analytic Code
• Time Frame: See Plan Description
• Access Criteria: See Plan Description
• URL: https://www.bms.com/researchers-and-partners/clinical-trials-and-research/disclosure-commitment.html

• Current Responsible Party: Celgene
• Original Responsible Party: Same as current
• Current Study Sponsor: Celgene
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Bristol-Myers Squibb; Bristol-Myers Squibb

• PRS Account: Celgene
• Verification Date: May 2023