Study of SYN818 With Olaparib for the Treatment of Locally Advanced or Metastatic Solid Tumors

Официальное название

A Phase Ib Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of SYN818 With Olaparib 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 with Olaparib in adult patients with locally advanced or metastatic solid tumors

Подробное описание

This study is a Phase Ib, open-label, multicentre study of SYN818 with Olaparib administered orally in patients with locally advanced or metastatic solid tumors harboring mutations in BRCA and/or defects in the homologous recombination repair (HRR) pathway

Вмешательства

• Препарат SYN818 and Olaparib will be administered
  Patients will orally receive SYN818 and Olaparib

Первичные конечные точки

• Maximum tolerated dose (MTD) [Срок оценки: Up to 3 years]
• 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]

Вторичные конечные точки (7)

• Pharmacokinetic (PK) parameters [Срок оценки: Up to 3 years]
• Pharmacokinetic (PK) parameters [Срок оценки: Up to 3 years]
• Pharmacokinetic (PK) parameters [Срок оценки: Up to 3 years]
• Pharmacokinetic (PK) parameters [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]

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;
• Participant has a histologically confirmed diagnosis of advanced or metastatic solid tumor and has exhausted all standard-of-care treatment options, with documented BRCA mutations and/or homologous recombination repair deficiency (Part 1).
• Participant has histologically or cytologically confirmed locally advanced or metastatic epithelial ovarian cancer or HER2-negative breast cancer, with documented BRCA mutations and/or homologous recombination repair deficiency (Part 2).
• At least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (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 DNA Polymerase Theta (POLQ) inhibitors;
• Current or previous other malignancy unless treated radically and with no evidence of recurrence or metastasis within the past 5 years;
• 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;
• 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;
• Treatment with an anti-cancer small molecule within 5 half-lives (t1/2), or 2 weeks, whichever is shorter;
• 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

• FuDan University Shanghai Cancer Center — Шанхай
• FuDan University Shanghai Cancer Center — Шанхай

Идентификаторы

NCT: NCT07156253 · SYN-818-102

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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