Phase 2 PF-08634404 trial tests PD-1×VEGF bispecific antibody in stage II–III NSCLC

This open-label Phase 2 Pfizer study (NCT07489066) evaluates PF-08634404—an investigational bispecific antibody that targets PD-1 (to relieve T-cell inhibition) and VEGF/VEGF-A (to reduce pro-angiogenic, immunosuppressive signaling)—given either with chemotherapy or as monotherapy across three peri-definitive settings. Part A gives neoadjuvant PF-08634404 plus chemotherapy before surgery in resectable stage II–IIIB NSCLC without actionable genomic alterations, aiming to improve pathologic response at resection. Part B gives adjuvant PF-08634404 monotherapy after prior neoadjuvant chemo-immunotherapy and surgery for patients who did not achieve a pathologic complete response, addressing a high-relapse-risk group despite modern perioperative PD-1/PD-L1 regimens. Part C gives PF-08634404 consolidation after definitive concurrent chemoradiotherapy in unresectable stage III NSCLC without progression, testing an alternative to today’s typical approach of platinum-based cCRT followed by durvalumab consolidation when eligible. The commercial/scientific angle is “PD-(1) plus VEGF” dual-pathway modulation in earlier-stage disease, a strategy supported by biology and multiple programs in advanced NSCLC, now being moved into neoadjuvant/adjuvant/consolidation windows.