Advanced Solid Tumors, Non-Small Cell Lung Cancer, Pancreatic Ductal Adenocarcinoma (mPDAC)
Conditions
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.
Interventions
DRUGHSK41959
Oral administration, QD
DRUGSintilimab
Specified dose on specified days
Specified dose on specified days
Specified dose on specified days
Specified dose on specified days
Specified dose on specified days
DRUGDocetaxel
Specified dose on specified days
Sponsors
Haisco Pharmaceutical Group Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| DLTs | 21 days for NSCLC cohorts; 28 days for PDAC cohorts | DLTs assessed during the protocol-defined DLT evaluation period. |
| AEs | Up to approximately 3 years | Rate and severity of adverse events of HSK41959 Tablets in Combination With Standard Therapy |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall response rate (ORR) | Up to approximately 3 years | ORR, defined as the proportion of patients who experience a best response of confirmed CR or PR according to RECIST 1.1 |
| Disease control rate (DCR) | Up to approximately 3 years | DCR, defined as the proportion of patients who experience a best response of CR, PR, or stable disease (SD) according to RECIST 1.1 |
| Progression free survival (PFS) | Up to approximately 3 years | PFS, defined as the time frocease or death due to any cause, whichever occurs first |
| Overall survival (OS) | Up to approximately 3 years | OS, defined as the time from the first dose of HSK41959 until the date of death due to any cause |
| 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 | — |
Countries
China
Outcome results
None listed