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Background SSGJ-707 (PF-08634404) is a fully human immunoglobulin G4 bispecific antibody that targets programmed death 1 (PD-1) and vascular endothelial growth factor (VEGF). Results from a phase 2 study demonstrated promising efficacy and manageable safety as monotherapy in first-line NSCLC with tumor proportion score (TPS) ≥1. We report safety and efficacy from the phase 2 study ( NCT06412471) of SSGJ-707 combined with platinum-based chemotherapy in first-line NSCLC.Methods This is an open-label, multicenter, randomized phase 2 trial of SSGJ-707 or tislelizumab (control arm) combined with platinum-based chemotherapy in advanced NSCLC. Patients with histologically confirmed treatment-naive NSCLC regardless of PD-L1 expression were eligible. Primary objectives were to evaluate the safety, tolerability, and antitumor activity of different dosing regimens of SSGJ-707 combined with chemotherapy given every 3 weeks (Q3W). In Part 1, patients with nonsquamous NSCLC received SSGJ-707 at 5/10/20 mg/kg or tislelizumab with carboplatin+pemetrexed. In Part 2 cohort A, patients with squamous NSCLC received SSGJ-707 at 5/10/20 mg/kg + carboplatin + paclitaxel. Based on the selected dose from cohort A, Part 2 cohort B evaluated SSGJ-707 10 mg/kg or tislelizumab with carboplatin + paclitaxel or SSGJ-707 10 mg/kg + carboplatin + nab-paclitaxel in squamous NSCLC.Results At the data cutoff of July 4, 2025, 119 patients with nonsquamous NSCLC and 125 with squamous NSCLC were enrolled in Parts 1 and 2, respectively. Majority of the patients were male (80%) and 50% were ≥65 years; 43% had TPS <1%, 36% had TPS 1%-49%, and 21% had TPS ≥50%. Across Parts 1 and 2, grade ≥3 treatment-related adverse events (TRAEs) occurred in 39.0% of patients receiving SSGJ-707 10 mg/kg and 32.8% receiving tislelizumab ( table 1). In SSGJ-707 10 mg/kg arm, TRAEs led to discontinuation in 2 patients (1.9%) and death in 3 (2.9%; hemoptysis in 2 and unknown cause in 1). With SSGJ-707 10 mg/kg, the confirmed objective response rate (ORR) was 58.6% in nonsquamous, 75.0% in squamous cohort A, and 37.5% (paclitaxel; majority pending confirmation) and 69.2% (nab-paclitaxel) in squamous cohort B; with tislelizumab, confirmed ORR was 38.7% in nonsquamous and 47.6% in squamous patients. Responses were observed irrespective of PD-L1 expression (figure 1).Conclusions SSGJ-707 combined with platinum-based chemotherapy demonstrated manageable safety and promising efficacy in first-line treatment of nonsquamous and squamous advanced NSCLC regardless of PD-L1 expression. ORRs with SSGJ-707 exceeded that of tislelizumab + chemotherapy. These results support further evaluation of SSGJ-707 10 mg/kg Q3W combined with chemotherapy in a phase 3 study in first-line NSCLC regardless of PD-L1 expression.Abstract 1328 Table 1Efficacy and safetyirAE, immune-related adverse event; PR, partial response; SAE, serious adverse event; TEAE, treatment-emergent adverse event. aIncluded all patients in the enrolled analysis set who received any amount of drug and who had ≥1 post-baseline tumor evaluation. 37 patients had no post-dose initial tumor assessment. bPatients with unconfirmed PRs that are awaiting confirmation and have the potential to become confirmed PRs. cDefined as a TEAE that was ‘related’ to SSGJ-707, ‘most possibly related to SSGJ-707,’ possibly related to SSGJ-707, or for which relationship to SSGJ-707 was missing. dGrade 5 TRAEs consisted of hemoptysis (n=2) and unknown cause (n=1). eDefined as gastrointestinal perforation and fistula, hemorrhage, thromboembolic event, hypertension, or proteinuria. fDefined as any TEAE that was potentially immune mediated and categorized as ‘related,’ ‘most possibly related,’ or ‘possibly related’ to SSGJ-707 or tislelizumab.Abstract 1328 Figure 1Waterfall plots for SSGJ-707 + chemotherapy in Part 1, Part 2 cohort A, and Part 2 cohort B