Clinical trial NCT04989322: 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
Overall status: UNKNOWN
Phase: PHASE2
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
Lead sponsor: The University of Hong Kong
Sponsor class: OTHER
First posted: 2021-08-04
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Overall response rate
timeFrame: 24 months
Secondary outcomes:
measure: Progression-free survival
timeFrame: 24 months
measure: Overall survival
timeFrame: 36 months
measure: The incidence, severity as graded by NCI CTCAE v5.0, seriousness and relationship to study medication of adverse events (AEs)
timeFrame: 24 months
Other outcomes:
Locations:
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
Study officials:
References: