Testing HSK41959 in patients with advanced solid tumors and 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

This study is testing a new oral medication called HSK41959 to see if it is safe and tolerable for patients with advanced solid tumors that have a specific gene deletion.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 245 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Haisco Pharmaceutical Group Co., Ltd. (industry)
• Locations: 3 sites (Guiyang, Guizhou and 2 other locations)
• Trial ID: NCT06968572 on ClinicalTrials.gov

What this trial studies

This phase I study evaluates the safety and tolerability of HSK41959, an oral medication, in patients with locally advanced or metastatic solid tumors that have a homozygous deletion of the MTAP gene. The study consists of two phases: a dose escalation phase (Phase Ia) and a dose expansion phase (Phase Ib). In Phase Ia, a '3+3' design will be used to determine the maximum tolerated dose, while Phase Ib will further assess the drug's effects in larger patient cohorts. The study aims to enroll approximately 30-50 subjects in Phase Ia and 10-50 subjects in each expansion cohort of Phase Ib.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with advanced solid tumors that have failed standard treatments and have a confirmed MTAP gene deletion.

Not a fit: Patients with prior treatment using PRMT5 or MAT2A inhibitors or those with unstable central nervous system metastases may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced solid tumors that have limited treatment alternatives.

How similar studies have performed: While this approach is novel in targeting MTAP deletion, similar studies targeting specific genetic alterations in tumors have shown promise in the past.

Eligibility criteria

Inclusion Criteria:

1. Age ≥ 18 years，Male and female patients, at time of signing informed consent form (ICF).
2. ECOG performance status 0-1.
3. Life expectancy ≥ 3 months.
4. 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).
5. Homozygous deletion of the MTAP gene detected in tumor tissue confirmed prior to the administration of HSK41959.
6. Measurable disease by RECIST 1.1 criteria.
7. Adequate hematologic, hepatic, and renal function.

Exclusion Criteria:

1. Prior treatment with a PRMT5 or MAT2A inhibitor therapy.
2. The presence of unstable, clinically symptomatic central nervous system metastases or leptomeningeal metastases.
3. 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.
4. Uncontrollable pleural effusion, ascites, or pericardial effusion per protocol.

   Treatment with any of the following:
5. 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.
6. 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.
7. Any disease which would preclude drug absorption, metabolism or pharmacokinetics, e.g. active peptic ulcer or chronic gastroesophageal reflux disease.
8. 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.
9. Any thromboembolic events within 6 months prior to the first dose of HSK41959; any familial or acquired thrombophilia.
10. 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.
11. Any unstable systemic disease, e.g. severe metabolic disease: liver cirrhosis, renal failure, or uremia.
12. Patient with cognitive dysfunction, or history of mental illness, other uncontrolled comorbidities, alcohol dependence, hormone dependence or drug abuse.
13. Other protocol-defined Inclusion/Exclusion criteria apply

Where this trial is running

Guiyang, Guizhou and 2 other locations

• The Affiliated Hospital of Guizhou Medical University — Guiyang, Guizhou, China (NOT_YET_RECRUITING)
• Nanjing Drum Tower Hospital — Nanjing, Jiangsu, China (RECRUITING)
• Shanghai East Hospital — Shanghai, Shanghai Municipality, China (RECRUITING)

Conditions: Advanced Solid Tumors