An Open-Label, Randomized Phase IB/II Study Evaluating Safety, Tolerability, and Clinical Activity of Forimtamig-Based Treatment Combinations in Participants With Relapsed or Refractory Multiple Myeloma
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Hoffmann-La Roche
- Enrollment
- 19
- Locations
- 7
- Primary Endpoint
- Percentage of Participants with Adverse Events (AEs)
Study Overview
Brief Summary
The purpose of this study is to evaluate the safety, tolerability, and preliminary anti-tumor activity of forimtamig when administered alone or in combination with carfilzomib or daratumumab or other combination partners in participants with relapsed or refractory multiple myeloma (r/r MM). The study consists of two phases: a dose exploration phase and a dose-expansion phase.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
- •Life expectancy of at least 12 weeks
- •Documented diagnosis of MM according to the IMWG diagnostic criteria
- •Evidence of progressive disease based on Investigator's determination of response by IMWG criteria on or after last dosing regimen
- •Measurable disease
- •AEs from prior anti-cancer therapy resolved to Grade ≤ 1,
- •Adequate organ functions
Exclusion Criteria
- •Pregnant or breastfeeding or intending to become pregnant during the study or within 3 months after the last dose of study drug
- •Plasma cell leukemia with circulating plasma cell count ≥ 5% or >500/microliter (µL)
- •Participants with known amyloidosis
- •Participants with myelodysplastic syndrome
- •Prior treatment with monoclonal antibody (mAb) and antibody-drug conjugate within 4 weeks or 5 half-lives of the drug, whichever is shorter
- •Prior anti-cancer therapy (chemotherapy, small molecule/tyrosine kinase inhibitors, radiotherapy) within 14 days prior to first forimtamig administration
- •Prior solid organ transplantation
- •Active auto-immune disease or flare within 6 months prior to start of study treatment
- •Known or suspected chronic active Epstein-Barr virus (EBV) infection
- •Hepatitis B virus (HBV) infection
- •Acute or chronic hepatitis C virus (HCV) infection
- •Known history of HIV seropositivity
- •Live vaccine(s) within one month prior to start of the treatment
- •Participants not fully vaccinated for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as per local recommendations
- •Previous refractoriness to carfilzomib
- •Participants who discontinued prior carfilzomib treatment due to treatment-related toxicity
- •Participants with known liver cirrhosis
- •Participants eligible for allogeneic stem cell transplantation (SCT) or autologous SCT at the time of enrollment for Study BP43437 are excluded
Arms & Interventions
Dose Exploration Phase: Forimtamig (Dose 1) + Carfilzomib
Participants will receive Dose 1 of forimtamig, subcutaneous (SC) injection in combination with carfilzomib, intravenous (IV) infusion until disease progression.
Intervention: Forimtamig (Drug)
Dose Exploration Phase: Forimtamig (Dose 1) + Carfilzomib
Participants will receive Dose 1 of forimtamig, subcutaneous (SC) injection in combination with carfilzomib, intravenous (IV) infusion until disease progression.
Intervention: Carfilzomib (Drug)
Dose Exploration Phase: Forimtamig (Dose 2) + Carfilzomib
Participants will receive Dose 2 of forimtamig, SC injection in combination with carfilzomib, IV infusion until disease progression.
Intervention: Forimtamig (Drug)
Dose Exploration Phase: Forimtamig (Dose 2) + Carfilzomib
Participants will receive Dose 2 of forimtamig, SC injection in combination with carfilzomib, IV infusion until disease progression.
Intervention: Carfilzomib (Drug)
Dose Exploration Phase: Forimtamig (Dose 3) + Carfilzomib
Participants will receive Dose 3 of forimtamig, SC injection in combination with carfilzomib, IV infusion until disease progression.
Intervention: Forimtamig (Drug)
Dose Exploration Phase: Forimtamig (Dose 3) + Carfilzomib
Participants will receive Dose 3 of forimtamig, SC injection in combination with carfilzomib, IV infusion until disease progression.
Intervention: Carfilzomib (Drug)
Dose Exploration Phase: Forimtamig (Dose 1) + Daratumumab
Participants will receive Dose 1 of forimtamig, SC injection in combination with daratumumab, SC injection until disease progression.
Intervention: Forimtamig (Drug)
Dose Exploration Phase: Forimtamig (Dose 1) + Daratumumab
Participants will receive Dose 1 of forimtamig, SC injection in combination with daratumumab, SC injection until disease progression.
Intervention: Daratumumab (Drug)
Dose Exploration Phase: Forimtamig (Dose 2) + Daratumumab
Participants will receive Dose 2 of forimtamig, SC injection in combination with daratumumab, SC injection until disease progression.
Intervention: Forimtamig (Drug)
Dose Exploration Phase: Forimtamig (Dose 2) + Daratumumab
Participants will receive Dose 2 of forimtamig, SC injection in combination with daratumumab, SC injection until disease progression.
Intervention: Daratumumab (Drug)
Dose Exploration Phase: Forimtamig (Dose 3) + Daratumumab
Participants will receive Dose 3 of forimtamig, SC injection in combination with daratumumab, SC injection until disease progression.
Intervention: Forimtamig (Drug)
Dose Exploration Phase: Forimtamig (Dose 3) + Daratumumab
Participants will receive Dose 3 of forimtamig, SC injection in combination with daratumumab, SC injection until disease progression.
Intervention: Daratumumab (Drug)
Dose Expansion Phase: Forimtamig
Participants will receive forimtamig, SC injection at a fixed dose determined during dose exploration phase until disease progression or completion of 12 months of treatment, whichever occurs first.
Intervention: Forimtamig (Drug)
Dose Expansion Phase: Forimtamig + Carfilzomib
Participants will receive forimtamig, SC injection at a fixed dose determined during dose exploration phase in combination with carfilzomib, IV infusion until disease progression.
Intervention: Forimtamig (Drug)
Dose Expansion Phase: Forimtamig + Carfilzomib
Participants will receive forimtamig, SC injection at a fixed dose determined during dose exploration phase in combination with carfilzomib, IV infusion until disease progression.
Intervention: Carfilzomib (Drug)
Dose Expansion Phase: Forimtamig + Daratumumab
Participants will receive forimtamig, SC injection at a fixed dose determined during dose exploration phase in combination with daratumumab, SC injection until disease progression.
Intervention: Forimtamig (Drug)
Dose Expansion Phase: Forimtamig + Daratumumab
Participants will receive forimtamig, SC injection at a fixed dose determined during dose exploration phase in combination with daratumumab, SC injection until disease progression.
Intervention: Daratumumab (Drug)
Outcomes
Primary Outcomes
Percentage of Participants with Adverse Events (AEs)
Time Frame: Up to approximately 24 months
Objective Response Rate (ORR) as Determined by the Investigator per International Myeloma Working Group (IMWG) Criteria
Time Frame: Up to approximately 24 months
Complete Response (CR)/Stringent Complete Response (sCR) Rate as Determined by the Investigator per IMWG Criteria
Time Frame: Up to approximately 24 months
Rate of Very Good Partial Response (VGPR) or Better as Determined by the Investigator per IMWG Criteria
Time Frame: Up to approximately 24 months
Secondary Outcomes
- Progression-Free Survival (PFS) as Determined by the Investigator per IMWG Criteria(Up to approximately 24 months)
- Duration of Response (DoR) for Participants who Achieve a Partial Response (PR) or Better as Determined by the Investigator per IMWG Criteria(Up to approximately 24 months)
- Time to First Response as Determined by the Investigator per IMWG Criteria(Up to approximately 24 months)
- Time to Best Response as Determined by the Investigator per IMWG Criteria(Up to approximately 24 months)
- Overall Survival (OS) as Determined by the Investigator per IMWG Criteria(Up to approximately 24 months)
- Serum Concentration of Forimtamig(Up to approximately 24 months)
- Percentage of Participants with Anti-Drug Antibodies (ADAs) to Forimtamig(Up to approximately 24 months)