Pembrolizumab, Lenvatinib and Chemotherapy After TKIs in NSCLC

Phase 2

Recruiting

• Conditions: Nsclc; EGF-R Positive Non-Small Cell Lung Cancer; ROS1 Gene Rearrangement; EGFR Activating Mutation; ALK Gene Rearrangement Positive; ROS1 Positive NSCLC - Reactive Oxygen Species 1 Positive Non-Small Cell Lung Cancer
• Interventions: Drug: Pembrolizumab; Drug: Lenvatinib; Drug: Pemetrexed; Drug: Carboplatin

• Registration Number: NCT04989322
• Lead Sponsor: Dr Joanne CHIU

Brief Summary

Adding chemotherapy or anti-VEGF to immunotherapy is an emerging strategy to enhance the efficacy of immunotherapy in many cancers. This phase 2 study aims to explore the preliminary efficacy of combination pembrolizumab with lenvatinib and chemotherapy in NSCLC patients with sensitizing EGFR, ALK, or ROS1 genetic aberration refractory to standard targeted therapy.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-07-26
• Study First Submitted QC: 2021-08-03
• Study First Posted: 2021-08-04
• Study Start: 2021-10-05
• Status Verified: 2021-11
• Last Update Submitted: 2021-11-25
• Last Update Posted: 2021-12-08
• Primary Completion: 2024-08
• Study Completion: 2024-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 46

Inclusion Criteria

• Histologically proven NSCLC
• Unresectable or metastatic NSCLC, including squamous cell carcinoma, harboring sensitizing EGFR, ALK, or ROS1 genetic aberrations who have received standard of care targeted therapy and have progressed on treatment. Patients with known T790M mutation should have received osimertinib and failed.
• Measurable disease per RECIST 1.1
• ECOG performance status ≤ 1
• Adequate organ function
• Adequately controlled blood pressure

Main

Exclusion Criteria

• Prior exposure to immunotherapy or chemotherapy
• Active untreated brain metastasis and/or carcinomatous meningitis
• Active, known or suspected autoimmune disease
• History of (noninfectious) pneumonitis that required systemic steroids or current pneumonitis/interstitial lung disease
• Condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications
• Baseline proteinuria ≥ 1 g/24 hrs
• Electrolyte abnormalities that have not been corrected
• Significant cardiovascular impairment
• Gastrointestinal pathology that might affect the absorption of lenvatinib
• Preexisting grade ≥ 3 gastrointestinal or non gastrointestinal fistula
• Bleeding or thrombotic disorders or subjects at risk for severe hemorrhage
• Radiographic evidence of intratumoral caviations, encasement, or invasion of a major blood vessel
• Known history of tuberculosis
• Active, acute, or chronic clinically significant infections requiring therapy, including hepatitis B, hepatitis C, and HIV
• ECG with long QTc interval ≥ 470 ms

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment	Carboplatin	-
Treatment	Lenvatinib	-
Treatment	Pemetrexed	-
Treatment	Pembrolizumab	-

Primary Outcome Measures

Name	Time	Method
Overall response rate	24 months	Proportion of patients who have a confirmed CR or PR per RECIST 1.1

Secondary Outcome Measures

Name	Time	Method
The incidence, severity as graded by NCI CTCAE v5.0, seriousness and relationship to study medication of adverse events (AEs)	24 months	Safety and tolerability
Overall survival	36 months	Time from randomization to death from any cause or last follow-up date
Progression-free survival	24 months	Time from randomization to the first documented disease progression per RECIST 1.1 or death due to any cause, whichever occurs first

Trial Locations

Locations (1)

Queen Mary Hospital; 🇭🇰 Hong Kong, Hong Kong