RecruitingPhase 1NCT06968572

Phase I Study of HSK41959 in Solid Tumors With MTAP Deletion

A Phase I, Open-label, Dose-escalation and Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetic and Pharmacodynamic of HSK41959 in Patients With MTAP Deletion Locally Advanced or Metastatic Solid Tumors

Sponsor

Haisco Pharmaceutical Group Co., Ltd.

Enrollment

245 participants

Start Date

Apr 11, 2025

Study Type

INTERVENTIONAL

Conditions

Advanced Solid Tumors

Summary

This is a phase I, open-label, dose-escalation and expansion study to evaluate the safety, tolerability, PK and PD of HSK41959 when given orally in patients with MTAP Deletion locally advanced or metastatic Solid Tumors.

Eligibility

Min Age: 18 Years

Inclusion Criteria7

Age ≥ 18 years，Male and female patients, at time of signing informed consent form (ICF).
ECOG performance status 0-1.
Life expectancy ≥ 3 months.
Patients with locally advanced or metastatic solid tumors confirmed by histology or cytology, who have failed standard treatment (disease progression after treatment or intolerable treatment).
Homozygous deletion of the MTAP gene detected in tumor tissue confirmed prior to the administration of HSK41959.
Measurable disease by RECIST 1.1 criteria.
Adequate hematologic, hepatic, and renal function.

Exclusion Criteria13

Prior treatment with a PRMT5 or MAT2A inhibitor therapy.
The presence of unstable, clinically symptomatic central nervous system metastases or leptomeningeal metastases.
Malignant tumor within 2 years, with the exception of cutaneous squamous cell carcinoma, cervical carcinoma in situ, papillary thyroid carcinoma, or other tumors with low malignancy.
Uncontrollable pleural effusion, ascites, or pericardial effusion per protocol.
Treatment with any of the following:
Prior treatment with anti-tumor drug within 4 weeks or approximately 5 × t1/2 prior to the first dose of HSK41959, whichever is shorter; Prior treatment with nitrosourea or mitomycin C within 6 weeks prior to the first dose of HSK41959; Prior treatment with palliative radiotherapy or anti-tumor herbs within 2 weeks prior to the first dose of HSK41959; Prior treatment with radiotherapy, electric field therapy, or other anti-tumor therapies within 4 weeks prior to the first dose of HSK41959.
Any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) grade 1 at the time of starting study treatment, with the exception of alopecia, dermal toxicity, and other toxicity considering no safety risks by investigator.
Any disease which would preclude drug absorption, metabolism or pharmacokinetics, e.g. active peptic ulcer or chronic gastroesophageal reflux disease.
Patients who have clinically significant or uncontrolled cardiac disease, include: QTc interval ≥ 450(male)/470(female) msec; any clinically significant arrhythmia; left ventricular ejection fraction < 50%; myocardial infarction, unstable angina, or class III/IV cardiac failure by the NYHA that occurred within 6 months prior to the first dose of HSK41959.
Any thromboembolic events within 6 months prior to the first dose of HSK41959; any familial or acquired thrombophilia.
Uncontrolled hypertension (systolic pressure≥160mmHg, or diastolic pressure≥100mmHg), diabetes (fasting blood-glucose≥10mmol/L), seizures, chronic obstructive pulmonary disease (COPD), interstitial pneumonia, pulmonary interstitial fibrosis, Parkinson's disease, active bleeding, or systemic active infection.
Any unstable systemic disease, e.g. severe metabolic disease: liver cirrhosis, renal failure, or uremia.
Patient with cognitive dysfunction, or history of mental illness, other uncontrolled comorbidities, alcohol dependence, hormone dependence or drug abuse.