A phase Ib/II study of AK112, a PD-1/VEGF bispecific antibody, as first- or second-line therapy for advanced non-small cell lung cancer (NSCLC).

9040 Background: Besides the well-known antiangiogenic effects, anti-VEGF agents also modulate the tumor immune micro-environment, leading to synergic anti-tumor effects. AK112 is a humanized IgG1 bispecific antibody against PD-1 and VEGF. Here, we reported results of an ongoing phase Ib/II trial of AK112 in advanced NSCLC pts. Methods: Pts with stage IIIB/IIIC/IV NSCLC, ECOG PS 0-1 and negative oncogenic drivers were enrolled and given AK112 (10 mg/kg Q3W, 20 mg/kg Q2W, 20 mg/kg Q3W or 30 mg/kg Q3W) intravenously. The primary endpoints were ORR per RECIST v1.1 and safety. Results: At data cutoff (January 5, 2022), 94 pts were enrolled: median age 66.0 years (range: 48-75), PS 1 90.4%, male 85.1%, non-squamous 48.9%, PD-L1 positive (TPS ≥1%) 70.2% and treatment-naïve 84.0%. Of 83 pts evaluable for efficacy, ORR (unconfirmed, similarly hereinafter) and DCR were 22.2%/88.9%, 44.0%/92.0%, 37.9%/93.1% and 100%/100% at doses of 10 mg/kg Q3W, 20 mg/kg Q2W, 20 mg/kg Q3W and 30 mg/kg Q3W, respectively. When doses of AK112 > 10mg/kg Q3W, ORR and DCR were 42.9% (24/56) and 92.9% (52/56) in 56 evaluable pts, 56.3% (18/32) and 100% (32/32) in pts with TPS≥1% at 1st line setting, and 23.5% (4/17) and 76.5% (13/17) in pts with PD-L1 TPS < 1%, respectively. Grade≥3 treatment-related adverse events (TRAEs) occurred in 10.6% (10/94) pts, in which the most common event (occurring in > 1 pt) was pneumonia (2.1%, 2/94). No TRAEs led to permanent treatment discontinuation. Most frequent TRAEs (incidence ≥10%) were proteinuria (17.0%), hypertension (16.0%), lipase increase (12.8%), alanine aminotransferase increase (12.8%), blood urea increase (10.6%), apolipoprotein E increase (10.6%) and hyperglycaemia (10.6%). No significant difference in the incidences of TRAEs were observed between non-squamous and squamous pts. Conclusions: In advanced NSCLC, AK112 was well-tolerated and presented remarkable anti-tumor efficacy. Further phase III studies are planned to validate the findings of this study. Clinical trial information: NCT04900363.