133P - The efficacy and safety of KN046 combined with axitinib for previously untreated and checkpoint inhibitor treated advanced non-small cell lung cancer: A single-arm, open-label, multicenter phase II clinical trial

Background

KN046 is a novel bispecific antibody that blocks both PD-1/PD-L1 and CTLA-4/CD80/CD86 pathways. Axitinib is a selective inhibitor of VEGFR, in combination with checkpoint inhibitors (CPIs) may sensitize tumors to CPIs. Preliminary data of KN046 combined with axitinib as 1L treatment for PD-L1 + advanced NSCLC have been reported (2023 ESMO 1449P).

Methods

Stage IIIB-IV non-small cell lung cancer (NSCLC) patients (pts) without driver mutations, will be enrolled in a phase 2 study in China (NCT05420220), and receive KN046 (5 mg/kg, IV, Q3W) and axitinib (5 mg, PO, BID). The primary endpoint is ORR, the secondary endpoints include safety, DCR, DoR, PFS and OS. The study includes Cohort A (previously untreated and PD-L1 TPS ≥1%), Cohort B (progressed on CPIs) and Cohort C (previously untreated and PD-L1 TPS ≥50%). Here, we report the results of Cohort A and B.

Results

As of Sep 1, 2024, 53 and 32 pts were treated in Cohort A and B, the median follow-up time was 14.6m and 11.2m, respectively. The median age was 62.0 y (min: 31, max: 73), 81.2% pts were male, 95.3% pts had ECOG PS=1, 85.9% pts had stage IV disease, 49.4% pts had squamous disease. By central lab testing, 67.1% and 24.7% pts had PD-L1 TPS ≥ 1% and ≥ 50%, respectively. In safety analysis set (SS) of Cohort A, the ORR in PD-L1 TPS ≥1% and ≥50% pts was 54.5% (95% CI 38.8, 69.6) and 66.7% (95% CI 38.4, 88.2). The mDoR in PD-L1 TPS ≥ 1% and ≥ 50% pts were 13.2 m (95% CI 6.6, NE) and NE (95% CI 4.1, NE). The mPFS in PD-L1 TPS ≥ 1% and ≥ 50% were 8.3 m (95% CI 6.8, 13.9) and 12.4 m (95% CI 4.9, NE). The mOS was not reached yet. In SS of Cohort B, the ORR was 9.4% (95% CI 2.0, 25.0) and the DCR was 81.3% (95% CI 63.6, 92.8). The mDoR was 7.4m (95% CI NE, NE). The mPFS was 5.6 m (95% CI 2.8, 7.0). The mOS was 11.9m (9.9, NE). 58.8% pts had grade ≥ 3 treatment-related adverse events (TRAEs). The most common grade ≥ 3 TRAEs were ALT increased, AST increased and hypertension (10.6%), PPE and diarrhoea (7.1%). 24.7% pts had immune-related adverse events, 10.6% were grade ≥ 3.

Conclusions

KN046-axitinib combination showed encouraging efficacy and tolerability in advanced NSCLC pts. Further validation in a large-scale trial is warranted.

Legal entity responsible for the study

Jiangsu Alphamab Biopharmaceuticals Co., Ltd.

Funding

Jiangsu Alphamab Biopharmaceuticals Co., Ltd.

Disclosure

L. Zhang: Financial Interests, Personal, Invited Speaker: Akesobio, Sichuan Biokin Pharmaceutical; Financial Interests, Institutional, Trial Chair: Akesobio, AZ, China Shiyao Pharma, Henrui Pharm, Kelun Pharm, Novartis, Pierre-Fabre, Pfizer, Qilu Pharm, Sichuan Biokin Pharmaceutical; Financial Interests, Institutional, Research Grant: AZ, Roche. All other authors have declared no conflicts of interest.