Phase III Randomized Study of Hetrombopag Olamine Efficacy and Safety in Patients with Chemotherapy-Induced Thrombocytopenia

The primary objectives of this study are to evaluate the pharmacokinetic characteristics of hetrombopag in non-Asian participants with chemotherapy-induced thrombocytopenia and to assess the efficacy of treatment in this population. 5, 6

The secondary objectives include:

• Evaluation of the efficacy and safety of hetrombopag treatment in non-Asian participants with chemotherapy-induced thrombocytopenia. 5, 4
• Assessment of the safety of hetrombopag treatment in participants with chemotherapy-induced thrombocytopenia. 4

The study involves 92 participants diagnosed with chemotherapy-induced thrombocytopenia. The population consists of male and female patients aged 18 years or older. Eligible subjects must have a histologically or cytologically confirmed solid tumor and be receiving chemotherapy regimens containing platinum or gemcitabine on 21-day cycles. Participants are required to have a platelet count of less than 75×10⁹/L at enrollment. For the efficacy evaluation, subjects must experience a treatment delay of 7 days or more per cycle due to low platelet levels. Inclusion requires an Eastern Cooperative Oncology Group performance status of 0-2, adequate organ and hematologic function, and non-Asian race or ethnicity for the pharmacokinetic assessment.

This Phase III, randomized, double-blind, controlled study is designed to evaluate the efficacy and safety of hetrombopag olamine compared to a placebo in patients with chemotherapy-induced thrombocytopenia. The research is divided into two parts. Part A focuses on evaluating the pharmacokinetic characteristics of the study drug in non-Asian participants. Part B evaluates the therapeutic efficacy of the treatment. Participants undergo a screening visit to confirm eligibility based on criteria such as histologically confirmed solid tumors, specific chemotherapy regimens, and a platelet count below 75×10⁹/L. Following enrollment, the study monitors clinical outcomes, including the proportion of treatment responders who achieve a platelet count of ≥100×10⁹/L within 14 days of initiating treatment without the use of rescue therapy. Secondary endpoints include the assessment of adverse events, safety laboratory parameters, and the duration of platelet response. The trial encompasses two consecutive chemotherapy cycles to monitor for treatment-induced modifications. The specific duration of participant involvement is not explicitly stated, though the overall study period is estimated to conclude by January 2028.

The experimental medication is hetrombopag olamine, which contains the active substance rafutrombopag ethanolamine. This substance is administered in the form of a film coated tablet via the oral route.

A placebo is utilized in this study, consisting of tablets without an active pharmaceutical ingredient designed to closely resemble the experimental medication.

The efficacy of hetrombopag olamine in patients with chemotherapy-induced thrombocytopenia is evaluated through several endpoints. The primary efficacy endpoint is the proportion of treatment responders meeting three specific criteria: a platelet count of ≥100×10⁹/L within 14 days after initiating investigational product treatment, the completion of two consecutive on-study chemotherapy cycles without thrombocytopenia-induced modification of any myelosuppressive agent, and the absence of rescue therapy for thrombocytopenia from the initiation of treatment until Day 21 of the second chemotherapy cycle.

Secondary efficacy assessments include:

• The proportion of participants completing two consecutive on-study chemotherapy cycles without thrombocytopenia-induced modification of any myelosuppressive agent.
• The proportion of participants achieving a platelet count of ≥100×10⁹/L without rescue therapy within 14 days after initiating treatment.
• The proportion of participants experiencing at least one incidence of rescue therapy.
• The time to the first rescue therapy-free platelet response of ≥100×10⁹/L.
• The cumulative duration of the platelet response of ≥100×10⁹/L without rescue therapy.
• The platelet count nadir from the first day of the first chemotherapy cycle until Day 21 of the second cycle.
• The cumulative duration of severe thrombocytopenia, defined as consecutive days with a platelet count of ≤50×10⁹/L.
• The proportion of participants completing two consecutive chemotherapy cycles without treatment regimen modification.
• The proportion of participants experiencing all-cause events leading to regimen modifications, such as dose reduction, delay, omission, or discontinuation.
• The proportion of participants free from serious bleeding events, as defined by the World Health Organization bleeding scale of Grade ≥2, from treatment initiation until Day 21 of the second chemotherapy cycle.
• The proportion of participants with neutropenia during the treatment period from initiation until Day 21 of the second chemotherapy cycle.