ALK Gene Rearrangement Positive, EGFR Activating Mutation, EGF-R Positive Non-Small Cell Lung Cancer, Nsclc, ROS1 Gene Rearrangement, ROS1 Positive NSCLC - Reactive Oxygen Species 1 Positive Non-Small Cell Lung Cancer
Conditions
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.
Interventions
DRUGPembrolizumab
200 mg Q3W
DRUGLenvatinib
8 mg daily
DRUGPemetrexed
500 mg/m2 Q3W
DRUGCarboplatin
AUC5 Q3W
Sponsors
Dr Joanne CHIU
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall response rate | 24 months | Proportion of patients who have a confirmed CR or PR per RECIST 1.1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
Hong Kong
Contacts
Primary ContactDr Joanne Chiu, MBBS
Backup ContactDr James Ho, MBBS
Outcome results
None listed