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

Roche

Status and phase: Completed; Phase 2; Phase 1

Conditions: Relapsed or Refractory Multiple Myeloma

Treatments: Drug: Daratumumab; Drug: Forimtamig; Drug: Carfilzomib

Study type: Interventional

Funder types: Industry

Identifiers

NCT06055075

2023-503689-21-00 (Other Identifier)

BP43437

Details and patient eligibility

About

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.

Enrollment: 19 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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

Exclusion criteria

• 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
• Participants who discontinued prior carfilzomib treatment due to treatment-related toxicity
• Participants with known liver cirrhosis
• Participants eligible for allogeneic stem cell transplantation (SCT) or autologous SCT at the time of enrollment for Study BP43437 are excluded

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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19 participants in 9 patient groups

Dose Exploration Phase: Forimtamig (Dose 1) + Carfilzomib

Experimental group

Description:

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

Treatment:

Drug: Carfilzomib

Drug: Forimtamig

Dose Exploration Phase: Forimtamig (Dose 2) + Carfilzomib

Experimental group

Description:

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

Treatment:

Drug: Carfilzomib

Drug: Forimtamig

Dose Exploration Phase: Forimtamig (Dose 3) + Carfilzomib

Experimental group

Description:

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

Treatment:

Drug: Carfilzomib

Drug: Forimtamig

Dose Exploration Phase: Forimtamig (Dose 1) + Daratumumab

Experimental group

Description:

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

Treatment:

Drug: Forimtamig

Drug: Daratumumab

Dose Exploration Phase: Forimtamig (Dose 2) + Daratumumab

Experimental group

Description:

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

Treatment:

Drug: Forimtamig

Drug: Daratumumab

Dose Exploration Phase: Forimtamig (Dose 3) + Daratumumab

Experimental group

Description:

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

Treatment:

Drug: Forimtamig

Drug: Daratumumab

Dose Expansion Phase: Forimtamig

Experimental group

Description:

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.

Treatment:

Drug: Forimtamig

Dose Expansion Phase: Forimtamig + Carfilzomib

Experimental group

Description:

Participants will receive forimtamig, SC injection at a fixed dose determined during dose exploration phase in combination with carfilzomib, IV infusion until disease progression.

Treatment:

Drug: Carfilzomib

Drug: Forimtamig

Dose Expansion Phase: Forimtamig + Daratumumab

Experimental group

Description:

Participants will receive forimtamig, SC injection at a fixed dose determined during dose exploration phase in combination with daratumumab, SC injection until disease progression.

Treatment:

Drug: Forimtamig

Drug: Daratumumab