A Study Evaluating the Safety, Pharmacokinetics, and Activity of the Combination of Cevostamab and Elranatamab in Participants With Relapsed or Refractory Multiple Myeloma (R/R MM)
Phase 1
Recruiting
- Conditions
- Relapsed or Refractory Multiple Myeloma
- Interventions
- Registration Number
- NCT05927571
- Lead Sponsor
- Genentech, Inc.
- Brief Summary
The purpose of the study is to evaluate safety and tolerability of the combination of cevostamab plus elranatamab and also determine the recommended Phase II dose (RP2D) for the study treatment. The study consists of a safety lead-in stage, and an expansion stage.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 120
Inclusion Criteria
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
- Diagnosis of R/R MM per IMWG criteria
- For female participants of childbearing potential: agreement to remain abstinent or use contraception
- For male participants: agreement to remain abstinent or use a condom
Exclusion Criteria
- Prior treatment with cevostamab or another agent targeting fragment crystallizable receptor-like 5 (FcRH5)
- Prior treatment with elranatamab
- Prior allogeneic stem cell transplantation (SCT)
- Absolute plasma cell count exceeding 500 per milliliter (mL) or 5% of the peripheral blood white cells
- Diagnosis of Waldenström macroglobulinemia or polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin changes (POEMS) syndrome
- Participants with known history of amyloidosis
- History of autoimmune disease
- History of confirmed progressive multifocal leukoencephalopathy
- Peripheral motor polyneuropathy of prespecified grade
- Known or suspected chronic cytomegalovirus (CMV) and/or Epstein-Barr virus (EBV) infection
- Known history of hemophagocytic lymphohistiocytosis (HLH) or macrophage activation syndrome (MAS)
- Acute or chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
- Human immunodeficiency virus (HIV) seropositivity
- History of central nervous system (CNS) myeloma disease
- Significant cardiovascular disease
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Dose Expansion Cohort Cevostamab Participants will receive cevostamab, IV, in combination with elranatamab, SC, with step-up dosing of each drug in pre-phase following which they will receive elranatamab, at the assigned dose as a SC injection until disease progression or unacceptable toxicity. Participants will also receive cevostamab at the assigned dose as IV infusion until disease progression or unacceptable toxicity or up to 1 year on treatment, whichever occurs first. Dose Expansion Cohort Elranatamab Participants will receive cevostamab, IV, in combination with elranatamab, SC, with step-up dosing of each drug in pre-phase following which they will receive elranatamab, at the assigned dose as a SC injection until disease progression or unacceptable toxicity. Participants will also receive cevostamab at the assigned dose as IV infusion until disease progression or unacceptable toxicity or up to 1 year on treatment, whichever occurs first. Safety Lead-In Cohort Cevostamab Participants will receive cevostamab, intravenously (IV), in combination with elranatamab, subcutaneously (SC), with step-up dosing of each drug in pre-phase following which they will receive elranatamab, at the assigned dose as a SC injection until disease progression or unacceptable toxicity. Participants will also receive cevostamab at the assigned dose as IV infusion until disease progression or unacceptable toxicity or up to 1 year on treatment, whichever occurs first. Safety Lead-In Cohort Tocilizumab Participants will receive cevostamab, intravenously (IV), in combination with elranatamab, subcutaneously (SC), with step-up dosing of each drug in pre-phase following which they will receive elranatamab, at the assigned dose as a SC injection until disease progression or unacceptable toxicity. Participants will also receive cevostamab at the assigned dose as IV infusion until disease progression or unacceptable toxicity or up to 1 year on treatment, whichever occurs first. Dose Expansion Cohort Tocilizumab Participants will receive cevostamab, IV, in combination with elranatamab, SC, with step-up dosing of each drug in pre-phase following which they will receive elranatamab, at the assigned dose as a SC injection until disease progression or unacceptable toxicity. Participants will also receive cevostamab at the assigned dose as IV infusion until disease progression or unacceptable toxicity or up to 1 year on treatment, whichever occurs first. Safety Lead-In Cohort Elranatamab Participants will receive cevostamab, intravenously (IV), in combination with elranatamab, subcutaneously (SC), with step-up dosing of each drug in pre-phase following which they will receive elranatamab, at the assigned dose as a SC injection until disease progression or unacceptable toxicity. Participants will also receive cevostamab at the assigned dose as IV infusion until disease progression or unacceptable toxicity or up to 1 year on treatment, whichever occurs first.
- Primary Outcome Measures
Name Time Method Number of Participants With Adverse Events (AEs) From signing of informed consent up to end of study (EOS) (approximately 36 months) Adverse events will be reported according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0). The severity of CRS, immune effector cell-associated neurotoxicity syndrome (ICANS) and hemophagocytic lymphohistiocytosis (HLH) will be graded based on the American Society for Transplantation and Cellular Therapy (ASTCT) Grading Scales.
- Secondary Outcome Measures
Name Time Method Objective Response Rate (ORR) as Determined by the Investigator per International Myeloma Working Group (IMWG) Criteria Up to approximately 36 months Time to Best Response (for Participants who Achieve a Response of PR or Better) Up to approximately 36 months Complete Response (CR)/ Stringent Complete Response (sCR) Rate as Determined by the Investigator per IMWG Criteria Up to approximately 36 months Rate of Very Good Partial Response (VGPR) or Better, as Determined by the Investigator per IMWG Criteria Up to approximately 36 months Duration of Response (DOR) as Determined by the Investigator (for Participants who Achieve a Response of Partial Response (PR) or Better) Up to approximately 36 months Overall Survival (OS) Up to approximately 36 months Progression-Free Survival as Determined by the Investigator per IMWG Criteria Up to approximately 36 months Serum Concentration of Cevostamab at Specified Timepoints Up to approximately 36 months Time to First Response (for Participants who Achieve a Response of PR or Better) Up to approximately 36 months Number of Participants with Anti-Drug Antibody (ADA) Against Cevostamab Up to approximately 36 months Serum Concentration of Elranatamab at Specified Timepoints Up to approximately 36 months Number of Participants with ADA Against Elranatamab Up to approximately 36 months
Trial Locations
- Locations (9)
Calvary Mater Newcastle
🇦🇺Waratah, New South Wales, Australia
Royal Prince Alfred Hospital
🇦🇺Camperdown, New South Wales, Australia
The Alfred Hospital
🇦🇺Prahan, Victoria, Australia
Rambam Health Care Campus
🇮🇱Haifa, Israel
Sheba Medical Center - PPDS
🇮🇱Ramat-Gan, Israel
Tel Aviv Sourasky Medical Center PPDS
🇮🇱Tel Aviv-Yafo, Israel
The Catholic University of Korea - Seoul St. Mary's Hospital (Kangnam St. Mary's Hospital)
🇰🇷Seocho, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center - PPDS
🇰🇷Seoul, Korea, Republic of