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: Recruiting
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: Forimtamig

• Study Type: Interventional
• Enrollment (Estimated): 480
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Reference Study ID Number: BP42233 https://forpatients.roche.com/; Phone Number: 888-662-6728 (U.S. and Canada); Email: global-roche-genentech-trials@gene.com

Study Locations

• Australia
  • Victoria
    • North Melbourne, Victoria, Australia, 3051
      • Active, not recruiting
      • Peter MacCallum Cancer Center
• Belgium
  • Gent, Belgium, 9000
    • Recruiting
    • UZ Gent
• Denmark
  • København Ø, Denmark, 2100
    • Recruiting
    • Rigshospitalet; Hæmatologisk Klinik, Klinisk Afprøvnings Team KAT
  • Odense C, Denmark, 5000
    • Recruiting
    • Odense Universitetshospital; Hæmatologisk Afdeling
• France
  • Lille, France, 59037
    • Recruiting
    • CHRU Lille - Hôpital Claude Huriez; Service des Maladies du Sang
  • Nantes, France, 44093
    • Recruiting
    • CHU NANTES - Hôtel Dieu; Service d'Hematologie Clinique
  • Pessac, France, 33604
    • Active, not recruiting
    • Hopital De Haut Leveque; Hematologie Clinique
• Italy
  • Campania
    • Napoli, Campania, Italy, 80131
      • Recruiting
      • IRCCS Istituto Nazionale dei Tumori di Napoli - Pascale Ematologia Oncologica
  • Emilia-Romagna
    • Bologna, Emilia-Romagna, Italy, 40138
      • Recruiting
      • Policlinico S.Orsola-Malpighi;Istituto di Ematologia "Seragnoli"
  • Lombardia
    • Milano, Lombardia, Italy, 20133
      • Recruiting
      • Fond. IRCCS Istituto Nazionale Tumori; S. C. Ematologia
    • Rozzano, Lombardia, Italy, 20089
      • Active, not recruiting
      • Instituto Clinico Humanitas; Med Onc & Hemat
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Active, not recruiting
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 06351
    • Recruiting
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 06591
    • Recruiting
    • Seoul St Mary's Hospital
  • Seoul, Korea, Republic of, 05505
    • Withdrawn
    • Asan Medical Center
• New Zealand
  • Auckland, New Zealand, 1010
    • Recruiting
    • New Zealand Clinical Research - Auckland
• Spain
  • Salamanca, Spain, 37007
    • Recruiting
    • Hospital Clinico Universitario de Salamanca;Servicio de Hematologia
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Active, not recruiting
      • Hospital Universitario Marques de Valdecilla; Servicio de Hematologia
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Recruiting
      • Clinica Universitaria de Navarra; Servicio de Hematologia
• United Kingdom
  • Leeds, United Kingdom, LS9 7TF
    • Recruiting
    • St James University Hospital; Institute of Oncology
  • London, United Kingdom, W1T 7HA
    • Recruiting
    • University College London Hospitals NHS Foundation Trust; NIHR UCLH Clinical Research Facility

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 the 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

Study record dates

Study Major Dates

• Study Start (Actual): November 11, 2020
• Primary Completion (Estimated): August 15, 2026
• Study Completion (Estimated): August 15, 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 8, 2024
• Last Update Submitted That Met QC Criteria: April 5, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell
• Other Study ID Numbers: BP42233; 2020-002012-46 (EudraCT Number); 2023-504571-25-00 (Registry Identifier: EU Trial Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

Drug and device information, study documents

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