Pembrolizumab, Lenvatinib and Chemotherapy After TKIs in NSCLC

NCT04989322 | Unknown Phase 2

• 2 other identifiers: 475-0708-MT-LungMK-3475-C50
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Overall response rate

  Proportion of patients who have a confirmed CR or PR per RECIST 1.1

  24 months

Secondary Outcomes (3)

• Progression-free survival

  24 months

• Overall survival

  36 months

• The incidence, severity as graded by NCI CTCAE v5.0, seriousness and relationship to study medication of adverse events (AEs)

  24 months

Study Arms (1)

Treatment

EXPERIMENTAL

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

Interventions

Pembrolizumab DRUG

200 mg Q3W

Treatment

Lenvatinib DRUG

8 mg daily

Treatment

Pemetrexed DRUG

500 mg/m2 Q3W

Treatment

Carboplatin DRUG

AUC5 Q3W

Treatment

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Dr Joanne CHIU: lead

Study Sites (1)

Queen Mary Hospital

Hong Kong, Hong Kong

RECRUITING

Related Publications (1)

• Chan HW, Tse CCL, Li YC, Leung R, Kwok GW, Wong JSL, Li KH, Tsang JWY, Li CW, Lo JWY, Tang V, Hui R, Yau T, Ho JCM, Chiu JWY. A phase 2, open-label, single-arm study evaluating the combination of pembrolizumab, lenvatinib, carboplatin and pemetrexed in patients with metastatic non-small cell lung cancer harbouring targetable genomic alterations who progressed on standard tyrosine kinase inhibitors. Invest New Drugs. 2025 Dec;43(6):1191-1200. doi: 10.1007/s10637-025-01589-6. Epub 2025 Nov 10.

  PMID: 41212380 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

pembrolizumab; lenvatinib; Pemetrexed; Carboplatin

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

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; Coordination Complexes; Organic Chemicals

Central Study Contacts

Dr Joanne Chiu, MBBS

CONTACT

+852-22553111; jwychiu@hku.hk

Dr James Ho, MBBS

CONTACT

+852-22553111; jhocm@hku.hk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: July 26, 2021
• First Posted: August 4, 2021
• Study Start: October 5, 2021
• Primary Completion: August 1, 2024
• Study Completion: December 1, 2024
• Last Updated: December 8, 2021

Record last verified: 2021-11

Locations

HK (1)