A Phase I Clinical Study to Evaluate the Safety, Tolerability and Pharmacokinetics of the Oral Pan-RAF Inhibitor QLH11906 in Subjects With Advanced Solid Tumors Harboring MAPK Pathway Alterations.

Qilu Pharmaceutical Co., Ltd.1 site in 1 country40 target enrollmentJune 14, 2022

ConditionsAdvanced Solid Tumors Harboring MAPK Pathway Alterations

InterventionsQLH11906

DrugsQLH11906

Overview

Phase: Phase 1
Intervention: QLH11906
Conditions: Advanced Solid Tumors Harboring MAPK Pathway Alterations
Sponsor: Qilu Pharmaceutical Co., Ltd.
Enrollment: 40
Locations: 1
Primary Endpoint: RP2D
Status: Recruiting
Last Updated: 3 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is an open label, phase 1 clinical study to evaluate the safety and tolerability of different doses of QLH11906 monotherapy in patients with relapsed/refractory, unresectable locally advanced or metastatic advanced solid tumors with abnormal MAPK pathway, and determine the Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD, if MTD cannot be determined) and Recommended Dose in Phase II Clinical Studies (Recommended Phase II Dose, RP2D).

Registry

clinicaltrials.gov

Start Date

June 14, 2022

End Date

July 1, 2025

Last Updated

3 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Qilu Pharmaceutical Co., Ltd.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•The subjects participated voluntarily, signed the informed consent, and were able to abide by the research procedures.
•Subjects with advanced (metastatic or unresectable) solid tumors with histologically confirmed MAPK signaling pathway alteration.
•Eastern Cooperative Oncology Group (ECOG) performance status ≤
•Subjects are able to swallow and retain oral medication without any clinically significant gastrointestinal abnormalities that alter absorption.
•Subjects (including women and men) agree to use effective contraception for contraception from the time of signing the informed consent form to 180 days after the last use of the study drug. Female subjects of childbearing age cannot be pregnant or breastfeeding.

Exclusion Criteria

•Subjects received systemic anticancer therapy within 2 weeks prior to the first dose.
•Subjects received radical radiotherapy within 4 weeks before the first administration, or received local palliative radiotherapy for bone metastases within 1 week.
•Subjects who have received inhibitors or inducers of CYP3A4 within 1 week before the first dose; or within 5 half-lives of the drug; or subjects who need to continue to receive these drugs during the study period.
•Active bacterial, fungal, or viral infection requiring systemic therapy within 1 week prior to the first dose.
•Subjects with symptomatic central nervous system (CNS) metastases and/or cancerous meningitis.
•Cardiovascular and cerebrovascular diseases with clinical significance.
•Clinically uncontrollable serous effusion (eg, pleural effusion that cannot be controlled by drainage or other methods).
•Active gastrointestinal disease or other conditions that significantly interfere with drug absorption.
•Known immediate or delayed hypersensitivity reactions or idiosyncratic reactions to the investigational treatment-related chemotherapeutic drugs and their excipients.
•Human immunodeficiency virus (HIV) positive test result and Treponema pallidum antibody positive.

Arms & Interventions

QLH11906

QLH11906 Tablets

Intervention: QLH11906

Outcomes

Primary Outcomes

RP2D

Time Frame: Up to 24 approximately months

Recommended dose for phase II trials

MTD/MAD

Time Frame: Up to 24 approximately months

The Maximum Tolerated Dose (MTD) will be determined during dose escalation using a Bayesian Optimal Interval (BOIN) design.The maximum administrated dose (MAD) is defined as the highest dose of all groups if MTD can not be determined.

Secondary Outcomes

Maximum concentration (Cmax)(Up to 24 approximately months)
Adverse Events (AEs) /Serious Adverse Events (SAEs)(Up to 24 approximately months)
Disease control rate (DCR)(Up to 24 approximately months)
Overall response rate (ORR)(Up to 24 approximately months)
Area under the concentration-time curve（AUC）(Up to 24 approximately months)
Duration of response (DoR)(Up to 24 approximately months)