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Endobronchial Ultrasound-guided Intratumoral Injection of Cisplatin for the Treatment of Isolated Mediastinal Recurrence of Lung Cancer
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A Phase I/II Study of Valemetostat (DS-3201b), an EZH1/2 Inhibitor, in Combination with Irinotecan in Patients with

Noura J Choudhury1,2, W Victoria Lai1, Alex Makhnin1

  • 1Thoracic Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|June 28, 2024
PubMed
Abstract

Insights

This trial found that combining valemetostat with irinotecan showed efficacy for recurrent small-cell lung cancer (SCLC) but was not well-tolerated. Further research is needed for valemetostat in SCLC treatment.

Area of Science:

  • Oncology
  • Pharmacology

Background:

  • Recurrent small-cell lung cancer (SCLC) presents limited treatment options.
  • The EZH2-SLFN11 pathway is implicated in chemoresistance and is a potential therapeutic target.

Purpose of the Study:

  • To evaluate the safety, tolerability, and efficacy of valemetostat, an EZH1/2 inhibitor, in combination with irinotecan for recurrent SCLC.
  • To determine the recommended phase II dose (RP2D) and assess overall response rate (ORR), duration of response (DoR), progression-free survival (PFS), and overall survival (OS).

Main Methods:

  • A phase I/II clinical trial involving patients with recurrent SCLC.
  • Phase I focused on dose-escalation to find the RP2D and assess safety and tolerability.
  • Phase II evaluated the ORR and other efficacy endpoints, with correlative analyses of tumor biopsies and pharmacokinetics.

Main Results:

  • Valemetostat 100 mg orally daily was selected as the RP2D.
  • The ORR was 21% (95% CI, 6%-46%). Median DoR, PFS, and OS were 4.6, 2.2, and 6.6 months, respectively.
  • Treatment-related adverse events included diarrhea, fatigue, nausea, and rash; three patients discontinued due to toxicity.

Conclusions:

  • Combination therapy with valemetostat and irinotecan demonstrated efficacy in recurrent SCLC but was not well-tolerated.
  • Valemetostat warrants further investigation in SCLC, particularly when combined with agents having non-overlapping toxicities.

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