A Study of Selpercatinib (LY3527723) in Participants With Advanced or Metastatic RET Fusion-Positive Non-Small Cell Lung Cancer

* Histologically or cytologically confirmed, Stage IIIB-IIIC or Stage IV non-squamous NSCLC that is not suitable for radical surgery or radiation therapy. * A RET gene fusion in tumor and/or blood from a qualified laboratory. * Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. * Adequate hematologic, hepatic and renal function. * Willingness of men and women of reproductive potential to observe conventional and highly effective birth control for the duration of treatment and for 6 months after. * Ability to swallow capsules.

* Additional validated oncogenic drivers in NSCLC if known. * Prior systemic therapy for metastatic disease. Treatment (chemotherapy, immunotherapy, or biological therapy) in the adjuvant/neoadjuvant setting is permitted if it was completed at least 6 months prior to randomization. * Major surgery within 3 weeks prior to planned start of selpercatinib. * Radiotherapy for palliation within 1 week of the first dose of study treatment or any radiotherapy within 6 months prior to the first dose of study treatment if more than 30 Gy to the lung. * Symptomatic central nervous system (CNS) metastases, carcinomatous meningitis, or untreated spinal cord compression. * Clinically significant active cardiovascular disease or history of myocardial infarction within 6 months prior to planned start of selpercatinib or prolongation of the QT interval corrected for heart rate using Fridericia's formula (QTcF) \> 470 milliseconds. * Active uncontrolled systemic bacterial, viral, or fungal infection or serious ongoing intercurrent illness, such as hypertension or diabetes, despite optimal treatment. * Clinically significant active malabsorption syndrome or other condition likely to affect gastrointestinal absorption of the study drug. * Pregnancy or lactation. * Other malignancy unless nonmelanoma skin cancer, carcinoma in situ of the cervix or other in situ cancers or a malignancy diagnosed ≥2 years previously and not currently active. * Uncontrolled, disease related pericardial effusion or pleural effusion. * Requiring chronic treatment with steroids. Exclusion Criteria for Participants Receiving Pembrolizumab: * History of interstitial lung disease or interstitial pneumonitis. * Active autoimmune disease or any illness or treatment that could compromise the immune system.