Investigational Drug
REGN5678
TrialFetch AI Analysis
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Overview
REGN5678, also called nezastomig, is an investigational bispecific antibody being studied in prostate cancer and other tumors associated with PSMA expression. Human results have been reported from an early-phase study in metastatic castration-resistant prostate cancer (mCRPC), chiefly for REGN5678 combined with cemiplimab. These results do not establish the effectiveness of REGN5678 alone. (cancer.gov)
Mechanism of action
REGN5678 binds prostate-specific membrane antigen (PSMA) on tumor cells and CD28, a costimulatory receptor on T cells. It is designed to bring these cells together and promote T-cell activity against PSMA-expressing cells. Cemiplimab blocks PD-1, a separate inhibitory immune checkpoint. (cancer.gov)
Efficacy
In a phase 1/2 study, 78 patients received REGN5678 plus cemiplimab. Responses were reported only among the 61 patients given REGN5678 doses of at least 30 mg weekly: 15/61 (25%) had a PSA decline of at least 50% (PSA50), and 10/61 (16%) had a decline of at least 90% (PSA90). Estimated median radiographic progression-free survival in this higher-dose group was 5.0 months. These are preliminary, nonrandomized findings; PSA declines are not the same as tumor shrinkage or a proven survival benefit. (aacrjournals.org)
Safety
Among the 78 patients, 60 (77%) had a treatment-related adverse event. The most frequently reported were fatigue (27%), cytokine-release syndrome (13%) and nausea (13%). Eleven patients (14%) had a grade 3 or higher immune-mediated adverse reaction, all after cemiplimab was added; two patients (3%) had fatal immune-mediated reactions—hemophagocytic lymphohistiocytosis and hepatitis. Investigators reported an association between responses and severe immune-mediated reactions and are exploring dosing and combination strategies. (aacrjournals.org)
Further reading
- Updated phase 1/2 results, AACR 2025 abstract
- Earlier phase 1/2 results, ASCO 2023 abstract
- NCI description of the ongoing study
Last updated: Sep 2026
Active trials using REGN5678
Found 3 active trials using this drug:
TrialFetch AI summary: Men with progressive metastatic castration-resistant prostate adenocarcinoma after at least two systemic treatment lines, including a second-generation antiandrogen, receive lead-in doses of REGN5678 followed by REGN5678 plus cemiplimab. REGN5678 is an investigational PSMA×CD28 bispecific antibody designed to activate T cells, while cemiplimab blocks PD-1.
ClinicalTrials.gov ID: NCT06826768
TrialFetch AI summary: For patients with metastatic castration-resistant prostate adenocarcinoma progressing after at least two prior systemic therapies, including a second-generation antiandrogen, this study evaluates REGN4336, a PSMA×CD3 T-cell–engaging bispecific antibody, alone or with the PD-1 inhibitor cemiplimab or REGN5678, an investigational PSMA×CD28 T-cell–costimulating bispecific antibody.
ClinicalTrials.gov ID: NCT05125016
TrialFetch AI summary: This study enrolls patients with previously treated metastatic castration-resistant prostate cancer or metastatic clear-cell renal cell carcinoma. It evaluates REGN5678 (nezastomig), an investigational PSMA×CD28 bispecific antibody that costimulates T cells near PSMA-expressing tumors, alone or, in earlier cohorts, with the PD-1 inhibitor cemiplimab.
ClinicalTrials.gov ID: NCT03972657
