Hetrombopag in patients with chemotherapy-induced thrombocytopenia: A global phase 3, randomized, double-blind study.

Abstract

TPS12162 Background: Chemotherapy-induced thrombocytopenia (CIT) is a common complication of cancer therapy, frequently resulting in chemotherapy modifications including dose reduction, delay, or discontinuation. Thrombopoietin receptor agonists (TPO-RAs) represent a therapeutic approach aimed at stimulating platelet production. Given there are limited society-sanctioned therapies, contemporary management converges on platelet transfusions which are limited in global supply or parenteral TPO-RAs which are inconvenient. Hetrombopag is an oral TPO-RA that supports platelet counts and facilitates chemotherapy delivery, as evidenced by a prior positive randomized, controlled study conducted in China (ASH 2025; NCT05864014). This global phase 3 study is designed to evaluate the efficacy and safety of hetrombopag in patients with CIT (NCT07286032). Methods: This study comprises two sequential parts: an open-label, single-arm, pharmacokinetic (PK) lead-in part (A) and a randomized, double-blind, placebo-controlled part (B). In Part A, approximately 8-12 non-Asian patients with CIT are planned to be enrolled to receive oral hetrombopag (15.0 mg once daily, fasted) to evaluate the PK profile. Part B will enroll approximately 138 patients with solid tumors who have experienced a ≥ 7-day chemotherapy delay due to CIT during platinum- and/or gemcitabine-based therapy at schedule of 21-day cycles. Eligible patients will be randomized in 2:1 to hetrombopag or placebo, stratified by baseline platelet count (PC; ≥50 ×10⁹/L vs. <50×10⁹/L) and enrollment region (Asia vs. rest of world). Hetrombopag will be initiated at 7.5-or 15 mg (dose will be finalized after considering results from Part A) once daily, with dose adjustments based on platelet counts. All enrolled patients are expected, per investigator assessment, to be eligible to complete two consecutive cycles of on-study chemotherapy (C1 and C2) of the same regimen administered prior to enrollment. Initiation of each chemotherapy cycle requires a PC ≥100×10 9 /L; if the PC remains <100×10⁹/L on day 14 after hetrombopag initiation (for C1) or at the C1D21 visit (for C2), the investigator may exercise discretion to proceed with the respective chemotherapy cycle and/or implement rescue therapy (platelet transfusions and/or approved TPO-RAs). The primary endpoint of Part A is the PK profile of hetrombopag in non-Asian patients with CIT; the primary endpoint of Part B is the proportion of treatment responders, defined as patients who achieve a PC ≥100×10⁹/L within 14 days of hetrombopag initiation and who complete two consecutive chemotherapy cycles without either thrombocytopenia-related modifications, or thrombocytopenia rescue therapy through C2D21. Clinical trial information: NCT07286032 .