The FDA ( Food and Drug Administration ) has approved Gavreto ( Pralsetinib ) for the treatment of adults with metastatic rearranged during transfection ( RET ) fusion-positive non-small cell lung cancer ( NSCLC ) as detected by an FDA approved test.
This indication was approved under the FDA’s Accelerated Approval programme, based on data from the phase I/II ARROW study. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
RET-activating fusions and mutations are key disease drivers in many cancer types, including NSCLC and medullary thyroid cancer ( MTC ), and treatment options that selectively target these genetic alterations are limited.
In NSCLC, RET fusions represent approximately 1-2% of patients.
The approval is based on the results from the phase I/II ARROW study, in which Pralsetinib produced durable clinical responses in people with RET fusion-positive NSCLC with or without prior therapy, and regardless of RET fusion partner or central nervous system involvement.
Pralsetinib demonstrated an overall response rate ( ORR ) of 57% ( 95% CI: 46%, 68% ) and complete response ( CR ) rate of 5.7% in the 87 people with NSCLC previously treated with Platinum-based chemotherapy, and the median duration of response ( DoR ) was not reached ( 95% CI: 15.2 months, not-reached ). In the 27 people with treatment-naïve NSCLC, the ORR was 70% ( 95% CI: 50%, 86% ), with an 11% CR rate.
The most common adverse reactions ( greater than or equal to 25% ) were fatigue, constipation, musculoskeletal pain and hypertension.
The FDA granted Breakthrough Therapy Designation to Gavreto for the treatment of RET fusion-positive NSCLC that has progressed following Platinum-based chemotherapy and for RET mutation-positive medullary thyroid cancer that requires systemic treatment and for which there are no acceptable alternative treatments.
The FDA has also granted Priority Review to Gavreto for the treatment of people with advanced or metastatic RET-mutant medullary thyroid cancer and RET fusion-positive thyroid cancer.
ARROW is an open-label, first-in-human study designed to evaluate the safety, tolerability and efficacy of Pralsetinib, administered orally in people with RET fusion-positive non-small cell lung cancer, RET-mutant medullary thyroid cancer, RET fusion-positive thyroid cancer and other RET-altered solid tumours.
The trial consists of two parts: a dose escalation portion, which is complete, and an expansion portion in people treated with 400 mg of Pralsetinib, once-daily.
ARROW is being conducted at multiple sites across the United States, European Union and Asia.
Pralsetinib is a once-daily, oral precision therapy designed to selectively target RET alterations, including fusions and mutations, regardless of the tissue of origin.
Preclinical data have shown that Pralsetinib inhibits primary RET fusions and mutations that cause cancer in subsets of patients, as well as secondary RET mutations predicted to drive resistance to treatment. ( Xagena )
Source: Roche, 2020