A Phase 1b/2 Open-Label, Multicenter Study to Evaluate the Safety and Efficacy of TAK-981 in Combination With Monoclonal Antibodies in Adult Patients With Relapsed and/or Refractory Multiple Myeloma

Who is this study for? Patients with Multiple Myeloma

What treatments are being studied? TAK-981

Status: Terminated

Location: See all (13) locations...

Intervention Type: Drug

Study Type: Interventional

Study Phase: Phase 1/Phase 2

SUMMARY

TAK-981 is being tested in combination with anti-CD38 monoclonal antibodies (mAbs) to treat participants who have relapsed or refractory multiple myeloma (RRMM). The main aims of the study are to evaluate the safety and efficacy of TAK-981 in combination with anti-CD38 (mAbs) and to determine the recommended Phase 2 dose (RP2D). Participants will be on this combination treatment for 28-day cycles. They will continue with this treatment until disease progression or unacceptable toxicity.

Eligibility

Participation Requirements

Sex: All

Minimum Age: 18

Healthy Volunteers: f

View:

⁃ Participants must have RRMM with measurable disease:

⁃ a) Has measurable disease defined as one of the following:

‣ Serum M-protein ≥0.5 g/dL (≥5 g/L).

‣ Urine M-protein ≥200 mg/24 hours.

‣ In participants without measurable M-protein in serum protein electrophoresis (SPEP) or urine protein electrophoresis (UPEP), a serum free light chain (FLC) assay result with involved FLC level ≥10 mg/dL (≥100 mg/L), provided serum FLC ratio is abnormal.

⁃ Has undergone stem cell transplant or is considered transplant ineligible.

⁃ Has failed at least 3 prior lines of anti-myeloma treatments and is either refractory, or intolerant to at least 1 immunomodulatory drug ( IMiD); (ie, lenalidomide or pomalidomide \[thalidomide excluded\]), at least 1 proteasome inhibitor (ie, bortezomib, ixazomib or carfilzomib), and refractory to at least 1 anti-CD38 antibody and who have demonstrated disease progression with the last therapy.

• Have a performance status of 0-2 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.

• Have recovered to Grade 1 or baseline from all toxicity associated with previous therapy or have the toxicity established as sequela.

Locations

United States

Arizona

Mayo Clinic Arizona - PPDS

Scottsdale

Florida

Mayo Clinic Jacksonville - PPDS

Jacksonville

Georgia

Winship Cancer Institute, Emory University

Atlanta

Indiana

Indiana University

Indianapolis

Maryland

American Oncology Partners of Maryland, PA

Bethesda

Minnesota

Mayo Clinic - Cancer Center - Rochester - PPDS

Rochester

Nebraska

Oncology Hematology West (Omaha) - USOR

Omaha

New York

Weill Cornell Medical Center

New York

Ohio

TriHealth Cancer Institute

Cincinnati

Texas

Baylor Sammons Cancer Center

Dallas

Northeast Texas Cancer and Research Institute

Tyler

Wisconsin

Medical College of Wisconsin Cancer Center

Milwaukee

Other Locations

Canada

Hopital Maisonneuve-Rosemont

Montreal

Time Frame

Start Date: 2021-04-20

Completion Date: 2023-11-09

Participants

Target number of participants: 27

Treatments

Experimental: Phase 1b, Part 1 - Dose Escalation: Arm A - TAK-981 Twice Weekly (BIW) + Mezagitamab

Mezagitamab: A fixed dose of 600 mg subcutaneous (SC) injection once weekly in Cycles 1 and 2 (each cycle is of 28 days), followed by once every 2 weeks in Cycle 3 through 6, then every 4 weeks up to Cycle 24 or until disease progression or unacceptable toxicity, or until any other discontinuation criterion is met, whichever occurs first.~TAK-981: Escalating doses of TAK-981 BIW intravenous (IV) infusion on Days 1, 4, 8, 11 and 15 in Cycle 1 and 2 (each Cycle is of 28 days) followed by every 2 weeks in Cycles 3 through 6, followed by once every 4 weeks up to Cycle 24 or until disease progression or unacceptable toxicity, or until any other discontinuation criterion is met, whichever occurs first.

Experimental: Phase 1b, Part 1 - Dose Escalation: Arm B - TAK-981 Weekly (QW) + Mezagitamab

Mezagitamab: A fixed dose of 600 mg SC injection once weekly in Cycles 1 and 2 (each cycle is of 28 days), followed by once every 2 weeks from Cycle 3 through 6, then every 4 weeks up to Cycle 24 or until disease progression or unacceptable toxicity, or until any other discontinuation criterion is met, whichever occurs first.~TAK-981: Escalating doses of TAK-981 QW IV infusion on Days 1, 8, 15, and 22 in Cycles 1 and 2 (each cycle is of 28 days), followed by every 2 weeks in Cycles 3 through 6, followed by once every 4 weeks. up to Cycle 24 or until disease progression or unacceptable toxicity, or until any other discontinuation criterion is met, whichever occurs first.

Experimental: Phase 1b, Part 2 - Lead-in Cohort: TAK-981 + Daratumumab and Hyaluronidase-fihj

Daratumumab and hyaluronidase-fihj: 1800 mg SC injection QW once weekly in Cycles 1 and 2 , (each cycle is of 28 days) followed by every 2 weeks in Cycle 3 through 6 , followed by every 4 weeks up to Cycle 24 until disease progression or unacceptable toxicity, or until any other discontinuation criterion is met, whichever occurs first.~TAK-981: As per dose and schedule of TAK-981 defined in Phase 1b Part 1.

Experimental: Phase 2 - Dose Expansion: TAK-981 + Daratumumab and Hyaluronidase-fihj or Mezagitamab

TAK-981 at RP2D as determined in Phase 1b. Mezagitamab at a fixed dose of 600 mg SC injection or Daratumumab and Hyaluronidase-fihj at a fixed dose of 1800 mg weekly in Cycles 1 and 2 (each cycle is of 28 days), followed by every 2 weeks in Cycle 3 through 6, followed by every 4 weeks up to Cycle 24 or until disease progression unacceptable toxicity, or until any other discontinuation criterion is met, whichever occurs first.

Authors

Habte Yimer, Stefano Tarantolo, Vivek Roy, Jeremy Larsen, Aaron Rosenberg, Ralph Boccia, Omar Nadeem, Shaji Kumar, Rafat Abonour, Moshe Levy, Sagar Lonial, Cara Rosenbaum

Related Therapeutic Areas

Multiple Myeloma

A Phase 1b/2 Open-Label, Multicenter Study to Evaluate the Safety and Efficacy of TAK-981 in Combination With Monoclonal Antibodies in Adult Patients With Relapsed and/or Refractory Multiple Myeloma

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