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Potent covalent irreversible inhibitor of KRAS G12C IBI351 in patients with advanced solid tumors: First-in-human

Qing Zhou1, Nong Yang2, Mingfang Zhao3

  • 1Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.

European Journal of Cancer (Oxford, England : 1990)
|October 2, 2024
PubMed
Abstract

Insights

IBI351, a KRAS G12C inhibitor, demonstrated good tolerability and promising antitumor activity in Chinese patients with advanced non-small cell lung cancer. The recommended phase 2 dose of 600 mg twice daily was established.

Area of Science:

  • Oncology
  • Pharmacology
  • Clinical Trials

Background:

  • IBI351 is an irreversible KRAS G12C inhibitor targeting a specific mutation in advanced solid tumors.
  • Existing KRAS G12C inhibitors present unmet needs for Chinese patients, necessitating optimal dosage evaluation.
  • This study focuses on the phase Ia/Ib evaluation of IBI351 monotherapy in a Chinese patient population.

Purpose of the Study:

  • To evaluate the safety, pharmacokinetics, and efficacy of IBI351 in Chinese patients with advanced solid tumors.
  • To determine the recommended phase 2 dose (RP2D) for IBI351 monotherapy.
  • To assess the antitumor activity of IBI351 in patients with KRAS G12C-mutated non-small cell lung cancer (NSCLC).

Main Methods:

  • Phase Ia dose escalation identified safe and potentially effective doses of IBI351 (250-900 mg QD, 450-750 mg BID).
  • Phase Ia dose expansion and Phase Ib cohorts further evaluated the RP2D in advanced NSCLC patients.
  • Safety, pharmacokinetics, and tumor response were assessed by investigators.

Main Results:

  • IBI351 was well tolerated with no dose-limiting toxicities observed across all tested doses.
  • The RP2D was determined to be 600 mg BID, balancing safety, efficacy, and pharmacokinetics.
  • In NSCLC patients, the confirmed objective response rate (ORR) was 45.5% overall and 46.8% at 600 mg BID, with a median progression-free survival of 9.6 months.

Conclusions:

  • IBI351 demonstrated favorable tolerability in Chinese patients with advanced solid tumors.
  • IBI351 exhibited promising antitumor activity, particularly in advanced NSCLC patients with KRAS G12C mutations.
  • The study supports further investigation of IBI351 in this patient population.
Keywords:
IBI351KRAS G12CNon-small cell lung cancerSolid tumor

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