A Phase Ⅰ Study of CS08399 in Participants With MTAP-deleted Solid Tumors and Lymphoma

Официальное название

A Phase Ⅰ Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamic and Preliminary Efficacy of CS08399 in Participants With MTAP-deleted Solid Tumors and Lymphoma

Обзор

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).

Вмешательства

• Препарат CS08399
  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.

Первичные конечные точки

• incidence of dose-limiting toxicity (DLT) [Срок оценки: 34 days after, that is 6 days after single-dose and 28 days after first administration in multiple-dose]
• maximum tolerated dose (MTD) [Срок оценки: dose escalation part, up to approximately 2 year]
• incidence of adverse events (AEs) [Срок оценки: from first administration to 28 days after last administration or next anti-tumor therapy, whichever occurs first]
• Pharmacokinetic parameters: Time to Maximum Concentration (Tmax) [Срок оценки: during treatment, up to approximately 2 year]
• Pharmacokinetic parameters: Maximum Concentration (Cmax) [Срок оценки: during treatment, up to approximately 2 year]
• Pharmacokinetic parameters: Area Under the Concentration-time Curve(AUC) [Срок оценки: during treatment, up to approximately 2 year]
• Pharmacokinetic parameters: Trough Concentration (Ctrough) [Срок оценки: during treatment, up to approximately 2 years]
• Pharmacokinetic parameters: Accumulation Ratio (Rac) [Срок оценки: during treatment, up to approximately 2 years]
• Pharmacokinetic parameters: Elimination Half-life (t1/2) [Срок оценки: during treatment, up to approximately 2 years]
• Pharmacokinetic parameters: Clearance over Fractional Bioavailability (CL/F) [Срок оценки: during treatment, up to approximately 2 years]

Вторичные конечные точки (7)

• Objective Response Rate (ORR) [Срок оценки: Up to approximately 4 years]
• Disease control rate (DCR) [Срок оценки: Up to approximately 4 years]
• Duration of Response (DOR) [Срок оценки: Up to approximately 4 years]
• Time to Progression (TTP) [Срок оценки: Up to approximately 4 years]
• Time to Response (TTR) [Срок оценки: Up to approximately 4 years]
• progression-free survival (PFS) [Срок оценки: Up to approximately 4 years]
• Overall Survival (OS) [Срок оценки: Up to approximately 4 years]

Критерии участия

Критерии включения

• Understand and sign the informed consent form voluntarily.
• ≥18 years old when signing the informed consent, regardless of sex.
• 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.
• 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.
• For glioblastoma: KPS score ≥60. For other solid tumors and lymphoma: ECOG performance status of 0 or 1.
• Adequate organ function.
• Life expectancy ≥3 months.
• Able to swallow and retain oral study medication.

Критерии исключения

• 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).
• Previously received MAT2A or PRMT5 inhibitors.
• Underwent major surgery (cranial, thoracic, or abdominal) within 28 days prior to the first dose or have unresolved wounds, ulcers, or fractures.
• Have unresolved toxicities from previous treatments that have not recovered to CTCAE v5.0 grade ≤1.
• History of other primary malignancies within 5 years prior to the first dose.
• For solid tumors : The presence of active, clinically symptomatic central nervous system metastases or leptomeningeal metastases or spinal cord compression at screening.
• Primary central nervous system lymphoma or systemic lymphoma with CNS involvement.
• Evidence of interstitial lung disease, pulmonary fibrosis, or non-infectious pneumonitis requiring treatment on chest imaging at screening.
• Active infection requiring systemic anti-infective treatment at screening.
• Received drainage of pleural effusion, ascites, or pericardial effusion within 1 month prior to the first dose or have significant clinical symptoms.
• Uncontrolled or significant cardiovascular disease.
• Poorly controlled diabetes.
• Significant gastrointestinal abnormalities at screening that may affect drug intake, transport, or absorption.
• History of gastrointestinal perforation, fistula, peptic ulcer, bowel obstruction, or biliary obstruction within 6 months prior to the first dose.
• 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.
• Serious thromboembolic events within 6 months prior to the first dose.
• Active tuberculosis at screening.
• Active hepatitis B or hepatitis C at screening.HIV infection or syphilis infection at screening.
• Allergy or hypersensitivity to any component of the trial drug or known excipients, or history of severe allergic diseases.
• History of organ transplantation or allogeneic hematopoietic stem cell transplantation.
• History of alcohol abuse or drug abuse.
• Any psychiatric or cognitive disorder that may limit understanding of informed consent, compliance with the protocol, or participation in the trial.
• Pregnant or breastfeeding women.
• Other conditions deemed unsuitable for participation in this trial by the investigator.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Fudan University Shanghai Cancer Center — Шанхай

Идентификаторы

NCT: NCT07583771 · CS08399-101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗