Pralsetinib a highly-selected RET inhibitor, achieved a favorable overall response rate with prolonged durability in patients with RET fusion–positive non–small cell lung cancer who were previously treated with platinum-based chemotherapy, according to top-line results from the phase I/II ARROW trial, announced the Blueprint Medicines Corporation in a press release.
Pralsetinib (BLU-667), a highly-selected RET inhibitor, achieved a favorable overall response rate (ORR) with prolonged durability in patients withRETfusionpositive non–small cell lung cancer (NSCLC) who were previously treated with platinum-based chemotherapy, according to top-line results from the phase I/II ARROW trial, announced the Blueprint Medicines Corporation in a press release.
Following the release of these positive results, the Blueprint Medicines Corporation initiated the submission of a rolling New Drug Application (NDA) to the FDA for pralsetinib as a treatment forRETfusionpositive NSCLC. The NDA submission is expected to be completed in the first quarter of 2020.
As of the data cutoff date of November 18, 2019, the ORR following treatment with pralsetinib 400 mg once daily was 61% (95% CI: 50%-72%) with 2 responses still pending in 80 evaluable patients withRETfusionpositive NSCLC who were previously treated with platinum-based chemotherapy. Tumor shrinkage was observed in 95% of the patients, which included complete regression of target tumors in 14% of patients. The median duration of response (DOR) was not reached (95% CI, 11.3 months-not estimable).
In the treatment-naïve population of patients withRETfusionpositive NSCLC (n = 26), the ORR was 73% (95% CI, 52%-88%). Overall, 12% of the patients in this group achieved a complete response, and all of the patients had tumor shrinkage.
Pralsetinib was well-tolerated in the study participants overall with a safety profile that was consistent with previously reported data. The majority of the adverse events were grade 1 or 2 in severity. Four patients discontinued treatment with pralsetinib due to treatment-emergent adverse events.
“As the clinical data for pralsetinib have matured, with deep and durable responses along with robust evidence of activity against brain metastases, our confidence has continued to grow in the potential of pralsetinib to provide lasting benefit to a broad population of patients withRETfusionpositive NSCLC, including those with newly diagnosed unresectable or metastatic disease,” Andy Boral, MD, PhD, chief medical officer of Blueprint Medicines, said in a press release.
The primary end point of the phase II portion of the ARROW trial was ORR and safety. In the phase I portion, the co-primary end points were the determination of the maximum tolerated dose of pralsetinib and safety. The study also had several secondary end points, including clinical benefit rate (CBR); DOR; disease control rate (DCR); progression-free survival (PFS); overall survival (OS); pharmacokinetics; andRETgene status and the correlation betweenRETgene status and ORR, CBR, DOR, DCR, PFS, and other antineoplastic measures.
To continue the research around treatment-naïveRETfusionpositive NSCLC, Blueprint Medicines is launching the phase III AcceleRET Lung trial in January 2020. The primary end point for the new study will be PFS of pralsetinib treatment compared with platinum-based chemotherapy with or without pembrolizumab (Keytruda) in patients with first-lineRETfusionpositive NSCLC. The secondary end points of the study will be OS, ORR, and DOR. The target enrollment for AcceleRET Lung will be 250 participants.
The full registration data set from the phase I/II ARROW trial will be presented at an upcoming scientific meeting. The study is actively recruiting patients with a target enrollment number of 527 patients. The expected completion date is March 2023.
Blueprint Medicines announces top-line data for pralsetinib and initiates rolling nda submission to FDA for the treatment of patients with RET fusion-positive non-small cell lung cancer [news release]. Cambridge, Massachusetts: Blueprint Medicine Corporation; January 8, 2020. https://bit.ly/2tJs57k. Accessed January 10, 2020.