BRAF V600 Mutation, Cancer, Colorectal Cancer, Melanoma, Nonsmall Cell Lung Cancer, Thyroid Cancer
Conditions
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.
Interventions
DRUGXP-102
XP-102 will be administered orally once or twice daily in a continuous regimen.
DRUGTrametinib
Trametinib will be administered 2mg orally once a day.
Sponsors
Xynomic Pharmaceuticals, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* ≥18 years of age * Advanced malignant solid tumor patients with a BRAF V600 mutation (limited to melanoma, colorectal cancer, non-small cell lung cancer, or thyroid cancer). * 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； * 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); * ECOG performance status of 0 or 1; * Expected survival ≥ 3 months; * Adequate liver, renal, coagulation, cardiac, and hematologic function. * A negative pregnancy test if female patient is of reproductive potential. * 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. * Patients must agree to, and be capable of, adhering to the study visit schedule and all other protocol requirements; * Patients must understand and voluntarily sign the written informed consent form, before the initiation of any study-specific procedures in the trial.
Exclusion criteria
* 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. * 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. * 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; * Patients who are allergic to active substances or excipients of XP-102 or trametinib. * 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; * According to the judgment of the investigator, patients with dysphagia, or any gastrointestinal diseases that may affect drug absorption or activity; * Administration of strong inhibitors or inducers of CYP3A4 liver metabolic enzymes within 14 days before the first dose of the investigational drug; * 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; * Symptomatic active fungal, bacterial and/or viral infections; including known HIV, active hepatitis B, active hepatitis C or active syphilis infection. * 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; * Other situations not suitable for participation in the study as judged by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Evaluate the pharmacokinetics of XP-102 + trametinib. | 28 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. |
| 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. |
Contacts
Primary ContactSophia Paspal, Ph.D.
Outcome results
None listed