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

NCT06055075 | Completed Phase 1 FDA Drug

• 2 other identifiers: BP434372023-503689-21-00
• Study Type: interventional
• Target: 19
• Locations: 6 countries
• Sites: 7

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.

Conditions

Relapsed or Refractory Multiple Myeloma

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (7)

• 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

Study Arms (9)

Dose Exploration Phase: Forimtamig (Dose 1) + Carfilzomib

EXPERIMENTAL

Participants will receive Dose 1 of forimtamig, subcutaneous (SC) injection in combination with carfilzomib, intravenous (IV) infusion until disease progression.

Drug: Forimtamig; Drug: Carfilzomib

Dose Exploration Phase: Forimtamig (Dose 2) + Carfilzomib

EXPERIMENTAL

Participants will receive Dose 2 of forimtamig, SC injection in combination with carfilzomib, IV infusion until disease progression.

Drug: Forimtamig; Drug: Carfilzomib

Dose Exploration Phase: Forimtamig (Dose 3) + Carfilzomib

EXPERIMENTAL

Participants will receive Dose 3 of forimtamig, SC injection in combination with carfilzomib, IV infusion until disease progression.

Drug: Forimtamig; Drug: Carfilzomib

Dose Exploration Phase: Forimtamig (Dose 1) + Daratumumab

EXPERIMENTAL

Participants will receive Dose 1 of forimtamig, SC injection in combination with daratumumab, SC injection until disease progression.

Drug: Forimtamig; Drug: Daratumumab

Dose Exploration Phase: Forimtamig (Dose 2) + Daratumumab

EXPERIMENTAL

Participants will receive Dose 2 of forimtamig, SC injection in combination with daratumumab, SC injection until disease progression.

Drug: Forimtamig; Drug: Daratumumab

Dose Exploration Phase: Forimtamig (Dose 3) + Daratumumab

EXPERIMENTAL

Participants will receive Dose 3 of forimtamig, SC injection in combination with daratumumab, SC injection until disease progression.

Drug: Forimtamig; Drug: Daratumumab

Dose Expansion Phase: Forimtamig

EXPERIMENTAL

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

Dose Expansion Phase: Forimtamig + Carfilzomib

EXPERIMENTAL

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; Drug: Carfilzomib

Dose Expansion Phase: Forimtamig + Daratumumab

EXPERIMENTAL

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; Drug: Daratumumab

Interventions

Forimtamig DRUG

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.

Dose Expansion Phase: Forimtamig; Dose Expansion Phase: Forimtamig + Carfilzomib; Dose Expansion Phase: Forimtamig + Daratumumab; Dose Exploration Phase: Forimtamig (Dose 1) + Carfilzomib; Dose Exploration Phase: Forimtamig (Dose 1) + Daratumumab; Dose Exploration Phase: Forimtamig (Dose 2) + Carfilzomib; Dose Exploration Phase: Forimtamig (Dose 2) + Daratumumab; Dose Exploration Phase: Forimtamig (Dose 3) + Carfilzomib; Dose Exploration Phase: Forimtamig (Dose 3) + Daratumumab

Carfilzomib DRUG

Carfilzomib will be administered via IV infusion in combination with forimtamig.

Dose Expansion Phase: Forimtamig + Carfilzomib; Dose Exploration Phase: Forimtamig (Dose 1) + Carfilzomib; Dose Exploration Phase: Forimtamig (Dose 2) + Carfilzomib; Dose Exploration Phase: Forimtamig (Dose 3) + Carfilzomib

Daratumumab DRUG

Daratumumab will be administered via SC injection in combination with forimtamig.

Dose Expansion Phase: Forimtamig + Daratumumab; Dose Exploration Phase: Forimtamig (Dose 1) + Daratumumab; Dose Exploration Phase: Forimtamig (Dose 2) + Daratumumab; Dose Exploration Phase: Forimtamig (Dose 3) + Daratumumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (7)

Princess Alexandra Hospital Woolloongabba

Woolloongabba, Queensland, 4102, Australia

Location

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

Hamilton Health Sciences

Hamilton, Ontario, L8V 5C2, Canada

Location

Istituto Clinico Humanitas

Rozzano, Lombardy, 20089, Italy

Location

New Zealand Clinical Research - Auckland

Auckland, 1010, New Zealand

Location

Seoul St Mary's Hospital

Seoul, 06591, South Korea

Location

Clinica Universitaria de Navarra

Pamplona, Navarre, 31008, Spain

Location

MeSH Terms

Conditions

Recurrence; Multiple Myeloma

Interventions

carfilzomib; daratumumab

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 20, 2023
• First Posted: September 26, 2023
• Study Start: December 12, 2023
• Primary Completion: July 8, 2025
• Study Completion: July 8, 2025
• Last Updated: July 14, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share

Locations

IT (1); KR (1); AU (2); ES (1); NZ (1); CA (1)