Background: PF-08634404 is a fully human IgG4 bispecific antibody that simultaneously targets 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 1L NSCLC. This study will evaluate PF-08634404 plus chemotherapy in patients with t-SCLC in the 1L setting.
Trial design: Symbiotic-Lung-14 is a multicenter, open-label, single-arm Ph2 trial (NCT07476287) in adults who have histologically or cytologically confirmed t-SCLC. Patients must have had a prior diagnosis of EGFR-mutated NSCLC that transformed to SCLC following treatment with ≥1 TKI and have not received prior systemic therapy for t-SCLC. Before enrollment, patients may receive 1 cycle of chemotherapy without ICIs for the management of life-threatening t-SCLC. Patients must have ≥1 measurable lesion per RECIST 1.1, sufficient tumor tissue from the diagnosis of t-SCLC, ECOG performance status of 0 or 1, life expectancy of ≥3 months, and adequate organ function. Patients with known active CNS lesions or leptomeningeal disease are excluded. However, patients with definitively treated (surgery and/or radiotherapy) brain metastases that are stable or untreated asymptomatic brain metastases may be included.
Approximately 40 patients will be enrolled to receive PF-08634404 plus etoposide and carboplatin, followed by maintenance therapy with PF-08634404. Tumor assessments will be performed every 6 weeks until week 48 and every 9 weeks thereafter. Treatment will continue until progressive disease, unacceptable toxicity, global deterioration of health status, initiation of new cancer therapy, withdrawal of consent, death, study termination, or protocol-specified criteria for treatment discontinuation, whichever occurs first.
Primary endpoints are confirmed ORR by investigator assessment per RECIST 1.1 and safety. Secondary endpoints are DOR and PFS by investigator assessment per RECIST 1.1, OS, additional safety measures, pharmacokinetics, and immunogenicity. Exploratory endpoints include QoL and biomarkers. Enrollment has begun.
Previously submitted at 2026 World Conference on Lung Cancer