LIBRETTO-431: This phase III trial is comparing a new oral therapy (Selpercatinib) with a standard treatment in patients with advanced non-small cell lung cancerA Multicenter, Randomized, Open-Label, Phase 3 Trial Comparing LOXO-292 to Platinum-Based and Pemetrexed Therapy With or Without Pembrolizumab as Initial Treatment of Advanced or Metastatic RET Fusion-Positive Non-Small Cell Lung Cancer

Exclusion

• 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.