SYN818 for advanced or metastatic solid tumors

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

This Phase 1 study will test oral SYN818 in adults with advanced or metastatic solid tumors, including breast, ovarian, and prostate cancers, whose standard treatments have been exhausted.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Hangzhou SynRx Therapeutics Biomedical Technology Co., Ltd (industry)
• Locations: 2 sites (Zhengzhou, Henan and 1 other locations)
• Trial ID: NCT06666270 on ClinicalTrials.gov

What this trial studies

This Phase 1, open-label, multicenter study gives SYN818 orally as a single agent to adults with advanced or metastatic solid tumors. The trial's primary goals are to characterize safety, tolerability, pharmacokinetics, and pharmacodynamics, with preliminary measures of anti-tumor activity. Eligible patients must have histologically or cytologically confirmed disease, measurable lesions by RECIST v1.1, ECOG 0–1, adequate organ and bone marrow function, and agree to provide tumor tissue or blood for NGS testing of BRCA or other homologous recombination pathway defects. Treatment and follow-up occur at participating centers in China while dose escalation and expansion cohorts define the drug's clinical profile.

Who should consider this trial

Good fit: Adults (≥18) with histologically or cytologically confirmed advanced or metastatic solid tumors—such as breast, ovarian, or prostate cancer—who have progressed after standard therapies, have ECOG 0–1, measurable disease, adequate organ function, and agree to genomic testing are ideal candidates.

Not a fit: Patients with life expectancy under 12 weeks, ECOG >1, significant uncontrolled hematologic, cardiopulmonary, liver, or kidney disease, or those still eligible for effective standard treatments are unlikely to benefit.

Why it matters

Potential benefit: If successful, SYN818 could become a new oral treatment option for patients with advanced solid tumors, particularly those with BRCA or other homologous recombination pathway deficiencies.

How similar studies have performed: Early-phase studies of novel oral targeted agents and therapies aimed at homologous recombination-deficient tumors have produced occasional responses, but SYN818 itself is at an early phase and has not yet demonstrated clinical benefit.

Eligibility criteria

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, 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.

Exclusion Criteria:

* 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.

Where this trial is running

Zhengzhou, Henan and 1 other locations

• Henan Cancer Hospital — Zhengzhou, Henan, China (RECRUITING)
• Fudan University Shanghai Cancer Center. — Shanghai, Shanghai Municipality, China (RECRUITING)

Study contacts

• Study coordinator: Tongfu Xu, PHD

Conditions: Advanced Solid Cancer, Metastatic Solid Tumor, Ovarian Cancer, Breast Cancer, Prostate Cancer, BRCA Mutation, HRR Deficiency