A Phase 1/2 Study of Oral Selpercatinib (LOXO-292) in Patients With Advanced Solid Tumors, Including RET Fusion-Positive Solid Tumors, Medullary Thyroid Cancer, and Other Tumors With RET Activation (LIBRETTO-001)

∙ For Phase 1:

• Participants with a locally advanced or metastatic solid tumor that:

• Has progressed on or is 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 non-measurable disease as determined by RECIST 1.1 or RANO as appropriate to tumor type

• Eastern Cooperative Oncology Group (ECOG) score of 0, 1, or 2 or Lansky Performance Score (LPS) greater than or equal to (≥) 40 percent (%) (age less than \[\<\] 16 years) with no sudden deterioration 2 weeks prior to the first dose of study treatment

• Adequate hematologic, hepatic and renal function

• Life expectancy of at least 3 months

∙ For Phase 2: As for phase 1 with the following modifications:

• For 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:

‣ Cohorts 1-4 without measurable disease

⁃ MCT not meeting the requirements for Cohorts 3 or 4

⁃ MTC syndrome spectrum cancers (e.g., MTC, pheochromocytoma), cancers with neuroendocrine features/differentiation, or poorly differentiated thyroid cancers with other RET alteration/activation may be allowed with prior Sponsor approval

⁃ 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 may be eligible with prior Sponsor approval

• Cohort 7: Participants with a histologically confirmed stage IB-IIIA NSCLC and a RET fusion; determined to be medically operable and tumor deemed resectable by a thoracic surgical oncologist, without prior systemic treatment for NSCLC