Clinical trial NCT05275374: XP-102 and XP-102 in Combination With Trametinib in Advanced Solid Tumor Patients With a BRAF V600 Mutation
Official title: A Dose-escalation and Expansion Phase I/IIa Study of XP-102 and XP-102 in Combination With Trametinib in Advanced Solid Tumor Patients With a BRAF V600 Mutation (ENHANCE)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Cancer
BRAF V600 Mutation
Melanoma
Colorectal Cancer
Thyroid Cancer
Nonsmall Cell Lung Cancer
Lead sponsor: Xynomic Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2022-03-11
Enrollment: 221
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Characterize the safety of XP-102.
timeFrame: 28 days
measure: Evaluate the pharmacokinetics of XP-102.
timeFrame: 28 days
measure: Establish maximum tolerated dose of XP-102.
timeFrame: 28 days
Secondary outcomes:
measure: Evaluate the pharmacokinetics of XP-102 + trametinib.
timeFrame: 28 days
measure: Characterize tolerability of XP-102 in combination with trametinib.
timeFrame: 28 days
measure: Evaluate the pharmacokinetics of XP-102 administered with food
timeFrame: 4 days
measure: Evaluate clinical activity/efficacy of XP-102.
timeFrame: Approximately every 8 weeks (up to 2 years)
Other outcomes:
Locations:
Study officials:
References: