Patients with EGFR or ALK positive tumour mutations should also have received targeted therapy before receiving Keytruda.

Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.

...Patients with histologically or cytologically confirmed:Metastatic NSCLC (adenocarcinoma) (Arm A), who have not received prior systemic treatment for their metastatic disease and who have:• no known sensitizing genetic aberrations where there are approved therapies (such as EGFR, KRAS G12C, BRAF V600E, MET skipping mutations, and RET mutations or rearrangements)orMetastatic SCCHN (Arm B) with no prior therapy and who have:• Histologically- or cytologically-confirmed recurrent (without metastases) or metastatic SCCHN considered incurable by local therapies. ...

...Do not have an EGFR sensitizing (activating) mutation or ALK translocation and have a PD-L1 “low” (<50%) tumor as determined by immunohistochemistry with anti-PD-L1 antibody (DAKO 22C3). ...

...- Cohort-specific: Cohort 1- EGFR mutation positive NSCLC patients previously treated with appropriate targeted therapy with progressive and measurable disease per RECIST 1.1 criteria tumor....

...Patients with epidermal growth factor (EGFR) mutation, anaplastic lymphoma kinase (ALK) gene rearrangement or ROS1 translocation must have received an approved EGFR, ALK, or ROS1-directed therapy and have signs of disease progression prior to receiving pembrolizumab....

...- Has documentation of epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) translocation status...

...In the presence of an EGFR mutation, an ALK or ROS1 rearrangement the patient must have received at least one specific targeted therapy line....

...Without activating mutation in EGFR or ALK chromosomal translocation....

...Documentation of the absence of tumor activating EGFR mutations, BRAF mutations, ALK gene rearrangements, and ROS1 gene rearrangements is required....

...- Has received an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (either erlotinib, gefitinib, or afatinib) if they have an EGFR sensitizing mutation...

...Participants must have been tested for mutations affecting EGFR and/or anaplastic lymphoma kinase (ALK)....

...- Histologic confirmation of NSCLC by biopsy or cytology (primary cancer are eligible: squamous cell carcinoma, adenocarcinoma; no sensitizing mutation in the epidermal growth factor receptor (EGFR) gene or anaplastic lymphoma kinase (ALK) gene translocation; stage IV according to the 8th version of the IASLC system); - Age >= 18 years; - Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1; - At least two lesions measurable according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1; - Life expectancy of at least 3 months; - Signature of informed consent form; - Patients must have adequate organ function. ...

...- Tumors with epidermal growth factor receptor mutation positive or anaplastic lymphoma kinase fusion oncogene positive treated with a tyrosine kinase inhibitor are permitted; however, subjects should have progressed on or be intolerant to the targeted therapy....

...- Have an EGFR mutation (sensitizing or non-sensitizing)...

...Subjects with a known mutation of EGFR and received EGFR TKI (erlotinib , gefitinib or experimental) and double platinum-based chemotherapy ( regardless of the order of administration)....

...For non-squamous NSCLCs and non-smoking squamous NSCLCs, no known activating mutations of EGFR and no ALK or ROS1 rearrangements.5. ...

...Has confirmation that EGFR-, ALK-, or ROS-1-directed therapy is not indicated as primary therapy (documentation of the absence of tumor-activating EGFR mutations [eg, DEL19 or L858R], AND absence of ALK and ROS-1 gene rearrangements).4. ...

...2.Confirmation that EGFR-, ALK-, or ROS1-directed therapy is not indicated as primary therapy (documentation of absence of tumor-activating EGFR mutations [eg, DEL19 or L858R] AND absence of ALK and ROS1 gene rearrangements). ...

...Note:Tumor testing for EGFR or ALK mutations is required if status is unknown 4)Have no known genomic alterations in ROS proto-oncogene 1 (ROS1), neurotrophic tyrosine receptor kinase (NTRK), proto-oncogene B-raf (BRAF), RET mutations, or other actionable driver oncogenes with approved therapies (actionable genomic alteration). ...

...To be checked before the induction phase (only for patient included before induction phase):1.Histologically or cytologically confirmed diagnosis of non-squamous non-small cell lung cancer (NSCLC).2.Non-operable / non-irradiable stage III or stage IV.3.Patient must be eligible to receive 3 or 4 cycles of induction treatment combination with pembrolizumab plus platinum (cisplatin or carboplatin) and pemetrexed.4.In the presence of an EGFR mutation, an ALK or ROS1 rearrangement the patient must have received at least one specific targeted therapy line.5. ...

...Patients with negative EGFR-sensitive mutation and ALK fusion gene test results by genetic testing; 7. ...

...Phase 2 Cohort 1: no Epidermal Growth Factor Receptor (EGFR) sensitization (activating) mutation or anaplastic lymphoma kinase (ALK)/ROS1 rearrangement. ...

...- Patients with known EGFR mutations (except exon 20 insertion), BRAF mutations (V600) or ALK or ROS1 translocations or other driver mutations that can be treated with oral tyrosine kinase inhibitors are excluded...

...Epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase (ALK) mutation-negative NSCLC patients and NSCLC patients with EGFR or ALK genomic tumor aberrations that have failed FDA-approved targeted therapy for these aberrations will be eligible for enrollment in the study....

...If the patient has a sensitizing EGFR mutation or ALK rearrangement, the patient must have received at least one prior targeted therapy for metastatic disease (ie, EGFR TKI therapy or ALK TKI therapy, respectively)....

...Patients with sensitive EGFR mutations should have disease progression on at least one of EGFR TKIs (including but...

...- Subjects whose tumors harbor a mutation in EGFR exon 19 or 21 or have gene rearrangements in ALK or ROS1 must have already been treated with standard targeted therapies....

...- Chemotherapy naïve NSCLC patients.For NSCLC patients with lung adenocarcinoma, tumors must be Epidermal Growth Factor Receptor (EGFR) and Anaplastic Lymphoma Kinase (ALK) wild-type; if a Kirsten Ras (KRAS) mutation is detected, EGFR and ALK testing is...

...In patients with non-squamous non-small cell lung cancer, investigators must be able to produce source documentation of the EGFR mutation status or ALK translocation status....

...- Histological or cytological diagnosis of Stage IV NSCLC lacking epidermal growth factor receptor (EGFR)-sensitizing mutation and/or anaplastic lymphoma kinase (ALK) translocation, and received...

Improved median overall survival was also observed in patients receiving pembrolizumab plus chemotherapy (26.7 [95% CI 22.6-30.8] vs. 13.4 months [95% CI 10.4-16.4], HR, 0.49 [95% CI 0.31-0.75], P = .0052). In addition, the overall response rate was higher in patients treated with than patients treated without pembrolizumab (34.1% and 20.7%, respectively)....The combination of pembrolizumab with chemotherapy is associated with improved efficacy and survival in patients with EGFR-mutant NSCLC after TKI resistance...

Patients with recurrent EGFR-mutated or ALK-rearranged NSCLC, previously treated with targeted therapy, were eligible. Patients were treated with carboplatin AUC5, pemetrexed 500 mg/m2 and pembrolizumab 200 mg I.V. every 3 weeks….Pembrolizumab in combination with chemotherapy demonstrated a response rate of 42% and median survival of 22 months among patients with recurrent EGFR-mutated NSCLC.

Patients with recurrent EGFR-mutated or ALK-rearranged NSCLC, previously treated with targeted therapy, were eligible. Patients were treated with carboplatin AUC5, pemetrexed 500 mg/m2 and pembrolizumab 200 mg I.V. every 3 weeks. After 4 cycles patients were maintained on pemetrexed and pembrolizumab for up to 2 years....Response rates (95%CI) were 42% (23%, 63%) and 29% (4%, 71%) among EGFR+ and ALK+ patients, respectively. Median duration of response was 6.1 months in all patients and in EGFR+ patients.

In this retrospective analysis, we compared the clinical efficacy of pembrolizumab monotherapy (PM), pembrolizumab combined with chemotherapy (P+C) and pembrolizumab combined with anlotinib (P+A) in NSCLC patients with EGFR mutation who had failed on EGFR-TKI and platinum-based chemotherapy....The addition of chemotherapy or antiangiogenic therapy to pembrolizumab resulted in significantly longer PFS, OS and ORR than pembrolizumab alone in our study.

R/M-NSCLC treated with pembrolizumab or nivolumab...In multivariable analysis, concordance of TPS ≥ 50% in both PD-L1 assays and the development of immune-related adverse events (irAEs) were two significant predictors of better ORR, PFS, and OS. EGFR mutation could also predict significantly worse OS outcomes.

We genotyped 190 patients with advanced lung adenocarcinomas who received nivolumab or pembrolizumab monotherapy...The progression-free survival was 0.6 (95% CI: 0.2-2.1) months for ALK-positive patients and 1.8 (95% CI: 1.2-2.1) months for EGFR-positive patients... Our data suggested that ICI treatment was significantly less efficacious in patients with ALK rearrangement than in patients with EGFR mutations...

In this phase 2 study, the combination of pembrolizumab plus docetaxel was well tolerated and substantially improved ORR and PFS in patients with advanced NSCLC who had previous progression after platinum-based chemotherapy, including NSCLC with EGFR variations.

The objective response rate to pembrolizumab of 14 patients was 36%, including 22% in patients with common EGFR mutations,