Selpercatinib
Trade name: Retevmo
Approved
May 8, 2020
Clinical trial activity
31 trials · 25 clinical orgs · 2 marketing orgs
Earliest trial started May 9, 2017 (NCT03157128)
Timeline
2010s
- Jan 1, 2017
Loxo Oncology — Earliest Phase 1 Sponsor(trial)
- Jan 1, 2019
- Oct 30, 2019
Orphan Drug Designation
Indications
Approved for
Studied for
- Carcinoma, Non-Small-Cell Lung · Phase 3
- Colonic Neoplasms · Phase 1
- Ependymoma · Phase 2
- Fibrosarcoma · Phase 1/Phase 2
- Glioma · Phase 2
- Healthy Volunteers · Phase 1/Phase 2
- Hepatoblastoma · Phase 2
- Histiocytosis, Langerhans-Cell · Phase 2
- Leukemia, Hairy Cell · Phase 2
- Liver Diseases · Phase 1/Phase 2
- Lung Neoplasms · Phase 2
- Lymphoma · Phase 2
- Lymphoma, Non-Hodgkin · Phase 2
- Medulloblastoma · Phase 2
- Neoplasm Metastasis · Phase 2
- Neoplasms · Phase 2
- Neoplasms, Germ Cell and Embryonal · Phase 2
- Neuroblastoma · Phase 2
- Neuroectodermal Tumors · Phase 2
- Osteosarcoma · Phase 2
- Renal Insufficiency · Phase 1
- Rhabdoid Tumor · Phase 2
- Rhabdomyosarcoma · Phase 2
- Sarcoma · Phase 2
- Sarcoma, Ewing · Phase 2
- Thyroid Cancer, Papillary · Phase 2
- Thyroid Neoplasms · Phase 3
- Wilms Tumor · Phase 2
Mechanism of action
- Proto-oncogene tyrosine-protein kinase receptor Ret /Nuclear receptor coactivator 4 fusion proteinANTAGONIST
Proto-oncogene tyrosine-protein kinase receptor Ret /Nuclear receptor coactivator 4 fusion protein antagonist
- Tyrosine-protein kinase receptor RETINHIBITOR
Tyrosine-protein kinase receptor RET inhibitor
Selpercatinib inhibited wild-type RET and multiple mutated RET isoforms (inc. RET V804M, and RET M918T). Mutations and rearrangements in RET can drive cancers. Selpercatinib also inhibited VEGFR1 and VEGFR3 (IC50 values 0.92 - 67.8 nM) and FGFR 1, 2, and 3 at higher concentrations. Active against RET in cell assays at 60-fold lower concentration than FGFR1/2 and 8-fold lower concentration than VEGFR3.
Coiled-coil domain-containing protein 6/Tyrosine-protein kinase receptor RET inhibitor
Selpercatinib inhibited wild-type RET and multiple mutated RET isoforms (inc. RET V804M, and RET M918T). Mutations and rearrangements in RET can drive cancers. Selpercatinib also inhibited VEGFR1 and VEGFR3 (IC50 values 0.92 - 67.8 nM) and FGFR 1, 2, and 3 at higher concentrations. Active against RET in cell assays at 60-fold lower concentration than FGFR1/2 and 8-fold lower concentration than VEGFR3.
Kinesin-1 heavy chain/ Tyrosine-protein kinase receptor RET inhibitor
Selpercatinib inhibited wild-type RET and multiple mutated RET isoforms (inc. RET V804M, and RET M918T). Mutations and rearrangements in RET can drive cancers. Selpercatinib also inhibited VEGFR1 and VEGFR3 (IC50 values 0.92 - 67.8 nM) and FGFR 1, 2, and 3 at higher concentrations. Active against RET in cell assays at 60-fold lower concentration than FGFR1/2 and 8-fold lower concentration than VEGFR3.
Approval history
- approvedPriority reviewAcceleratedBreakthroughMay 8, 2020
Chemistry & pharmacology
SMILES
COc1ccc(CN2C3CC2CN(c2ccc(-c4cc(OCC(C)(C)O)cn5ncc(C#N)c45)cn2)C3)cn1- Mol. weight
- 525.61 g/mol
- Lipinski Ro5
- 1 violation(s)
- Rule of 3
- No
- Chirality
- Achiral Molecule
- Inorganic
- No
- Polymer
- No
- Delivery
- Oral
- Availability
- Prescription Only
Oral
Yes
Parenteral
No
Topical
No
Sources
- ChEMBLCHEMBL4559134 ↗
Also known as
- loxo-292
Clinical trials
| NCT ID | Phase | Start date | Sponsor(s) |
|---|---|---|---|
| NCT07146893 | Early Phase 1 (Phase 1) | Nov 30, 2025 | University of Oklahoma |
| NCT07010393 | Phase 4 | Jul 1, 2025 | Fujian Medical University |
| NCT06458036 | Phase 2 | Jul 29, 2024 | Department of Defense, Eli Lilly, University of Pennsylvania |
| NCT05906836 | Phase 1 | Jul 27, 2023 | Eli Lilly |
| NCT05668962 | Phase 2 | Jan 31, 2023 | Eli Lilly, Harvard University |
| NCT05364645 | Phase 2 | Jul 25, 2022 | National Cancer Institute (NCI), Southwest Oncology Group |
| NCT05324124 | Phase 1 | Apr 19, 2022 | Eli Lilly, Loxo Oncology |
| NCT05136404 | Phase 1 | Dec 1, 2021 | Eli Lilly, Loxo Oncology |
| NCT05089019 | Phase 1 | Oct 29, 2021 | Eli Lilly, Loxo Oncology |
| NCT04819100 | Phase 3 | Aug 31, 2021 | Eli Lilly, Loxo Oncology |
| NCT04782076 | Phase 1 | Mar 5, 2021 | Eli Lilly, Loxo Oncology |
| NCT04759911 | Phase 2 | Feb 26, 2021 | University of Texas at Houston |
| NCT04320888 | Phase 2 | Apr 30, 2020 | National Cancer Institute (NCI) |
| NCT04280081 | Phase 2 | Mar 31, 2020 | Eli Lilly, Loxo Oncology |
| NCT04268550 | Phase 2 | Mar 7, 2020 | National Cancer Institute (NCI), Southwest Oncology Group |
| NCT06195228 | Phase 4 | Jan 1, 2020 | Anhui College of Traditional Chinese Medicine, Central South University, Changhai Hospital, Chinese Academy of Medical Sciences, Dalian Medical University, Fudan University, Fujian Medical University, Henan Medical University, Huazhong University of Science and Technology, Inner Mongolia Medical University, Jiangsu Cancer Institute & Hospital, Jiao Tong University, Shanxi Medical University, Sun Yat-Sen University, Tianjin Medical University, Zhejiang University |
| NCT04211337 | Phase 3 | Dec 24, 2019 | Eli Lilly, Loxo Oncology |
| NCT04194944 | Phase 3 | Dec 10, 2019 | Eli Lilly, Loxo Oncology |
| NCT05338502 | Phase 1/Phase 2 (Phase 2) | Jul 8, 2019 | Eli Lilly, Loxo Oncology |
| NCT03899792 | Phase 1/Phase 2 (Phase 2) | May 31, 2019 | Loxo Oncology |
Organizations
Research & Development (25)
| Organization | Org type | Trials | As lead sponsor | Phases | Earliest year |
|---|---|---|---|---|---|
| Eli Lilly | For profit | 22 | 14 | 4 | 2018 |
| Loxo Oncology | For profit | 21 | 8 | 4 | 2017 |
| National Cancer Institute (NCI) | Government | 3 | 1 | 1 | 2020 |
| Fujian Medical University | Academic/Hospital | 2 | 1 | 1 | 2020 |
| Southwest Oncology Group | Academic/Hospital | 2 | 2 | 1 | 2020 |
| Anhui College of Traditional Chinese Medicine | Academic/Hospital | 1 | 0 | 1 | 2020 |
| Central South University | Academic/Hospital | 1 | 0 | 1 | 2020 |
| Changhai Hospital | Academic/Hospital | 1 | 0 | 1 | 2020 |
| Chinese Academy of Medical Sciences | Academic/Hospital | 1 | 0 | 1 | 2020 |
| Dalian Medical University | Academic/Hospital | 1 | 0 | 1 | 2020 |
| Department of Defense | Government | 1 | 0 | 1 | 2024 |
| Fudan University | Academic/Hospital | 1 | 1 | 1 | 2020 |
| Harvard University | Academic/Hospital | 1 | 1 | 1 | 2023 |
| Henan Medical University | Academic/Hospital | 1 | 0 | 1 | 2020 |
| Huazhong University of Science and Technology | Academic/Hospital | 1 | 0 | 1 | 2020 |
| Inner Mongolia Medical University | Academic/Hospital | 1 | 0 | 1 | 2020 |
| Jiangsu Cancer Institute & Hospital | Academic/Hospital | 1 | 0 | 1 | 2020 |
| Jiao Tong University | Academic/Hospital | 1 | 0 | 1 | 2020 |
| Shanxi Medical University | Academic/Hospital | 1 | 0 | 1 | 2020 |
| Sun Yat-Sen University | Academic/Hospital | 1 | 0 | 1 | 2020 |
Marketing (5)
| Organization | Org type | Relationship | Date |
|---|---|---|---|
| Eli Lilly | For profit | MKTG | May 8, 2020 |
| Eli Lilly | For profit | NDA2 | May 8, 2020 |
| Eli Lilly | For profit | NDA | May 8, 2020 |
| Eli Lilly | For profit | SYN | May 8, 2020 |
| Loxo Oncology | For profit | MKTG | May 8, 2020 |