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

Study Overview
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Brief Summary
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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).

Official Title
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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

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: Forimtamig


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part I: Dose Escalation<br>Participants will receive forimtamig as intravenous (IV) infusion and/or subcutaneous (SC) injection in a step-up dosing fashion. | Drug: Forimtamig<br>* 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.<br>* Other names: RO7425781;|
| Experimental: Part II: Dose Expansion<br>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<br>* 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.<br>* Other names: RO7425781;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 |