Study of SYN818 for the Treatment of Advanced or Metastatic Solid Tumors

Официальное название

A First-in-human, Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Anti-tumor Activity of SYN818, a DNA Polymerase Theta (POLQ) Inhibitor Alone in Patients With Locally Advanced or Metastatic Solid Tumors

Обзор

This interventional study will evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary efficacy of SYN818 as monotherapy in adult patients with advanced solid tumors

Подробное описание

This study is a Phase I, open-label, multicentre study of SYN818 administered orally in patients with advanced solid tumors

Вмешательства

• Препарат SYN818
  Patients will orally receive SYN818

Первичные конечные точки

• Number of participants with Dose Limiting Toxicities (DLTs) [Срок оценки: From first dose of study treatment until the end of Cycle 1 (each cycle is 21-days)]
• Number of participants experiencing adverse events (AEs)/serious adverse events (SAEs) [Срок оценки: From time of information consent to 30 days post last dose, up to 3 years]
• Maximum tolerated dose (MTD) [Срок оценки: Up to 3 years]

Вторичные конечные точки (5)

• Pharmacokinetic (PK) parameters and Pharmacodynamic (PD) marker change [Срок оценки: Up to 3 years]
• Objective Response Rate (ORR) [Срок оценки: Up to 3 years]
• Duration of Response (DoR) and Time to Response (TTR) [Срок оценки: Up to 3 years]
• Progression Free Survival (PFS) [Срок оценки: Up to 3 years]
• Serum tumor marker change: CA125, etc. (OC), prostatic specific antigen (PSA, prostate cancer) decreased, and specific tumor markers for other tumor types may also be included (to be assessed by clinical investigators) [Срок оценки: Up to 3 years]

Критерии участия

Критерии включения

• Having signed the written Informed Consent Form (ICF);
• Male or female aged ≥18 years;
• Life expectancy ≥12 weeks;
• Eastern Cooperative Oncology Group (ECOG) Performance Score 0 or 1;
• Patients with histologically or cytologically confirmed locally advanced or metastatic breast cancer, ovarian cancer, prostate cancer or other advanced solid tumors who have experienced disease progression, and available SOC therapies had been exhausted;
• be willing to provide tumor tissue samples (fresh frozen \[SF\] or previously retained paraffin-embedded \[FFPE\] tumor tissue samples) or peripheral blood germline DNA or ctDNA sample to detect BRCA mutation, or other deficiency in the HR pathway (by the detection method of next generation sequencing \[NGS\])
• At least one measurable lesion according to RECIST v1.1;
• No serious hematological, cardiopulmonary, or liver or kidney diseases other than the primary disease;
• Adequate organ function and bone marrow function.

Критерии исключения

• Previous or current use of POLQ inhibitors;
• Hypersensitivity to the active pharmaceutical ingredient or any excipient of SYN818;
• Central nervous system (CNS) metastasis or meningeal metastasis with clinical symptoms, or other evidence indicating that CNS metastasis or meningeal metastasis has not been adequately controlled;
• Other malignant tumors than the study tumors within 5 years prior to the first dose of the study drug, except for localized cancers that have been evidently cured or disease-free for at least 3 years, such as basal or squamous cell skin cancer, superficial bladder cancer, prostate carcinoma in situ, carcinoma in situ of cervix, or carcinoma in situ of breast;
• Patients with Myelodysplastic syndrome (MDS)/Acute myeloid leukemia (AML) or with features suggestive of MDS/AML;
• Dysphagia or refractory nausea and vomiting, malabsorption, extracorporeal biliary shunts, or gastrointestinal disorders that affect drug absorption, e.g., Crohn's disease, ulcerative colitis, or short bowel syndrome, or other malabsorption conditions;
• Major surgery or serious trauma within 4 weeks prior to the first dose of the study treatment or major surgery planned during the trial period, and none of the AEs related to surgery or major trauma have resolved (to ≤ CTCAE v5.0 Grade 1 or baseline level) before the first dose of the study drug;
• History of use within 2 weeks prior to the first dose of the study treatment and need to use protocol-prohibited potent inhibitors or potent inducers of cytochrome P450 (CYP) 3A4/BCRP/P-gp during the study;
• Serious systemic diseases or laboratory abnormalities or other conditions that, at the Investigator's discretion, will make it unsuitable for the patient to participate in this clinical trial.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 2 центра

• Henan Cancer Hospital — Чжэнчжоу
• Fudan University Shanghai Cancer Center. — Шанхай

Идентификаторы

NCT: NCT06666270 · SYN-818-101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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