Ramucirumab and Pembrolizumab for the Treatment of EGFR Mutant Recurrent or Metastatic Non-small Cell Lung Cancer

Inclusion Criteria

• •1. Adult patients aged ≥18 years
• •2. Histologically confirmed recurrent or metastatic non-small cell carcinoma of the lung with sensitizing EGFR mutations. Exon 20 resistance mutations will not be permitted but uncommon sensitizing mutations are allowed.
• •3. Prior Systemic Anticancer Therapy: Neo/adjuvant therapy or prior therapy for locally advanced disease will be permitted. Patients with prior exposure to PD/PD-L1 inhibitors will be excluded. No limit on prior EGFR TKIs (erlotinib, gefitinib, afatinib, dacomitinib or osimertinib). Prior chemotherapy for metastatic disease is permitted only. A 7 day washout period or four half-lives after the last treatment dose, whichever is longer, is required for TKI. A 4 week washout is required for cytotoxic chemotherapy.
• •4. Measurable disease per RECIST criteria
• •5. ECOG performance status of 0-1
• •6. Adequate organ function, hematologic, hepatic, renal and coagulation parameters as defined in the protocol.
• •7. Because the teratogenicity of ramucirumab is not known, the patient, if sexually active, must be postmenopausal, surgically sterile, or using effective contraception (hormonal or barrier methods).
• •8. Female patients of childbearing potential must have a negative serum pregnancy test within 72 hours prior to first dose of protocol therapy.
• •10. Hemoptysis (defined as bright red blood or ≥ 1/2 teaspoon) within 2 months prior to first dose of protocol therapy or with radiographic evidence of intratumor cavitation or has radiologically documented evidence of major blood vessel invasion or encasement by cancer.
• •11. Uncontrolled or poorly-controlled hypertension (\>160 mmHg systolic or \> 100 mmHg diastolic for \>4 weeks) despite standard medical management.
• •12. Any arterial thromboembolic events, including but not limited to myocardial infarction, transient ischemic attack, cerebrovascular accident, or unstable angina, within 6 months prior to first dose of protocol therapy.
• •13. Major surgery within 28 days or device placement within 7 days prior to the first dose of protocol therapy. Patient has elective or planned major surgery to be performed during the course of the clinical trial.
• •14. Serious or non-healing wound, ulcer, or bone fracture within 28 days of study treatment.
• •15. Prior history of GI perforation/fistula (within 6 months of first dose of protocol therapy) or risk factors for perforation.
• •16. Small cell or mixed (small cell/non-small cell) lung cancer
• •17. Pregnancy or breastfeeding.
• •18. Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
• •19. History of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
• •20. History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
• •21. Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• •22. Severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
• •23. Active infection requiring systemic therapy.
• •24. Known history of active TB (Bacillus Tuberculosis).