NCT04967079

Trametinib Plus Anlotinib in Non-G12C KRAS-Mutant NSCLC Patients

Combined MEK Inhibitor Trametinib and RTK Inhibitor Anlotinib Therapy in Non-G12C KRAS-Mutant Non-Small Cell Lung Cancer Patients

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 33 (actual)
• Sponsor: Shanghai Chest Hospital · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

This is a Phase I exploratory study. The study is divided into two parts (A/B).In part A, the primary endpoint is the determination of the recommended phase 2 dose (RP2D). Secondary endpoint for phase Ia includes evaluating the objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and adverse events (AEs). Following the establishment of the RP2D, the expansion cohort will be initiated. Transitioning to part B, 20 patients will be enrolled to further evaluate the ORR. All patients will receive the trametinib plus anlotinib regimen based on the RP2D determined in part A. The primary endpoint for part B is to assess the ORR, while secondary endpoint includes evaluating PFS, overall survival (OS), DCR, AEs, and duration of overall response (DoR). In part A, the study plans to enroll eligible patients to receive the MEK inhibitor trametinib (2 mg) in combination with anlotinib (6mg, 8 mg, 10 mg, 12 mg). The number of subjects is determined according to the actual situation of dose climbing. In part B, another 20 eligible patients will be enrolled and treated with trametinib (2mg) + anlotinib (RP2D), until the disease progression (PD) or unacceptable toxicity occurs to further evaluate the safety, tolerability and efficacy. Patients participated in safety follow-up after the first course of treatment until 3 months after discontinuation due to PD or toxicity. Dose-limiting toxicities from the first cycle were collected. Therapeutic efficacy evaluation was scheduled according to RECIST version 1.1 every 4-8 weeks. After the investigators' evaluation, the assessment cycle could extend to 12 weeks or longer due to the uncontrollable factors during the treatment period. Blood samples will be collected for pharmacokinetic analysis and biomarker discovery at baseline and at each periodic assessment.

Conditions

• Non Small Cell Lung Cancer

Interventions

Type	Name	Description
DRUG	Trametinib	Trametinib 2 mg given orally, once daily
DRUG	Anlotinib	Anlotinib given orally, every two weeks followed by a one-week discontinuation cycle

Timeline

• Start date: 2021-08-01
• Primary completion: 2023-07-01
• Completion: 2024-03-26
• First posted: 2021-07-19
• Last updated: 2024-04-23

Locations

1 site across 1 country: China