FDA Approves Pralsetinib for Treatment of Adults with Metastatic RET Fusion-Positive NSCLC

OncologyONCOLOGY Vol 34 Issue 10

The FDA granted approval for Pralsetinib as well as a companion diagnostic to test for RET fusions.

The US FDA has granted accelerated approval to pralsetinib (Gavreto) for the treatment of adult patients with metastatic RET fusion–positive non–small cell lung cancer (NSCLC) as detected by an FDA approved test.1

Pralsetinib is a once-daily oral RET-targeted therapy designed to inhibit RET alterations. RET alterations drive a number of cancer types, including approximately 1% to 2% of patients with NSCLC. Currently, RET is 1 of 7 NSCLC biomarkers that can be targeted with an FDA-approved therapy.2


The approval of pralsetinib was based on results observed in the phase 1/2 ARROW clinical trial (NCT03037385), which demonstrated efficacy for pralsetinib in patients with RET fusion–positive NSCLC with or without prior therapy, and regardless of RET fusion partner or central nervous system involvement. The main measures of efficacy were overall response rate (ORR) and response duration, as determined by a blinded independent review committee using RECIST 1.1.

In 87 patients who were previously treated with platinum-based chemotherapy, the ORR was 57% (95% CI, 46%-68%) with a 5.7% complete response (CR) rate. Although the median duration of response (DOR) was not estimable (95% CI, 15.2 months to not estimable), 80% of responding patients had responses that lasted 6 months or longer.1,2 The ORR was 70% (95% CI, 50%-86%) among the 27 treatment-naïve patients who were ineligible for platinum-based chemotherapy per the study protocol, with 11% of patients showing a CR. Median DOR was 9.0 months (95% CI, 6.3 months to not estimable), with 58% of patients having responses that lasted 6 months or longer.1,2

“Patients treated with [pralsetinib] had durable clinical responses, with a subset achieving complete responses characterized by the resolution of all target lesions, an uncommon outcome in metastatic lung cancer,” Vivek Subbiah, MD, associate professor in the investigational cancer therapeutics department and center clinical medical director of the Clinical Center for Targeted Therapy, cancer medicine division, at The University of Texas MD Anderson Cancer Center, as well as an investigator on the ARROW trial, said in a press release.2

“This approval represents an important advance with the potential to change standards of care for patients with RET fusion–positive non–small cell lung cancer, who have historically had limited treatment options,” added Subbiah.

The phase 1/2 ARROW trial is an open-label, first-in-human study designed to evaluate the safety, tolerability, and efficacy of pralsetinib administered in patients with RET fusion–positive NSCLC, RET-mutant medullary thyroid cancer (MTC), RET fusion–positive thyroid cancer, and other RET-altered solid tumors. The study is being conducted at multiple sites across the United States, European Union, and Asia.3

Overall, the most common adverse events observed in the study were fatigue, constipation, musculoskeletal pain, and hypertension. Importantly, pralsetinib also has warnings and precautions of interstitial lung disease/pneumonitis, hypertension, hepatotoxicity, hemorrhagic events, risk of impaired wound healing, and risk of embryo-fetal toxicity.1

The FDA also granted priority review to a new drug application for pralsetinib for the treatment of patients with advanced or metastatic RET-mutant MTC and RET fusion–positive thyroid cancer. A prescription drug user fee act date was set by the FDA for February 28, 2021.

Companion Diagnostic

The FDA also approved the Oncomine Dx Target Test as a companion diagnostic for pralsetinib.4

Biomarker testing for RET is the only way to identify patients with metastatic NSCLC who are candidates for treatment with pralsetinib. RET fusions can be identified via next-generation sequencing with tumor tissue or liquid biopsies. In the ARROW trial, RET fusions were detected using next-generation sequencing, fluorescence in situ hybridization, or other methods. Initially approved in 2017 as the first targeted next-generation sequencing-based companion diagnostic, the Oncomine Dx Target Test was granted premarket approval by the FDA. It becomes the first and only FDA-approved test of its kind for a targeted treatment for RET fusion–positive NSCLC.4 The Oncomine Dx Target Test is a qualitative in vitro diagnostic assay that simultaneously evaluates 23 genes that are known to be clinically associated with NSCLC. Sequence variations are detected via DNA and RNA extracted from formalin- fixed, paraffin-embedded tumor tissue samples collected from patients with NSCLC using the Ion PGM Dx System.5 The Oncomine Dx Target Test is also indicated as a companion diagnostic to identify ROS1 fusion–positive NSCLC, BRAF V600E–positive NSCLC and EGFR L858R– and exon deletion–positive NSCLC.


1. FDA approves pralsetinib for lung cancer with RET gene fusions. U.S. Food & Drug Administration. September 4, 2020. Updated September 8, 2020. Accessed September 14, 2020. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pralsetinib-lung-cancer-ret-gene-fusions

2. Blueprint Medicines announces FDA approval of Gavreto (pralsetinib) for the treatment of adults with metastatic RET fusion-positive non-small cell lung cancer. News release. BioSpace; September 5, 2020. Accessed September 8, 2020. https://www.biospace.com/article/releases/blueprint-medicines-announces-fda-approval-of-gavreto-pralsetinib-for-the-treatment-of-adults-with-metastatic-ret-fusion-positive-non-small-cell-lung-cancer/

3. Genentech announces FDA approval of Gavreto (pralsetinib) for the treatment of adults with metastatic RET fusion-positive non-small cell lung cancer. News release. Genentech; September 4, 2020. Accessed September 8, 2020. https://www.gene.com/media/press-releases/14875/2020-09-04/genentech-announces-fda-approval-of-gavr

4. FDA approves first NGS-based companion diagnostic for RET fusion-positive non-small cell lung cancer. News release. ThermoFisher Scientific; September 8, 2020. Accessed September 14, 2020. https://thermofisher.mediaroom.com/2020-09-08-FDA-Approves-First-NGS-Based-Companion-Diagnostic-for-RET-Fusion-Positive-Non-Small-Cell-Lung-Cancer

5. Oncomine Dx Target Test. ThermoFisher Scientific. Accessed September 14, 2020. https://www.thermofisher.com/order/catalog/product/A32451#/A32451

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