1449P - The preliminary data from a single-arm, open-label, multicenter phase II clinical trial: KN046 combined with axitinib as first-line (1L) treatment for NSCLC

Background

KN046 is a novel bispecific domain antibody, which blocks both PD-L1 and CTLA-4. KN046 combined with platinum-based chemotherapy as 1L treatment for NSCLC had shown promising efficacy and tolerability in the previous clinical trial. (2022 ESMO 1029P). Herein, we present the promising preliminary data of KN046 combination with axitinib as 1L treatment for NSCLC.

Methods

Eligible subjects with recurrent/metastatic NSCLC, treatment-naive and PD-L1 expression ≥1% will be enrolled and receive KN046 5mg/kg IV Q3W and axitinib 5mg orally bid. This study adopts a Simon’s optimal two-stage design. In the 1^st stage, 17 subjects will be enrolled, and the 2^nd stage enrollment will be discontinued if objective response (CR or PR) observed in less than 5 subjects. Otherwise, 37 subjects will be enrolled in the 2^nd stage. The primary endpoint is ORR. The secondary endpoints include DoR, safety, PFS and OS.

Results

As of data cut-off date (Mar 17, 2023), 22 subjects were enrolled, the median age was 64.5y (min:37, max:73), 90.9% were male. ECOG score was 0 (4.5%) and 1 (95.5%). PD-L1 expression was ≥50% in 22.7% of the subjects. 15 subjects completed at least one tumor assessment. In the efficacy analysis set, the ORR was 66.7% (10/15). The median follow-up for DoR was 4.21 m (95% CI,1.22, NE). The 3-m DoR rate was 100% (95% CI, 100.00, 100.00). The median study follow-up was 2.83 m (95% CI,0.72, 5.12). The 6-m PFS rate was 76.6 % (95% CI, 41.16, 92.28), The mPFS and mOS was not reached. The incidence of TEAE was 81.8% (18/22), of which KN046-related TRAE was 63.6% (14/22). Majority was grade 1-2. The incidence of KN046-related CTCAE Grade ≥3 TRAE was 9.1% (2/22). The most frequent TRAE was AST increased 9.1% (2/22) and ALT increased 4.5% (1/22). The incidence of irAE was 13.6% (3/22), No CTCAE Grade ≥3 irAE was found. There was no KN046-related death.

Conclusions

KN046 combined with axitinib is well tolerated and has shown very promising efficacy and safety signal in 1L treatment for advanced NSCLC. The 2^nd stage of enrollment is ongoing and a phase 3 RCT is planned to further confirm the clinical benefit of KN046 and axitinb combo as a viable chemo free option for the 1st line NSCLC patient.

Clinical trial identification

NCT05420220.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Jiangsu Alphamab Biopharmaceuticals Co.,Ltd., Suzhou, China.

Disclosure

All authors have declared no conflicts of interest.