Advanced Solid Tumors, BRCA 1 /2 and / or HRD, Breast Cancer, Metastatic Solid Tumor, Ovarian Cancer
Conditions
Brief summary
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
Detailed description
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
Interventions
DRUGSYN818 and Olaparib will be administered
Patients will orally receive SYN818 and Olaparib
Sponsors
Hangzhou SynRx Therapeutics Biomedical Technology Co., Ltd
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum tolerated dose (MTD) | Up to 3 years | MTD is defined as the maximum dose level at which ≤1 patient have dose limiting toxicities (DLTs) during the DLT observation period, and it should be determined with 6 evaluable patients. |
| Number of participants with Dose Limiting Toxicities (DLTs) | From first dose of study treatment until the end of Cycle 1 (each cycle is 21-days) | Severity of adverse events as assessed by the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) v5.0. |
| Number of participants experiencing adverse events (AEs)/serious adverse events (SAEs) | From time of information consent to 30 days post last dose, up to 3 years | Number of participants with incidence of adverse events and with serious adverse events including changes from baseline in laboratory parameters, vital signs, Electrocardiogram (ECG), and physical examination, etc. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic (PK) parameters | Up to 3 years | To characterize the PK Peak Plasma Concentration (Cmax) of the SYN818 and Olaparib combination therapy |
| Progression Free Survival (PFS) | Up to 3 years | PFS is defined as the time from the first study treatment to the date of the first documentation of objective progression of disease (PD) or death due to any cause. |
| Objective Response Rate (ORR) | Up to 3 years | ORR is defined as proportion of patients who achieved complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 recorded from first investigational product treatment until disease progression or death due to any cause. The confirmation of response for patients who has PR or CR at first time should be performed by at least 4 weeks. For castration-resistant prostate cancer (CRPC) patients, bone lesion will be assessed according to Prostate Cancer Working Group 3 (PCWG3) criteria. |
| Duration of Response (DoR) and Time to Response (TTR) | Up to 3 years | DOR is defined, for patients with an objective response, as the time from first documentation of objective tumor response (CR or PR) to the first documentation of objective tumor progression or death due to any cause. |
Countries
China
Contacts
Primary ContactDuo Wu
Outcome results
None listed