Study of SYN608 for the Treatment of Advanced or Metastatic Solid Tumors

A First-in-Human Phase 1 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of SYN608, a Poly ADP-ribose Glycohydrolase (PARG) Inhibitor in Patients With Locally Advanced or Metastatic Solid Tumors

This interventional study will evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary efficacy of SYN608 as monotherapy in adult patients with advanced solid tumors

This study is a Phase I, open-label, multicentre study of SYN608 administered orally in patients with advanced solid tumors

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;
• Patients with histologically or cytologically confirmed locally advanced or metastatic breast cancer, ovarian cancer or other advanced solid tumors who have experienced disease progression, and available standard of care (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 Homologous Recombination (HR) pathway (by the detection method of next generation sequencing [NGS])
• 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 Poly (ADP) ribose glycohydrolase (PARG) inhibitors;
• Serious allergy to the study drug or any of its excipients;
• 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;
• History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease;
• 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.