A Clinical Study on the Efficacy and Safety of Hetrombopag in the Treatment of Thrombocytopenia Induced by Gynecological Tumor Therapy

A Clinical Study on the Efficacy and Safety of Hetrombopag in the Treatment of Thrombocytopenia Induced by Gynecological Tumor Therapy

The study consists of five sequential periods:

• Screening (≤ 4 weeks)

• Correction phase

• Maintenance phase (first treatment cycle, Cycle 1)

• Observation phase (second treatment cycle, Cycle 2)

• Follow-up Eligible subjects are gynaecological-cancer patients who developed ≥ grade-2 cancer-therapy-induced thrombocytopenia (CTIT) after anti-tumour therapy, i.e. platelet count < 75 × 10⁹/L.

  • Stage 1** - Prospective, multicentre, randomised clinical study (to inform the confirmatory stage 2) **Cohort 1 (n = 30)** Correction: hetrombopag 7.5 mg p.o. daily until PLT ≥ 100 × 10⁹/L. Within 24 h after completion of Cycle 1 anti-cancer therapy (end of chemotherapy if combined; otherwise end of investigational product on that day) restart hetrombopag 7.5 mg p.o. daily and continue until the last day of Cycle 1 (C1D21).

**Cohort 2 (n = 30)** Correction: hetrombopag 7.5 mg p.o. daily until PLT ≥ 100 × 10⁹/L. During Cycle 1, monitor PLT closely; if PLT falls < 75 × 10⁹/L, initiate hetrombopag 7.5 mg p.o. daily and continue until C1D21.

**Stage 2** - Prospective, multicentre, randomised, controlled clinical study *(preliminary design; sample size and details will be refined after stage-1 results)* **Experimental arm (n = 92)** Correction: hetrombopag 7.5 mg p.o. daily until PLT ≥ 100 × 10⁹/L. Restart within 24 h after completion of Cycle 1 therapy and continue daily until C1D21.

**Control arm (n = 92)** Correction: hetrombopag 7.5 mg p.o. daily until PLT ≥ 100 × 10⁹/L. During Cycle 1, monitor PLT; if PLT < 75 × 10⁹/L, initiate hetrombopag 7.5 mg p.o. daily until C1D21.

**Correction-phase rules** Discontinue hetrombopag once PLT ≥ 100 × 10⁹/L. If after ≥ 14 days of hetrombopag correction PLT remains < 100 × 10⁹/L and the next treatment cycle has not started, the investigator may resume hetrombopag or institute alternative platelet-enhancing rescue therapy at their discretion.

Key eligibility criteria:

1. Female, aged 18-75 years (inclusive).
2. Histopathologically or cytologically confirmed ovarian, cervical, endometrial, or other gynecologic malignancy.
3. Thrombocytopenia (platelet count < 75 × 10⁹/L) attributable to anti-cancer therapy, with ≥ 2 further treatment cycles planned.
4. ECOG performance status 0-1.
5. Estimated life expectancy ≥ 12 weeks.
6. Women of child-bearing potential must have a negative serum pregnancy test within 7 days before first dose, not be breastfeeding, and agree to use effective contraception from study entry through 7 days after the last dose.
7. Able to provide written informed consent and comply with study procedures.

Exclusion criteria:

1. Pregnant or lactating women.

2. Unable to understand the study nature or give informed consent.

3. History of any arterial or venous thrombosis (stroke, TIA, MI, DVT, PE) or clinical/laboratory evidence of thrombophilia.

4. Cardiac disease within 3 months before screening: NYHA class III/IV heart failure, symptomatic arrhythmia requiring therapy, MI, arrhythmias increasing thrombotic risk (e.g., atrial fibrillation), or QTc prolongation.

5. Thrombocytopenia not related to anti-cancer therapy, active severe bleeding, or refractory persistent thrombocytopenia.

6. Significant hepatic impairment:

   • No liver metastases: ALT/AST > 3 × ULN or TBL > 3 × ULN
   • Liver metastases: ALT/AST ≥ 5 × ULN or TBL ≥ 5 × ULN

7. Known or suspected hypersensitivity/intolerance to TPO-receptor agonists or hetrombopag excipients.

8. Concomitant use of agents that may affect platelet count (e.g., Chinese herbal medicines, other thrombopoietic agents, antiplatelet drugs).

9. Receipt within 1 month before screening of TPO-RAs (eltrombopag, romiplostim, etc.), rhTPO, or rhIL-11.

10. Platelet transfusion within 3 days before randomisation/first dose.

11. Any condition that, in the investigator's opinion, renders the patient unsuitable for the study.