FDA Approves Pralsetinib in RET Fusion-Positive Non–Small Cell Lung Cancer


The FDA has approved pralsetinib for the treatment of adult patients with metastatic RET fusion–positive non–small cell lung cancer, as detected by an FDA-approved test.

The FDA has approved pralsetinib (formerly BLU-667, 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

"Targeted therapies have dramatically improved care for patients with non–small cell lung cancer driven by oncogenes, including EGFR and ALK, and the approval of the selective RET inhibitor pralsetinib, or Gavreto, marks another milestone in a paradigm shift toward precision medicine," said ARROW lead investigator Vivek Subbiah, MD, associate professor of investigational cancer therapeutics and center medical director of the Clinical Center for Targeted Therapy at The University of Texas MD Anderson Cancer Center, in a statement. "Patients treated with Gavreto 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. We observed this activity with or without prior therapy and regardless of RET fusion partner or the presence of brain metastases. 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."

Accelerated approval for pralsetinib in this indication was granted based on findings from the phase 1/2 ARROW trial. As approval was granted through the accelerated approval program, continued approval may be contingent upon verification of clinical benefit in a confirmatory trial.

The ARROW trial (NCT03037385) is a first-in-human trial to examine the safety and efficacy of the RET inhibitor. It consisted of a completed dose-escalation phase and an expansion phase. The phase 2 portion of the study included cohorts for patients with RET fusion–positive NSCLC, RET mutation–positive medullary thyroid cancer, and those with other RET fusion–positive solid tumors. Eligible patients were those with advanced solid tumors harboring RET alterations and no other driver mutations. Treatment in the phase 2 portion was administered at 400 mg orally once daily.

Primary end points of the phase 2 portion include centrally reviewed objective response rate (ORR) per RECIST v1.1 criteria and safety.

In the RET fusion–positive NSCLC population of the ARROW trial, durable clinical responses were observed in both patients who were previously treated and untreated and regardless of RET fusion partner or central nervous system involvement.

Among the patients who were previously treated with platinum-based chemotherapy (n = 87), the ORR was 57% (95% CI, 46%-68%) and complete responses were observed in 5.7%. The median duration of response was not reached at the time of data cutoff.

In the treatment-naïve group (n = 27), the ORR was 70% (95% CI, 50%-86%) and complete responses were reported in 11%.

According to safety findings presented at the 2020 American Society of Clinical Oncology Virtual Scientific Program, among all 354 patients treated with the RET inhibitor, the most common any-grade treatment-related adverse events (TRAEs) in the overall patient population were aspartate aminotransferase increase (31%), anemia (22%), alanine aminotransferase increase (21%), constipation (21%), hypertension (20%), and neutropenia (19%). Common grade ≥3 TRAEs were hypertension (10%), neutropenia (10%), and anemia (8%). Discontinuations due to TRAEs were reported in 4% of patients.2

“The FDA approval of Gavreto for RET fusion–positive non–small cell lung cancer is an important step towards our goal of providing an effective treatment option for every person diagnosed with lung cancer, no matter how rare or hard-to-treat their type of disease,” Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development, Genentech (Roche), said in a statement. “We remain committed to finding personalized treatment options for people with cancer based on specific genomic or molecular alterations, and we look forward to partnering with Blueprint Medicines to further explore the potential of Gavreto across multiple RET-altered tumor types.”

Previously the FDA granted a breakthrough therapy designation to pralsetinib for this indication in patients who progressed following platinum-based chemotherapy as well as for the treatment of patients with RET-mutant medullary thyroid cancer requiring systemic treatment for which there are no acceptable alternative treatments.


1. 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 4, 2020. https://bit.ly/2EYHZRe

2. Gainor JF, Curigliano G, Kim DW, et al. Registrational dataset from the phase I/II ARROW trial of pralsetinib (BLU-667) in patients (pts) with advanced RET fusion+ non-small cell lung cancer (NSCLC). J Clin Oncol. 2020;38(suppl):9515. doi:10.1200/JCO.2020.38.15_suppl.9515

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