Background: PF-08634404 (PF’4404) is an IgG4 bispecific simultaneously targeting PD-1/VEGF. Earlier results (NCT06412471) demonstrated encouraging efficacy and manageable safety with PF’4404+platinum-based chemo (PBC) as 1L treatment of NSCLC regardless of PD-L1 expression.
Methods: This open-label randomized Ph2 trial evaluated PF’4404 or tislelizumab+PBC in 1L NSCLC. In part 1, patients with non-squamous NSCLC were randomized to PF’4404 or tislelizumab+carbo/pemetrexed. In part 2, patients with squamous NSCLC were randomized to different doses of PF’4404+carbo/paclitaxel in cohort A; or PF’4404 or tislelizumab+carbo/paclitaxel or PF’4404+carbo/nab-paclitaxel in cohort B. Primary objectives were safety and antitumor activity. Efficacy results are shown from the recommended Ph3 dose of 10 mg/kg Q3W; safety and ctDNA include all doses evaluated.
Results: As of Feb 28, 2026, 261 patients were enrolled (122 non-squamous, 139 squamous); 44% had PD-L1 TPS <1%, 36% TPS 1%–49%, and 20% TPS ≥50%. Median f/u exceeded 10.3 months across cohorts. In non-squamous, cORR was 75.0% with PF’4404 vs 44.7% with tislelizumab. In squamous, cORR with PF’4404 was 82.5% (carbo/paclitaxel) and 69.2% (carbo/nab-paclitaxel) vs 67.7% with tislelizumab. PF’4404 responses occurred irrespective of PD-L1 expression. 12-month PFS trends were favorable in PF’4404 vs tislelizumab in non-squamous and squamous NSCLC. Safety of PF’4404+PBC was comparable to that of tislelizumab+PBC.
In PF’4404-treated patients with ctDNA detected at baseline and paired samples at C3D1 (n=126), 61.9% cleared their ctDNA and had mPFS of 13.8 months vs 9.6 months in patients without ctDNA clearance.
Conclusions: PF’4404+PBC continues to demonstrate clinically meaningful antitumor activity with cORR of 69%-82% and promising durability as 1L treatment for NSCLC irrespective of histology or PD-L1 expression. Safety was manageable and consistent in both histologies. ctDNA clearance correlated with improved PFS. These findings support ongoing Ph3 evaluation of PF’4404+chemo in Symbiotic-Lung-01 (NCT07222566).