XP-102 and XP-102 in Combination With Trametinib in Advanced Solid Tumor Patients With a BRAF V600 Mutation

Phase 1

Not yet recruiting

• Conditions: Melanoma; Nonsmall Cell Lung Cancer; Cancer; BRAF V600 Mutation; Colorectal Cancer; Thyroid Cancer
• Interventions: Drug: XP-102; Drug: Trametinib

• Registration Number: NCT05275374
• Lead Sponsor: Xynomic Pharmaceuticals, Inc.

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-02-20
• Study First Submitted QC: 2022-03-01
• Study First Posted: 2022-03-11
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-09
• Last Update Posted: 2025-04-10
• Study Start: 2025-12-31
• Primary Completion: 2027-12-30
• Study Completion: 2028-12-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 221

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Part 1 - XP-102 Dose Escalation	XP-102	XP-102
Part 3 - XP-102 + Trametinib Dose Expansion	XP-102	XP-102 plus Trametinib
Part 2 - XP-102 + Trametinib Dose Escalation	XP-102	XP-102 plus Trametinib
Part 2 - XP-102 + Trametinib Dose Escalation	Trametinib	XP-102 plus Trametinib
Part 3 - XP-102 + Trametinib Dose Expansion	Trametinib	XP-102 plus Trametinib

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Evaluate clinical activity/efficacy of XP-102.	Approximately every 8 weeks (up to 2 years)	Overall Response Rate with RECIST criteria v1.1.
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.