Pembrolizumab, Lenvatinib and Chemotherapy After TKIs in NSCLC

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 2 Open-label Single-arm Study to Evaluate the Combination of Pembrolizumab, Lenvatinib and Chemotherapy in Non-small Cell Lung Cancer (NSCLC) Harbouring Targetable Mutation and Failed Standard Tyrosine Kinase Inhibitors

Conditions
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Nsclc, EGFR Activating Mutation, EGF-R Positive Non-Small Cell Lung Cancer, ALK Gene Rearrangement Positive, ROS1 Gene Rearrangement, ROS1 Positive NSCLC - Reactive Oxygen Species 1 Positive Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Pembrolizumab
* Drug: Lenvatinib
* Drug: Pemetrexed
* Drug: Carboplatin


Participation Criteria
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Eligibility Criteria
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Main 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br> | Drug: Pembrolizumab<br>* 200 mg Q3W<br>Drug: Lenvatinib<br>* 8 mg daily<br>Drug: Pemetrexed<br>* 500 mg/m2 Q3W<br>Drug: Carboplatin<br>* AUC5 Q3W<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate | Proportion of patients who have a confirmed CR or PR per RECIST 1.1 | 24 months | 

Secondary Outcome Measures

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