A Study Evaluating the Safety and Pharmacokinetics of Escalating Doses of Forimtamig in Participants With Relapsed or Refractory Multiple Myeloma (r/r MM)

An Open-Label, Multicenter, Phase I Study Evaluating the Safety and Pharmacokinetics of Escalating Doses of Forimtamig (RO7425781) in Participants With Relapsed or Refractory Multiple Myeloma

This is a first-in-human, open-label, uncontrolled, multi-center, monotherapy, dose-escalation and dose expansion study. Forimtamig will be administered to participants with r/r MM for whom no standard-of-care treatment exists or who are intolerant to those established therapies. The study consists of two parts: dose-escalation of forimtamig (Part 1) and a randomized dose expansion of forimtamig (Part 2).

Study Overview

• Status: Completed
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: Forimtamig

• Study Type: Interventional
• Enrollment (Actual): 225
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3000
      • Peter MacCallum Cancer Center
• Belgium
  • Ghent, Belgium, 9000
    • UZ Gent
• Denmark
  • København Ø, Denmark, 2100
    • Rigshospitalet
  • Odense C, Denmark, 5000
    • Odense Universitetshospital
• France
  • Lille, France, 59037
    • CHRU Lille - Hôpital Claude Huriez
  • Nantes, France, 44093
    • CHU Nantes - Hotel Dieu
  • Pessac, France, 33604
    • Hopital De Haut Leveque
• Italy
  • Campania
    • Naples, Campania, Italy, 80131
      • IRCCS Istituto Nazionale dei Tumori di Napoli - Pascale Ematologia Oncologica
  • Emilia-Romagna
    • Bologna, Emilia-Romagna, Italy, 40138
      • Policlinico S.Orsola-Malpighi
  • Lombardy
    • Milan, Lombardy, Italy, 20133
      • Fond. IRCCS Istituto Nazionale Tumori
    • Rozzano, Lombardy, Italy, 20089
      • Instituto Clinico Humanitas
• New Zealand
  • Auckland, New Zealand, 1010
    • New Zealand Clinical Research - Auckland
• South Korea
  • Seoul, South Korea, 03080
    • Seoul National University Hospital
  • Seoul, South Korea, 06351
    • Samsung Medical Center
  • Seoul, South Korea, 06591
    • Seoul St Mary's Hospital
• Spain
  • Salamanca, Spain, 37007
    • Hospital Clinico Universitario de Salamanca
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Hospital Universitario Marques de Valdecilla
  • Navarre
    • Pamplona, Navarre, Spain, 31008
      • Clinica Universitaria De Navarra
• United Kingdom
  • Leeds, United Kingdom, LS9 7TF
    • St James University Hospital
  • London, United Kingdom, W1T 7HA
    • University College London Hospitals Nhs Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Previously diagnosed with Multiple Myeloma (MM) based on standard criteria.
• Dose Escalation Phase and Dose Expansion Phase: Participants with r/r MM who have previously received therapy with an Immunomodulatory drug (IMiD) and Proteasome Inhibitor (PI) and are intolerant to or have no other option for standard-of-care treatment according to the Investigator.
• Life expectancy of at least 12 weeks.
• Agreement to provide protocol-specific biopsy material.
• AEs from prior anti-cancer therapy resolved to Grade =<1.
• Measurable disease.
• For female participants of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse), use contraceptive measures and refrain from donating eggs.
• For male participants: agreement to remain abstinent (refrain from heterosexual intercourse), use contraceptive measures and refrain from donating sperm.

Exclusion Criteria:

• Inability to comply with protocol-mandated hospitalization and activities restrictions.
• Pregnant or breastfeeding or intending to become pregnant during the study or within 3 months after last dose of study drug.
• Prior use of any monoclonal antibody, radioimmunoconjugate, or antibody-drug conjugate for MM treatment within 2 weeks before first forimtamig administration.
• Prior treatment with systemic immunotherapeutic agents within 2 weeks before first forimtamig administration.
• Treatment-related, immune-mediated AEs associated with prior immunotherapeutic agents.
• Treatment with radiotherapy, any chemotherapeutic agent, or treatment with any other anti-cancer agent (investigational or otherwise) within 2 weeks, prior to first forimtamig administration. Limited field palliative radiotherapy for bone pain or for soft tissue lesions is allowed.
• Autologous or allogeneic stem cell transplantation (SCT) within 100 days prior to first forimtamig infusion and/or signs of chronic graft versus host disease or ongoing immunosuppressive medication.
• Prior solid organ transplantation.
• Active auto-immune disease or flare within 6 months prior to start of study treatment
• Any medical condition or abnormality in clinical laboratory tests that, in the Investigator's or Medical Monitor's judgment, precludes the participant's safe participation in and completion of the study, or which could affect compliance with the protocol or interpretation of results.

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part II: Dose Expansion; Dose Expansion cohorts with IV and/or SC administration, respectively, will be initiated at the Recommended Phase 2 Doses (RP2Ds) determined in Part I: Dose Escalation phase.	Drug: Forimtamig; Forimtamig will be administered via IV/SC administration. The RP2Ds determined during Part I: Dose Escalation will be administered during Part II: Dose Expansion. Forimtamig will be administered as per the dosing schedule defined in Part I.; Other Names: RO7425781
Experimental: Part I: Dose Escalation; Participants will receive forimtamig as intravenous (IV) infusion and/or subcutaneous (SC) injection in a step-up dosing fashion.	Drug: Forimtamig; Forimtamig will be administered via IV/SC administration. The RP2Ds determined during Part I: Dose Escalation will be administered during Part II: Dose Expansion. Forimtamig will be administered as per the dosing schedule defined in Part I.; Other Names: RO7425781

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of Participants with Adverse Events (AEs)	Up to 104 weeks
Percentage of Participants with Dose Limiting Toxicities (DLTs)	Cycle 1 Day 1 up to Cycle 1 Day 35

Secondary Outcome Measures

Outcome Measure	Time Frame
Objective Response Rate (ORR)	Up to 104 weeks
Duration of Response (DOR)	Up to 104 weeks
Progression-Free Survival (PFS)	Up to 104 weeks
Overall Survival (OS)	Up to 104 weeks
Percentage of Participants with Anti-Drug Antibodies (ADAs) to Forimtamig	Up to 104 weeks
Maximum Concentration (Cmax) of Forimtamig	Up to 104 weeks
Time of Maximum Concentration (Tmax) of Forimtamig	Up to 104 weeks
Minimum Concentration (Cmin) of Forimtamig	Up to 104 weeks
SC Bioavailability (F) of Forimtamig	Up to 104 weeks
Apparent Clearance (CL/F) of Forimtamig	Up to 104 weeks
Volume of Distribution at Steady State (Vss) of Forimtamig (IV only)	Up to 104 weeks
Area Under the Curve (AUC) at Various Time Intervals of Forimtamig	Up to 104 weeks

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Eckmann J, Fauti T, Biehl M, Zabaleta A, Blanco L, Lelios I, Gottwald S, Rae R, Lechner S, Bayer C, Dekempe Q, Osl F, Carrie N, Kassem S, Lorenz S, Christopeit T, Carpy A, Bujotzek A, Broske AM, Dekhtiarenko I, Attig J, Kunz L, Cremasco F, Adelfio R, Fertig G, Dengl S, Gassner C, Bormann F, Kirstenpfad C, Kraft T, Diggelmann S, Knobloch M, Hage C, Feddersen R, Heidkamp G, Poschinger T, Mayoux M, Bernasconi L, Prosper F, Dumontet C, Martinet L, Leclair S, Xu W, Paiva B, Klein C, Umana P. Forimtamig, a novel GPRC5D-targeting T-cell bispecific antibody with a 2+1 format, for the treatment of multiple myeloma. Blood. 2025 Jan 9;145(2):202-219. doi: 10.1182/blood.2024025987.

Study record dates

Study Major Dates

• Study Start (Actual): November 11, 2020
• Primary Completion (Actual): March 17, 2026
• Study Completion (Actual): March 17, 2026

Study Registration Dates

• First Submitted: September 17, 2020
• First Submitted That Met QC Criteria: September 17, 2020
• First Posted (Actual): September 21, 2020

Study Record Updates

• Last Update Posted (Actual): April 13, 2026
• Last Update Submitted That Met QC Criteria: April 10, 2026
• Last Verified: April 1, 2026

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; Neoplasms, Plasma Cell; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Hemic and Lymphatic Diseases; Multiple Myeloma
• Other Study ID Numbers: BP42233; 2020-002012-46 (EudraCT Number); 2023-504571-25-00 (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