1330P - Updated results of the efficacy and safety of KN046 (a bispecific anti-PD-L1/CTLA-4) in patients with metastatic non-small cell lung cancer (NSCLC) who failed prior EGFR-TKI(s)

Background

KN046 is a novel bispecific antibody that inhibits both PD-L1/PD1 and CTLA-4/CD80/CD86 pathways. We previously showed the efficacy and safety of KN046 plus chemotherapy in advanced NSCLC with EGFR sensitivity mutation who progressed after tyrosine kinase inhibitor(s) (TKIs) from Cohort D of the phase II trial. Here, we report the updated survival and safety data.

Methods

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 EGFR sensitizing mutation (Ex19del or L858R), who had failed from prior EGFR-TKI(s) without platinum-based chemotherapy were enrolled. All subjects enrolled received KN046 5 mg/kg Q3W combined with chemotherapy (Pemetrexed, 500 mg/m², Q3W and carboplatin AUC5, Q3W), until disease progression, intolerable toxicity and other discontinuation criteria. Primary endpoint was objective confirmed response rate (ORR) per RECIST version 1.1.

Results

From Jan 7, 2020 to Dec 17, 2021, 26 patients with metastatic NSCLC were enrolled. The median follow-up was 17.8 months (95% CI, 13.0, 19.5) at the data cutoff of Jul 30, 2022. The ORR was 26.9% (7/26, 95% CI, 11.6，47.8%), DCR was 84.6% (22/26, 95% CI, 65.1, 95.6%) with 7 PR and 15 SD. The CBR was 38.5% (10/26, 95% CI, 20.2, 59.4%). The mPFS was 5.5 months (95% CI, 4.2, 6.8) and the mOS was 20.2 months (95% CI, 11.5, -). Grade 3 or higher TRAEs occurred in 15 (57.7%) of the 26 patients due to chemotherapy or KN046. The most common grade 3 or higher TRAEs were infusion reaction (5/26 [19.2%]), decreased platelet count (4/26 [15.4%]) and anemia (3/26 [11.5%]).

Conclusions

KN046 demonstrated encouraging OS benefit and a favorable safety profile in advanced NSCLC with EGFR sensitivity mutation who progressed after EGFR-TKI(s). Further study is warranted to confirm the clinical results.

Clinical trial identification

NCT03838848.

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.

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.