Testing REGN7945 with linvoseltamab for relapsed multiple myeloma

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

This study is testing a new drug called REGN7945 combined with linvoseltamab to see if it helps adults with relapsed multiple myeloma better than linvoseltamab alone.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 186 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Regeneron Pharmaceuticals (industry)
• Drugs / interventions: CAR-T, prednisone, linvoseltamab
• Locations: 7 sites (Wollongong, New South Wales and 6 other locations)
• Trial ID: NCT06669247 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety and anti-tumor activity of an experimental drug REGN7945 in combination with linvoseltamab in adults with relapsed or refractory multiple myeloma. It aims to determine how well this combination works compared to linvoseltamab alone, focusing on side effects, effectiveness, and duration of benefit. This is the first time REGN7945 will be tested in humans, while linvoseltamab has been previously studied on its own. Participants will be monitored for improvements in their condition and overall tolerability of the treatment.

Who should consider this trial

Good fit: Ideal candidates are adults with relapsed or refractory multiple myeloma who have undergone at least three lines of prior therapy.

Not a fit: Patients with plasma cell leukemia, primary systemic light-chain amyloidosis, Waldenström macroglobulinemia, or POEMS syndrome may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new effective option for patients with relapsed or refractory multiple myeloma.

How similar studies have performed: While linvoseltamab has been previously studied, the combination with REGN7945 is a novel approach that has not been tested before.

Eligibility criteria

Key Inclusion Criteria:

1. Eastern Cooperative Oncology Group (ECOG) performance status ≤1 as described in the protocol
2. 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
3. Participants must have the measurable disease for response assessment as described in the protocol
4. Adequate hematologic, hepatic, and renal function as described in the protocol

Key Exclusion Criteria:

1. 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)
2. Treatment with any systemic anti-cancer therapy within 5 half-lives or within 28 days before first administration of study drug, whichever is shorter
3. History of allogeneic stem cell transplantation within 6 months, or autologous stem cell transplantation within 12 weeks of the start of study treatment
4. 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
5. 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
6. Live or live attenuated vaccination within 28 days before first study drug administration with a vector that has replicative potential
7. Has received a COVID-19 vaccination within 1 week of planned start of study medication as described in the protocol
8. 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
9. Significant cardiovascular disease as described in the protocol
10. Uncontrolled infection with HIV, Hep B or Hep C infection, or other uncontrolled infection, such as CMV, as described in the protocol
11. Known hypersensitivity to both allopurinol and rasburicase

Note: Other protocol-defined Inclusion/ Exclusion Criteria apply

Where this trial is running

Wollongong, New South Wales and 6 other locations

• Illawarra Cancer Care Centre — Wollongong, New South Wales, Australia (RECRUITING)
• Pindara Private Hospital — Benowa, Queensland, Australia (RECRUITING)
• Royal Adelaide Hospital — Adelaide, South Australia, Australia (RECRUITING)
• Alfred Hospital — Melbourne, Victoria, Australia (RECRUITING)
• St Vincents Hospital Melbourne — Melbourne, Victoria, Australia (RECRUITING)
• University College London Hospitals — London, United Kingdom (RECRUITING)
• The Christie NHS Foundation Trust — Manchester, United Kingdom (RECRUITING)

Study contacts

• Study coordinator: Clinical Trials Administrator

Conditions: Relapsed/Refractory Multiple Myeloma, R/RMM