Overview
Pralsetinib, similar to the previously approved selpercatinib, is a kinase inhibitor with enhanced specificity for RET tyrosine kinase receptors (RTKs) over other RTK classes. Enhanced RET (Rearranged during transfection) oncogene expression is a hallmark of many cancers, including non-small cell lung cancer. Although multikinase inhibitors, including cabozantinib, ponatinib, sorafenib, sunitinib, and vandetanib, have shown efficacy in RET-driven cancers, their lack of specificity is generally associated with substantial toxicity. Pralsetinib (BLU-667) and selpercatinib (LOXO-292) represent the first generation of specific RET RTK inhibitors for the treatment of RET-driven cancers. Although a phase 1/2 trial of pralsetinib termed ARROW (NCT03037385) is still ongoing, pralsetinib was granted accelerated FDA approval on September 4, 2020, for the treatment of metastatic RET-fusion positive non-small cell lung cancer. It is currently marketed under the brand name GAVRETO™ by Blueprint Medicines.
Indication
Pralsetinib is indicated for the treatment of metastatic non-small cell lung cancer (NSCLC) in adult patients who are confirmed to possess a rearranged during transfection (RET) gene fusion, as determined by an FDA approved test. It is also indicated in adult and pediatric patients 12 years of age and older for the treatment of advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and for whom radioactive iodine is not appropriate. The indication for advanced or metastatic RET fusion-positive thyroid cancer was approved under accelerated approval based on the overall response rate and duration of response, and continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
Associated Conditions
- Advanced RET-fusion Non Small Cell Lung Cancer
- Advanced RET-fusion thyroid cancer
- Metastatic RET-fusion Non Small Cell Lung Cancer
- Metastatic RET-fusion thyroid cancer
Research Report
Pralsetinib (Gavreto): A Comprehensive Monograph on a Selective RET Kinase Inhibitor
Executive Summary
Pralsetinib, marketed under the brand name Gavreto, is an orally administered, small-molecule, targeted antineoplastic agent. It represents a significant advancement in the field of precision oncology as a highly potent and selective inhibitor of the Rearranged during Transfection (RET) receptor tyrosine kinase. The development of pralsetinib was driven by the need to overcome the limitations of older, less specific multi-kinase inhibitors, which exhibited activity against RET but were often associated with substantial off-target toxicities. Pralsetinib's mechanism of action involves the direct inhibition of wild-type RET as well as oncogenic RET fusions and mutations that serve as key drivers in various solid tumors.
Clinical development, centered on the pivotal Phase 1/2 ARROW trial, has demonstrated profound and durable clinical responses in biomarker-selected patient populations. Pralsetinib has secured regulatory approval for the treatment of adult patients with metastatic RET fusion-positive non-small cell lung cancer (NSCLC) and for certain pediatric and adult patients with RET fusion-positive thyroid cancer. The efficacy data from the ARROW study underscore its transformative potential, with high overall response rates and prolonged durations of response, even in heavily pretreated patient populations.
Clinical Trials
Title | Posted | Study ID | Phase | Status | Sponsor |
|---|---|---|---|---|---|
2025/06/08 | Phase 4 | Not yet recruiting | Fujian Medical University | ||
2024/08/21 | Phase 2 | Recruiting | Sun Yat-sen University | ||
2024/07/01 | Phase 2 | Recruiting | |||
2024/01/08 | Phase 4 | Recruiting | |||
2022/09/02 | N/A | Recruiting | |||
2021/02/18 | Phase 3 | Withdrawn | |||
2020/11/17 | Phase 2 | Completed | |||
2020/10/19 | Phase 2 | Recruiting | |||
2020/10/19 | Phase 2 | Active, not recruiting | |||
2020/03/10 | Phase 2 | Recruiting |
FDA Drug Approvals
Approved Product | Manufacturer | NDC Code | Route | Strength | Effective Date |
|---|---|---|---|---|---|
| Genentech, Inc. | 50242-210 | ORAL | 100 mg in 1 1 | 8/14/2023 |
EMA Drug Approvals
Approved Product | Authorization Holder | Status | Issued Date |
|---|---|---|---|
Withdrawn | 11/18/2021 |
HSA Drug Approvals
Approved Product | Manufacturer | Approval Number | Dosage Form | Strength | Approval Date |
|---|---|---|---|---|---|
| GAVRETO HARD CAPSULES 100mg | SIN16755P | CAPSULE | 100.0mg | 4/6/2023 |
NMPA Drug Approvals
Approved Product | Company | Approval Number | Drug Type | Dosage Form | Approval Date |
|---|---|---|---|---|---|
| No NMPA approvals found for this drug. | |||||
PPB Drug Approvals
Approved Product | Registration No. | Company | Licence No. | Strength | Registration Date |
|---|---|---|---|---|---|
| No PPB approvals found for this drug. | |||||
TGA Drug Approvals
Approved Product | ARTG ID | Sponsor | Registration Type | Status | Registration Date |
|---|---|---|---|---|---|
| No TGA approvals found for this drug. | |||||
Health Canada Drug Approvals
Approved Product | Company | DIN | Dosage Form | Strength | Market Date |
|---|---|---|---|---|---|
| GAVRETO | Hoffmann-La Roche Limited | 02517590 | Capsule - Oral | 100 MG | 11/12/2021 |
CIMA AEMPS Drug Approvals
Approved Product | Company | Registration Number | Pharmaceutical Form | Prescription Type | Status |
|---|---|---|---|---|---|
| GAVRETO 100 MG CAPSULAS DURAS | 1211555001 | CÁPSULA DURA | Diagnóstico Hospitalario | Not Commercialized |
Philippines FDA Drug Approvals
Approved Product | Company | License Number | Dosage Form | Strength | Approval Date |
|---|---|---|---|---|---|
| No Philippines FDA approvals found for this drug. | |||||
Saudi SFDA Drug Approvals
Approved Product | Company | License Number | Dosage Form | Strength | Approval Date |
|---|---|---|---|---|---|
| No Saudi SFDA approvals found for this drug. | |||||
Malaysia NPRA Drug Approvals
Approved Product | Company | Registration Number | Dosage Form | Strength | Approval Date |
|---|---|---|---|---|---|
| No Malaysia NPRA approvals found for this drug. | |||||
UK EMC Drug Information
Medicine Name | MA Holder | MA Number | Pharmaceutical Form | Active Ingredient | Authorization Date |
|---|---|---|---|---|---|
| No UK EMC drug information found for this drug. | |||||
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