Data from the ongoing phase I/II ARROW clinical trial will be used to support a new drug application submission for pralsetinib to the FDA for the treatment of patients with RET fusion-positive non-small cell lung cancer.
Independent centrally reviewed top-line data for pralsetinib in patients with RET fusion-positive non-small cell lung cancer (NSCLC) was announced by Blueprint Medicines, the developer of the agent.
The company has initiated the submission of a rolling new drug application (NDA) to the FDA for pralsetinib for the treatment of patients with RET fusion-positive NSCLC. The submission is expected to be completed in the first quarter of 2020. Additionally, in the second quarter of the year, the company expects to submit an NDA to the FDA for pralsetinib for the treatment of patients with medullary thyroid cancer (MTC) previously treated with an approved multikinase inhibitor.
“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 with RET fusion-positive NSCLC, including those with newly diagnosed unresectable or metastatic disease,” Andy Boral, MD, PhD, chief medical officer at Blueprint Medicines, said in a press release. “Now, with strong, centrally reviewed top-line data, we feel a profound sense of urgency and have taken the first step toward making pralsetinib broadly available to patients by initiating a rolling NDA submission to the FDA.”
The data from the ongoing phase I/II ARROW clinical trial of pralsetinib in patients with RET fusion-positive NSCLC, previously treated with platinum-based chemotherapy, induced a 61% objective response rate (ORR) and prolonged durability, with a median duration of response (DOR) not reached. All patients were given the proposed indicated dose of 400 mg once daily.
In 80 patients with RET fusion-positive NSCLC previously treated with platinum-based chemotherapy, the ORR was 61% (95% CI, 50-72). Ninety-five percent of these patients had tumor shrinkage, including 14% who saw a complete regression of target tumors. The median DOR was not reached (95% CI, 11.3 months to not estimable).
In 26 patients who had treatment-naÃ¯ve RET fusion-positive NSCLC, the ORR was 73% (95% CI, 52-88). Twelve percent of these patients achieved a complete response, with all patients seeing tumor shrinkage.
Researchers suggested that top-line safety data was consistent with data previously reported. Pralsetinib was well-tolerated by participants, and most adverse events (AEs) were grade 1 or 2. Across all patients enrolled in the trial treated with the proposed dose (n = 354), only 4% discontinued treatment with pralsetinib due to treatment-related AEs.
Blueprint Medicines intends to initiate the first clinical trial site for its phase III AcceleRET Lung clinical trial in January 2020. The primary objective of the study is to evaluate the potential of pralsetinib to extend progression free survival (PFS) compared to platinum-based chemotherapy with or without pembrolizumab (Keytruda) in patients with RET fusion-positive NSCLC who have received no prior systemic therapy for metastatic disease.
The trial will enroll approximately 250 patients who will be randomized to receive either pralsetinib or the platinum-based chemotherapy regimen with or without pembrolizumab. Secondary endpoints of the trial include overall survival, ORR, and DOR.
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. Published January 8, 2020. ir.blueprintmedicines.com/news-releases/news-release-details/blueprint-medicines-announces-top-line-data-pralsetinib-and. Accessed January 10, 2020.