xp-102 and xp-102 in combination with trametinib in advanced solid tumor patients with a braf v600 mutation

Conditions: Cancer; BRAF V600 Mutation; Melanoma; Colorectal Cancer; Thyroid Cancer; Nonsmall Cell Lung Cancer

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.


Eligibility criteria:
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.