Lenvatinib in Combination With Carboplatin Pemetrexed and Pembrolizumab for NSCLC With EGFR Mutations

NCT05258279 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: NEJ052
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 10

Brief Summary

The purpose of this study is to assess the safety and efficacy of pemetrexed + carboplatin + pembrolizumab (MK-3475) with lenvatinib (MK-7902/E7080) in patients with advanced nonsquamous non-small cell lung cancer harboring EGFR mutations.

Conditions

Non-squamous Non-small-cell Lung Cancer; EGFR Activating Mutation

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR) as Assessed by BICR according to RECIST 1.1

  ORR is defined as the percentage of participants in the analysis population who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1.

  Up to approximately 18 months

Secondary Outcomes (6)

• Objective Response Rate (ORR) as Assessed by investigators according to RECIST 1.1.

  Up to approximately 18 months

• Progression-free Survival (PFS) as Assessed by investigators according to RECIST 1.1

  Up to approximately 30 months

• Overall Survival (OS)

  Up to approximately 30 months

• Duration of Response (DOR) as Assessed by investigators according to RECIST 1.1.

  Up to approximately 30 months

• Number of Participants with One or More Adverse Events

  Up to approximately 30 months

Study Arms (1)

Pemetrexed+Carboplatin+Pembrolizumab+Lenvatinib

EXPERIMENTAL

Participants receive carboplatin Area Under Curve 5 mg/mL/min (AUC5) via intravenous (IV) infusion on Day 1 of each 3-week cycle (Q3W) for 4 cycles PLUS pemetrexed 500 mg/m\^2 via IV infusion Q3W for 4 cycles PLUS pembrolizumab via IV infusion Q3W for up to 35 cycles (up to 2 years) PLUS lenvatinib via oral capsule once daily for up to 2 years.

Drug: Pembrolizumab; Drug: Lenvatinib; Drug: Carboplatin; Drug: Pemetrexed

Interventions

Pembrolizumab DRUG

IV infusion Q3W

Also known as: MK-3475

Pemetrexed+Carboplatin+Pembrolizumab+Lenvatinib

Lenvatinib DRUG

Oral capsule once daily

Also known as: MK-7902, E7080

Pemetrexed+Carboplatin+Pembrolizumab+Lenvatinib

Carboplatin DRUG

IV infusion Q3W

Pemetrexed+Carboplatin+Pembrolizumab+Lenvatinib

Pemetrexed DRUG

IV infusion Q3W

Pemetrexed+Carboplatin+Pembrolizumab+Lenvatinib

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have a histologically or cytologically confirmed diagnosis of incurable Stage IIIB, IIIC, IVA, IVB (American Joint Committee on Cancer \[AJCC\], version 8) non-squamous NSCLC. Postoperative recurrence is acceptable if the disease is not curable.
• Have documentation of tumor activating EGFR mutation, specifically either exon 19 deletion or exon 21 L858R.
• Have investigator determined radiographic disease progression per RECIST 1.1 after treatment with EGFR-TKI therapy:
• Participants previously treated with 1st or 2nd generation EGFR TKI (eg, erlotinib/afatinib/gefitinib) are required to have confirmed documented absence of EGFR T790M mutation.
• Participants with confirmed acquired T790M mutation after 1st or 2nd generation EGFR-TKI (eg, erlotinib/afatinib/gefitinib) are required to have osimertinib TKI treatment failure prior to enrollment.
• Participants previously failed osimertinib TKI treatment as 1st line therapy are eligible regardless of their EGFR T790M mutation status.
• Participants treated with a combination of EGFR TKIs and antibodies targeting the VEGF pathway will also be eligible.
• Have measurable disease per RECIST 1.1.
• Be male or female ≥ 20 years of age inclusive, at the time of signing the informed consent form (ICF).
• Have a life expectancy of at least 3 months.
• Have an ECOG performance status of 0 or 1 within 7 days prior to the first dose of study intervention but before registration.
• A male participant must agree to use a contraception during the treatment period.
• A female participant is eligible to participate if she is not pregnant, not breastfeeding
• The participant provides written informed consent for the study.
• Have adequate organ function.

You may not qualify if:

• Has known untreated central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, clinically stable, and have not required steroids for at least 14 days prior to the first dose of study intervention.
• Has history of (noninfectious) pneumonitis that required systemic steroids or current pneumonitis/interstitial lung disease.
• Has a known history of an additional malignancy, except if the participant has undergone potentially curative therapy with no evidence of that disease of that disease recurrence for at least 3 year since initiation of that therapy.
• Has an autoimmune disease that has required systemic treatment in the past 2 years (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is allowed.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (doses exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study intervention.
• Has had an allogeneic tissue/solid organ transplant.
• Has a known history of human immunodeficiency virus (HIV) infection. HIV testing is not required unless mandated by the local health authority.
• Has a known history of Hepatitis B (defined as Hepatitis B surface antigen \[HBsAg\] reactive or HBV-DNA detected) or known active Hepatitis C virus (HCV antibody reactive).
• Has a history of a gastrointestinal condition or procedure that in the opinion of the investigator may affect oral drug absorption.
• Has active hemoptysis (at least 0.5 tsp of bright red blood) within 2 weeks prior to the first dose of study intervention.
• Has significant cardiovascular impairment within 12 months prior to the first dose of study intervention, including history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction, cerebrovascular accident (CVA)/stroke, or cardiac arrhythmia associated with hemodynamic instability.
• Has a known history of active tuberculosis.
• Has an active infection requiring systemic therapy.
• Has had major surgery within 3 weeks prior to first dose of study interventions.
• Note: Adequate wound healing after major surgery must be assessed clinically, independent of time elapsed for eligibility.

Sponsors & Collaborators

• Juntendo University: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (10)

Juntendo Urayasu Hospital

Urayasu, Chiba, 279-0021, Japan

Location

St. Marianna University Hospital

Kawasaki, Kanagawa, 216-8511, Japan

Location

Kanagawa Cardiovascular and Respiratory Center

Yokohama, Kanagawa, 236-0051, Japan

Location

Kanagawa Cancer Center

Yokohama, Kanagawa, 241-8515, Japan

Location

Saitama Medical University International Medical Center

Hidaka, Saitama, 350-1298, Japan

Location

Saitama Cancer Center

Shinden, Saitama, 362-0806, Japan

Location

Shizuoka Cancer Center

Nagaizumi-cho, Shizuoka, 411-8777, Japan

Location

Juntendo University Hospital

Bunkyo-ku, Tokyo, 113-8431, Japan

Location

Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital

Bunkyo-ku, Tokyo, 113-8677, Japan

Location

Chiba University Hospital

Chiba, 26-8677, Japan

Location

MeSH Terms

Interventions

pembrolizumab; lenvatinib; Carboplatin; Pemetrexed

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic

Study Officials

• Ryo Ko, MD, PhD

  Department of Respiratory Medicine, Juntendo University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant professor, Department of Respiratory Medicine

Study Record Dates

• First Submitted: February 17, 2022
• First Posted: February 28, 2022
• Study Start: July 1, 2022
• Primary Completion: October 31, 2023
• Study Completion: October 1, 2024
• Last Updated: August 28, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

JP (10)