a study of oral loxo-292 (selpercatinib) in pediatric participants with advanced solid or primary central nervous system (cns) tumors

Conditions: Medullary Thyroid Cancer; Infantile Myofibromatosis; Infantile Fibrosarcoma; Papillary Thyroid Cancer; Soft Tissue Sarcoma

Summary: this is an open-label, multi-center phase 1/2 study of oral loxo-292 in pediatric participants with an activating rearranged during transfection (ret) alteration and an advanced solid or primary cns tumor.

this study includes 2 parts: phase 1 (dose escalation) and phase 2 (dose expansion). in phase 1, participants will be enrolled using a rolling 6 dose escalation scheme. the starting dose of loxo-292 is equivalent to the adult recommended phase 2 dose of 160 milligrams (mg) twice a day (bid). once the maximum tolerated dose (mtd) and/or recommended phase 2 dose (rp2d) is identified, participants will be enrolled to one of four phase 2 dose expansion cohorts depending on tumor histology and tumor genotype. cycle length will be 28 days.

Eligibility criteria:
inclusion criteria: * advanced or metastatic solid or primary cns tumor which has failed standard of care therapies * evidence of an activating ret gene alteration in the tumor and/or blood * measurable or non-measurable disease * karnofsky (participants 16 years and older) or lansky (participants younger than 16) performance score of at least 50 * participant with primary cns tumors or cerebral metastases must be neurologically stable for 7 days prior and must not have required increasing doses of steroids within the last 7 days * adequate hematologic, hepatic and renal function. * ability to receive study drug therapy orally or via gastric access * willingness of men and women of reproductive potential to observe conventional and effective birth control exclusion criteria: * major surgery within two weeks prior to planned start of loxo-292 * clinically significant, uncontrolled cardiac, cardiovascular disease or history of myocardial infarction within 6 months prior to planned start of loxo-292 * active uncontrolled systemic bacterial, viral, fungal or parasitic infection * clinically significant active malabsorption syndrome * pregnancy or lactation * uncontrolled symptomatic hyperthyroidism or hypothyroidism (i.e. the participant required a modification to current thyroid medication in the 7 days before start of loxo-292) * uncontrolled symptomatic hypercalcemia or hypocalcemia * known hypersensitivity to any of the components of the investigational agent, loxo-292 or ora-sweet® sf and oraplus®, for participants who will receive loxo-292 suspension * prior treatment with a selective ret inhibitor(s) (including investigational selective ret inhibitor\[s\])

Keywords: loxo loxo-292 kif5b-ret m918t ccdc6-ret ret-ptc1 ncoa4-ret ret-ptc ret-ptc3 ret-ptc4 prkar1a-ret ret-ptc2 golga5-ret ret-ptc5 erc1-ret ktn1-ret ret-ptc8 hook3-ret pcm1-ret trim24-ret ret-ptc6 trim27-ret trim33-ret ret-ptc7 akap13-ret fkbp15-ret specc1l-ret tbl1xr1-ret bcr-ret fgrf1op-ret rfg8-ret ret-ptc9 acbd5-ret myh13-ret cux1-ret kiaa1468-ret frmd4a-ret sqstm1-ret afap1l2-ret ppfibp2-ret eml4-ret pard3-ret g533c c609f c609g c609r c609s c609y c611f c611g c611s c611y c611w c618f c618r c618s c620f c620r c620s c630r c630y d631y c634f c634g c634r c634s c634w c634y k666e e768d l790f v804l v804m a883f s891a r912p clip1-ret y806c ret fusion ret alteration ret mutation ret rearrangement ret translocation neoplasms by site neoplasms non-small cell lung cancer lung neoplasms carcinoma, non-small-cell lung cancer of lung cancer of the lung lung cancer neoplasms, lung neoplasms, pulmonary pulmonary cancer pulmonary neoplasms respiratory tract neoplasms lung diseases respiratory tract diseases carcinoma, bronchogenic bronchial neoplasms medullary thyroid cancer papillary thyroid cancer thyroid diseases thyroid neoplasms cancer of the thyroid cancer of thyroid neoplasms, thyroid thyroid adenoma thyroid cancer thyroid carcinoma endocrine system diseases endocrine gland neoplasms head and neck neoplasms thoracic neoplasms cns tumor primary cns tumor colonic neoplasms cancer of colon cancer of the colon colon cancer colon neoplasms colonic cancer neoplasms, colonic malignant tumor of breast mammary cancer mammary carcinoma, human mammary neoplasm, human neoplasms, breast tumors, breast human mammary carcinoma malignant neoplasm of breast breast carcinoma breast tumors cancer of the breast breast neoplasms breast cancer ret inhibitor mtc nsclc soft tissue sarcoma infantile myofibromatosis infantile fibrosarcoma