Phase 1

Participants with a locally advanced or metastatic solid tumor who:
- Progressed on or are intolerant to standard therapy, or
- For which no standard therapy exists, or in the opinion of the investigator, are not candidates for or would be unlikely to tolerate or derive significant clinical benefit from standard therapy, or
- Decline standard therapy
Prior multikinase inhibitors (MKIs) with anti-RET activity are allowed
A RET gene alteration is not required initially. Once adequate PK exposure is achieved, evidence of RET gene alteration in tumor and/or blood is required as identified through molecular assays, as performed for clinical evaluation
Measurable or nonmeasurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or Response Assessment in Neuro-Oncology (RANO) as appropriate to tumor type
Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 or Lansky Performance Score (LPS) ≥40% (age <16 years) with no sudden deterioration 2 weeks prior to the first dose of study treatment
≥12 years of age
Adequate hematologic, hepatic, and renal function
Life expectancy of ≥3 months

Phase 2
Phase 1 criteria with the following modifications:

Cohort 1: Participants must have received prior standard therapy appropriate for their tumor type and stage of disease, or in the opinion of the investigator, would be unlikely to tolerate or derive clinical benefit from appropriate standard of care therapy
Cohorts 1 and 2:
- Enrollment will be restricted to participants with evidence of a RET gene alteration in tumor
- At least one measurable lesion as defined by RECIST 1.1 or RANO, as appropriate to tumor type and not previously irradiated
Cohorts 3 and 4: Enrollment closed
Cohort 5:
- Without measurable disease but otherwise meet criteria for cohorts 1 and 2
- Medullary thyroid cancer (MTC) syndrome spectrum cancers (eg, MTC, pheochromocytoma), cancers with neuroendocrine features/differentiation, or poorly differentiated thyroid cancers with other RET alteration/activation may be allowed with prior sponsor approval
- Cell-free DNA (cfDNA) positive for a RET gene alteration not known to be present in a tumor sample
Cohort 6: Participants who otherwise are eligible for cohorts 1, 2, or 5, who discontinued another RET inhibitor due to intolerance, may be eligible with prior sponsor approval (closed)
Cohort 7: Participants must have a histologically confirmed stage IB-IIIA non-small cell lung cancer (NSCLC) by the American Joint Committee on Cancer (AJCC) version 8. The tumor must have been deemed resectable by a thoracic surgeon, the participant must be determined to be medically operable based on the determination of a thoracic surgeon, and the participant must not have received prior systemic therapy, including prior radiation therapy, for NSCLC (closed)