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

Cancer Clinical Trial

— ENHANCE  

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)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05275374
• Other study ID #: XYN-701
• Status: Not yet recruiting
• Phase: Phase 1/Phase 2
• Start date: December 2024
• Est. completion date: December 2026

Study information

• Verified date: January 2024
• Source: Xynomic Pharmaceuticals, Inc.
• Contact: Sophia Paspal, Ph.D.
• Phone: 610-405-5974
• Email: Sophia.paspal[@]xynomicpharma.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 221
• Est. completion date: December 2026
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• BRAF V600 Mutation
• Cancer
• Carcinoma, Non-Small-Cell Lung
• Colorectal Cancer
• Melanoma
• Nonsmall Cell Lung Cancer
• Thyroid Cancer

Intervention

Drug:
• XP-102
XP-102 will be administered orally once or twice daily in a continuous regimen.
• Trametinib
Trametinib will be administered 2mg orally once a day.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Xynomic Pharmaceuticals, Inc.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Characterize the safety of XP-102.	Number of participants with treatment related adverse events.	28 days
Primary	Evaluate the pharmacokinetics of XP-102.	Blood plasma concentration.	28 days
Primary	Establish maximum tolerated dose of XP-102.	Number of participants with dose limiting toxicity	28 days
Secondary	Evaluate the pharmacokinetics of XP-102 + trametinib.	Blood plasma concentration.	28 days
Secondary	Characterize tolerability of XP-102 in combination with trametinib.	Number of participants with dose limiting toxicity	28 days
Secondary	Evaluate the pharmacokinetics of XP-102 administered with food	Blood plasma concentration.	4 days
Secondary	Evaluate clinical activity/efficacy of XP-102.	Overall Response Rate with RECIST criteria v1.1.	Approximately every 8 weeks (up to 2 years)