MTAP Deletion
Conditions
Keywords
Advanced Solid Tumors
Brief summary
This is a Phase I, multicenter, open-label clinical trial with dose escalation/dose expansion phases, designed to evaluate the safety, tolerability, pharmacokinetic/pharmacodynamic (PK/PD) profiles, and antitumor efficacy characteristics of HS-10587 in patients with MTAP-deleted advanced solid tumors.
Interventions
DRUGHS-10587
HS-10587 tablet
Sponsors
Jiangsu Hansoh Pharmaceutical Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Participants who voluntarily participate in this clinical study, understand the study procedures, and are able to sign a written ICF. 2. Participants with locally advanced or recurrent metastatic malignant solid tumors confirmed by histopathology or cytopathology who have failed or are intolerant to at least one line of prior standard treatment, or for whom no standard treatment exists. 3. Evidence of MTAP deletion in the tumor tissue. 4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 5. Life expectancy ≥12 weeks. 6. At least one measurable lesion that would qualify as target lesion by Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1). 7. Female participants of childbearing potential are willing to take appropriate contraceptive measures and should not breastfeed; male participants are willing to use barrier contraception.
Exclusion criteria
1. History of other primary malignancies. 2. Presence of pleural/abdominal effusion or pericardial effusion requiring clinical intervention. 3. Presence of leptomeningeal metastasis, spinal cord compression, or brainstem metastasis; known untreated brain metastases, or symptomatic/unstable brain metastases. 4. Participants who have any Grade ≥ 2 residual toxicity according to Common Terminology Criteria for Adverse Events (CTCAE, version 6.0) from prior anti-tumor therapies (except alopecia, pigmentation, and residual neurotoxicity). 5. Inadequate bone marrow reserve or hepatic and renal functions. 6. Severe, uncontrolled, or active cardiovascular diseases. 7. Severe or poorly controlled diabetes. 8. Severe or poorly controlled hypertension. 9. Severe infection within 4 weeks prior to the first dose. 10. Long-term corticosteroid therapy, history of other acquired/congenital immunodeficiency disorders, or organ transplantation. 11. Known active infectious diseases. 12. Clinically significant gastrointestinal dysfunction. 13. Moderate to severe pulmonary diseases that seriously affect respiratory function. 14. Prior history of severe neurological or mental disorders. 15. Female participants who are pregnant or breastfeeding, or plan to become pregnant during the study. 16. History of severe allergies, or history of hypersensitivity reactions to any active or inactive ingredients of HS-10587 or to drugs with similar chemical structures to HS-10587 or drugs of the same class as HS-10587. 17. Participants with any conditions that may jeopardize participant safety or interfere with study assessments, as judged by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of DLT | Up to 21 days after the first administration. (first cycle) | dose-limiting toxicities |
| MTD or MAD | Up to 21 days after the first administration. (first cycle) | maximum tolerated dose (MTD) or maximum applicable dose (MAD) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of adverse events (AEs) and serious adverse events (SAEs) | From time of informed consent to 28 days post last dose of HS-10587. | Number of participants with AEs and SAEs |
| Pharmacokinetics (PK) profile of HS-10587 in patients with advanced solid tumors | Predose and postdose up to end of treatment, approximately 2 years | Maximum concentration (Cmax). |
| Efficacy of HS-10587 in patients with advanced solid tumors | Predose and post dose up to end of treatment, approximately 2 years | Objective response rate (ORR) evaluated as per RECIST v1.1 |
| Efficacy of HS-10587 in patients with advanced solid tumors. | Predose and post dose up to end of treatment, approximately 2 years. | Duration of response (DOR) evaluated as per RECIST v1.1 |
Outcome results
None listed