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

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT06055075
• Collaborator: (none)
• Enrollment: 316
• Arms: 9
• Anticipated Duration (Months): 43.3

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Relapsed or Refractory Multiple Myeloma	Drug: Forimtamig; Drug: Carfilzomib; Drug: Daratumumab	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 316 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label, Randomized Phase IB/II Study Evaluating Safety, Tolerability, and Clinical Activity of Forimtamig-Based Treatment Combinations in Participants With Relapsed or Refractory Multiple Myeloma
• Anticipated Study Start Date: Oct 30, 2023
• Anticipated Primary Completion Date: Jun 10, 2027
• Anticipated Study Completion Date: Jun 10, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dose Exploration Phase: Forimtamig (Dose 1) + Carfilzomib Participants will receive Dose 1 of forimtamig, subcutaneous (SC) injection in combination with carfilzomib, intravenous (IV) infusion until disease progression.	Drug: Forimtamig; Forimtamig will be administered SC at different doses during dose exploration phase. Forimtamig will be administered at a fixed dose determined during dose exploration phase in dose expansion phase.; Drug: Carfilzomib; Carfilzomib will be administered via IV infusion in combination with forimtamig.
Experimental: Dose Exploration Phase: Forimtamig (Dose 2) + Carfilzomib Participants will receive Dose 2 of forimtamig, SC injection in combination with carfilzomib, IV infusion until disease progression.	Drug: Forimtamig; Forimtamig will be administered SC at different doses during dose exploration phase. Forimtamig will be administered at a fixed dose determined during dose exploration phase in dose expansion phase.; Drug: Carfilzomib; Carfilzomib will be administered via IV infusion in combination with forimtamig.
Experimental: Dose Exploration Phase: Forimtamig (Dose 3) + Carfilzomib Participants will receive Dose 3 of forimtamig, SC injection in combination with carfilzomib, IV infusion until disease progression.	Drug: Forimtamig; Forimtamig will be administered SC at different doses during dose exploration phase. Forimtamig will be administered at a fixed dose determined during dose exploration phase in dose expansion phase.; Drug: Carfilzomib; Carfilzomib will be administered via IV infusion in combination with forimtamig.
Experimental: Dose Exploration Phase: Forimtamig (Dose 1) + Daratumumab Participants will receive Dose 1 of forimtamig, SC injection in combination with daratumumab, SC injection until disease progression.	Drug: Forimtamig; Forimtamig will be administered SC at different doses during dose exploration phase. Forimtamig will be administered at a fixed dose determined during dose exploration phase in dose expansion phase.; Drug: Daratumumab; Daratumumab will be administered via SC injection in combination with forimtamig.
Experimental: Dose Exploration Phase: Forimtamig (Dose 2) + Daratumumab Participants will receive Dose 2 of forimtamig, SC injection in combination with daratumumab, SC injection until disease progression.	Drug: Forimtamig; Forimtamig will be administered SC at different doses during dose exploration phase. Forimtamig will be administered at a fixed dose determined during dose exploration phase in dose expansion phase.; Drug: Daratumumab; Daratumumab will be administered via SC injection in combination with forimtamig.
Experimental: Dose Exploration Phase: Forimtamig (Dose 3) + Daratumumab Participants will receive Dose 3 of forimtamig, SC injection in combination with daratumumab, SC injection until disease progression.	Drug: Forimtamig; Forimtamig will be administered SC at different doses during dose exploration phase. Forimtamig will be administered at a fixed dose determined during dose exploration phase in dose expansion phase.; Drug: Daratumumab; Daratumumab will be administered via SC injection in combination with forimtamig.
Experimental: Dose Expansion Phase: Forimtamig 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.	Drug: Forimtamig; Forimtamig will be administered SC at different doses during dose exploration phase. Forimtamig will be administered at a fixed dose determined during dose exploration phase in dose expansion phase.
Experimental: Dose Expansion Phase: Forimtamig + Carfilzomib Participants will receive forimtamig, SC injection at a fixed dose determined during dose exploration phase in combination with carfilzomib, IV infusion until disease progression.	Drug: Forimtamig; Forimtamig will be administered SC at different doses during dose exploration phase. Forimtamig will be administered at a fixed dose determined during dose exploration phase in dose expansion phase.; Drug: Carfilzomib; Carfilzomib will be administered via IV infusion in combination with forimtamig.
Experimental: Dose Expansion Phase: Forimtamig + Daratumumab Participants will receive forimtamig, SC injection at a fixed dose determined during dose exploration phase in combination with daratumumab, SC injection until disease progression.	Drug: Forimtamig; Forimtamig will be administered SC at different doses during dose exploration phase. Forimtamig will be administered at a fixed dose determined during dose exploration phase in dose expansion phase.; Drug: Daratumumab; Daratumumab will be administered via SC injection in combination with forimtamig.

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants with Adverse Events (AEs) [Up to approximately 24 months]

2. Objective Response Rate (ORR) as Determined by the Investigator per International Myeloma Working Group (IMWG) Criteria [Up to approximately 24 months]

3. Complete Response (CR)/Stringent Complete Response (sCR) Rate as Determined by the Investigator per IMWG Criteria [Up to approximately 24 months]

4. Rate of Very Good Partial Response (VGPR) or Better as Determined by the Investigator per IMWG Criteria [Up to approximately 24 months]

Secondary Outcome Measures

1. Progression-Free Survival (PFS) as Determined by the Investigator per IMWG Criteria [Up to approximately 24 months]

2. Duration of Response (DoR) for Participants who Achieve a Partial Response (PR) or Better as Determined by the Investigator per IMWG Criteria [Up to approximately 24 months]

3. Time to First Response as Determined by the Investigator per IMWG Criteria [Up to approximately 24 months]

4. Time to Best Response as Determined by the Investigator per IMWG Criteria [Up to approximately 24 months]

5. Overall Survival (OS) as Determined by the Investigator per IMWG Criteria [Up to approximately 24 months]

6. Serum Concentration of Forimtamig [Up to approximately 24 months]

7. Percentage of Participants with Anti-Drug Antibodies (ADAs) to Forimtamig [Up to approximately 24 months]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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 current 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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT06055075
• Other Study ID Numbers: BP43437; 2023-503689-21-00
• First Posted: Sep 26, 2023
• Last Update Posted: Sep 26, 2023
• Last Verified: Sep 1, 2023

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Daratumumab

Study Results

No Results Posted as of Sep 26, 2023