Drug intelligence / Profile preview

FOLFIRI + zimberelimab + domvanalimab

Development stage: Unknown
Lead developer: Arcus Biosciences
Modality: Monoclonal Antibodies → Antibody-Based Therapeutics, Small Molecules
Administration: Intravenous

Overview

This combination therapy is an investigational regimen being evaluated for the second-line treatment of advanced gastro-entero-pancreatic or unknown origin neuroendocrine carcinoma (NEC). It combines the standard-of-care FOLFIRI chemotherapy (comprising folinic acid, fluorouracil, and irinotecan) with two novel immune checkpoint inhibitors: zimberelimab (an anti-PD-1 monoclonal antibody) and domvanalimab (an Fc-silent anti-TIGIT monoclonal antibody). The rationale behind this combination is to leverage the cytotoxic effects of chemotherapy alongside dual blockade of the PD-1 and TIGIT pathways to overcome immune resistance and improve clinical outcomes in patients who have progressed on first-line platinum-etoposide therapy. The regimen is currently being studied in the Phase II REWENEC-01 trial sponsored by Hospices Civils de Lyon.

Other names: FOLFIRI + AB122 + AB154

Targets

PDCD1 (Programmed cell death protein 1 receptor)TIGIT (T cell immunoreceptor with Ig and ITIM domains)TOP1 (DNA Topoisomerase I)TS (Thymidylate synthase)

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