Phase 1/2 Study of the Highly-selective RET Inhibitor, Pralsetinib (BLU-667), in Participants With Thyroid Cancer, Non-Small Cell Lung Cancer, and Other Advanced Solid Tumors

* Group 8 - participants must have pathologically documented, definitively diagnosed locally advanced or metastatic NSCLC with a RET fusion that was previously treated with a platinum based chemotherapy (China only).

* Group 9 - participants must have pathologically documented, definitively diagnosed advanced MTC that had progressed within 14 months prior to the Screening Visit, and was not previously treated with systemic therapy (except prior cytotoxic chemotherapy is allowed) for advanced or metastatic disease (China only).

Participants must have non-resectable disease.

Dose expansion (Phase 2): Participants in all groups (except Group 7) must have measurable disease per RECIST v1.1 (or RANO, criteria if appropriate for tumor type).

Participants agrees to provide tumor tissue (archived, if available or a fresh biopsy) for RET status confirmation and is willing to consider an on-treatment tumor biopsy, if considered safe and medically feasible by the treating Investigator. For Phase 2, Group 6, participants are required to undergo a pretreatment biopsy to define baseline RET status in tumor tissue.

Participants has Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1.

Participant'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.

Participants had 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

Participants in Groups 1-5 and 7 (Phase 2) previously treated with a selective RET inhibitor

Participant had a major surgical procedure within 14 days of the first dose of study drug

Participant had a history of another primary malignancy that had been diagnosed or required therapy within the a year prior to the study

Pregnant or breastfeeding female participants

What this study is about