FDA Grants Surufatinib Fast Track Status in pNETS and Other Neuroendocrine Tumors

The FDA has granted Fast Track Designations to surufatinib for the treatment of advanced and progressive pancreatic neuroendocrine tumors (pNETs) and extra-pancreatic NETs in patients who are not amenable for surgery, according to Chi-Med, the developer of surufatinib.¹

Surufatinib is an inhibitor of VEGFR, FGFR, and CSF-1R. The Fast Track designations will expedite the development and review of the treatment in patients with NETs.

Chi-Med, the developer of surufatinib, previously reported results from a preplanned interim analysis of the phase III SANET-p trial (NCT02589821) showing 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 endpoint of PFS.

In November 2019, the FDA granted an orphan drug designation to surufatinib for the treatment of patients with pNETs. Additionally, Chi-Med 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 the phase III SANET-p study, 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 ≥18 years old, had previously progressed on ≤2 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 ≥12 weeks, and an absolute neutrophil count of ≥1.5 x 109/L, platelet count of ≥100 x 109/L, and hemoglobin of ≥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 ORRs 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 treatment-related adverse events included hypertension (33%), proteinuria (12%), hyperuricemia (10%), hypertriglyceridemia (6%), diarrhea (6%), and increased alanine aminotransferase (5%).

References

1. Chi-Med Announces Surufatinib Granted U.S. FDA Fast Track Designations for the Treatment of Both Pancreatic and Non-Pancreatic Neuroendocrine Tumors. Published April 17, 2020. https://bit.ly/2VihBav. April 17, 2020.
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 [news release]: London, UK. Hutchison China MediTech Limited. 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.