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

Phase 1TerminatedNCT04036461

Celgene47 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Multiple Myeloma

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (20)

Local Institution - 107

La Jolla, California, United States

Local Institution - 105

Sarasota, Florida, United States

Local Institution - 103

Buffalo, New York, United States

Local Institution - 106

New York, New York, United States

Local Institution - 101

Portland, Oregon, United States

Local Institution - 104

Dallas, Texas, United States

Local Institution - 102

Seattle, Washington, United States

Local Institution - 202

Toronto, Ontario, Canada

Local Institution - 201

Montreal, Quebec, Canada

Institut Paoli Calmettes

Marseille, France

...and 10 more locations

Outcomes

Primary Outcomes

Adverse Events (AEs)

Number of participants with adverse event

Time frame: 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.

Time frame: 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

Time frame: Up to 28 days

Secondary Outcomes

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.

Time frame: 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).

Time frame: 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.

Time frame: 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.

Time frame: Up to 3 years

Overall Survival (OS)

Is defined as the time from the first dose of CC-99712 to death from any cause.

Time frame: Up to 3 years

Pharmacokinetics- Cmax

Maximum plasma concentration of drug

Time frame: Up to 3 years

Pharmacokinetics- Tmax

Time to peak (maximum) serum concentration

Time frame: Up to 3 years

Pharmacokinetics- AUC(TAU)

Area under the serum concentration time-curve

Time frame: Up to 3 years

Pharmacokinetics- CLT

Total body clearance of the drug from the serum

Time frame: Up to 3 years

Pharmacokinetics- Ctrough

Lowest concentration of drug immediately prior to administration of the next dose

Time frame: Up to 3 years

Presence and frequency of ADA using a validated bridging immunoassay with electrochemiluminescence detection

Anti-CC-99712 antibodies

Time frame: Up to 3 years