The Selective Personalized Radio-Immunotherapy for Locally Advanced NSCLC Trial

Participants are eligible to be included in the study only if all the following criteria apply: 1. Male/female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of non-small cell lung cancer will be enrolled in this study. 2. Previously untreated, pathologically proven NSCLC with measurable disease (at least 1 unidimensional, radiographically measurable lesion based on RECIST v1.1) and one of the following stages: (prior resection for early stage disease is allowed) 1. AJCC version 8 Stage II disease, medically or technically unresectable 2. AJCC version 8 Stage III disease 3. Whole body PET/CT within 42 days prior to study entry demonstrating hypermetabolic pulmonary lesion(s) and/or thoracic lymph node(s). If PET/CT was obtained more than 42 days prior to study entry and is not repeated, CT within 28 days prior to study entry demonstrating no evidence of metastatic disease is required. 4. MRI of the brain or head CT with contrast within 42 days prior to study entry. 5. PFTs within 42 days of study entry 6. ECOG performance status 0-1 7. Adequate end-organ function, based on routine clinical and laboratory workup: 1. ANC \>1,500 cells/µl, Platelets ≥ 100,000 cells/µl, Hemoglobin ≥ 9.0 g/dl 2. Serum creatinine ≤ 1.5 x ULN or calculated creatinine clearance ≥ 50 ml/min 3. Total bilirubin ≤ 1.5 x ULN (or direct bilirubin below the ULN), AST and ALT ≤ 2.5 x ULN 4. International normalized ratio (INR) (or prothrombin time (PT)) and activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN unless participant is receiving anticoagulant therapy, as long as values are within the intended therapeutic range 5. Thyroid stimulating hormone (TSH) within normal limits. If TSH is not within normal limits, the participant may be eligible if T3 and free T4 are within normal limits. 8. A female participant is eligible to participate if she is not pregnant (see

), not breastfeeding, and at least one of the following conditions applies: 1. Not a woman of childbearing potential (WOCBP) as defined in the Appendix 2. A WOCBP who agrees to follow the contraceptive guidance in the Appendix during the treatment period and for at least 120 days after the last dose of study treatment with pembrolizumab (pembroRT cohort) or at least 180 days after the last dose of chemotherapy (chemoRT cohort). 9. A male participant must agree to use contraception during the treatment period and for at least 28 days after the last dose of study treatment and refrain from donating sperm during this period. 10. The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.