Phase Ib/II study on the safety, tolerability, and preliminary efficacy of pegylated irinotecan (JK1201I) as second-line monotherapy for patients with small-cell lung cancer

Cancer Med. 2024 Sep;13(17):e70059. doi: 10.1002/cam4.70059.

Abstract

Purpose: To evaluate the safety, tolerability, and preliminary efficacy of multiple doses of pegylated irinotecan (JK1201I) as a second-line monotherapy for treating small-cell lung cancer (SCLC) patients.

Methods: According to the "3 + 3" dose-escalation principle, patients received intravenous JK1201I at 180 or 220 mg/m2 once every 3 weeks for four cycles. Progression-free survival (PFS), overall survival (OS), median progression-free survival (mPFS), and median overall survival (mOS) were evaluated. The Kaplan-Meier method was used to analyze PFS and overall OS. Brookmeyer and Crowley's method was used for mPFS and mOS.

Results: This study included 29 patients with stage III-IV SCLC (stage IIIa, n = 1; stage IIIb, n = 1; and stage IV, n = 27). Of these, 26 patients were enrolled in the 180 mg/m2 dose group, and 3 patients were enrolled in the 220 mg/m2 dose group. No dose-limiting toxicity (DLT) was noted during the first 28 days of treatment. Grade 3 or higher adverse events were recorded in the 180 mg/m2 group, including diarrhea (11.5%, 3/26), neutropenia (7.7%, 2/26), and leukopenia (7.7%, 2/26). In the 220 mg/m2 group, one patient (33.3%, 1/3) experienced neutropenia or leukopenia. In the 180 mg/m2 group, 38.5% (10/26) of patients achieved an objective response rate (ORR), with a disease control rate (DCR) of 73.1% (19/26). The mPFS and mOS were 3.4 and 12.1 months, respectively. In the 220 mg/m2 group, one patient had stable disease, and one had progressive disease (PD). The ORR, DCR, mPFS, and mOS were 0% (0/3) and 33.3% (1/3), 2.7 months and 2.7 months, respectively.

Conclusion: JK1201I exhibits promising efficacy and relatively low toxicities as a second-line monotherapy for SCLC, warranting further large-scale clinical studies to evaluate its efficacy in greater detail.

Keywords: overall survival; safety; second‐line monotherapy; small‐cell lung cancer.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Female
  • Humans
  • Irinotecan* / administration & dosage
  • Irinotecan* / adverse effects
  • Irinotecan* / therapeutic use
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / mortality
  • Lung Neoplasms* / pathology
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Polyethylene Glycols* / administration & dosage
  • Polyethylene Glycols* / adverse effects
  • Polyethylene Glycols* / therapeutic use
  • Progression-Free Survival
  • Small Cell Lung Carcinoma* / drug therapy
  • Small Cell Lung Carcinoma* / mortality
  • Small Cell Lung Carcinoma* / pathology
  • Treatment Outcome

Substances

  • Irinotecan
  • Polyethylene Glycols