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

Study Overview
=================
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.

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

Conditions
-----------------
Relapsed or Refractory Multiple Myeloma

Intervention / Treatment
-----------------
* Drug: Forimtamig
* Drug: Carfilzomib
* Drug: Daratumumab


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Exploration Phase: Forimtamig (Dose 1) + Carfilzomib<br>Participants will receive Dose 1 of forimtamig, subcutaneous (SC) injection in combination with carfilzomib, intravenous (IV) infusion until disease progression. | Drug: Forimtamig<br>* 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.<br>Drug: Carfilzomib<br>* Carfilzomib will be administered via IV infusion in combination with forimtamig.<br>|
| Experimental: Dose Exploration Phase: Forimtamig (Dose 2) + Carfilzomib<br>Participants will receive Dose 2 of forimtamig, SC injection in combination with carfilzomib, IV infusion until disease progression. | Drug: Forimtamig<br>* 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.<br>Drug: Carfilzomib<br>* Carfilzomib will be administered via IV infusion in combination with forimtamig.<br>|
| Experimental: Dose Exploration Phase: Forimtamig (Dose 3) + Carfilzomib<br>Participants will receive Dose 3 of forimtamig, SC injection in combination with carfilzomib, IV infusion until disease progression. | Drug: Forimtamig<br>* 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.<br>Drug: Carfilzomib<br>* Carfilzomib will be administered via IV infusion in combination with forimtamig.<br>|
| Experimental: Dose Exploration Phase: Forimtamig (Dose 1) + Daratumumab<br>Participants will receive Dose 1 of forimtamig, SC injection in combination with daratumumab, SC injection until disease progression. | Drug: Forimtamig<br>* 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.<br>Drug: Daratumumab<br>* Daratumumab will be administered via SC injection in combination with forimtamig.<br>|
| Experimental: Dose Exploration Phase: Forimtamig (Dose 2) + Daratumumab<br>Participants will receive Dose 2 of forimtamig, SC injection in combination with daratumumab, SC injection until disease progression. | Drug: Forimtamig<br>* 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.<br>Drug: Daratumumab<br>* Daratumumab will be administered via SC injection in combination with forimtamig.<br>|
| Experimental: Dose Exploration Phase: Forimtamig (Dose 3) + Daratumumab<br>Participants will receive Dose 3 of forimtamig, SC injection in combination with daratumumab, SC injection until disease progression. | Drug: Forimtamig<br>* 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.<br>Drug: Daratumumab<br>* Daratumumab will be administered via SC injection in combination with forimtamig.<br>|
| Experimental: Dose Expansion Phase: Forimtamig<br>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<br>* 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.<br>|
| Experimental: Dose Expansion Phase: Forimtamig + Carfilzomib<br>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<br>* 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.<br>Drug: Carfilzomib<br>* Carfilzomib will be administered via IV infusion in combination with forimtamig.<br>|
| Experimental: Dose Expansion Phase: Forimtamig + Daratumumab<br>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<br>* 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.<br>Drug: Daratumumab<br>* Daratumumab will be administered via SC injection in combination with forimtamig.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with Adverse Events (AEs) |  | Up to approximately 24 months | 
| Objective Response Rate (ORR) as Determined by the Investigator per International Myeloma Working Group (IMWG) Criteria |  | Up to approximately 24 months | 
| Complete Response (CR)/Stringent Complete Response (sCR) Rate as Determined by the Investigator per IMWG Criteria |  | Up to approximately 24 months | 
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) as Determined by the Investigator per IMWG Criteria |  | Up to approximately 24 months | 
| 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 | 
| Time to First Response as Determined by the Investigator per IMWG Criteria |  | Up to approximately 24 months | 
| Time to Best Response as Determined by the Investigator per IMWG Criteria |  | Up to approximately 24 months | 
| Overall Survival (OS) as Determined by the Investigator per IMWG Criteria |  | Up to approximately 24 months | 
| Serum Concentration of Forimtamig |  | Up to approximately 24 months | 
| Percentage of Participants with Anti-Drug Antibodies (ADAs) to Forimtamig |  | Up to approximately 24 months |