HSK41959 With Standard Therapy in Solid Tumors With MTAP Deletion

Phase Ib Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of HSK41959 Tablets in Combination With Standard Therapy in Patients With MTAP Deletion Locally Advanced or Metastatic Solid Tumors

This is a Phase Ib, open-label, multicenter study of HSK41959 tablets in combination with standard therapy in patients with MTAP-deficient advanced solid tumors. The study consists of dose-escalation and dose-expansion parts and is intended to evaluate the safety, tolerability, dose-limiting toxicity, maximum tolerated dose, pharmacokinetics, pharmacodynamics, and preliminary efficacy of HSK41959 tablets when used together with standard therapy.

Study Overview

• Status: Not yet recruiting
• Conditions: Non-Small Cell Lung Cancer; Advanced Solid Tumors; Pancreatic Ductal Adenocarcinoma (mPDAC)
• Intervention / Treatment: Drug: Docetaxel; Drug: HSK41959; Drug: Sintilimab; Drug: Pemetrexed + Cisplatin /Carboplatin; Drug: Paclitaxel + Carboplatin; Drug: Nab-paclitaxel + Carboplatin; Drug: Nab-paclitaxel + Gemcitabine

• Study Type: Interventional
• Enrollment (Estimated): 258
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China
      • Shanghai East Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Adult participants aged 18 years or older.
2. ECOG performance status of 0 to 1.
3. Life expectancy of at least 3 months.
4. Histologically or cytologically confirmed advanced malignant tumor with MTAP deficiency identified by a validated assay.
5. At least one measurable lesion according to RECIST version 1.1.
6. For NSCLC cohorts: advanced or metastatic NSCLC meeting protocol-specified disease characteristics and prior treatment requirements.
7. For PDAC cohorts: advanced or metastatic PDAC meeting protocol-specified disease characteristics and prior treatment requirements.
8. Adequate bone marrow, hepatic, renal, and coagulation function.
9. Willingness to provide tumor tissue and/or undergo protocol-required biomarker testing, if applicable.

Exclusion Criteria:

1. Prior exposure to agents targeting the MAT2A or PRMT5 pathway.
2. Prior antitumor therapy or unresolved toxicities not meeting protocol-defined washout/recovery requirements.
3. Known actionable driver alterations or prior therapies excluded by the protocol for specific NSCLC cohorts (for example EGFR, ALK, ROS1, BRAF, NTRK, MET, RET, KRAS G12C, HER2, as applicable).
4. Significant gastrointestinal disorders that may affect drug absorption.
5. Clinically significant cardiovascular disease, including clinically relevant QTc prolongation, reduced left ventricular ejection fraction, or severe heart failure.
6. Uncontrolled metabolic disease, uncontrolled hypertension, or active infection.
7. Known HIV infection, active hepatitis B with significant viral replication, or active hepatitis C infection.
8. Use of prohibited concomitant medications, including strong inhibitors or inducers of CYP3A4, P-gp, BCRP, or other protocol-specified transporters/enzymes within the required washout period.
9. Other serious medical or psychiatric conditions that, in the investigator's judgment, would make study participation inappropriate.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Factorial Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose-Escalation Arm	Drug: HSK41959; Oral administration, QD; Drug: Sintilimab; Specified dose on specified days; Drug: Pemetrexed + Cisplatin /Carboplatin; Specified dose on specified days; Drug: Paclitaxel + Carboplatin; Specified dose on specified days; Drug: Nab-paclitaxel + Carboplatin; Specified dose on specified days
Experimental: Dose-Expansion：First-line NSCLC cohort	Drug: HSK41959; Oral administration, QD; Drug: Sintilimab; Specified dose on specified days; Drug: Pemetrexed + Cisplatin /Carboplatin; Specified dose on specified days; Drug: Paclitaxel + Carboplatin; Specified dose on specified days; Drug: Nab-paclitaxel + Carboplatin; Specified dose on specified days
Experimental: Dose-Expansion Second-line NSCLC cohort	Drug: Docetaxel; Specified dose on specified days; Drug: HSK41959; Oral administration, QD
Experimental: Dose-Expansion First-line PDAC cohort	Drug: HSK41959; Oral administration, QD; Drug: Nab-paclitaxel + Gemcitabine; Specified dose on specified days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DLTs	DLTs assessed during the protocol-defined DLT evaluation period.	21 days for NSCLC cohorts; 28 days for PDAC cohorts
AEs	Rate and severity of adverse events of HSK41959 Tablets in Combination With Standard Therapy	Up to approximately 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate (ORR)	ORR, defined as the proportion of patients who experience a best response of confirmed CR or PR according to RECIST 1.1	Up to approximately 3 years
Disease control rate (DCR)	DCR, defined as the proportion of patients who experience a best response of CR, PR, or stable disease (SD) according to RECIST 1.1	Up to approximately 3 years
Progression free survival (PFS)	PFS, defined as the time frocease or death due to any cause, whichever occurs first	Up to approximately 3 years
Overall survival (OS)	OS, defined as the time from the first dose of HSK41959 until the date of death due to any cause	Up to approximately 3 years
Area under the curve (AUC) of HSK41959 Tablets in Combination With Standard Therapy		Up to approximately 6 months
maximum plasma concentration (Cmax) of HSK41959 Tablets in Combination With Standard Therapy		Up to approximately 6 months
Tmax(Time to maximum plasma concentration) of HSK41959 Tablets in Combination With Standard Therapy		Up to approximately 6 months

Collaborators and Investigators

• Sponsor: Haisco Pharmaceutical Group Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): April 1, 2029
• Study Completion (Estimated): November 1, 2029

Study Registration Dates

• First Submitted: June 26, 2026
• First Submitted That Met QC Criteria: July 7, 2026
• First Posted (Actual): July 13, 2026

Study Record Updates

• Last Update Posted (Actual): July 14, 2026
• Last Update Submitted That Met QC Criteria: July 12, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; Amino Acids, Peptides, and Proteins; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Inorganic Chemicals; Chlorine Compounds; Nitrogen Compounds; Coordination Complexes; Guanine; Hypoxanthines; Purinones; Purines; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic; Taxoids; Cyclodecanes; Diterpenes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Platinum Compounds; Docetaxel; Pemetrexed; Gemcitabine; Carboplatin; Cisplatin; 130-nm albumin-bound paclitaxel; sintilimab; CP protocol
• Other Study ID Numbers: HSK41959-102

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No