Pembrolizumab, Carboplatin, and Pemetrexed in Treating Patients with EGFR Mutant and ALK Positive Non-small Cell Lung Cancer

Inclusion Criteria

• COHORT I: EGFR mutation positive NSCLC patients previously treated with appropriate targeted therapy with progressive and measurable disease per RECIST 1.1 criteria tumor.
• COHORT II: Other genetically altered NSCLC patients previously treated with appropriate targeted therapy with progressive and measurable tumor. Patients could have received more than 1 targeted therapy. Patients taken off an appropriate targeted therapy due to intolerance are eligible.
• Tumor tissue for PD-L1 assessment should be available unless PD-L1 assessment results are already available
• Patients should not have received any systemic chemotherapy for advanced NSCLC. Patients who have received neoadjuvant, adjuvant or as part of concurrent chemotherapy and radiation are eligible if they received the chemotherapy 12 months or more before the start of study therapy
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1
• Patients should have recovered to =< grade 1 from clinically meaningful (example alopecia is not considered clinically meaningful) adverse events related to prior treatments
• Patients should be willing and able to provide written informed consent for the trial
• Be >= 18 years of age on day of signing informed consent
• Absolute neutrophil count (ANC) >= 1,500 /mcL (performed within 14 days of treatment initiation)
• Platelets >= 100,000 / mcL (performed within 14 days of treatment initiation)
• Hemoglobin >= 9 g/dL or >= 5.6 mmol/L (performed within 14 days of treatment initiation)
• Serum creatinine =< 1.5 X upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) OR >= 45 mL/min for subject with creatinine levels > 1.5 X institutional ULN (performed within 14 days of treatment initiation)
• Serum total bilirubin =< 1.5 X ULN OR direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 ULN (performed within 14 days of treatment initiation)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X ULN OR =< 5 X ULN for subjects with liver metastases (performed within 14 days of treatment initiation)
• Female subject of childbearing potential should have a negative urine or serum pregnancy within 1 week of enrollment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Patients may need the pregnancy test repeated if the test done prior to enrollment is more than 1 week prior to receiving the first dose of study medication
• Female subjects of childbearing potential must be willing to use an adequate method of contraception. Contraception for the course of the study through 120 days after the last dose of study medication. Note- Abstinence is acceptable if this is the usual lifestyle and preferred contraception of the subject
• Male subjects of child bearing potential must agree to use an adequate method of contraception. Contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject

Exclusion Criteria

• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment. If the half-life of the drug is known then starting therapy 5 half-lives after the end of the last therapy is acceptable
• Has a diagnosis of immunodeficiency. Patient should not be on any immunosuppressive therapy or steroids > prednisone 10 mg/day or its equivalent on the day of the start of therapy
• Has a known history of active TB (Bacillus tuberculosis)
• Hypersensitivity to pembrolizumab, carboplatin or pemetrexed or any of its excipients
• Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier
• Has had targeted small molecule therapy, or palliative radiation therapy within 1 week prior to study day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to a previously administered agent. Patients who received stereotactic radiotherapy can start on therapy without any delay as long as they have recovered from any adverse events to =< grade 1. Also it is well recognized that some EGFR and ALK patients after discontinuing their TKI can develop tumor flare. Therefore if it is felt that in the best interest of the patient the prior TKI should be continued until the day prior to start of this study therapy it is acceptable * Note: Subjects with =< grade 2 neuropathy are an exception to this criterion and may qualify for the study * Patients with grade 2 or greater toxicities from prior therapy, such as alopecia, that are not considered clinically meaningful and not likely to impact administration of study therapy may start study therapy. An approval from the principal investigator of the study is required for adverse events (AEs) related to prior therapies other than alopecia that are not grade 1 * Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
• Has a known additional malignancy that is progressing or requires active treatment or the treating physician believes will require therapy within 1 year. Discussion with principal investigator is required before enrolling a patient with known history of another malignancy
• Has symptomatic central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with asymptomatic brain metastases may participate provided they are clinically stable and are not using steroids equivalent to > 10 mg of prednisone day prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of whether it is symptomatic or not
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
• Has known history of non-infectious pneumonitis that required steroids or has current pneumonitis. Has known history of interstitial lung disease
• Has an active infection requiring systemic therapy
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject’s participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
• Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
• Has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected)
• Has received a live vaccine within 30 days of planned start of study therapy. * Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines, and are not allowed