Efficacy and safety of KN046, a novel bispecific antibody against PD-L1 and CTLA-4, in patients with non-small cell lung cancer who failed platinum-based chemotherapy: a phase II study

Eur J Cancer. 2023 Sep:190:112936. doi: 10.1016/j.ejca.2023.05.024. Epub 2023 Jun 5.

Abstract

Background: This study aimed to evaluate the efficacy and safety of KN046, a novel recombinant humanised antibody targeting PD-L1 and CTLA-4 in advanced non-small cell lung cancer (NSCLC) patients after failure or intolerance to platinum-based chemotherapy.

Methods: In this multi-centre, open-label phase II clinical trial, patients were enroled after failure or intolerance to platinum-based chemotherapy. KN046 at 3 mg/kg or 5 mg/kg was administered intravenously every 2weeks. The primary end-point was objective response rate (ORR) evaluated by a blinded independent review committee (BIRC).

Results: A total of 30 and 34 patients were included in the 3 mg/kg (cohort A) and 5 mg/kg (cohort B) cohorts. On 31st August 2021, the median follow-up duration was 24.08 months (interquartile [IQR], 22.28, 24.84) and 19.35months (IQR, 17.25, 20.90) in the 3 mg/kg and 5 mg/kg cohorts, respectively. BIRC-assessed ORRs were 13.3% and 14.7% in the 3 mg/kg and 5 mg/kg cohorts, respectively. Median progression-free survival was 3.68 (95% confidence interval [CI] 3.22-7.29) and 3.68 (95%CI 1.81-7.39) months, while overall survival was 19.70 (95.5%CI 15.44-not estimated [NE]) and 13.04 (95.5%CI 9.86-NE) months, respectively. The most common treatment-related adverse events (TRAEs) were anaemia (28.1%), hyperglycaemia (26.7%), and infusion-related reactions (26.7%). The incidence rates of grade ≥ 3 TRAEs and TRAEs leading to treatment discontinuation were 42.2% and 14.1%, respectively.

Conclusions: Both 3 mg/kg and 5 mg/kg KN046 showed promising efficacy and favourable safety profile for advanced NSCLC after failure or intolerance to previous platinum-based chemotherapy.

Trial registration number: NCT03838848.

Keywords: Bispecific antibody; Immune checkpoint inhibitors; KN046; Non-small-cell lung carcinoma; Platinum.

Publication types

  • Multicenter Study
  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antineoplastic Agents* / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • B7-H1 Antigen
  • CTLA-4 Antigen
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Humans
  • Lung Neoplasms*
  • Platinum / therapeutic use

Substances

  • Platinum
  • B7-H1 Antigen
  • CTLA-4 Antigen
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents

Associated data

  • ClinicalTrials.gov/NCT03838848