HSK41959 With Standard Therapy in Solid Tumors With MTAP Deletion

NCT07699757 | Not Yet Recruiting Phase 1

• 1 other identifier: HSK41959-102
• Study Type: interventional
• Target: 258
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Non-Small Cell Lung Cancer; Pancreatic Ductal Adenocarcinoma (mPDAC); Advanced Solid Tumors

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (7)

• Overall response rate (ORR)

  Up to approximately 3 years

• Disease control rate (DCR)

  Up to approximately 3 years

• Progression free survival (PFS)

  Up to approximately 3 years

• Overall survival (OS)

  Up to approximately 3 years

• Area under the curve (AUC) of HSK41959 Tablets in Combination With Standard Therapy

  Up to approximately 6 months

Study Arms (4)

Dose-Escalation Arm

EXPERIMENTAL

Drug: HSK41959; Drug: Sintilimab; Drug: Pemetrexed + Cisplatin /Carboplatin; Drug: Paclitaxel + Carboplatin; Drug: Nab-paclitaxel + Carboplatin

Dose-Expansion：First-line NSCLC cohort

EXPERIMENTAL

Drug: HSK41959; Drug: Sintilimab; Drug: Pemetrexed + Cisplatin /Carboplatin; Drug: Paclitaxel + Carboplatin; Drug: Nab-paclitaxel + Carboplatin

Dose-Expansion Second-line NSCLC cohort

EXPERIMENTAL

Drug: HSK41959; Drug: Docetaxel

Dose-Expansion First-line PDAC cohort

EXPERIMENTAL

Drug: HSK41959; Drug: Nab-paclitaxel + Gemcitabine

Interventions

HSK41959 DRUG

Oral administration, QD

Dose-Escalation Arm; Dose-Expansion First-line PDAC cohort; Dose-Expansion Second-line NSCLC cohort; Dose-Expansion：First-line NSCLC cohort

Sintilimab DRUG

Specified dose on specified days

Dose-Escalation Arm; Dose-Expansion：First-line NSCLC cohort

Pemetrexed + Cisplatin /Carboplatin DRUG

Specified dose on specified days

Dose-Escalation Arm; Dose-Expansion：First-line NSCLC cohort

Paclitaxel + Carboplatin DRUG

Specified dose on specified days

Dose-Escalation Arm; Dose-Expansion：First-line NSCLC cohort

Nab-paclitaxel + Carboplatin DRUG

Specified dose on specified days

Dose-Escalation Arm; Dose-Expansion：First-line NSCLC cohort

Nab-paclitaxel + Gemcitabine DRUG

Specified dose on specified days

Dose-Expansion First-line PDAC cohort

Docetaxel DRUG

Specified dose on specified days

Dose-Expansion Second-line NSCLC cohort

Eligibility Criteria

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

You may qualify if:

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

You may not qualify if:

• Prior exposure to agents targeting the MAT2A or PRMT5 pathway.
• Prior antitumor therapy or unresolved toxicities not meeting protocol-defined washout/recovery requirements.
• 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).
• Significant gastrointestinal disorders that may affect drug absorption.
• Clinically significant cardiovascular disease, including clinically relevant QTc prolongation, reduced left ventricular ejection fraction, or severe heart failure.
• Uncontrolled metabolic disease, uncontrolled hypertension, or active infection.
• Known HIV infection, active hepatitis B with significant viral replication, or active hepatitis C infection.
• 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.
• Other serious medical or psychiatric conditions that, in the investigator's judgment, would make study participation inappropriate.

Sponsors & Collaborators

• Haisco Pharmaceutical Group Co., Ltd.: lead

Study Sites (1)

Shanghai East Hospital

Shanghai, Shanghai Municipality, China

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

sintilimab; Pemetrexed; Cisplatin; Carboplatin; CP protocol; 130-nm albumin-bound paclitaxel; Gemcitabine; Docetaxel

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 26, 2026
• First Posted: July 13, 2026
• Study Start: July 1, 2026
• Primary Completion (Estimated): April 1, 2029
• Study Completion (Estimated): November 1, 2029
• Last Updated: July 14, 2026

Record last verified: 2026-07

Locations

CN (1)