A Study Evaluating Safety, Tolerability, and Clinical Activity of Forimtamig-Based Treatment Combinations in Participants With Relapsed or Refractory Multiple Myeloma
Phase 1
Active, not recruiting
- Conditions
- Relapsed or Refractory Multiple Myeloma
- Interventions
- Registration Number
- NCT06055075
- Lead Sponsor
- Hoffmann-La Roche
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 316
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Dose Expansion Phase: Forimtamig + Daratumumab Forimtamig Participants will receive forimtamig, SC injection at a fixed dose determined during dose exploration phase in combination with daratumumab, SC injection until disease progression. Dose Exploration Phase: Forimtamig (Dose 1) + Daratumumab Forimtamig Participants will receive Dose 1 of forimtamig, SC injection in combination with daratumumab, SC injection until disease progression. Dose Exploration Phase: Forimtamig (Dose 1) + Daratumumab Daratumumab Participants will receive Dose 1 of forimtamig, SC injection in combination with daratumumab, SC injection until disease progression. Dose Exploration Phase: Forimtamig (Dose 1) + Carfilzomib Forimtamig Participants will receive Dose 1 of forimtamig, subcutaneous (SC) injection in combination with carfilzomib, intravenous (IV) infusion until disease progression. Dose Exploration Phase: Forimtamig (Dose 1) + Carfilzomib Carfilzomib Participants will receive Dose 1 of forimtamig, subcutaneous (SC) injection in combination with carfilzomib, intravenous (IV) infusion until disease progression. Dose Exploration Phase: Forimtamig (Dose 2) + Carfilzomib Forimtamig Participants will receive Dose 2 of forimtamig, SC injection in combination with carfilzomib, IV infusion until disease progression. Dose Exploration Phase: Forimtamig (Dose 2) + Carfilzomib Carfilzomib Participants will receive Dose 2 of forimtamig, SC injection in combination with carfilzomib, IV infusion until disease progression. Dose Exploration Phase: Forimtamig (Dose 3) + Carfilzomib Forimtamig Participants will receive Dose 3 of forimtamig, SC injection in combination with carfilzomib, IV infusion until disease progression. Dose Exploration Phase: Forimtamig (Dose 2) + Daratumumab Forimtamig Participants will receive Dose 2 of forimtamig, SC injection in combination with daratumumab, SC injection until disease progression. Dose Exploration Phase: Forimtamig (Dose 2) + Daratumumab Daratumumab Participants will receive Dose 2 of forimtamig, SC injection in combination with daratumumab, SC injection until disease progression. Dose Exploration Phase: Forimtamig (Dose 3) + Daratumumab Forimtamig Participants will receive Dose 3 of forimtamig, SC injection in combination with daratumumab, SC injection until disease progression. Dose Expansion Phase: Forimtamig 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. Dose Expansion Phase: Forimtamig + Carfilzomib Forimtamig Participants will receive forimtamig, SC injection at a fixed dose determined during dose exploration phase in combination with carfilzomib, IV infusion until disease progression. Dose Exploration Phase: Forimtamig (Dose 3) + Carfilzomib Carfilzomib Participants will receive Dose 3 of forimtamig, SC injection in combination with carfilzomib, IV infusion until disease progression. Dose Exploration Phase: Forimtamig (Dose 3) + Daratumumab Daratumumab Participants will receive Dose 3 of forimtamig, SC injection in combination with daratumumab, SC injection until disease progression. Dose Expansion Phase: Forimtamig + Carfilzomib 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. Dose Expansion Phase: Forimtamig + Daratumumab 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.
- Primary Outcome Measures
Name Time Method Percentage of Participants with Adverse Events (AEs) Up to approximately 24 months Objective Response Rate (ORR) as Determined by the Investigator per International Myeloma Working Group (IMWG) Criteria Up to approximately 24 months Complete Response (CR)/Stringent Complete Response (sCR) Rate as Determined by the Investigator per IMWG Criteria Up to approximately 24 months Rate of Very Good Partial Response (VGPR) or Better as Determined by the Investigator per IMWG Criteria Up to approximately 24 months
- Secondary Outcome Measures
Name Time Method 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 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
Trial Locations
- Locations (8)
Princess Alexandra Hospital Woolloongabba
🇦🇺Woolloongabba, Queensland, Australia
Royal Adelaide Hospital
🇦🇺Adelaide, South Australia, Australia
Hamilton Health Sciences
🇨🇦Hamilton, Ontario, Canada
Istituto Clinico Humanitas
🇮🇹Rozzano, Lombardia, Italy
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Seoul St Mary's Hospital
🇰🇷Seoul, Korea, Republic of
New Zealand Clinical Research - Auckland
🇳🇿Auckland, New Zealand
Clinica Universitaria de Navarra
🇪🇸Pamplona, Navarra, Spain