Background: PF-08634404 is a fully human IgG4 bispecific antibody simultaneously targeting PD-1 and VEGF. Ph2 studies have shown promising efficacy and manageable safety with PF-08634404 as a monotherapy and in combination with chemotherapy in locally advanced (LA)/metastatic NSCLC. This study will evaluate PF-08634404 as monotherapy or in combination with chemotherapy in early-stage resectable and unresectable NSCLC.
Trial design: Symbiotic-Lung-10 is a multicenter, open-label, multi-arm Ph2 trial (NCT07489066) in adults with squamous and non-squamous NSCLC without actionable genomic alterations and independent of PD-L1 expression. Approximately 120 patients will be enrolled into 3 independent parts, each with different treatment settings and simultaneous enrollment (approximately 40 in each part).
Part A will enroll patients with treatment-naïve, early-stage or LA, resectable stage II or IIIA/B NSCLC who are candidates for neoadjuvant therapy followed by surgery. Patients will receive neoadjuvant PF-08634404+platinum-doublet chemotherapy (carboplatin+paclitaxel for squamous or carboplatin+pemetrexed for non-squamous) for 3 cycles, with an optional fourth cycle for patients deriving clinical benefit. Patients who remain candidates for surgery will undergo surgery within 5-8 weeks after the last dose of neoadjuvant PF-08634404. Primary endpoints are safety, surgical feasibility, and pathologic complete response (pCR) rate by central pathology review.
Part B will enroll patients with completely resected, early-stage or LA, stage II or IIIA/B NSCLC who received standard-of-care neoadjuvant chemoimmunotherapy, did not achieve pCR, and are candidates for adjuvant treatment. Patients will receive PF-08634404 monotherapy for up to 18 cycles/1yr, whichever comes first. The primary endpoint is safety.
Part C will enroll patients with LA, unresectable stage III NSCLC who did not have progressive disease per RECIST 1.1 after definitive platinum-based concurrent chemoradiotherapy and are candidates for consolidation therapy. Patients must not have had prior curative-intent surgery for NSCLC. Patients will receive PF-08634404 monotherapy for up to 18 cycles/1yr, whichever comes first. The primary endpoint is safety.