Abstract 1029P
Background
KN046 is a novel bispecific domain antibody, which blocks both PD-L1 and CTLA-4. Primary analysis of this phase II trial (data as of January 19, 2021) showed promising efficacy and well tolerated safety in advanced NSCLC pts. Herein, we present an updated analysis.
Methods
Eligible pts with confirmed advanced NSCLC were enrolled in this study. Non-Sq NSCLC pts were enrolled in cohort 1, receiving KN046 5 mg/kg combined with Carboplatin AUC 5 and Pemetrexed 500 mg/m2 for 4 cycles, with maintenance KN046 combined with Pemetrexed. Sq-NSCLC pts were enrolled in cohort 2, receiving KN046 combined with Carboplatin AUC 5 and Paclitaxel 175 mg/m2 for 4 cycles, with maintenance KN046 monotherapy. The primary endpoints were ORR and duration of response (DoR). The secondary endpoints included safety, PFS and OS.
Results
At data cut-off date (Mar 15, 2022), the median follow-up was 23.1 m (Interquartile Range [IQR] 20.7,26.9). 87 pts were enrolled (cohort 1 n = 51, cohort 2 n = 36), median age 61 years, with male 75.9%, ECOG 0 (17.2%) and 1 (82.8%). Confirmed ORR was 46% (95% CI: 35.2, 57.0) for the whole population. Confirmed ORR of cohort 1 and cohort 2 were 43.1% (95% CI: 29.3, 57.8) and 50% (95% CI: 32.9, 67.1), with a DoR 9.7m (95% CI:4.01, 20.73) and 7.3m (95% CI:3.52, -), respectively. Median PFS was 5.8 m (95% CI: 5.26, 7.10) and median OS was 26.6 m (95% CI: 16.92, -). Median PFS of cohort 1 and cohort 2 were 5.8 m (95% CI: 4.80, 7.16) and 5.7 m (95% CI: 4.17, 8.71), and median OS were 27.2 m (95% CI: 15.18, -) and 26.6 m (95% CI: 12.19, -) respectively. Incidence rate ≥20% treatment emergent adverse event (≥Grade 3)were neutropenia (n=31, 35.6%) and leucopenia (n=22, 25.3%) Incidence rate≥20% irAE were pruritus (n=25, 28.7 %), aspartate aminotransferase increased (n=21, 24.1%) and rash (n=18, 20.7%).
Conclusions
KN046 combined with platinum doublet chemotherapy is well tolerated and has shown promising clinical benefit as 1L treatment for NSCLC. Median OS in both cohorts were over 2 years, which is very encouraging. Robust efficacy and safety data will be further confirmed in an ongoing large-scale phase III clinical trial.
Clinical trial identification
NCT04054531.
Editorial acknowledgement
Writing support was provided by Jiangsu Alphamab Biopharmaceuticals, Co., Ltd., funded by Jiangsu Alphamab Biopharmaceuticals, Co., Ltd.
Legal entity responsible for the study
Jiangsu Alphamab Biopharmaceuticals Co., Ltd., Suzhou, China.
Funding
Jiangsu Alphamab Biopharmaceuticals Co., Ltd., Suzhou, China.
Disclosure
All authors have declared no conflicts of interest.