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

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

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.