Phase 1/2 Study of REGN17372 in Combination with Linvoseltamab in Participants with Relapsed/Refractory Multiple Myeloma

The primary objective of this study is to evaluate the safety and tolerability of REGN17372 in combination with linvoseltamab, as well as to determine the recommended phase 2 dose (RP2D) in participants with relapsed/refractory multiple myeloma. During the phase 2 dose expansion, the study aims to assess the preliminary anti-tumor activity of the two identified RP2D regimens of REGN17372 combined with linvoseltamab, in comparison to linvoseltamab monotherapy.

Secondary objectives include:

• Evaluation of the pharmacokinetics of REGN17372 and linvoseltamab when administered in combination.
• Assessment of the immunogenicity of both REGN17372 and linvoseltamab.
• Evaluation of preliminary anti-tumor activity in phase 1.
• Assessment of the safety and tolerability of the study treatments in phase 2.
• Evaluation of the impact of the combination therapy on health-related quality of life (HRQoL), including patient-reported functioning and symptoms.
• Monitoring of patient-reported tolerability specifically related to cutaneous and oral symptomatic toxicities.

The study involves 73 participants diagnosed with relapsed/refractory multiple myeloma. The population includes both males and females within specific age categories. Eligible individuals must have received at least three lines of therapy and have exhausted available therapeutic options expected to provide clinical benefit. Key requirements include an ECOG performance status score of ≤1 and the presence of measurable disease for response assessment. Participants are required to demonstrate adequate hematologic, cardiac, hepatic, and renal function.

This is a first-in-human, Phase 1/2 study designed to evaluate the safety, tolerability, and preliminary anti-tumor activity of REGN17372 in combination with linvoseltamab in individuals with relapsed/refractory multiple myeloma. The research is structured into two distinct stages: Phase 1 focuses on dose escalation to identify the recommended phase 2 dose (RP2D), while Phase 2 involves dose expansion to assess anti-tumor activity through regimens of the combination therapy and linvoseltamab monotherapy. The study involves a screening period to assess eligibility based on ECOG performance status, measurable disease, and adequate organ function. Participants are monitored for dose-limiting toxicities and treatment-emergent adverse events. The trial is estimated to conclude by December 2035.

Linvoseltamab is an experimental bispecific monoclonal antibody administered via intravenous use as a solution for infusion. The available formulations include concentrations of 5 mg and 200 mg.

REGN17372 is an experimental powder for solution for infusion administered through intravenous use.

Dexamethasone is utilized as an auxiliary treatment in the form of a solution for injection/infusion for intravenous use.

Diphenhydramine hydrochloride is provided as an auxiliary medication in two pharmaceutical forms: a solution for injection for intravenous use and 25 mg tablets for oral administration.

Paracetamol is administered as an auxiliary treatment in the form of 1000 mg tablets for oral administration.

Efficacy assessment in this study of relapsed/refractory multiple myeloma involves several parameters across two phases. In Phase 2, primary efficacy endpoints include the achievement of very good partial response (VGPR) or better, as well as partial response (PR) or better, determined by the investigator using the International Myeloma Working Group (IMWG) response criteria for both combination therapy and linvoseltamab monotherapy.

Secondary efficacy endpoints include:

• Objective response rate (ORR), complete response (CR), duration of response (DOR), and progression free survival (PFS) as assessed by IMWG criteria.
• Minimal residual disease (MRD) negative status at 10^-5 in participants achieving CR or better.
• Overall survival (OS).
• Serum concentrations of REGN17372 and linvoseltamab.
• Incidence and magnitude of anti-drug antibodies (ADA) to REGN17372 and linvoseltamab.

Patient-reported outcomes are utilized to evaluate quality of life and treatment impact. These assessments include changes from baseline and time to definitive deterioration or first improvement in the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) across various domains, including global health status (GHS/QoL), physical functioning (PF), role functioning (RF), pain, and fatigue. Additionally, the EORTC QLQ-Multiple Myeloma Module (MY20) is used to assess disease symptoms (DS) and treatment side effects (TSE). Further assessments include the EuroQoL-5 Dimensions, 5-level Questionnaire (EQ-5D-5L) visual analogue score (VAS), the Functional Assessment of Cancer Therapy (FACIT) Item GP5 for overall impact of toxicity, and patient reported outcome-common terminology criteria for adverse events (PRO-CTCAE) to measure tolerability.