A Study Evaluating Safety, Tolerability, and Clinical Activity of Forimtamig-Based Treatment Combinations in Participants With Relapsed or Refractory Multiple Myeloma

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

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 Overview

• Status: Completed
• Conditions: Relapsed or Refractory Multiple Myeloma
• Intervention / Treatment: Drug: Forimtamig; Drug: Carfilzomib; Drug: Daratumumab

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • Queensland
    • Woolloongabba, Queensland, Australia, 4102
      • Princess Alexandra Hospital Woolloongabba
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8V 5C2
      • Hamilton Health Sciences
• Italy
  • Lombardia
    • Rozzano, Lombardia, Italy, 20089
      • Istituto Clinico Humanitas
• Korea, Republic of
  • Seoul, Korea, Republic of, 06591
    • Seoul St Mary's Hospital
• New Zealand
  • Auckland, New Zealand, 1010
    • New Zealand Clinical Research - Auckland
• Spain
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Clinica Universitaria De Navarra

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Forimtamig; Forimtamig will be administered SC at different doses during dose exploration phase. Forimtamig will be administered at a fixed dose determined during dose exploration phase in dose expansion phase.; Drug: Carfilzomib; Carfilzomib will be administered via IV infusion in combination with forimtamig.
Experimental: 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.	Drug: Forimtamig; Forimtamig will be administered SC at different doses during dose exploration phase. Forimtamig will be administered at a fixed dose determined during dose exploration phase in dose expansion phase.; Drug: Carfilzomib; Carfilzomib will be administered via IV infusion in combination with forimtamig.
Experimental: 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.	Drug: Forimtamig; Forimtamig will be administered SC at different doses during dose exploration phase. Forimtamig will be administered at a fixed dose determined during dose exploration phase in dose expansion phase.; Drug: Carfilzomib; Carfilzomib will be administered via IV infusion in combination with forimtamig.
Experimental: 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.	Drug: Forimtamig; Forimtamig will be administered SC at different doses during dose exploration phase. Forimtamig will be administered at a fixed dose determined during dose exploration phase in dose expansion phase.; Drug: Daratumumab; Daratumumab will be administered via SC injection in combination with forimtamig.
Experimental: 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.	Drug: Forimtamig; Forimtamig will be administered SC at different doses during dose exploration phase. Forimtamig will be administered at a fixed dose determined during dose exploration phase in dose expansion phase.; Drug: Daratumumab; Daratumumab will be administered via SC injection in combination with forimtamig.
Experimental: 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.	Drug: Forimtamig; Forimtamig will be administered SC at different doses during dose exploration phase. Forimtamig will be administered at a fixed dose determined during dose exploration phase in dose expansion phase.; Drug: Daratumumab; Daratumumab will be administered via SC injection in combination with forimtamig.
Experimental: 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.	Drug: Forimtamig; Forimtamig will be administered SC at different doses during dose exploration phase. Forimtamig will be administered at a fixed dose determined during dose exploration phase in dose expansion phase.
Experimental: 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.	Drug: Forimtamig; Forimtamig will be administered SC at different doses during dose exploration phase. Forimtamig will be administered at a fixed dose determined during dose exploration phase in dose expansion phase.; Drug: Carfilzomib; Carfilzomib will be administered via IV infusion in combination with forimtamig.
Experimental: 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.	Drug: Forimtamig; Forimtamig will be administered SC at different doses during dose exploration phase. Forimtamig will be administered at a fixed dose determined during dose exploration phase in dose expansion phase.; Drug: Daratumumab; Daratumumab will be administered via SC injection in combination with forimtamig.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): December 12, 2023
• Primary Completion (Actual): July 8, 2025
• Study Completion (Actual): July 8, 2025

Study Registration Dates

• First Submitted: September 20, 2023
• First Submitted That Met QC Criteria: September 20, 2023
• First Posted (Actual): September 26, 2023

Study Record Updates

• Last Update Posted (Actual): July 14, 2025
• Last Update Submitted That Met QC Criteria: July 10, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Antineoplastic Agents; Daratumumab
• Other Study ID Numbers: BP43437; 2023-503689-21-00 (Ctis: EU Trial Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data_sharing

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No