A phase Ib/II study of cadonilimab (PD-1/CTLA-4 bispecific antibody) plus anlotinib as first-line treatment in patients with advanced non-small cell lung cancer

Br J Cancer. 2024 Feb;130(3):450-456. doi: 10.1038/s41416-023-02519-0. Epub 2023 Dec 18.

Abstract

Background: Cadonilimab is a bispecific antibody that simultaneously targets programmed cell death receptor-1 and cytotoxic T lymphocyte-associated antigen-4. This study aimed to assess the safety and efficacy of cadonilimab plus anlotinib for the first-line treatment of advanced non-small cell lung cancer (NSCLC) without sensitizing EGFR/ALK/ROS1 mutations.

Methods: Patients received cadonilimab 15 mg/kg and 10 mg/kg every three weeks (Q3W) plus anlotinib at doses of 10 or 12 mg once daily for two weeks on a one-week-off schedule. The primary endpoints included safety and objective response rate (ORR).

Results: Sixty-nine treatment-naïve patients received cadonilimab 15 mg/kg Q3W combination (n = 49) and 10 mg/kg Q3W combination (n = 20). Treatment-related adverse events (TRAEs) were reported in 48 (98.0%) and 19 (95.0%) patients, with grade ≥3 TRAEs occurring in 29 (59.2%) and five (25.0%) patients, respectively. TRAEs leading to cadonilimab discontinuation occurred in eight (16.3%) and one (5.0%) patients in the cadonilimab 15 mg/kg Q3W and 10 mg/kg Q3W dosing groups. The confirmed ORRs were 51.0% (25/49) and 60.0% (12/20) accordingly.

Conclusions: Cadonilimab 10 mg/kg Q3W plus anlotinib showed manageable safety and promising efficacy as a first-line chemo-free treatment for advanced NSCLC.

Gov identifier: NCT04646330.

Publication types

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

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • CTLA-4 Antigen
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Humans
  • Indoles*
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / genetics
  • Programmed Cell Death 1 Receptor / therapeutic use
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins
  • Quinolines*

Substances

  • anlotinib
  • CTLA-4 Antigen
  • Indoles
  • Programmed Cell Death 1 Receptor
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins
  • Quinolines

Associated data

  • ClinicalTrials.gov/NCT04646330