Phase 1/2 Trial of REGN7945 and Lenvoceltamab to Evaluate CD28 Co-stimulation Synergy
CD28 Co-stimulation Added to Bispecific Antibody Combination
Regeneron Pharmaceuticals (REGN) is evaluating the combination of REGN7945 and lenvoceltamab in the COSTIMM clinical trial (NCT06669247). REGN7945 is an investigational CD38×CD28 co-stimulatory bispecific antibody, and lenvoceltamab-gcpt, the active ingredient in Lynozyfic, is a BCMA×CD3 T-cell engaging bispecific antibody. The combination is designed to enhance immune response by having REGN7945 deliver CD28 signals in the vicinity of CD38-expressing multiple myeloma cells, while lenvoceltamab directs T cells to BCMA-expressing cells, creating a stronger immune response than single T-cell engagers. A key aspect is that this is the first-in-human study of REGN7945, designed to validate the pre-clinical combination activity in actual patients.
Phase 1/2 Trial with 186 Patients
This is an ongoing Phase 1/2 study involving approximately 186 adult patients with relapsed or refractory multiple myeloma. Phase 1 is a non-randomized dose-escalation phase to evaluate dose-limiting toxicities (DLTs) up to day 21 after the first combination dose, and to determine the recommended Phase 2 dose. Phase 2 is a randomized comparison of the combination arm versus the lenvoceltamab monotherapy arm, assessing objective response rate (ORR), duration of response (DOR), progression-free survival (PFS), pharmacokinetics, anti-drug antibodies, and patient-reported outcomes. The actual study began on December 11, 2024, with a primary completion date of November 2033 and an overall completion date of November 2035, indicating a long development timeline for an early-stage asset.
Life Cycle Strategy Built on Approved Drug
Lynozyfic received conditional approval in the European Union on April 23, 2025, and the U.S. FDA granted accelerated approval on July 2, 2025, for patients who have received four or more prior lines of therapy. In the pivotal LINKER-MM1 study, the independent central review ORR was 70%, and the estimated 12-month duration of response in responders was 72%. However, cytokine release syndrome (CRS) occurred in 46% of patients and neurotoxicity in 54% of patients in the recommended dose group, leading to a boxed warning and a risk evaluation and mitigation strategy (REMS) in the U.S. COSTIMM is an expansion strategy to improve the depth and duration of response of the approved lenvoceltamab; however, the extent to which the addition of CD28 co-stimulation amplifies toxicity is a critical factor for clinical value.
Differentiation Needed in a Crowded BCMA Market
Competitors include BCMA×CD3 bispecific antibodies such as Tecvayli (teclistamab-cqyv) from Johnson & Johnson (JNJ) and Elrexfio (elranatamab-bcmm) from Pfizer (PFE), as well as BCMA CAR-T therapies such as Carvykti (ciltacabtagene autoleucel) and Abecma (idecabtagene vicleucel). Talvey (talquetamab-tgvs), a GPRC5D×CD3 bispecific antibody, and Darzalex (daratumumab), a CD38 antibody, are also in competition in terms of treatment sequence. The global multiple myeloma market was estimated at $29.24 billion in 2025 and is projected to reach $49.79 billion in 2034, indicating significant commercial potential. However, REGN7945 must demonstrate clinically meaningful efficacy improvements and manageable safety compared to lenvoceltamab alone to differentiate itself in the crowded late-line treatment market.
From an investor perspective, COSTIMM represents an early clinical option to extend the product life of Lynozyfic, which has already received accelerated approval in the U.S. and conditional approval in Europe, and to increase market share in the multiple myeloma market, which is valued at $29.24 billion in 2025. For researchers, the study is significant because it involves a Phase 1/2 trial with 186 patients, directly comparing the combination arm and the monotherapy arm to determine whether combining CD38×CD28 co-stimulation with BCMA×CD3-induced T-cell responses improves the depth and duration of response. For the industry, it sets a benchmark that, in an environment where Tecvayli, Elrexfio, Carvykti, Abecma, and Talvey are already competing, it is necessary to demonstrate not only convenience but also a favorable benefit-risk profile in terms of ORR, DOR, PFS, CRS, and neurotoxicity. Short-term catalysts include Phase 1 DLT and the recommended Phase 2 dose, while long-term corporate value depends on whether the Phase 2 randomized data demonstrate a clinically meaningful improvement over the 70% ORR of lenvoceltamab monotherapy in the LINKER-MM1 study without compromising safety.
Source: ClinicalTrials.gov (api_ct)