A Phase I Study of WM-S1-030 in Patients With Advanced Solid Tumors
Study Details
Study Description
Brief Summary
This study evaluates the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of WM-S1-030 in patients with advanced solid tumors.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Detailed Description
This is a Phase I, open-label, multicenter, dose-escalation, and dose-expansion study of WM-S1-030 in patients with advanced or metastatic solid tumors. The study will be conducted in 2 parts; a dose-escalation phase (Part 1) and a dose-expansion phase (Part 2). Part 1 will investigate oral administration of WM-S1-030 as monotherapy. Once the MTD or recommended dose is identified in Part 1, additional patients will be enrolled into Part 2 to further investigate efficacy, safety, PK, pharmacodynamics, dosing interval or schedule, and food effect on the single-dose PK of WM-S1-030.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: WM-S1-030 Dose escalation (part 1) and Dose expansion (part 2) |
Drug: WM-S1-030
WM-S1-030 orally administered once daily (QD) for 28 days of each cycle.
|
Outcome Measures
Primary Outcome Measures
- Incidence of Dose-limiting toxicities (DLT) [During Cycle 1 in Part 1 (each cycle is 28 days)]
- Incidence of adverse events (AE)/serious adverse events (SAE) [From Baseline to 28 days after last dose]
Secondary Outcome Measures
- Maximum plasma concentration (Cmax) [Cycle 1, Cycle 2, Subsequent Cycles up to 2 years (each cycle is 28 days)]
- Area under the plasma concentration time curve (AUC) [Cycle 1, Cycle 2, Subsequent Cycles up to 2 years (each cycle is 28 days)]
- Time to maximum plasma concentration (Tmax) [Cycle 1, Cycle 2, Subsequent Cycles up to 2 years (each cycle is 28 days)]
- Trough plasma concentration (Ctrough) [Cycle 1, Cycle 2, Subsequent Cycles up to 2 years (each cycle is 28 days)]
- Elimination half-life (T1/2) [Cycle 1, Cycle 2, Subsequent Cycles up to 2 years (each cycle is 28 days)]
- Apparent volume of distribution during terminal phase (Vz/F) [Cycle 1, Cycle 2, Subsequent Cycles up to 2 years (each cycle is 28 days)]
- Accumulation ratio (Rac) [Cycle 1, Cycle 2, Subsequent Cycles up to 2 years (each cycle is 28 days)]
- Overall response rate (ORR) based on RECIST v1.1 [Screening, Subsequent Cycles (every 8 weeks for 6 month, and then every 12 weeks up to 2 years), within 28 days after last dose (each cycle is 28 days)]
- Progression-free survival (PFS) [From baseline, every 12 weeks, up to within 28 days after last dose]
Other Outcome Measures
- Predictive biomarker analyses for genotyping mutation [Screening, Subsequent Cycles up to 2 years, within 28 days after last dose (each cycle is 28 days)]
Eligibility Criteria
Criteria
Inclusion Criteria:
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Aged ≥18 years.
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Able and willing to sign the informed consent form (ICF).
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Have at least 1 evaluable lesion based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
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Have histologically or cytologically confirmed locally advanced unresectable or metastatic solid tumor which has progressed after treatment with standard therapies and for which no effective standard therapy is available or patient has refused, has a contraindication, or is intolerant to standard therapies.
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Have Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
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Must have archived frozen tissue available (collected within 3 months before screening) or consent to a pre-treatment biopsy.
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Must be willing to consent to up to 2 on-treatment biopsies.
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Have a life expectancy of at least 12 weeks.
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Have adequate hematological functions and blood coagulation.
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Have adequate hepatic function at screening.
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Have adequate renal function at screening.
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QT interval corrected for heart rate using Fridericia's method ≤470 msec.
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Agree to abide by contraception requirements.
Exclusion Criteria:
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Have received any cytotoxic chemotherapy, investigational agent (or medical device), anticancer drug, hormone therapy, or radiation therapy for treatment within 4 weeks or therapeutic radiopharmaceuticals taken within 8 weeks prior to the first administration of IP.
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Have known hypersensitivity to WM-S1-030 and/or excipient.
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Have ≥ Grade 2 unresolved toxicity related to prior anticancer therapy excluding alopecia.
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Have received drugs or herbal supplements within 2 weeks prior to the first administration of IP which are known to be inhibitors or inducers of cytochrome P450 (CYP) 3A4 including, but not limited to, cannabinoids, ketoconazole, itraconazole, posaconazole, voriconazole, rifampicin, phenytoin, St. John's Wort, carbamazepine, or hyperforin.
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Have any primary central nervous system (CNS) tumors or known CNS metastases unless clinically stable.
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Have previously undergone drainage of ascites and/or pleural effusion within 4 weeks prior to screening, or have clinically significant effusions at screening.
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Have had major surgery within 4 weeks prior to the first administration of IP. Patients should have recovered from the effects of major surgery or significant traumatic injury within 14 days prior to administration of the IP.
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Have serious non-healing wounds, ulcers, or bone fractures, except for traumatic fractures not requiring surgical intervention.
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Have an active infection treated with systemic anti-infectives within 2 weeks prior to the first administration of IP.
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Have concurrent unstable or uncontrolled systemic diseases.
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Have a history of gastrointestinal or trachea-esophageal fistulas.
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Current (or planned) pregnancy or breastfeeding from screening to at least 3 months following the last IP administration.
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Any condition, at the discretion of the investigator, which puts the patient at risk to participate in the study.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Monash Medical Center | Clayton | Victoria | Australia | 3168 |
| 2 | Linear Clinical Research Limited | Nedlands | Western Australia | Australia | 6009 |
Sponsors and Collaborators
- Wellmarker Bio
- Covance
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- WMS1030-101