Clinical trial NCT04036461: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Multiple Myeloma
Keywords: Multiple Myeloma
Relapsed and refractory
CC-99712
BCMA
Antibody drug conjugate
BMS-986405
Lead sponsor: Celgene
Sponsor class: INDUSTRY
First posted: 2019-07-29
Enrollment: 47
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Adverse Events (AEs)
timeFrame: From enrollment until at least 42 days after completion of study treatment
measure: Maximum Tolerated Dose (MTD) in participants with relapsed and refractory MM
timeFrame: Up to 28 days
measure: Dose Limiting Toxicity (DLT) in participants with relapsed and refractory MM
timeFrame: Up to 28 days
Secondary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: Up to 3 years
measure: Time to Response
timeFrame: Up to 3 years
measure: Duration of Response
timeFrame: Up to 3 years
measure: Progression-free Survival (PFS)
timeFrame: Up to 3 years
measure: Overall Survival (OS)
timeFrame: Up to 3 years
measure: Pharmacokinetics- Cmax
timeFrame: Up to 3 years
measure: Pharmacokinetics- Tmax
timeFrame: Up to 3 years
measure: Pharmacokinetics- AUC(TAU)
timeFrame: Up to 3 years
measure: Pharmacokinetics- CLT
timeFrame: Up to 3 years
measure: Pharmacokinetics- Ctrough
timeFrame: Up to 3 years
measure: Presence and frequency of ADA using a validated bridging immunoassay with electrochemiluminescence detection
timeFrame: Up to 3 years
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: Local Institution - 107
state: California
city: Sarasota
country: United States
facility: Local Institution - 105
state: Florida
city: Buffalo
country: United States
facility: Local Institution - 103
state: New York
city: New York
country: United States
facility: Local Institution - 106
state: New York
city: Portland
country: United States
facility: Local Institution - 101
state: Oregon
city: Dallas
country: United States
facility: Local Institution - 104
state: Texas
city: Seattle
country: United States
facility: Local Institution - 102
state: Washington
city: Toronto
country: Canada
facility: Local Institution - 202
state: Ontario
city: Montreal
country: Canada
facility: Local Institution - 201
state: Quebec
city: Marseille Cedex 9
country: France
facility: Institut Paoli Calmettes
city: Montpellier CEDEX 5
country: France
facility: CHU Montpellier - Hôpital Saint Eloi
city: Paris
country: France
facility: Hopital Saint Antoine
city: Pierre Bénite
country: France
facility: Local Institution - 305
city: Bologna
country: Italy
facility: Local Institution - 501
city: Barcelona
country: Spain
facility: Local Institution - 405
city: Madrid
country: Spain
facility: Local Institution - 401
city: Malaga
country: Spain
facility: Local Institution - 0505
city: Salamanca
country: Spain
facility: Local Institution - 402
city: Sevillla
country: Spain
facility: Local Institution - 404
city: Valencia
country: Spain
facility: Local Institution - 403
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: