1022P A phase II study of KN046 (a bispecific anti-PD-L1/CTLA-4) in patients with metastatic non-small cell lung cancer (NSCLC) who failed first line treatment

Abstract

KN046 is a novel bispecific antibody that blocks both PD-L1 interaction with PD1 and CTLA-4 interaction with CD80/CD86. In the phase II study, promising anti-tumor activity was seen with KN046 in subjects with non-small cell lung cancer (NSCLC). Here, we reported the efficacy and safety results of KN046 in second line treatment of advanced NSCLC from Cohort A and B in this study. This is an open-label, multi-center, multiple cohorts, single arm study to evaluate the efficacy, safety and tolerability of KN046 in NSCLC. Subjects with NSCLC who had failed from first line platinum-based doublet chemotherapy without PD-(L)1 immune checkpoint blockade were enrolled. Subjects with EGFR mutation and/or ALK translocation will be excluded. All subjects enrolled will receive KN046 3 mg/kg (Cohort A) and 5 mg/kg (Cohort B) Q2W IV administration, respectively. Primary endpoint was objective response rate (ORR) per RECIST version 1.1 by BICR. Between May 16, 2019 and April 30, 2020, 64 subjects with metastatic NSCLC who failed first line treatment were enrolled. At the data cutoff of August 31, 2021, the median follow-up was 21.6 months (95% CI, 20.3, 23.2). Among all 64 subjects, the ORR was 14.1% (9/64, 95% CI, 6.64, 25.02%), median progression-free survival (mPFS) was 3.7 months (95% CI, 2.9, 5.5) and median overall survival (mOS) was 18.4 months (95% CI, 12.9, 21.9). Furthermore, the ORR was 17.1% (7/41, 95% CI, 7.15, 32.06%), mPFS was 3.7 months (95% CI, 2.76, 5.45) and mOS was 19.8 months (95% CI, 13.04, 23.36) in non-squamous NSCLC (n=41). And in squamous NSCLC (n=20), the ORR was 10.0% (2/20, 95% CI, 1.23, 31.70%), mPFS was 7.4 months (95% CI, 1.81, 14.39) and mOS was 12.9months (95% CI, 8.97, -). 27(42.2%) out of the 64 subjects had experienced treatment-related adverse event (TRAE) at grade 3 or higher levels. The most common TRAEs of grade 3 or higher were infusion reaction (7/64 [10.9%]), hepatic dysfunction (3/64 [4.7%]), pneumonia (2/64 [3.1%]), etc. The bispecific antibody, KN046 was well tolerated and effective as second line treatment of advanced NSCLC. KN046 showed promising OS benefit in both squamous and non-squamous NSCLC.