Multiple Myeloma
Conditions
Keywords
Multiple Myeloma, Relapsed and refractory, CC-99712, BCMA, Antibody drug conjugate, BMS-986405
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.
Interventions
DRUGCC-99712
CC-99712
DRUGBMS-986405
BMS-986405
Sponsors
Celgene
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events (AEs) | 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 | 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 | Up to 28 days | Is defined as any of the following toxicities occurring within the DLT assessment window |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response | 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) | 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. |
| Pharmacokinetics- Ctrough | Up to 3 years | Lowest concentration of drug immediately prior to administration of the next dose |
| Overall Survival (OS) | Up to 3 years | Is defined as the time from the first dose of CC-99712 to death from any cause. |
| Pharmacokinetics- CLT | Up to 3 years | Total body clearance of the drug from the serum |
| Pharmacokinetics- Tmax | Up to 3 years | Time to peak (maximum) serum concentration |
| Pharmacokinetics- AUC(TAU) | Up to 3 years | Area under the serum concentration time-curve |
| Presence and frequency of ADA using a validated bridging immunoassay with electrochemiluminescence detection | Up to 3 years | Anti-CC-99712 antibodies |
| Pharmacokinetics- Cmax | Up to 3 years | Maximum plasma concentration of drug |
| Overall Response Rate (ORR) | 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 | 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). |
Countries
Canada, France, Italy, Spain, United States
Outcome results
None listed