A Study to Assess the Safety and Anti-Tumor Activity of REGN7945 in Combination With Linvoseltamab in Adult Participants With Relapsed/Refractory Multiple Myeloma

Official title

A First-in-Human (FIH) Phase 1/2 Study to Assess Safety, Tolerability, and Preliminary Anti-Tumor Activity of REGN7945, an Anti-CD38 x Anti-CD28 Costimulatory Bispecific Monoclonal Antibody, in Combination With Linvoseltamab, an Anti-BCMA x Anti-CD3 Bispecific Monoclonal Antibody, in Participants With Relapsed/Refractory Multiple Myeloma

Overview

This study is researching an experimental drug called REGN7945 in combination with another experimental drug called linvoseltamab, (also known as REGN5458) (each individually called a "study drug" or "study drugs" when combined). This study is the first time REGN7945 will be tested in humans. Linvoseltamab has previously been studied by itself (without other cancer drugs) in participants who had advanced multiple myeloma that returned and needed to be treated again after several other therapies had failed. The aim of the study is to see how safe, tolerable, and effective REGN7945 is when given in combination with linvoseltamab, compared with linvoseltamab alone. The study is looking at several other research questions, including: * What side effects may happen from taking the study drug(s) * How many people treated with REGN7945 and linvoseltamab compared to linvoseltamab alone have improvement of their multiple myeloma and by how much * How long people benefit from receiving REGN7945 in combination with linvoseltamab compared with linvoseltamab alone * How much study drug(s) is in the blood at different times * Whether the body makes antibodies against the study drugs(s) (which could make the study drug(s) less effective or could lead to side effects) * If there is any change in pain and cancer-related symptoms, how well people are able to function, and their quality of life when taking the study drug(s)

Interventions

• Drug Linvoseltamab
  Administered per protocol
• Drug REGN7945+Linvoseltamab
  Administered per protocol

Primary outcome measures

• Incidence of dose limiting toxicities (DLTs) from the first dose of REGN7945 in combination with linvoseltamab [Time frame: Up to 21 days]
• Incidence of treatment emergent adverse events (TEAEs) during the treatment period with REGN7945 in combination with linvoseltamab [Time frame: Up to 5 years]
• Severity of TEAEs during the treatment period with REGN7945 in combination with linvoseltamab [Time frame: Up to 5 years]
• Very Good Partial Response (VGPR) or better as determined by the investigator using the International Myeloma Working Group (IMWG) response criteria in patients receiving combination therapy [Time frame: Within 12 weeks of starting cycle 1]
• VGPR or better as determined by the investigator using the IMWG response criteria in patients receiving linvoseltamab monotherapy [Time frame: Within 12 weeks of starting cycle 1]
• Partial Response (PR) or better as determined by the investigator using the IMWG response criteria in patients receiving combination therapy [Time frame: Within 12 weeks of starting cycle 1]
• PR or better as determined by the investigator using the IMWG response criteria in patients receiving linvoseltamab monotherapy [Time frame: Within 12 weeks of starting cycle 1]

Secondary outcome measures (12)

• Incidence of TEAEs [Time frame: Up to 5 years]
• Severity of TEAEs [Time frame: Up to 5 years]
• Concentrations of REGN7945 in the serum [Time frame: Up to 5 years]
• Concentrations of linvoseltamab in the serum [Time frame: Up to 5 years]
• Incidence of anti-drug antibodies (ADA) to REGN7945 [Time frame: Up to 5 years]
• Titer of ADA to REGN7945 [Time frame: Up to 5 years]
• Incidence of ADA to linvoseltamab [Time frame: Up to 5 years]
• Titer of ADA to linvoseltamab [Time frame: Up to 5 years]
• Change in European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) Global Health Status / Quality of Life (GHS/QoL) [Time frame: Up to 5 years]
• Change in EORTC QLQ-C30 Physical Functioning (PF) [Time frame: Up to 5 years]
• Change in EORTC QLQ-C30 Role Functioning (RF) [Time frame: Up to 5 years]
• Change in EORTC QLQ-C30 pain [Time frame: Up to 5 years]

Eligibility criteria

Inclusion criteria

• Eastern Cooperative Oncology Group (ECOG) performance status ≤1 as described in the protocol
• Received at least 3 lines of therapy including exposure to at least 1 anti-CD38 antibody, 1 immunomodulatory imide drug (IMiD), and 1 proteasome inhibitor (PI) and have demonstrated disease progression on or after the last therapy, as defined in the protocol. Prior treatment with other BCMA directed immunotherapies, including BCMA CAR-T cells and BCMA antibody-drug conjugates (Phase 1 and 2), and with BCMA x CD3 bispecific antibodies (Phase 1 only), is allowed
• Participants must have the measurable disease for response assessment as described in the protocol
• Adequate hematologic, hepatic, and renal function as described in the protocol

Exclusion criteria

• Diagnosis of plasma cell leukemia, primary systemic light-chain amyloidosis (including myeloma associated amyloidosis), Waldenström macroglobulinemia (lymphoplasmacytic lymphoma), or POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
• Treatment with any systemic anti-cancer therapy within 5 half-lives or within 28 days before first administration of study drug, whichever is shorter
• History of allogeneic stem cell transplantation within 6 months, or autologous stem cell transplantation within 12 weeks of the start of study treatment
• Treatment with systemic corticosteroid treatment with more than 10 mg per day of prednisone or steroid equivalent within 72 hours of start of study drug
• Participants who have known central nervous system (CNS) involvement with MM or known or suspected progressive multifocal leukoencephalopathy (PML), history of a neurocognitive condition or CNS disorder, or history of seizure within 12 months prior to study enrollment
• Live or live attenuated vaccination within 28 days before first study drug administration with a vector that has replicative potential
• Has received a COVID-19 vaccination within 1 week of planned start of study medication as described in the protocol
• Myelodysplastic syndrome or another malignancy in the past 3 years, except for nonmelanoma skin cancer, in situ carcinoma, thyroid cancer, or low-risk early stage prostate adenocarcinoma, as described in the protocol
• Significant cardiovascular disease as described in the protocol
• Uncontrolled infection with HIV, Hep B or Hep C infection, or other uncontrolled infection, such as CMV, as described in the protocol
• Known hypersensitivity to both allopurinol and rasburicase

Note: Other protocol-defined Inclusion/ Exclusion Criteria apply

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Australia · 6 centers

• Royal Prince Alfred Hospital — Sydney
• Illawarra Cancer Care Centre — Wollongong
• Pindara Private Hospital — Benowa
• Royal Adelaide Hospital — Adelaide
• Alfred Hospital — Melbourne
• St Vincents Hospital Melbourne — Melbourne

United Kingdom · 3 centers

• University College London Hospitals — London
• St Thomas Hospital — London
• The Christie NHS Foundation Trust — Manchester

Identifiers

NCT: NCT06669247 · R7945-ONC-22110 · 2024-513126-39-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗