The filing of a new drug application has been initiated with the FDA for surufatinib for the treatment of patients with pancreatic and non-pancreatic neuroendocrine tumors.
The filing of a new drug application (NDA) has been initiated with the FDA for surufatinib for the treatment of patients with pancreatic and non-pancreatic neuroendocrine tumors.1
Hutchison China MediTech Limited (Chi-Med), the developer of surufatinib, which is an inhibitor of VEGFR, FGFR, and CSF-1R, plans to complete the NDA submission in the first half of 2021.
In April 2020, the FDA granted a fast track designation to surufatinib for this indication. The NDA is based on findings from 2 phase 3 Chinese trials of surufatinib in NETs, as well as US studies of surufatinib in patients with non-pancreatic and pancreatic NETs.
“With the initiation of our first regulatory filing in the [United States], we are executing our strategy of building a global pharmaceutical company that brings innovative cancer therapies to patients worldwide," said Marek Kania, MD, managing director and chief medical officer of Chi-Med. "There is a great need for additional therapies to treat neuroendocrine tumors, and surufatinib has demonstrated significant clinical benefit in patients with advanced tumors. The NDA filing to the US FDA represents a significant step toward our goal of commercializing surufatinib and other novel therapies globally.”
Previously, Chi-Med said that that it had reached an agreement with the FDA during a pre-NDA meeting that these studies could serve as the basis to support an NDA submission. The data package will also be used to file a Marketing Authorization Application with the European Medicines Agency in 2021.
Chi-Med also stated that it plans to initiate an Expanded Access Protocol to "ensure patients with limited therapeutic options have access to this important treatment."
Enrollment into the program is anticipated to begin in the first quarter of 2021, once regulatory clearance of the protocol has been granted by the FDA.
Chi-Med previously reported data from a preplanned interim analysis of the phase 3 SANET-p trial (NCT02589821), which demonstrated that surufatinib improved progression-free survival (PFS) compared with placebo in patients with low- or intermediate-grade advanced pNETs for whom there is no effective therapy.2 Due to the positive efficacy, an independent data monitoring committee recommended that the study be stopped early, as the trial met the predefined primary end point of PFS.
In November 2019, the FDA granted an orphan drug designation to surufatinib for the treatment of patients with pNETs. Additionally, Chi-Med had stated that a China new drug application for surufatinib as a treatment for patients with advanced extra-pancreatic NETS was accepted for review by the China National Medical Products Administration, and was subsequently granted a priority review designation in December 2019.
In SANET-p, approximately 195 Chinese patients with low- or intermediate-grade advanced pNETs for whom there is no effective therapy were randomized 2:1 to receive either 300 mg of oral surufatinib daily or placebo on a 28-day cycle.
To be eligible for enrollment, patients had to be at least 18 years old, had previously progressed on 2 or more types of systemic therapy, had radiological documentation of disease progression within 12 months prior to randomization, had measurable lesions according to RECIST v1.1 criteria, had an ECOG performance status of 0 or 1, an expected survival of at least 12 weeks, and an absolute neutrophil count of at least 1.5 x 109/L, platelet count of at least 100 x 109/L, and hemoglobin of at least 9 g/dL, among other criteria.
Patients who have high-grade neuroendocrine cancer, adenocarcinoid, pancreatic islet cell carcinoma, goblet cell carcinoid, large cell neuroendocrine carcinoma and small cell carcinoma were excluded from enrollment. Additionally, patients could not have functional NETs that required treatment with long-acting somatostatin analogs to control disease-related syndromes, nor could they receive prior treatment with and had disease progression on a VEGF inhibitor.
The primary endpoint of the study is PFS; secondary endpoints include objective response rate (ORR), disease control rate, time to response, duration of response, overall survival, safety, and tolerability.
Previously, a multicenter, single-arm, open-label, phase Ib/II trial evaluated surufatinib in patients with histologically well-differentiated, low- or intermittent-grade, inoperable or metastatic NETs. Patients were stratified by pancreatic (n = 42) or extrapancreatic subtype (n = 39).
Results showed that the objective response rates were 19% (95% CI, 9%-34%) in the pancreatic NETs cohort and 15% (95% CI, 6%-31%) in the extrapancreatic NET cohort.3 The median PFS was 21.2 months (95% CI, 15.9-24.8) and 13.4 months (95% CI, 7.6-19.3), respectively. Regarding safety, the most common grade 3 or higher treatment-related adverse events included hypertension (33%), proteinuria (12%), hyperuricemia (10%), hypertriglyceridemia (6%), diarrhea (6%), and increased alanine aminotransferase (5%).
1. Chi-Med Initiates Rolling Submission of NDA to U.S. FDA for Surufatinib for the Treatment of Advanced Neuroendocrine Tumors. Hutchison China MediTech Limited. News release. December 28, 2020. Accessed December 28, 2020. https://yhoo.it/2WOrZXg
2. Chi-Med announces that surufatinib phase III SANET-p study has already achieved its primary endpoint in advanced pancreatic neuroendocrine tumors in China and will stop early. Hutchison China MediTech Limited. News release. Published January 20, 2020. https://bit.ly/2NOnrvT. Accessed January 21, 2020.
3. Xu J, Li J, Bai C, et al. Surufatinib in advanced well-differentiated neuroendocrine tumors: a multicenter, single-arm, open-label, phase Ib/II trial. Clin Cancer Res. 2019;25(12):3486-3494. doi: 10.1158/1078-0432.CCR-18-2994.