November 19, 2021: “Roche announced that the European Commission (EC) has granted conditional marketing authorisation for Gavreto® (pralsetinib) as a monotherapy for the treatment of adults with rearranged during transfection (RET) fusion-positive advanced non-small cell lung cancer (NSCLC) not previously treated with a RET inhibitor.
Gavreto is the first and only precision medicine approved in the European Union (EU) for the first-line treatment of people with RET fusion-positive advanced NSCLC.
“Today’s approval represents an important step forward in delivering precision medicine to people with RET fusion-positive advanced non-small cell lung cancer, for whom treatment options have historically been limited,” said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development.
“By using cancer genomic profiling upfront, healthcare professionals may identify specific genetic alterations that predict clinical benefit of targeted treatment options like Gavreto in the first-line setting.”
The approval is based on results of the ongoing phase I/II ARROW study, in which Gavreto led to durable responses in people with advanced RET fusion-positive NSCLC.
In 75 treatment-naïve patients, Gavreto demonstrated an overall response rate (ORR) of 72.0% (95% CI: 60.4%, 81.8%), and median duration of response (DOR) was not reached (NR) (95% CI: 9.0 months, NR).
In 136 patients who had previously received platinum-based chemotherapy, Gavreto demonstrated an ORR of 58.8% (95% CI: 50.1%, 67.2%), and median DOR was 22.3 months (95% CI: 15.1 months, NR).
Gavreto was also generally well-tolerated, with a low rate of treatment discontinuation; common grade 3-4 adverse reactions were neutropenia (reported in 20.1% of patients), anaemia (17.6%) and hypertension (16.1%).
Approximately 37,500 people are diagnosed with RET fusion-positive NSCLC worldwide each year; the disease often affects people with minimal to no history of smoking, and who are typically younger than the average person diagnosed with lung cancer.
Roche is committed to providing a tailored treatment option for every person with lung cancer, no matter how rare or difficult-to-treat their type of disease.
Gavreto in RET fusion-positive advanced NSCLC, along with Alecensa® (alectinib) in ALK-positive advanced NSCLC and Rozlytrek® (entrectinib) in ROS1-positive advanced NSCLC, is part of Roche’s growing portfolio of precision medicines.
Together, they offer personalised treatment options for almost one in ten people with advanced NSCLC, and biomarker testing is the most effective way to identify those people who may benefit.
Beyond NSCLC, RET alterations are also key disease drivers in other cancer types, such as thyroid cancers.
Gavreto has shown activity across multiple solid tumour types, reflecting tumour-agnostic potential.
It is approved by the U.S. Food and Drug Administration (FDA) for the treatment of adults with metastatic RET fusion-positive NSCLC, and for the treatment of adult and paediatric patients 12 years of age and older with advanced RET-altered thyroid cancers.
Gavreto is also approved in Canada, mainland China and Switzerland. In the EU, a submission for RET-altered thyroid cancers is planned.
Regulatory submissions for advanced RET fusion-positive NSCLC and RET-altered thyroid cancers are also underway in multiple countries worldwide.
Blueprint Medicines and Roche are co-developing Gavreto globally, with the exception of certain territories in Asia, including China.*
Blueprint Medicines and Genentech, a wholly owned member of the Roche Group, are commercialising Gavreto in the US and Roche has exclusive commercialisation rights for Gavreto outside of the US, with the exception of certain territories in Asia, including China.
About the ARROW study
ARROW is an ongoing phase I/II, open-label, first-in-human study designed to evaluate the safety, tolerability and efficacy of Gavreto, administered orally in people with rearranged during transfection (RET) fusion-positive non-small cell lung cancer (NSCLC), RET-mutant medullary thyroid cancer, RET fusion-positive thyroid cancer and other RET-altered solid tumours.
ARROW is being conducted at multiple sites across the United States, Europe and Asia.
About rearranged during transfection (RET)-altered cancers
RET gene alterations, such as fusions and mutations, are key disease drivers in many types of cancer, including non-small cell lung cancer (NSCLC) and several types of thyroid cancer.
There are approximately 2.21 million cases of lung cancer diagnosed each year worldwide, of which approximately 1.8 million are NSCLC and RET fusions are present in approximately 1-2% of these patients, meaning RET fusion-positive NSCLC affects up to 37,500 people each year.
Additionally, approximately 10-20% of people with papillary thyroid cancer (the most common type of thyroid cancer) have RET fusion-positive tumours, and roughly 90% of people with advanced medullary thyroid cancer (a less prevalent form of thyroid cancer) carry RET mutations.
Oncogenic RET fusions also are observed at low frequencies in other cancers, including cholangiocarcinoma, colorectal, neuroendocrine, ovarian, pancreatic and thymus cancers.
About Gavreto® (pralsetinib)
Gavreto is a once-daily, oral precision medicine designed to selectively target rearranged during transfection (RET) alterations, including fusions and mutations, regardless of the tissue of origin.
Preclinical data have shown that Gavreto 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.
Blueprint Medicines and Roche are co-developing Gavreto for the treatment of people with various types of RET-altered cancers.”
