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

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-001_NSCLC)
- 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-001_NSCLC)

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-001_RET)

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-001_thyroid)
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-001_thyroid)

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