Phase I Study of HSK41959 in Solid Tumors With MTAP Deletion

NCT06968572 | Recruiting Phase 1

• 1 other identifier: HSK41959-101
• Study Type: interventional
• Target: 245
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

Advanced Solid Tumors

Outcome Measures

Primary Outcomes (4)

• DLTs

  Incidence of dose-limiting toxicities (DLTs) at Cycle 0 and Cycle1

  24 days

• MTD

  MTD determination: dose limiting toxicity (DLT) rate

  24 days

• AEs

  Rate and severity of adverse events of HSK41959 as monotherapy

  Up to approximately 3 years

• RP2D

  RP2D determination: DLT, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary safety and anticancer activity data

  Up to approximately 1 year

Secondary Outcomes (9)

• Overall response rate (ORR)

  Up to approximately 3 years

• Disease control rate (DCR)

  Up to approximately 3 years

• Duration of response (DOR)

  Up to approximately 3 years

• Progression free survival (PFS)

  Up to approximately 3 years

• Overall survival (OS)

  Up to approximately 3 years

Other Outcomes (1)

• Changes in SDMA concentration

  Up to approximately 6 months

Study Arms (3)

Phase Ia (Part A): HSK41959 as monotherapy

EXPERIMENTAL

Phase 1a (Part A): dose escalation of HSK41959 as monotherapy at various dose levels

Drug: HSK41959

Phase Ia (Part B): HSK41959 as monotherapy

EXPERIMENTAL

Phase 1a (Part B): dose extention of HSK41959 as monotherapy at certain dose levels

Drug: HSK41959

Phase Ib: HSK41959 as monotherapy

EXPERIMENTAL

Phase 1b: dose expansion for HSK41959 as monotherapy at a dose determined during Phase 1a (Part B) in patients with MTAP Deletion locally advanced or metastatic solid tumors

Drug: HSK41959

Interventions

HSK41959 DRUG

Oral administration, QD

Phase Ia (Part A): HSK41959 as monotherapy; Phase Ia (Part B): HSK41959 as monotherapy; Phase Ib: HSK41959 as monotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Haisco Pharmaceutical Group Co., Ltd.: lead

Study Sites (3)

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, 200120, China

RECRUITING

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 9, 2025
• First Posted: May 13, 2025
• Study Start: April 11, 2025
• Primary Completion: March 26, 2026
• Study Completion (Estimated): May 8, 2028
• Last Updated: May 13, 2025

Record last verified: 2025-05

Locations

CN (3)