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

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)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Melanoma; Cancer; Colorectal Cancer; Nonsmall Cell Lung Cancer; Thyroid Cancer; BRAF V600 Mutation
• Intervention / Treatment: Drug: XP-102; Drug: Trametinib

• Study Type: Interventional
• Enrollment (Estimated): 221
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Sophia Paspal, Ph.D.; Phone Number: 610-405-5974; Email: Sophia.paspal@xynomicpharma.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Characterize the safety of XP-102.	Number of participants with treatment related adverse events.	28 days
Evaluate the pharmacokinetics of XP-102.	Blood plasma concentration.	28 days
Establish maximum tolerated dose of XP-102.	Number of participants with dose limiting toxicity	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the pharmacokinetics of XP-102 + trametinib.	Blood plasma concentration.	28 days
Characterize tolerability of XP-102 in combination with trametinib.	Number of participants with dose limiting toxicity	28 days
Evaluate the pharmacokinetics of XP-102 administered with food	Blood plasma concentration.	4 days
Evaluate clinical activity/efficacy of XP-102.	Overall Response Rate with RECIST criteria v1.1.	Approximately every 8 weeks (up to 2 years)

Collaborators and Investigators

• Sponsor: Xynomic Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2024
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: February 20, 2022
• First Submitted That Met QC Criteria: March 1, 2022
• First Posted (Actual): March 11, 2022

Study Record Updates

• Last Update Posted (Actual): January 23, 2024
• Last Update Submitted That Met QC Criteria: January 22, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Trametinib
• Other Study ID Numbers: XYN-701

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No