A Study of Pralsetinib Versus Standard of Care (SOC) for Treatment of RET-Mutated Medullary Thyroid Cancer (MTC).
A Study of Pralsetinib Versus Standard of Care (SOC) for Treatment of RET-Mutated Medullary Thyroid Cancer (MTC).
A study to evaluate the efficacy and safety of pralsetinib compared with SOC treatment
 (cabozantinib or vandetanib) for participants with RET (rearranged during
 transfection)-mutant MTC who have not previously received a SOC MultiKinase Inhibitor (MKI)
 therapy. Participants will be randomized in a 1:1 ratio into one of two treatment arms: Arm A
 (pralsetinib) or Arm B (investigator's choice of either cabozantinib or vandetanib).
 Participants whose disease progresses during SOC treatment will be offered the option to
 cross over to receive pralsetinib after confirmation of progressive disease by blinded
 independent central review (BICR).
Inclusion Criteria:

 -  Must have histologically confirmed unresectable locally advanced or metastatic MTC and
 be a candidate for systemic therapy with SOC MKI.

 -  Must have received no prior systemic anticancer treatment with MKI therapies for
 advanced or metastatic MTC.

 -  Must have radiologically confirmed progressive disease within the last 14 months and
 at least one of the following: [1] A MTC-associated symptom and [2] CLN (Calcitonin)
 and CEA (carcinoembryonic antigen) level doubling time of less than 24 months.

 -  Confirmed RET mutation.

 -  Must be able to swallow an oral medication.

 -  Must have an ECOG (Eastern Cooperative Oncology Group) Performance Status of 0-2.

 -  For women of childbearing potential: agreement to remain abstinent (refrain from
 heterosexual intercourse) or use appropriate contraception during the treatment period
 and for the respective period of time after final dose of study drug.

 -  For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use
 appropriate contraception during the treatment period and for the respective period of
 time after final dose of study drug and to refrain from donating sperm.

 Exclusion Criteria:

 -  Participants who are pregnant or breastfeeding, or intending to become pregnant during
 the study within 14 days after the final dose of pralsetinib or within 4 months after
 the final dose of vandetanib or cabozantinib.

 -  Have disease that is suitable for surgery or radiotherapy administered with curative
 intent.

 -  Have been previously treated with any systemic kinase inhibitor therapy regimens,
 including a selective RET inhibitor, given for recurrent and/or metastatic disease.

 -  Have received any radiation therapy within 14 days prior to Day 1 of Cycle 1 and any
 related toxicity must be resolved to Grade 1 or better.

 -  Participant's tumor has any additional known primary driver alterations other than
 RET.

 -  Have known hypersensitivity to pralsetinib, vandetanib, or cabozantinib, or any of
 their ingredients.

 -  Have a history of pneumonitis within the last 12 months.

 -  Have ongoing treatment with chronic immunosuppressants or systemic steroids >10
 mg/day.

 -  Have any history of hereditary bleeding disorder or any evidence of hematemesis.

 -  Have had major surgery or invasive dental procedure within 3 weeks prior to Day 1 of
 Cycle 1.

 -  Have CNS metastases that are associated with progressive neurologic symptoms,
 untreated spinal cord compression or requires increasing doses of corticosteroids to
 control the CNS disease.

 -  Have clinically significant, uncontrolled, cardiovascular disease.

 -  Have required treatment with a prohibited medication or herbal remedy.

 -  Have received hematopoietic growth factor support or transfusion within 14 days of the
 first dose of study drug.

 -  Had a major surgical procedure within 14 days of the first dose of study drug.

 -  Have a history of another primary malignancy that has been diagnosed or required
 therapy within the past 2 years before randomisation.

 -  Have a serious infection requiring intravenous (IV) antibiotics within 7 days prior to
 initiation of study treatment.

 -  Have an active, uncontrolled infection (viral, bacterial, or fungal) or is positive
 for Hepatitis B or C infection (HBV/HCV).

 -  Have received organ or allogenic bone marrow or peripheral blood stem cell transplant.

 -  Is a female who is unwilling to abstain from sexual intercourse or employ highly
 effective contraception from the time of informed consent and for at least 6 months
 after the last dose of study drug.

 -  Is a male who is unwilling to abstain from sexual intercourse or employ highly
 effective contraception from the time of informed consent and for at least 120 days
 after the final dose of study drug.

 -  Have prior or ongoing clinically significant illness, medical condition, surgical
 history, physical finding, or laboratory abnormality that, in the Investigator's or
 Sponsor's opinion, could affect the safety of the patient or impair the assessment of
 study results.