Advanced Solid Tumors, Diffuse Large B-Cell Lymphoma (DLBCL), Lymphoma, Non Small Cell Lung Cancer, Pancreatic Adenocarcinoma
Conditions
Brief summary
This is a phase I, open-label, first-in-human study of CS08399, comprising two phases: dose escalation (including single-dose and multiple-dose) and cohort expansion. The primary objectives of this study are to evaluate the safety, tolerability and pharmacokinetic (PK) characteristics of CS08399 in participants with MTAP-deleted solid tumors and Lymphoma, and to recommended Phase 2 dose(s) (RP2D) of CS08399 in appropriate tumor(s).
Interventions
DRUGCS08399
Oral tablet. Only one dose on C0D1 in single-dose period. Once or twice daily from C1D1 until disease progression, death, intolerable toxicity, loss to follow-up, withdrawal of informed consent, or the end of the trial, whichever occurs first, in multiple-dose period in both escalation and cohort expansion phases.
Sponsors
Chipscreen Biosciences, Ltd.
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Understand and sign the informed consent form voluntarily. 2. ≥18 years old when signing the informed consent, regardless of sex. 3. Histologically or cytologically confirmed locally advanced or metastatic solid tumors, or relapsed/refractory lymphoma, for which standard therapy has failed or is not tolerated, and no further standard therapy is available. Homozygous MTAP or CDKN2A deletion confirmed by tissue or peripheral blood testing. 4. For glioblastoma: at least one measurable intracranial tumor lesion according to the RANO 2.0 criteria. For other solid tumors: at least one measurable lesion according to RECIST v1.1 criteria. For lymphoma: at least one measurable lesion according to Lugano 2014 criteria. 5. For glioblastoma: KPS score ≥60. For other solid tumors and lymphoma: ECOG performance status of 0 or 1. 6. Adequate organ function. 7. Life expectancy ≥3 months. 8. Able to swallow and retain oral study medication.
Exclusion criteria
1. Received any anti-tumor therapy (including but not limited to chemotherapy, targeted therapy, anti angiogenic therapy, immunotherapy, cell therapy, radiotherapy, tumor embolization, etc.) or experimental drugs/devices that have not been approved for marketing within 28 days prior to the first dose or are still within 5 half-lives of such drugs (whichever is shorter). 2. Previously received MAT2A or PRMT5 inhibitors. 3. Underwent major surgery (cranial, thoracic, or abdominal) within 28 days prior to the first dose or have unresolved wounds, ulcers, or fractures. 4. Have unresolved toxicities from previous treatments that have not recovered to CTCAE v5.0 grade ≤1. 5. History of other primary malignancies within 5 years prior to the first dose. 6. For solid tumors : The presence of active, clinically symptomatic central nervous system metastases or leptomeningeal metastases or spinal cord compression at screening. 7. Primary central nervous system lymphoma or systemic lymphoma with CNS involvement. 8. Evidence of interstitial lung disease, pulmonary fibrosis, or non-infectious pneumonitis requiring treatment on chest imaging at screening. 9. Active infection requiring systemic anti-infective treatment at screening. 10. Received drainage of pleural effusion, ascites, or pericardial effusion within 1 month prior to the first dose or have significant clinical symptoms. 11. Uncontrolled or significant cardiovascular disease. 12. Poorly controlled diabetes. 13. Significant gastrointestinal abnormalities at screening that may affect drug intake, transport, or absorption. 14. History of gastrointestinal perforation, fistula, peptic ulcer, bowel obstruction, or biliary obstruction within 6 months prior to the first dose. 15. Clinically significant hemoptysis or tumor bleeding within 14 days prior to the first dose; significant active bleeding within 2 months prior to the first dose; currently on anticoagulants; high-risk bleeding tendency at screening. 16. Serious thromboembolic events within 6 months prior to the first dose. 17. Active tuberculosis at screening. 18. Active hepatitis B or hepatitis C at screening.HIV infection or syphilis infection at screening. 19. Allergy or hypersensitivity to any component of the trial drug or known excipients, or history of severe allergic diseases. 20. History of organ transplantation or allogeneic hematopoietic stem cell transplantation. 21. History of alcohol abuse or drug abuse. 22. Any psychiatric or cognitive disorder that may limit understanding of informed consent, compliance with the protocol, or participation in the trial. 23. Pregnant or breastfeeding women. 24. Other conditions deemed unsuitable for participation in this trial by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| incidence of dose-limiting toxicity (DLT) | 34 days after, that is 6 days after single-dose and 28 days after first administration in multiple-dose | — |
| maximum tolerated dose (MTD) | dose escalation part, up to approximately 2 year | — |
| incidence of adverse events (AEs) | from first administration to 28 days after last administration or next anti-tumor therapy, whichever occurs first | Number of participants with AE(s) |
| Pharmacokinetic parameters: Time to Maximum Concentration (Tmax) | during treatment, up to approximately 2 year | — |
| Pharmacokinetic parameters: Maximum Concentration (Cmax) | during treatment, up to approximately 2 year | — |
| Pharmacokinetic parameters: Area Under the Concentration-time Curve(AUC) | during treatment, up to approximately 2 year | — |
| Pharmacokinetic parameters: Trough Concentration (Ctrough) | during treatment, up to approximately 2 years | — |
| Pharmacokinetic parameters: Accumulation Ratio (Rac) | during treatment, up to approximately 2 years | — |
| Pharmacokinetic parameters: Elimination Half-life (t1/2) | during treatment, up to approximately 2 years | — |
| Pharmacokinetic parameters: Clearance over Fractional Bioavailability (CL/F) | during treatment, up to approximately 2 years | — |
| Pharmacokinetic parameters: Volume of Distribution at Steady State over Fractional Bioavailability (Vz/F) | during treatment, up to approximately 2 years | — |
Secondary
| Measure | Time frame |
|---|---|
| Objective Response Rate (ORR) | Up to approximately 4 years |
| Disease control rate (DCR) | Up to approximately 4 years |
| Duration of Response (DOR) | Up to approximately 4 years |
| Time to Progression (TTP) | Up to approximately 4 years |
| Time to Response (TTR) | Up to approximately 4 years |
| progression-free survival (PFS) | Up to approximately 4 years |
| Overall Survival (OS) | Up to approximately 4 years |
Countries
China
Contacts
CONTACTXuelian Zhou
Outcome results
None listed