1459P - Preliminary efficacy and safety of KN046 (a bispecific anti-PD-L1/CTLA-4) in patients with metastatic non-small cell lung cancer who previously treated with immune checkpoint inhibitor(s)

Background

KN046 is a novel bispecific antibody that inhibits both PD-L1/PD1 and CTLA-4/CD80/CD86 pathways. Previous phase I (KN046-CHN-001, NCT03733951) and phase II (KN046-201, NCT03838848) trials showed promising anti-tumor effects of KN046 in non-small cell lung cancer (NSCLC) patients who had failed prior immune checkpoint inhibitor(s) (ICIs) therapy. We present the efficacy and safety outcomes of KN046 in this population from KN046-CHN-001 and Cohort C of KN046-201.

Methods

KN046-CHN-001 and KN046-201 assessed the efficacy, safety and tolerability of KN046 in NSCLC. Eligible patients had NSCLC that progressed after ICI(s) and platinum-based chemotherapy. Patients with EGFR mutation and/or ALK translocation were excluded. All patients received KN046 (26 at 5 mg/kg Q2W, 2 at 5 mg/kg Q3W, 2 at 300mg Q3W and 1 at 3 mg/kg Q2W) by IV infusion. The primary endpoints were confirmed ORR by RECIST version 1.1 (KN046-201) and safety (KN046-CHN-001).

Results

Between April 19, 2019 and July 13, 2020, 31 pts with metastatic NSCLC who failed ICI(s) and platinum-based chemotherapy were enrolled. At the data cutoff of July 30, 2022 for KN046-201 and August 31, 2021 for KN046-CHN-001, the median follow-up was 25.0months (95% CI, 24.4, NE). Among all 31 pts, the ORR was 3.2% (1/31, 95% CI, 0.1, 16.7%), disease control rate (DCR) was 38.7% (12/31, 95% CI, 21.8, 57.8%), clinical benefit rate (CBR) was16.1% (5/31, 95% CI, 5.5, 33.7%). Median progression-free survival (mPFS) was 2.8 months (95% CI, 1.8, 3.7) and median overall survival (mOS) was 13.3 months (95% CI, 6.5, 17.5). 7(22.6%) out of the 31 subjects had experienced treatment-related adverse event (TRAE) at grade 3 or higher levels. Commonly reported TRAEs of grade 3 or higher were anemia (9.7%), febrile neutropenia (3.2%), fatigue (3.2%).

Conclusions

KN046 was well tolerated and demonstrated encouraging OS benefit in NSCLC patients who had failed prior ICI(s) therapy. Further study is warranted to confirm the clinical results.

Clinical trial identification

KN046-201, NCT 03838848; KN046-CHN-001, NCT03733951.

Editorial acknowledgement

Alphamab Biopharma, Inc would like to thank the patients, investigators and site staff for their participation in this study.

Legal entity responsible for the study

Jiangsu Alphamab Biopharmaceuticals, Co., Ltd.

Funding

Jiangsu Alphamab Biopharmaceuticals, Co., Ltd.

Disclosure

C. Zhou: Financial Interests, Personal, Invited Speaker, Honoraria: Eli Lily, Roche, Sanofi, Qilu Pharma, Hengrui, Innovent Biologics, C-Stone, Luye Pharma, TopAlliance Biosciences Inc; Financial Interests, Personal, Invited Speaker, BI: BI; Financial Interests, Personal, Invited Speaker, MSD: MSD; Financial Interests, Personal, Advisory Board, Advisor: Amoy Diagnostics. All other authors have declared no conflicts of interest.