A phase II trial to evaluate the safety and efficacy of SSGJ-707, a bispecific antibody targeting PD-1 and VEGF, as a monotherapy in patients with advanced NSCLC.

8543 Background: SSGJ-707 is a recombinant humanized bispecific molecule built on IgG4 that targets the human programmed death 1 (PD-1) and vascular endothelial growth factor (VEGF). The increase of SSGJ-707 affinity for PD-1 was 10-fold more than that of Ivonescimab in the presence of VEGF. Here, we report the initial results from a phase II study of SSGJ-707 monotherapy in patients (pts) with advanced NSCLC(SSGJ-707-NSCLC-II-01, NCT06361927). Methods: Pts with treatment naive advanced NSCLC (without actionable genomic alterations and PD-L1 expression≥1%) were enrolled to receive SSGJ-707 monotherapy until disease progression or unacceptable toxicity. Tumor assessments based on RECIST 1.1 were performed every 6 weeks by investigators. Results: As of Jan 10, 2025, 83 NSCLC pts have received SSGJ-707 at dose of 5mg/kg Q3W (n=31), 10mg/kg Q3W (n=34), 20mg/kg Q3W (n=12), 30mg/kg Q3W(n=6). Overall, the median age was 64 years, 83.1% had ECOG PS of 1, 44.6% of pts with squamous cell carcinoma, 66.3% and 33.7% of pts had PD-L1 expression 1%-49% and ≥50%. Among the 76 pts completed at least one efficacy evaluation, ORR and DCR were 29.6% (8/27)/85.2% (23/27), 61.8%(21/34)97.1% (33/34), 54.5% (6/11)/90.9% (10/11) and 25% (1/4)/75% (3/4) at doses of 5mg/kg Q3W, 10mg/kg Q3W, 20mg/kg Q3W and 30 mg/kg Q3W, respectively. SSGJ-707 10mg/kg Q3W demonstrated promising efficacy results in treatment naive advanced NSCLC. Select subgroups are summarized in SSGJ-707 10mg/kg Q3W. The ORR were 54.5% (12/22) and 75%(9/12) in non-squamous and squamous pts respectively. And the ORR were 57% (12/21) and 69%(9/13) in PD-L1 TPS 1%-49% and ≥ 50% pts respectively. 25 pts completed at least two efficacy evaluation in SSGJ-707 10mg/kg Q3W, the ORR was 72% (18/25), DCR was 100% (25/25). For the 83 pts, 65 pts (78.3%) experienced treatment related adverse events (TRAEs), 20 pts (24.1%) experienced grade≥3 TRAEs. The most common TRAEs included hypercholesterolaemia (18.1%,15/83), hypertriglyceridaemia (18.1%,15/83), alanine aminotransferase increased (15.7%,13/83) and aspartate aminotransferase increased (15.7%,13/83). TRAE leading to discontinuation occurred in 6% of pts. Conclusions: SSGJ-707 monotherapy demonstrated promising efficacy results in treatment naive advanced NSCLC with manageable safety profile. Monotherapy and combination trials with chemotherapy for NSCLC are still ongoing. Research Sponsor: 3S BIO.COM. Clinical trial information: NCT06361927 .