Pembrolizumab, Lenvatinib and Chemotherapy After TKIs in NSCLC

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

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.

Study Overview

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

• Study Type: Interventional
• Enrollment (Anticipated): 46
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Dr Joanne Chiu, MBBS; Phone Number: +852-22553111; Email: jwychiu@hku.hk
• Study Contact Backup: Name: Dr James Ho, MBBS; Phone Number: +852-22553111; Email: jhocm@hku.hk

Study Locations

• Hong Kong
  • Hong Kong, Hong Kong
    • Recruiting
    • Queen Mary Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment	Drug: Pembrolizumab; 200 mg Q3W; Drug: Lenvatinib; 8 mg daily; Drug: Pemetrexed; 500 mg/m2 Q3W; Drug: Carboplatin; AUC5 Q3W

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Dr Joanne CHIU

Study record dates

Study Major Dates

• Study Start (Actual): October 5, 2021
• Primary Completion (Anticipated): August 1, 2024
• Study Completion (Anticipated): December 1, 2024

Study Registration Dates

• First Submitted: July 26, 2021
• First Submitted That Met QC Criteria: August 3, 2021
• First Posted (Actual): August 4, 2021

Study Record Updates

• Last Update Posted (Actual): December 8, 2021
• Last Update Submitted That Met QC Criteria: November 25, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Immunological; Protein Kinase Inhibitors; Folic Acid Antagonists; Carboplatin; Pembrolizumab; Pemetrexed; Lenvatinib
• Other Study ID Numbers: 475-0708-MT-Lung; MK-3475-C50 (Other Identifier: MSD)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No