Patient description: A 16-year-old girl came to the clinic complaining of weight gain and abnormal menstrual cycles. Her BMI was 24, but she has gained 5 kg in the past few weeks. She gets tired more frequently and does not have energy to go dancing with her friends. Her lab results were remarkable for high TSH levels (15 mU/L) and low free T4 levels (0.18 ng/dl). Her anti-TPO levels were extremely high (136 IU/ml). She was diagnosed with Hashimoto disease. She does not smoke and she is not sexually active.

Clinical trial eligibility criteria: eligible ages (years): 18.0-999.0,  RET-altered Non Small Cell Lung Cancer Medullary Thyroid Cancer RET-altered Papillary Thyroid Cancer RET-altered Colon Cancer RET-altered Solid Tumors Lung Neoplasm Carcinoma, Non-Small-Cell Lung Thyroid Diseases Thyroid Neoplasm Thyroid Cancer, Papillary Carcinoma, Neuroendocrine Respiratory Tract Neoplasms Thoracic Neoplasms Neoplasms by Site Neoplasms Lung Diseases Respiratory Tract Disease Carcinoma, Bronchogenic Bronchial Neoplasms Endocrine System Diseases Endocrine Gland Neoplasm Head and Neck Neoplasms Adenocarcinoma, Papillary Adenocarcinoma Carcinoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neuroendocrine Tumors Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms, Nerve Tissue Colonic Neoplasms Colorectal Neoplasms Intestinal Neoplasms Gastrointestinal Neoplasms Digestive System Neoplasm Digestive System Disease Gastrointestinal Disease Colonic Diseases Intestinal Disease Key Diagnosis during dose escalation (Phase 1) Pathologically documented, definitively diagnosed non-resectable advanced solid tumor All patients treated at doses > 120 mg per day must have medullary thyroid cancer (MTC), or a RET-altered solid tumor per local assessment of tumor tissue and/or blood Diagnosis during dose expansion (Phase 2) All patients (with the exception of patients with MTC enrolled in Groups 3, 4, and 9) must have an oncogenic RET-rearrangement/fusion or mutation (excluding synonymous, frameshift, and nonsense mutations) solid tumor, as determined by local or central testing of tumor or circulating tumor nucleic acid in blood; as detailed below Group 1 patients must have pathologically documented, definitively diagnosed locally advanced or metastatic NSCLC with a RET fusion previously treated with a platinum-based chemotherapy Group 2 patients must have pathologically documented, definitively diagnosed locally advanced or metastatic NSCLC with a RET fusion not previously treated with a platinum-based chemotherapy, including those who have not had any systemic therapy. Prior platinum chemotherapy in the neoadjuvant and adjuvant setting is permitted if the last dose of platinum was 4 months or more before the first dose of study drug  Patient's cancer has a known primary driver alteration other than RET. For example, NSCLC with a targetable mutation in EGFR, ALK, ROS1 or BRAF; colorectal with an oncogenic KRAS, NRAS, or BRAF mutation Patient has any of the following within 14 days prior to the first dose of study drug: 1. Platelet count < 75 × 10^9/L. 2. Absolute neutrophil count <1.0 × 10^9/L. 3. Hemoglobin < 9.0 g/dL (red blood cell transfusion and erythropoietin may be used to reach at least 9.0 g/dL, but must have been administered at least 2 weeks prior to the first dose of study drug. 4. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 × the upper limit of normal (ULN) if no hepatic metastases are present; >5 × ULN if hepatic metastases are present. 5. Total bilirubin > 1.5 × ULN; > 3 × ULN with direct bilirubin > 1.5 × ULN in presence of Gilbert's disease. 6. Estimated (Cockcroft-Gault formula) or measured creatinine clearance <40 mL/min. 7. Total serum phosphorus >5.5 mg/dL QT interval corrected using Fridericia's formula (QTcF) >470 msec or history of prolonged QT syndrome or Torsades de pointes, or familial history of prolonged QT syndrome Clinically significant, uncontrolled, cardiovascular disease Central nervous system (CNS) metastases or a primary CNS tumor that is associated with progressive neurological symptoms Clinically symptomatic interstitial lung disease or interstitial pneumonitis including radiation pneumonitis Patients in Groups 1-5 and 7 (Phase 2) previously treated with a selective RET inhibitor