Back to resultsPembrolizumab, Lenvatinib and Chemotherapy After TKIs in NSCLC
Primary Purpose
Nsclc, EGFR Activating Mutation, EGF-R Positive Non-Small Cell Lung Cancer
Status
Recruiting
Phase
Phase 2
Locations
Hong Kong
Study Type
Interventional
Intervention
Pembrolizumab
Lenvatinib
Pemetrexed
Carboplatin
Sponsored by
About this trial
This is an interventional treatment trial for Nsclc
Eligibility Criteria
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
Sites / Locations
- Queen Mary HospitalRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Treatment
Arm Description
Outcomes
Primary Outcome Measures
Overall response rate
Proportion of patients who have a confirmed CR or PR per RECIST 1.1
Secondary Outcome Measures
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
Overall survival
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)
Safety and tolerability
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04989322
Brief Title
Pembrolizumab, Lenvatinib and Chemotherapy After TKIs in NSCLC
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
Study Type
Interventional
2. Study Status
Record Verification Date
November 2021
Overall Recruitment Status
Recruiting
Study Start Date
October 5, 2021 (Actual)
Primary Completion Date
August 2024 (Anticipated)
Study Completion Date
December 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Dr Joanne CHIU
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
46 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Treatment
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Pembrolizumab
Intervention Description
200 mg Q3W
Intervention Type
Drug
Intervention Name(s)
Lenvatinib
Intervention Description
8 mg daily
Intervention Type
Drug
Intervention Name(s)
Pemetrexed
Intervention Description
500 mg/m2 Q3W
Intervention Type
Drug
Intervention Name(s)
Carboplatin
Intervention Description
AUC5 Q3W
Primary Outcome Measure Information:
Title
Overall response rate
Description
Proportion of patients who have a confirmed CR or PR per RECIST 1.1
Time Frame
24 months
Secondary Outcome Measure Information:
Title
Progression-free survival
Description
Time from randomization to the first documented disease progression per RECIST 1.1 or death due to any cause, whichever occurs first
Time Frame
24 months
Title
Overall survival
Description
Time from randomization to death from any cause or last follow-up date
Time Frame
36 months
Title
The incidence, severity as graded by NCI CTCAE v5.0, seriousness and relationship to study medication of adverse events (AEs)
Description
Safety and tolerability
Time Frame
24 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Dr Joanne Chiu, MBBS
Phone
+852-22553111
Email
jwychiu@hku.hk
First Name & Middle Initial & Last Name or Official Title & Degree
Dr James Ho, MBBS
Phone
+852-22553111
Email
jhocm@hku.hk
Facility Information:
Facility Name
Queen Mary Hospital
City
Hong Kong
Country
Hong Kong
Individual Site Status
Recruiting
12. IPD Sharing Statement
Learn more about this trial
Pembrolizumab, Lenvatinib and Chemotherapy After TKIs in NSCLC
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