SYN818 plus olaparib for advanced or metastatic BRCA‑mutant or HRD solid tumors

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

This study tests whether combining SYN818 with olaparib is safe and helps control advanced or metastatic solid tumors in adults whose cancers have BRCA mutations or homologous recombination repair defects.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 110 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Hangzhou SynRx Therapeutics Biomedical Technology Co., Ltd (Industry-sponsored)
• Locations: 2 sites (Shanghai, Shanghai Municipality and 1 other locations)
• Trial ID: NCT07156253 on ClinicalTrials.gov

What this trial studies

This Phase Ib, open‑label, multicenter trial gives SYN818 together with oral olaparib to adults with locally advanced or metastatic solid tumors that harbor BRCA mutations or homologous recombination repair (HRR) defects. It enrolls patients in defined cohorts and collects safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary anti‑tumor activity data, with responses assessed by RECIST v1.1. Eligible participants include adults with measurable disease and ECOG 0–1 who have adequate organ and bone marrow function; some cohorts focus specifically on epithelial ovarian cancer or HER2‑negative breast cancer. Primary objectives are early safety and tolerability while secondary objectives include PK/PD profiling and initial signals of clinical benefit.

Who should consider this trial

Good fit: Adults (≥18) with locally advanced or metastatic solid tumors—particularly BRCA‑mutant or HRR‑deficient cancers, including epithelial ovarian or HER2‑negative breast cancer—with measurable disease, ECOG 0–1, adequate organ function, and appropriate prior treatment history are the ideal candidates.

Not a fit: Patients without BRCA mutations or HRR deficiency, those with poor organ function or ECOG >1, pregnant individuals, or patients who still have effective standard treatments available are less likely to benefit from this combination.

Why it matters

Potential benefit: If successful, the combination could provide a new treatment option that improves tumor control for patients with BRCA‑mutant or HRR‑deficient advanced solid tumors.

How similar studies have performed: Olaparib and other PARP inhibitors have established benefit in BRCA‑mutant ovarian and breast cancer, and early combination studies with novel agents have shown encouraging but not yet definitive results.

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;
* 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.

Where this trial is running

Shanghai, Shanghai Municipality and 1 other locations

• FuDan University Shanghai Cancer Center — Shanghai, Shanghai Municipality, China (Recruiting)
• FuDan University Shanghai Cancer Center — Shanghai, Shanghai Municipality, China (Recruiting)

Study contacts

• Study coordinator: Duo Wu

Conditions Metastatic Solid Tumor; Ovarian Cancer; Breast Cancer; BRCA 1 /2 and / or HRD; Advanced Solid Tumors