A Study to Evaluate Pembrolizumab Plus Lenvatinib in PD-L1 Positive TKI Resistant NSCLC Patients

NCT05078931 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: TBA
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

This study will investigate the efficacy and safety of the combination of pembrolizumab and lenvatinib in PD-L1 positive patients with TKI-resistant EGFR-mutated advanced NSCLC.

Conditions

NSCLC

Keywords

Pembrolizumab; Lenvatinib; NSCLC

Outcome Measures

Primary Outcomes (1)

• Progression-free survival

  the time from the start of intervention to evidence of radiographic progression as defined by RECIST criteria or death from any cause without evidence of disease progression, whichever occurs first. Cases with incomplete follow up or without adequate disease evaluations will be censored at date last documented to be progression free.

  Up to approximately 12 months

Secondary Outcomes (3)

• Overall survival

  Up to approximately 24 months

• Objective Response Rate

  Up to approximately 24 months

• Duration of Response

  Up to approximately 24 months

Study Arms (1)

Pembrolizumab + Lenvatinib in PD-L1 Positive TKI resistant NSCLC patients

EXPERIMENTAL

The PD-L1 positive patients with TKI-resistant EGFR-mutated advanced NSCLC will receive the combination of pembrolizumab and lenvatinib.

Drug: Pembrolizumab; Drug: Lenvatinib

Interventions

Pembrolizumab DRUG

Pembrolizumab 200 mg will be administered as a 30-minute IV infusion every 3 weeks for up to 35 cycles

Also known as: Keytruda

Pembrolizumab + Lenvatinib in PD-L1 Positive TKI resistant NSCLC patients

Lenvatinib DRUG

Lenvatinib 20mg will be administered orally daily.

Also known as: Lenvima

Pembrolizumab + Lenvatinib in PD-L1 Positive TKI resistant NSCLC patients

Eligibility Criteria

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

You may qualify if:

• Have a histologically or cytologically confirmed stage IV NSCLC by American Joint Committee on Cancer Version 8
• Have confirmation with sensitizing EGFR mutations, either DEL19 or L858R
• Have undergone failure 1-2 prior EGFR-TKI (Osimertinib exposure required for T790M+)
• Have measurable disease based on RECIST 1.1, as determined by the local site.
• \- Note: Lesions that appear measurable but are situated in a previously irradiated area can be considered measurable (eligible for selection as target lesions) if they have shown documented growth since the completion of radiation.
• Tumor tissue that demonstrates PD-L1 expression in ≥1% of tumor cells (TPS ≥1%) as assessed by IHC 22C3 pharmDx.
• Note: Assessment of PD-L1 expression must be made from provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated. (A fine-needle aspirate, frozen sample, plastic embedded sample, cell block, clot, bone, bone marrow, cytologic specimen, or decalcified or formalin-fixed sample that was frozen at any point will not be acceptable for analysis). Formalin-fixed, paraffin-embedded tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue.

You may not qualify if:

• Has known untreated central nervous system metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable (ie, without evidence of progression for at least 4 weeks by repeat imaging (note: repeat imaging should be performed during study screening), clinically stable, and without requirement of steroid treatment for at least 14 days before first dose of study intervention.
• Has clinically significant hemoptysis (at least 0.5 teaspoon of bright red blood) or tumor bleeding within 2 weeks before the first dose of study intervention.
• Bleeding or thrombotic disorders or subjects at risk for severe hemorrhage. The degree of tumor invasion/infiltration of major blood vessels should be considered because of the potential risk of severe hemorrhage associated with tumor shrinkage/necrosis after lenvatinib therapy.
• Has a known history of an additional malignancy, except if the participant has undergone potentially curative therapy with no evidence of that disease recurrence for at least 3 years since initiation of that therapy.
• \- Note: The time requirement for no evidence of disease for at least 3 years does not apply to the NSCLC for which a participant is enrolled in the study. The time requirement also does not apply to participants who underwent successful definitive resection of basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, in situ cervical cancer, or other in situ cancers.
• Has an active autoimmune disease that has required systemic treatment in the past 2 years (ie, with the 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 not considered a form of systemic treatment and is allowed.
• 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 history of (noninfectious) pneumonitis that required systemic steroids or current pneumonitis/interstitial lung disease.
• Has a known history of hepatitis B (defined as hepatitis B surface antigen \[HBsAg\] reactive or hepatitis B virus \[HBV\]-DNA detected) or known active hepatitis C virus (HCV, defined as HCV-RNA \[qualitative\] detected or HCV antibody reactive, if HCV-RNA is not the local SOC) infection.
• \- Note: No testing for hepatitis B and hepatitis C is required unless mandated by the local health authority.
• Has a history of a gastrointestinal condition or procedure that in the opinion of the investigator may affect oral study drug absorption.
• Has significant cardiovascular impairment within 12 months of the first dose of study intervention, such as a history of congestive heart failure greater than New York Heart Association Class II, unstable angina, myocardial infarction, cerebrovascular accident (CVA)/stroke, or cardiac arrhythmia associated with hemodynamic instability.
• Has not recovered adequately from any toxicity and/or complications from major surgery before starting therapy.
• Has a known history of active tuberculosis (TB).

Sponsors & Collaborators

• Shanghai Chest Hospital: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Department of Oncology, Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University

Shanghai, 200030, China

Location

MeSH Terms

Interventions

pembrolizumab; lenvatinib

Study Officials

• Shun Lu

  Shanghai Chest Hospital

  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: Chief of Shanghai Lung Cancer Center

Model Details: This is an open-label, single-arm phase II study of lenvatinib plus pembrolizumab in PD-L1 positive patients with TKI-resistant EGFR-mutated advanced non-small cell lung cancer.

Study Record Dates

• First Submitted: September 14, 2021
• First Posted: October 15, 2021
• Study Start: October 27, 2021
• Primary Completion: December 30, 2025
• Study Completion (Estimated): December 30, 2026
• Last Updated: July 30, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)