ENHANCE: XP-102 and XP-102 in Combination With Trametinib in Advanced Solid Tumor Patients With a BRAF V600 Mutation
Study Details
Study Description
Brief Summary
This is a first-in-human multi-center study which will be conducted in advanced malignant solid tumors patients. The solid tumor type is limited to melanoma, colorectal, non-small-cell lung, and thyroid cancer with positive BRAF V600 mutation. This study is divided into three stages: Phase Ia: a dose-escalation phase of XP-102; Phase Ib: a dose-escalation and sample size expansion phase of XP-102 plus trametinib; Phase IIa: an expansion phase of XP-102 plus trametinib.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1/Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Part 1 - XP-102 Dose Escalation XP-102 |
Drug: XP-102
XP-102 will be administered orally once or twice daily in a continuous regimen.
|
| Experimental: Part 2 - XP-102 + Trametinib Dose Escalation XP-102 plus Trametinib |
Drug: XP-102
XP-102 will be administered orally once or twice daily in a continuous regimen.
Drug: Trametinib
Trametinib will be administered 2mg orally once a day.
|
| Experimental: Part 3 - XP-102 + Trametinib Dose Expansion XP-102 plus Trametinib |
Drug: XP-102
XP-102 will be administered orally once or twice daily in a continuous regimen.
Drug: Trametinib
Trametinib will be administered 2mg orally once a day.
|
Outcome Measures
Primary Outcome Measures
- Characterize the safety of XP-102. [28 days]
Number of participants with treatment related adverse events.
- Evaluate the pharmacokinetics of XP-102. [28 days]
Blood plasma concentration.
- Establish maximum tolerated dose of XP-102. [28 days]
Number of participants with dose limiting toxicity
Secondary Outcome Measures
- Evaluate the pharmacokinetics of XP-102 + trametinib. [28 days]
Blood plasma concentration.
- Characterize tolerability of XP-102 in combination with trametinib. [28 days]
Number of participants with dose limiting toxicity
- Evaluate the pharmacokinetics of XP-102 administered with food [4 days]
Blood plasma concentration.
- Evaluate clinical activity/efficacy of XP-102. [Approximately every 8 weeks (up to 2 years)]
Overall Response Rate with RECIST criteria v1.1.
Eligibility Criteria
Criteria
Inclusion Criteria:
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≥18 years of age
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Advanced malignant solid tumor patients with a BRAF V600 mutation (limited to melanoma, colorectal cancer, non-small cell lung cancer, or thyroid cancer).
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Must have failed conventional treatment or for whom no therapy of proven efficacy exists or who is not eligible for established treatment options. Prior treatment with BRAF inhibitors and/or MEK inhibitors is permitted；
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At least one measurable lesion (brain metastasis must not be the only measurable lesion) according to Response Evaluation Criteria in Solid Tumours (RECIST v1.1);
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ECOG performance status of 0 or 1;
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Expected survival ≥ 3 months;
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Adequate liver, renal, coagulation, cardiac, and hematologic function.
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A negative pregnancy test if female patient is of reproductive potential.
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For men and women of reproductive potential, agreement to use an effective contraceptive method from the time of screening and throughout their time on study.
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Patients must agree to, and be capable of, adhering to the study visit schedule and all other protocol requirements;
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Patients must understand and voluntarily sign the written informed consent form, before the initiation of any study-specific procedures in the trial.
Exclusion Criteria:
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Active central nervous system (CNS) lesions. However, patients with asymptomatic and brain metastases who received treatment (including targeted brain radiotherapy, surgical treatment, glucocorticoid or other treatments) without disease progression for ≥ 3 months are eligible.
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Patients who received radiotherapy, immunotherapy, hormone therapy, targeted therapy, biotherapy, traditional Chinese medicine therapy, chemotherapy or any clinical trial treatment within 14 days before the first dose.
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Patients who have persistent toxicity caused by previous chemotherapeutic drugs or radiotherapy has not recovered to lower than grade 2 (except hair loss) according to CTCAE version 5.0;
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Patients who are allergic to active substances or excipients of XP-102 or trametinib.
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Significant traumatic injury within 28 days before the first dose of the investigational drug, or if major surgery is anticipated during the course of study treatment;
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According to the judgment of the investigator, patients with dysphagia, or any gastrointestinal diseases that may affect drug absorption or activity;
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Administration of strong inhibitors or inducers of CYP3A4 liver metabolic enzymes within 14 days before the first dose of the investigational drug;
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Patients who are receiving drugs that may prolong QT interval and unable or unwilling to stop treatment or switch to other alternative treatment before study enrollment;
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Symptomatic active fungal, bacterial and/or viral infections; including known HIV, active hepatitis B, active hepatitis C or active syphilis infection.
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Any poorly controlled disorders (such as serious mental, neurological, cardiovascular, respiratory, digestive, urinary, bleeding and coagulation, or other system diseases) that may significantly affect the clinical trial;
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Other situations not suitable for participation in the study as judged by the investigator.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Xynomic Pharmaceuticals, Inc.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- XYN-701