Pembrolizumab, Lenvatinib and Chemotherapy After TKIs in NSCLC

Nsclc Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04989322
• Other study ID #: 475-0708-MT-Lung
• Secondary ID: MK-3475-C50
• Status: Recruiting
• Phase: Phase 2
• Start date: October 5, 2021
• Est. completion date: December 2024

Study information

• Verified date: November 2021
• Source: The University of Hong Kong
• Contact: Dr Joanne Chiu, MBBS
• Phone: +852-22553111
• Email: jwychiu[@]hku.hk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 46
• Est. completion date: December 2024
• Est. primary completion date: August 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• ALK Gene Rearrangement Positive
• Carcinoma, Non-Small-Cell Lung
• EGF-R Positive Non-Small Cell Lung Cancer
• EGFR Activating Mutation
• Lung Neoplasms
• Nsclc
• ROS1 Gene Rearrangement

Intervention

Drug:
• Pembrolizumab
200 mg Q3W
• Lenvatinib
8 mg daily
• Pemetrexed
500 mg/m2 Q3W
• Carboplatin
AUC5 Q3W

Locations

Country	Name	City	State
Hong Kong	Queen Mary Hospital	Hong Kong

Sponsors (1)

Lead Sponsor	Collaborator
Dr Joanne CHIU

Country where clinical trial is conducted

Hong Kong, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall response rate	Proportion of patients who have a confirmed CR or PR per RECIST 1.1	24 months
Secondary	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
Secondary	Overall survival	Time from randomization to death from any cause or last follow-up date	36 months
Secondary	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