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

Conditions: Solid Tumor; Medullary Thyroid Cancer

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.

Keywords: non-small cell lung cancer nsclc targeted therapy medullary thyroid carcinoma thyroid cancer ret alteration mtc