Key Inclusion Criteria:

        For Phase 1

          -  Patients with a locally advanced or metastatic solid tumor who:

               -  have progressed on or are intolerant to standard therapy, or

               -  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 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) ≥ 40% (age < 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 Cohorts 1 and 3 Subjects 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 1-4: enrollment will be restricted to patients with evidence of a RET gene
             alteration in tumor. However, a positive germline DNA test for a RET gene mutation is
             acceptable in the absence of tumor tissue testing for patients with MTC.

          -  Cohorts 1-4: at least one measurable lesion as defined by RECIST 1.1 or RANO, as
             appropriate to tumor type and not previously irradiated.

          -  Cohort 4: radiographic PD within the previous 14 months.

        Note: Patients otherwise eligible for cohort 4 who do not demonstrate radiographic PD
        within the previous 14 months may be enrolled to cohort 5 if a compelling rationale is
        provided by the investigator and approved by the Sponsor.

          -  Cohort 5: (up to 150 patients):

               -  Cohorts 1-4 without measurable disease;

               -  MTC not meeting the requirements for Cohorts 3 or 4; (a known RET mutation is not
                  required)

               -  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: Patients who otherwise are eligible for Cohorts 1-5 who discontinued another
             RET inhibitor due to intolerance may be eligible with prior Sponsor approval.

        Key Exclusion Criteria (Phase 1 and Phase 2):

          -  Phase 2 Cohorts 1-4: an additional known oncogenic driver.

          -  Cohorts 1-5: prior treatment with a selective RET inhibitor

        Notes:

        Patients otherwise eligible for Cohorts 1-5 who discontinued another selective RET
        inhibitor may be eligible for Phase 2 Cohort 6 with prior Sponsor approval.

        Notes:

        Patients otherwise eligible for Cohorts 1-5 who discontinued another selective RET
        inhibitor may be eligible for Phase 2 Cohort 6 with prior Sponsor approval.

        Notes:

        Patients otherwise eligible for Cohorts 1-5 who discontinued another selective RET
        inhibitor may be eligible for Phase 2 Cohort 6 with prior Sponsor approval.

        - Investigational agent or anticancer therapy (including chemotherapy, biologic therapy,
        immunotherapy, anticancer Chinese medicine or other anticancer herbal remedy) within 5
        half-lives or 2 weeks (whichever is shorter) prior to planned start of LOXO-292. In
        addition, no concurrent investigational anti-cancer therapy is permitted.

        Note:

        Potential exception for this exclusion criterion will require a valid scientific
        justification and approval from the Sponsor.

          -  Major surgery (excluding placement of vascular access) within 4 weeks prior to planned
             start of LOXO-292.

          -  Radiotherapy with a limited field of radiation for palliation within 1 week of planned
             start of LOXO-292, with the exception of patients receiving radiation to more than 30%
             of the bone marrow or with a wide field of radiation, which must be completed at least
             4 weeks prior to the first dose of study treatment.

          -  Any unresolved toxicities from prior therapy greater than CTCAE Grade 1 at the time of
             starting study treatment with the exception of alopecia and Grade 2, prior
             platinum-therapy related neuropathy.

          -  Symptomatic primary CNS tumor, metastases, leptomeningeal carcinomatosis, or untreated
             spinal cord compression. Patients are eligible if neurological symptoms and CNS
             imaging are stable and steroid dose is stable for 14 days prior to the first dose of
             LOXO-292 and no CNS surgery or radiation has been performed for 28 days, 14 days if
             stereotactic radiosurgery [SRS].

          -  Clinically significant active cardiovascular disease or history of myocardial
             infarction within 6 months prior to planned start of LOXO-292 or prolongation of the
             QT interval corrected (QTcF) > 470 msec.

          -  Required treatment with certain strong CYP3A4 inhibitors or inducers and certain
             prohibited concomitant medications.