UK Center for Clinical and Translational Science

Applicable to all patients: 1. Must be ≥18 years of age, with documented RET-altered cancers 2. Patients should be well informed and consented about alternative treatment options including approved RET-targeted therapies 3. ECOG performance status of 0 or 1 and life expectancy >3 months at screening 4. Ability to understand and provide written informed consent and able to participate in all required evaluations and procedures 5. Additional cohort specific criteria apply

Patients with any of the following will not be included in the study: 1. Any known major driver gene alterations other than RET. 2. Spinal cord compression or brain metastases. Patients with stable brain metastases can be enrolled. 3. Active infection requiring systemic antibiotic, antifungal, or antiviral medication 4. Severe or uncontrolled medical condition or psychiatric condition 5. Chronic glomerulonephritis or renal transplant 6. Patients with active hepatitis B infection or active hepatitis C 7. Patients with active HIV infection. Patients living with HIV may be eligible if they have adequate CD4+ T-cell count and no history of AIDS-defining opportunistic infections in the past 12 months 8. Receipt of any strong inhibitor or inducer of CYP3A4 9. Impaired hepatic or renal function, inadequate bone marrow reserve or organ function 10. Any clinically important abnormalities in rhythm, conduction, or morphology on resting ECG or any factor that increases the risk of QTc prolongation or of arrhythmic events , or congestive heart failure Grade II-IV according to the New York Heart Association, myocardial infarction, or unstable angina within the previous 6 months 11. Uncontrolled hypertension 12. Corneal ulceration at screening