A Study of Selpercatinib (LY3527723) in Participants With Advanced Solid Tumors Including RET Fusion-positive Solid Tumors, Medullary Thyroid Cancer and Other Tumors With RET Activation
Condition: Solid Tumor; Medullary Thyroid Cancer
MeSH terms: Thyroid Neoplasms; Carcinoma, Neuroendocrine; Brain Stem Neoplasms; Thyroid Diseases
Intervention: Selpercatinib
Intervention description: Administered orally
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 77.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Non-Small Cell Lung Cancer; NSCLC; Targeted Therapy; Medullary Thyroid Carcinoma; Thyroid Cancer; RET Alteration; MTC

Summary:

      The reason for this study is to see if the study drug selpercatinib is safe and effective in
      participants in China with rearranged during transfection (RET) fusion-positive solid tumors,
      medullary thyroid cancer (MTC) and other tumors with RET activation.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Participants with a locally advanced or metastatic solid tumor.

          -  Evidence of a RET gene alteration in tumor and/or blood.

          -  Measurable or non-measurable disease as determined by Response Evaluation Criteria in
             Solid Tumors (RECIST) v1.1.

          -  Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2, with
             no sudden deterioration 2 weeks prior to the first dose of study treatment.

          -  Archived tumor tissue sample available for cohort 1 and 2.

          -  Cohorts 1 and 2: failed or intolerant to standard of care.

          -  Cohorts 1-2: enrollment will be restricted to participants with evidence of a RET gene
             alteration in tumor (i.e., not just blood). However, a positive germline DNA test for
             a RET gene mutation as defined in the protocol is acceptable in the absence of tumor
             tissue testing for participants with MTC.

          -  Cohorts 1-2: at least one measurable lesion as defined by RECIST v1.1 and not
             previously irradiated (unless progressive disease for the irradiated lesion[s] has
             been radiographically documented).

        Exclusion Criteria:

          -  Cohorts 1-2, an additional validated oncogenic driver that could cause resistance to
             selpercatinib treatment if known.

          -  Prior treatment with a selective RET inhibitor(s) (including investigational selective
             RET inhibitor(s), such as BLU-667, RXDX-105, etc).

          -  Are currently enrolled in any other clinical study involving an investigational
             product or any other type of medical research judged not to be scientifically or
             medically compatible with this study.

          -  Any unresolved toxicities from prior therapy greater than common terminology criteria
             for adverse events (CTCAE) Grade 1 except where otherwise noted in this eligibility
             criteria at the time of starting study treatment with the exception of alopecia and
             Grade 2, prior platinum therapy-related neuropathy.

          -  Symptomatic primary central nervous system (CNS) tumor, symptomatic CNS metastasis,
             leptomeningeal carcinomatosis, or untreated spinal cord compression.

          -  Clinically significant active cardiovascular disease or history of myocardial
             infarction within 6 months prior to planned start of selpercatinib or prolongation of
             the QT interval corrected for heart rate using Fridericia's formula (QTcF) > 470
             milliseconds.

          -  History of Human Immunodeficiency Virus (known HIV 1/2 antibodies positive);
             participants with unknown HIV status do not need to be tested.

          -  History of active hepatitis B (known positive hepatitis B surface antigen [HbsAg] and
             quantitative hepatitis B DNA greater than the upper limit of detection of the assay)
             or C (known positive hepatitis C antibody and quantitative hepatitis C RNA greater
             than the upper limit of detection of the assay); participants with unknown hepatitis
             B/hepatitis C status do not need to be tested.

          -  Active uncontrolled systemic bacterial, viral, or fungal infection or serious ongoing
             intercurrent illness, such as hypertension or diabetes, despite optimal treatment.
             Screening for chronic conditions is not required.

          -  Clinically significant active malabsorption syndrome or other condition likely to
             affect gastrointestinal absorption of the study drug.

          -  Uncontrolled symptomatic hyperthyroidism or hypothyroidism

          -  Uncontrolled symptomatic hypercalcemia or hypocalcemia.

          -  Concurrent use of drugs known to prolong QTc.

          -  Pregnancy or lactation. Breast-feeding should be interrupted when selpercatinib is
             started; breast-feeding can be resumed 3 months after discontinuation of
             selpercatinib.

          -  Active second malignancy other than minor treatment of indolent cancers with prior
             sponsor approval.