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

Phase 1
Active, not recruiting
Conditions
Multiple Myeloma
Interventions
Registration Number
NCT04557150
Lead Sponsor
Hoffmann-La Roche
Brief Summary

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).

Detailed Description

Not available

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
225
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 & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
Part II: Dose ExpansionForimtamigDose 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.
Part I: Dose EscalationForimtamigParticipants will receive forimtamig as intravenous (IV) infusion and/or subcutaneous (SC) injection in a step-up dosing fashion.
Primary Outcome Measures
NameTimeMethod
Percentage of Participants with Dose Limiting Toxicities (DLTs)Cycle 1 Day 1 up to Cycle 1 Day 35
Percentage of Participants with Adverse Events (AEs)Up to 104 weeks
Secondary Outcome Measures
NameTimeMethod
Time of Maximum Concentration (Tmax) of ForimtamigUp to 104 weeks
Maximum Concentration (Cmax) of ForimtamigUp to 104 weeks
Duration of Response (DOR)Up to 104 weeks
SC Bioavailability (F) of ForimtamigUp to 104 weeks
Volume of Distribution at Steady State (Vss) of Forimtamig (IV only)Up to 104 weeks
Progression-Free Survival (PFS)Up to 104 weeks
Overall Survival (OS)Up to 104 weeks
Area Under the Curve (AUC) at Various Time Intervals of ForimtamigUp to 104 weeks
Percentage of Participants with Anti-Drug Antibodies (ADAs) to ForimtamigUp to 104 weeks
Minimum Concentration (Cmin) of ForimtamigUp to 104 weeks
Apparent Clearance (CL/F) of ForimtamigUp to 104 weeks
Objective Response Rate (ORR)Up to 104 weeks

Trial Locations

Locations (20)

Peter MacCallum Cancer Center

🇦🇺

Melbourne, Victoria, Australia

UZ Gent

🇧🇪

Gent, Belgium

Rigshospitalet

🇩🇰

København Ø, Denmark

Odense Universitetshospital

🇩🇰

Odense C, Denmark

CHRU Lille - Hôpital Claude Huriez

🇫🇷

Lille, France

CHU NANTES - Hôtel Dieu

🇫🇷

Nantes, France

Hopital De Haut Leveque

🇫🇷

Pessac, France

IRCCS Istituto Nazionale dei Tumori di Napoli - Pascale Ematologia Oncologica

🇮🇹

Napoli, Campania, Italy

Policlinico S.Orsola-Malpighi

🇮🇹

Bologna, Emilia-Romagna, Italy

Fond. IRCCS Istituto Nazionale Tumori

🇮🇹

Milano, Lombardia, Italy

Instituto Clinico Humanitas

🇮🇹

Rozzano, Lombardia, Italy

Seoul National University Hospital

🇰🇷

Seoul, Korea, Republic of

Samsung Medical Center

🇰🇷

Seoul, Korea, Republic of

Seoul St Mary's Hospital

🇰🇷

Seoul, Korea, Republic of

New Zealand Clinical Research - Auckland

🇳🇿

Auckland, New Zealand

Hospital Universitario Marques de Valdecilla

🇪🇸

Santander, Cantabria, Spain

Clinica Universitaria de Navarra

🇪🇸

Pamplona, Navarra, Spain

Hospital Clinico Universitario de Salamanca

🇪🇸

Salamanca, Spain

St James University Hospital

🇬🇧

Leeds, United Kingdom

University College London Hospitals NHS Foundation Trust

🇬🇧

London, United Kingdom

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