A Study to Evaluate Safety, Drug Levels and Effectiveness of CC-92480 (BMS-986348) in Combination With Other Treatments in Participants With Relapsed or Refractory Multiple Myeloma CA057-003
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What's the purpose of this trial?

The purpose of this study is to assess the safety, tolerability and preliminary effectiveness of CC-92480 (BMS-986348) in novel therapeutic combinations for the treatment of Relapsed or Refractory Multiple Myeloma (RRMM).

This trial is currently open and accepting patients.


What will happen during the trial?

You may be able to join this trial if you:

The following criteria is a partial list of reasons why patients may be eligible to participate in this clinical trial. Further evaluation with a medical professional is required.

Inclusion Criteria:

  • Relapsed or refractory multiple myeloma (MM) and must:
    • have documented disease progression during or after their last myeloma therapy
    • be refractory to, intolerant to, or not a candidate for available, established therapies known to provide clinical benefit in MM
  • Must have measurable disease
  • Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1
  • Agree to follow the CC-92480 Pregnancy Prevention Plan (PPP)

Exclusion Criteria:

  • Known active or history of central nervous system (CNS) involvement of MM
  • Plasma cell leukemia; Waldenstrom's macroglobulinemia; polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome; or clinically significant light-chain amyloidosis.
  • Impaired cardiac function or clinically significant cardiac disease
  • Previous SARS-CoV-2 infection within 14 days for asymptomatic or mild symptomatic infections or 28 days for severe/critical illness prior to Cycle 1 Day 1 (C1D1)
  • For Part 1: received prior therapy with CC-92480
  • For Part 2: received prior therapy with CC-92480, tazemetostat, BMS-986158, or trametinib
  • Previously received allogeneic stem-cell transplant at any time or received autologous stem-cell transplant within 12 weeks of initiating study treatment
  • Received any of the following within 14 days prior to initiating study treatment:
    • Plasmapheresis
    • Major surgery
    • Radiation therapy other than local therapy for myeloma associated bone lesions
    • Use of any systemic anti-myeloma drug therapy
  • Used any investigational agents within 28 days or 5 half-lives (whichever is shorter) prior to initiating study treatment
  • COVID-19 vaccine within 14 days prior to C1D1

Other protocol-defined inclusion/exclusion criteria apply


Additional Trial Information

Phase 1/2

Enrollment: 220 patients (estimated)

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Published Results

Mezigdomide (MEZI) in Novel-Novel Combinations for Relapsed or Refractory Multiple Myeloma (RRMM): Preliminary Results from the CA057-003 Trial

December 08, 2024

Results: As of May 8, 2024, 14 pts received MEZId + TAZ, 16 MEZId + BMS-986158, and 15 MEZId + TRAM. Across all cohorts, median (range) age was 63 (37–83) y and median time since initial diagnosis was 7.5 (2.0–18.4) y. Eight (18%) pts were Black/African American, 35 (78%) White, and race was not collected/unknown (NA) in 2 (4%); 6 (13%) were Hispanic/Latino and 36 (80%) were not (NA = 3 [7%] pts); 56% were in the United States. Extramedullary plasmacytomas were present in 16 (36%) pts. The median number of prior antimyeloma regimens was 5 (2–20). Prior therapies included autologous stem cell transplantation (78%), IMiD agents (100%), proteasome inhibitors (PIs; 100%), anti-CD38 monoclonal antibodies (mAbs; 100%), and T cell-redirecting therapy (58%); 82% had triple-class refractory disease (to an IMiD agent, PI, and anti-CD38 mAb).

At data cutoff, 7 (50%) pts continued on treatment in the MEZId + TAZ cohort, 8 (50%) in the MEZId + BMS-986158 cohort, and 10 (67%) in the MEZId + TRAM cohort. The main reason for discontinuation in all 3 cohorts was PD. Median follow-up was 4.1 (1.0–11.0) mo (MEZId + TAZ), 2.9 (1.0–6.5) mo (MEZId + BMS-986158), and 3.6 (0–10.6) mo (MEZId + TRAM).

The most frequent grade (Gr) 3/4 treatment-emergent adverse event (TEAE) across all 3 cohorts was neutropenia (43–73%); Gr 3/4 non-hematologic TEAEs were low or absent. Three pts had dose-limiting toxicities (1 with 0.3 mg MEZId + BMS-986158, 1 with 1.0 mg MEZId + BMS-986158, and 1 with 1.0 mg MEZId + TRAM).

In the efficacy-evaluable population, overall response rate (≥ partial response [PR]) was 54% (7/13 pts) with MEZId + TAZ; 36% (5/14) with MEZId + BMS-986158; and 92% (11/12) with MEZId + TRAM. In the MEZId + TAZ and MEZId + BMS-986158 cohorts, deeper responses (≥ very good PR), including 1 stringent complete response (sCR) with MEZId + TAZ, were observed with 1.0 mg MEZI, and in the MEZId + TRAM cohort with ≥0.6 mg MEZI (including 1 sCR), and 100% (5/5 pts) at 1.0 mg MEZI were ongoing responses with this combination.

Exposures increased in a dose-linear manner over the dose range and were consistent across treatment cohorts, demonstrating no drug-drug interaction between MEZI and novel therapeutic agents. MEZI remained pharmacodynamically active, inducing Ikaros/Aiolos degradation and B-cell reduction with all combination agents at all dose levels, with the greatest effect observed at MEZI 1.0 mg.

Conclusions: MEZId combined with the novel therapeutic agents TAZ, BMS-986158, or TRAM showed promising efficacy and a manageable safety profile in patients with RRMM. No new safety signals were identified, with neutropenia being the most common Gr 3/4 TEAE in all 3 cohorts. These results provide a rationale for further exploration of these novel all-oral combinations. Accrual continues and updated results will be presented at the meeting.

Trial Locations

All Trial Locations

View all clinical trial locations sorted by state.

Alabama

University of Alabama at Birmingham O'Neal Comprehensive Cancer Center

Birmingham, AL

Open and Accepting

Maryland

Sidney Kimmel Comprehensive Cancer Center Johns Hopkins Medicine

Baltimore, MD

Open and Accepting

Massachusetts

Dana-Farber Cancer Institute

Boston, MA

Open and Accepting

New Jersey

New York

Memorial Sloan Kettering Cancer Center

New York, NY

Open and Accepting
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