pralsetinib
Trade name: Gavreto
Approved
Sep 4, 2020
Clinical trial activity
8 trials · 19 clinical orgs · 3 marketing orgs
Earliest trial started Jan 1, 2020 (NCT06195228)
Timeline
2010s
- Apr 11, 2018
Orphan Drug Designation
2020s
- Jan 1, 2020
Blueprint Medicines Corporation — Earliest Phase 3 Sponsor(trial)
- Sep 4, 2020
Roche — Earliest FDA Approval
- Sep 4, 2020
Genentech — Marketing Organization
- Sep 4, 2020
Blueprint Medicines Corporation — Marketing Organization
- Sep 4, 2020
Roche — NDA Secondary Org
- Sep 4, 2020
Roche — NDA Organization
- Dec 1, 2020
Blueprint Medicines Corporation — NDA Secondary Org
- Jan 1, 2021
Earliest Phase 2 Sponsor(trial)
Indications
Studied for
- Adenocarcinoma · Phase 3
- Bronchial Diseases · Phase 3
- Carcinoma · Phase 3
- Carcinoma, Bronchogenic · Phase 3
- Carcinoma, Non-Small-Cell Lung · Phase 3
- Head and Neck Neoplasms · Phase 3
- Lung Diseases · Phase 3
- Lung Neoplasms · Phase 3
- Mutation · Phase 2
- Neoplasms · Phase 3
- Neoplasms by Histologic Type · Phase 3
- Neoplasms by Site · Phase 3
- Neoplasms, Germ Cell and Embryonal · Phase 3
- Neoplasms, Nerve Tissue · Phase 3
- Respiratory Tract Diseases · Phase 3
- Respiratory Tract Neoplasms · Phase 3
- Small Cell Lung Carcinoma · Phase 3
- Thoracic Neoplasms · Phase 3
- Thyroid Neoplasms · Phase 4
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
Inhibits wild-type and oncogenic RET fusions and mutations (CCDC6-RET, RET V804L, RET V804M, RET M918T) with IC50s < 0.5 nM. Mutations can drive tumorigenesis.
Inhibits wild-type and oncogenic RET fusions and mutations (CCDC6-RET, KIF5B-RET, RET V804L, RET V804M, C634W, RET V804E and RET M918T). Also inhibited DDR1, TRKC, FLT3, JAK1-2, TRKA, VEGFR2, PDGFRb, and FGFR1 in vitro at clinically relevant concentrations. In cellular assays, inhibited RET at approximately 14-, 40-, and 12-fold lower concentrations than VEGFR2, FGFR2, and JAK2, respectively.
Coiled-coil domain-containing protein 6/Tyrosine-protein kinase receptor RET inhibitor
Inhibits wild-type and oncogenic RET fusions and mutations (CCDC6-RET, RET V804L, RET V804M, RET M918T) with IC50s < 0.5 nM. Mutations can drive tumorigenesis.
Inhibits wild-type and oncogenic RET fusions and mutations (CCDC6-RET, KIF5B-RET, RET V804L, RET V804M, C634W, RET V804E and RET M918T). Also inhibited DDR1, TRKC, FLT3, JAK1-2, TRKA, VEGFR2, PDGFRb, and FGFR1 in vitro at clinically relevant concentrations. In cellular assays, inhibited RET at approximately 14-, 40-, and 12-fold lower concentrations than VEGFR2, FGFR2, and JAK2, respectively.
Kinesin-1 heavy chain/ Tyrosine-protein kinase receptor RET inhibitor
Inhibits wild-type and oncogenic RET fusions and mutations (CCDC6-RET, RET V804L, RET V804M, RET M918T) with IC50s < 0.5 nM. Mutations can drive tumorigenesis.
Inhibits wild-type and oncogenic RET fusions and mutations (CCDC6-RET, KIF5B-RET, RET V804L, RET V804M, C634W, RET V804E and RET M918T). Also inhibited DDR1, TRKC, FLT3, JAK1-2, TRKA, VEGFR2, PDGFRb, and FGFR1 in vitro at clinically relevant concentrations. In cellular assays, inhibited RET at approximately 14-, 40-, and 12-fold lower concentrations than VEGFR2, FGFR2, and JAK2, respectively.
Approval history
- approvedPriority reviewAcceleratedBreakthroughSep 4, 2020
Chemistry & pharmacology
SMILES
CO[C@]1(C(=O)N[C@@H](C)c2ccc(-n3cc(F)cn3)nc2)CC[C@H](c2nc(C)cc(Nc3cc(C)[nH]n3)n2)CC1- Mol. weight
- 533.61 g/mol
- Lipinski Ro5
- 1 violation(s)
- Rule of 3
- No
- Chirality
- Single Stereoisomer
- Inorganic
- No
- Polymer
- No
- Delivery
- Oral
- Availability
- Prescription Only
Oral
Yes
Parenteral
No
Topical
No
Sources
- ChEMBLCHEMBL4582651 ↗
Clinical trials
| NCT ID | Phase | Start date | Sponsor(s) |
|---|---|---|---|
| NCT07010393 | Phase 4 | Jul 1, 2025 | Fujian Medical University |
| NCT06563999 | Phase 2 | Dec 1, 2024 | Sun Yat-Sen University |
| NCT05170204 | Phase 3 | Nov 1, 2022 | Roche |
| NCT04760288 | Phase 3 | Jan 9, 2022 | Roche |
| NCT06482086 | Phase 2 | Jun 1, 2021 | Sichuan University |
| NCT04222972 | Phase 3 | Jan 10, 2020 | Blueprint Medicines Corporation |
| 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 |
| NCT04204928 | N/A | — | Blueprint Medicines Corporation |
Organizations
Research & Development (19)
| Organization | Org type | Trials | As lead sponsor | Phases | Earliest year |
|---|---|---|---|---|---|
| Blueprint Medicines Corporation | For profit | 2 | 2 | 2 | 2020 |
| Fujian Medical University | Academic/Hospital | 2 | 1 | 1 | 2020 |
| Roche | For profit | 2 | 2 | 1 | 2022 |
| Sun Yat-Sen University | Academic/Hospital | 2 | 1 | 2 | 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 |
| Fudan University | Academic/Hospital | 1 | 1 | 1 | 2020 |
| 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 |
| Sichuan University | Academic/Hospital | 1 | 1 | 1 | 2021 |
| Tianjin Medical University | Academic/Hospital | 1 | 0 | 1 | 2020 |
| Zhejiang University | Academic/Hospital | 1 | 0 | 1 | 2020 |
Marketing (5)
| Organization | Org type | Relationship | Date |
|---|---|---|---|
| Blueprint Medicines Corporation | For profit | MKTG | Sep 4, 2020 |
| Blueprint Medicines Corporation | For profit | NDA2 | Dec 1, 2020 |
| Genentech | For profit | MKTG | Sep 4, 2020 |
| Roche | For profit | NDA2 | Sep 4, 2020 |
| Roche | For profit | NDA | Sep 4, 2020 |