NCT06456138

Trametinib Plus Anlotinib Combined With Tislelizumab in KRAS-mutant NSCLC

Trametinib Plus Anlotinib Combined With Tislelizumab in KRAS-mutant Advanced Non-small Cell Lung Cancer Patients: a Multi-center, Open-label, Phase 1/2 Study

• Status: Not Yet Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Sponsor: Shanghai Chest Hospital · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

Lung cancer is the most common cause of cancer-related death worldwide. Approximately 85% to 90% of lung cancer cases are non-small cell lung cancer (NSCLC), of which KRAS is one of the most common driver genes, occurring in 25-30% of lung adenocarcinomas and 3-5% of squamous cell carcinomas. KRAS-mutant NSCLC had been considered undruggable in past decades. This research sought to address a significant challenge in treating NSCLC with KRAS mutations, which are notoriously difficult to target effectively. Here, we proposal that the combined use of anlotinib and trametinib combined with tislelizumab may form an effective strategy for the treatment of KRAS-mutant NSCLC patients.

Detailed description

This is a phase 1/2, open-label, multi-center study aimed at exploring the potential therapeutic efficacy of tislelizumab (intravenous), trametinib (oral) and anlotinib (oral) in KRAS-mutant advanced non-small cell lung cancer patients. The primary objectives were safety, recommended phase 2 dose (RP2D) in Phase I and PFS in Phase II. The secondary aim of the study is to evaluate the progression-free survival (PFS), overall survival (OS), adverse events (AEs), and duration of response (DOR) of the combined strategy in these patients. If the RP2D is reached in Phase I, Phase II will be started; if RP2D is not reached in Phase I, Phase II will not be started. The number of subjects is determined according to the actual situation of dose climbing. All patients will be of histo- and/or cytopathology confirmed. Determination of the KRAS mutation type will be performed in the pathological department of Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine. Both ARMS method or targeted sequencing are acceptable. It is not acceptable for subjects with the presence of other driver gene mutation. All eligible subjects must have adequate renal, hepatic, and hematologic function, as defined in "inclusion criteria".

Conditions

• KRAS Mutation-Related Tumors
• Advanced Lung Cancer
• Refractory Tumor

Interventions

Type	Name	Description
DRUG	Trametinib	Trametinib will be administrated orally every day.
DRUG	Anlotinib	Anlotinib will be administrated orally from day 1 to day 14 per 21-day cycle.
DRUG	Tislelizumab	Tislelizumab will be administered at full dose (200mg, Q3W) on the patient who received the efficacy evaluation of stable disease (SD) or partial response (PR) or complete response (CR) after 2 cycles' treatment of trametinib plus anlotinib.

Timeline

• Start date: 2024-07-01
• Primary completion: 2026-06-30
• Completion: 2028-12-31
• First posted: 2024-06-13
• Last updated: 2024-06-13

Locations

1 site across 1 country: China