Pembrolizumab, Lenvatinib and Chemotherapy After TKIs in NSCLC

Sponsor

Dr Joanne CHIU (Other)

Overall Status

Recruiting

CT.gov ID

NCT04989322

Collaborator

(none)

Enrollment

Location

Arm

37.9

Anticipated Duration (Months)

1.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
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	Drug: Pembrolizumab Drug: Lenvatinib Drug: Pemetrexed Drug: Carboplatin	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

46 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Oct 5, 2021

Anticipated Primary Completion Date :

Aug 1, 2024

Anticipated Study Completion Date :

Dec 1, 2024

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Overall response rate [24 months]
Proportion of patients who have a confirmed CR or PR per RECIST 1.1

Secondary Outcome Measures

Progression-free survival [24 months]
Time from randomization to the first documented disease progression per RECIST 1.1 or death due to any cause, whichever occurs first
Overall survival [36 months]
Time from randomization to death from any cause or last follow-up date
The incidence, severity as graded by NCI CTCAE v5.0, seriousness and relationship to study medication of adverse events (AEs) [24 months]
Safety and tolerability

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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