Aim: To report results from a phase 2 study (NCT06522828) of first-line PF‑08634404+chemotherapy in advanced/recurrent EC.
Methods: Patients with newly diagnosed stage lIl/IV or recurrent EC with low potential for cure by radiation therapy/surgery and systemic treatment-naive received PF‑08634404 5 or 10 mg/kg Q3W+chemotherpy (carboplatin AUC 5+paclitaxel 175 mg/m2) Q3W for 6 cycles, followed by PF‑08634404 maintenance treatment (up to 2 years). Primary endpoints were safety and objective response rate (ORR; RECIST 1.1).
Results: 32 patients received PF‑08634404+chemotherapy: 5 mg/kg, n=16 (14 mismatch repair proficient [pMMR], 2 MMR deficient [dMMR]); 10 mg/kg, n=16 (12 pMMR, 4 dMMR). 23 patients (72%) remained on treatment at data cutoff (Feb 1, 2026). Median duration of response (DOR) follow-up was 5.8 months (95% CI: 4.6, 7.2). Confirmed ORR in the pMMR and dMMR groups was 83% and 100% for the 5 mg/kg dose, 91% and 75% for the 10 mg/kg dose, respectively. Median progression-free survival, overall survival, and DOR were not reached for either dose. Any-grade treatment-related adverse events (TRAEs) were reported in 94% and grade ≥3 TRAEs in 69% of patients. Most common TRAEs included white blood cell count decreased (66%), neutrophil count decreased (63%), anemia (59%), and platelet count decreased (59%). No TRAEs led to death. TRAEs led to PF‑08634404 discontinuation in 2 patients (6%). Immune-related AEs occurred in 6 patients (19%): hypothyroidism (n=4), hyperthyroidism (n=3), and rash (n=2). VEGF-related AEs occurred in 17 patients (53%), most commonly blood pressure elevation (n=7) and proteinuria (n=7).
Conclusions: The promising efficacy and manageable safety profile of PF‑08634404+chemotherapy for treatment-naive advanced/recurrent EC supports further investigation of PF-08634404 in the phase 3 Symbiotic-GYN-18 study (GOG-3145/ENGOT-EN37/APGOT-EN6/LACOG 0426-EVA; NCT07578649).