Selpercatinib (Retevmo)

==Mechanism of action==
From the NCI Drug Dictionary: An orally bioavailable selective inhibitor of wild-type, mutant and fusion products involving the proto-oncogene receptor tyrosine kinase rearranged during transfection (RET), with potential antineoplastic activity. Upon oral administration, LOXO-292 selectively binds to and targets various RET mutants and RET-containing fusion products. This results in an inhibition of cell growth of tumors cells that exhibit increased RET activity.
==Diseases for which it is established==
*RET-positive NSCLC
*RET-mutant medullary thyroid cancer
*RET-positive thyroid cancer
*RET+ solid tumors (tissue-agnostic)
==History of changes in FDA indication==
===Non-small cell lung cancer===
*2020-05-08: Granted accelerated approval for adult patients with metastatic RET fusion-positive non-small cell lung cancer (NSCLC). (Based on LIBRETTO-001NSCLC)
**2022-09-21: Granted regular approval for adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with a rearranged during transfection (RET) gene fusion. (Based on LIBRETTO-001NSCLC)
===RET (tissue-agnostic)===
*2022-09-21: Granted accelerated approval for adult patients with locally advanced or metastatic solid tumors with a rearranged during transfection (RET) gene fusion that have progressed on or following prior systemic treatment or who have no satisfactory alternative treatment options. (Based on LIBRETTO-001RET)
*2024-05-29: Granted accelerated approval for pediatric patients two years of age and older with locally advanced or metastatic solid tumors with a RET gene fusion, as detected by an FDA-approved test, that have progressed on or following prior systemic treatment or who have no satisfactory alternative treatment options. (Based on LIBRETTO-121)
===Thyroid cancer===
*2020-05-08: Granted accelerated approval for adult and pediatric patients at least 12 years of age with advanced or metastatic RET-mutant medullary thyroid cancer (MTC) who require systemic therapy. (Based on LIBRETTO-001thyroid)
**2024-09-27: Granted regular approval for adult and pediatric patients 2 years of age and older with advanced or metastatic medullary thyroid cancer (MTC) with a RET mutation, as detected by an FDA-approved test, who require systemic therapy. (Based on LIBRETTO-531)
*2020-05-08: Granted accelerated approval for adult and pediatric patients at least 12 years of age with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate). (Based on LIBRETTO-001thyroid)
**2023-06-12: Regular approval for adult and pediatric patients 2 years of age and older with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate). (Based on LIBRETTO-001thyroid)
*2024-05-29: Granted accelerated approval for pediatric patients two years of age and older with advanced or metastatic medullary thyroid cancer (MTC) with a RET mutation, as detected by an FDA-approved test, who require systemic therapy. (Based on LIBRETTO-121)
*2024-05-29: Granted accelerated approval for pediatric patients two years of age and older with advanced or metastatic thyroid cancer with a RET gene fusion, as detected by an FDA-approved test, who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate). (Based on LIBRETTO-121)
==History of changes in EMA indication==
*2021-02-11: Initial conditional authorization as Retsevmo.
==History of changes in Health Canada indication==
*2021-06-15: Initial notice of compliance with conditions as monotherapy for the treatment of metastatic RET fusion-positive non-small cell lung cancer (NSCLC) in adult patients.
*2021-06-15: Initial notice of compliance with conditions as monotherapy for the treatment of RET-mutant medullary thyroid cancer (MTC) in adult and pediatric patients 12 years of age and older with unresectable advanced or metastatic disease.
*2021-06-15: Initial notice of compliance with conditions as monotherapy for the treatment of RET fusion-positive differentiated thyroid carcinoma in adult patients with advanced or metastatic disease (not amenable to surgery or radioactive iodine therapy) following prior treatment with sorafenib and/or lenvatinib.
==History of changes in PMDA indication==
*2021-09-27: Newly indicated for the treatment of RET fusion gene-positive unresectable advanced or recurrent non-small cell lung cancer.
*2022-02-25: New indication and a new dosage for the treatment of RET fusion gene-positive unresectable thyroid cancer.
*2022-02-25: New indication and a new dosage for the treatment of RET gene mutation-positive unresectable medullary thyroid cancer.
==Also known as==
*Code name: LOXO-292
*Brand names: Retevmo, Retsevmo
Category:Drugs
Category:Oral medications
Category:Mutation-specific medications
Category:RET inhibitors
Category:Non-small cell lung cancer medications
Category:Malignant solid neoplasm, RET-mutated medications
Category:Thyroid cancer medications
Category:EMA approved in 2021
Category:FDA approved in 2020
Category:Health Canada approved in 2021
Category:PMDA approved in 2021