FDA Approval Sought for Surufatinib in Pancreatic and Extra-Pancreatic NETs

A rolling submission of a new drug application (NDA) to the FDA has been initiated for surufatinib (previously HMPL 012) as a potential treatment option for patients with pancreatic and extra-pancreatic (non-pancreatic) neuroendocrine tumors (NETs), announced the developer, HUTCHMED Limited, in a press release.¹

Data from 2 clinical trials, SANET-p (NCT02589821) and SANET-ep (NCT02588170) will support the NDA for surufatinib after both trials showed a progression-free survival (PFS) benefit. The agent also demonstrated an acceptable safety profile in both studies. A pre-NDA meeting was conducted with the agency to ensure that these clinical trials were sufficient for the support of the application for FDA approval.

“Having successfully launched surufatinib in China early this year, we are now looking forward, subject to its approval, to being able to provide access to this important new therapeutic option for NETs patients in the US and beyond. Our surufatinib NDA submission to the FDA was completed by our rapidly expanding international team of over 70 personnel based mainly in the U.S., working side by side with our discovery and development colleagues in China,” said Marek Kania, MD, MBA, managing director and chief medical officer, HUTCHMED International Corporation, in a statement.

In the SANET-p study, 172 patients with either pancreatic NETs were randomly assigned 2:1 to receive surufatinib or placebo.² At a median follow-up of 19.3 months (95% CI, 9.3-19.4) in the experimental arm and 11.1 months (95% CI, 5.7-35.9) in the placebo arm, the investigator-assessed PFS was 10.9 months (95% CI, 7.5-13.8) with surufatinib compared with 3.7 months (95% CI, 2.8-5.6) with placebo (HR, 0.49; 95% CI, 0.32-0.76; P = .0011).

The most common treatment-relate adverse events (TRAEs) of grade 3 or higher observed with surufatinb versus placebo included hypertension (38% vs. 7%), proteinuria (10% vs. 2%), and hypertriglyceridemia (7% vs. 0%). Serious TRAEs occurred in 22% of the surufatinb arm versus 7% of the placebo arm. Three patients treated with surufatinb died during the study. Two of the deaths were related to an AE, and the remaining patient died as a result of disease progression. There was also 1 death in the placebo arm related to disease progression.

Exploration of surufatinb as treatment of patients with extra-pancreatic NETs was carried out in the SANET-ep clinical trial.³ Patients in the study (n = 198) were randomized 2:1 to receive surufatinb or placebo. Patients treated with surufatinib were followed for a median of 13.8 months (95% CI, 11.1-16.7) and the placebo arm was followed for a median of 16.6 months (95% C, 9.2 months to not calculable). Per investigator assessment, the median PFS was 9.2 months (95% CI, 7.4-11.1) in the surufatinib-treated population compared with 3.8 months (95% CI, 3.7-5.7) in the placebo group (HR, 0.33; 95% CI, 0.22-0.50; P < .0001).

Proteinuria was the most commonly observed grade 3 or higher TRAE in the study, which occurred in 19% of the surufatinib arm compared with no patients in the placebo arm. Cases of serious TRAEs were seen in 25% of the experimental arm versus 68% of the control arm. There were 3 treatment-related deaths in the experimental group which were caused by intravascular coagulation and hepatic encephalopathy, liver injury, or death for an unknown reason. There was also 1 death in the placebo arm caused by cachexia and respiratory failure.

In both the SANET-p and SANET-ep, patients with either pancreatic or extra-pancreatic NETs were administered oral surufatinib 300 mg once daily on a 28-day cycle or a matching placebo. The trials had similar inclusion criteria, which required patients to be at least 18 years of age with histologically pathology diagnosis of low- or intermediate grade advanced disease, had previously progressed on 2 or fewer types of systemic anti-cancer therapies, radiological documentation of progression of disease within 12 months prior to randomization, measurable disease per RECIST v1.1 criteria, adequate laboratory values at screening, and ECOG performance status of 0 or 1 and a life expectancy of at least 12 weeks.

Surufatinib was previously granted 2 fast track designations and 1 orphan drug designation by the FDA. The investigational drug is an oral angio-immuno kinase inhibitor that selectively inhibits the tyrosine kinase activity that impacts vascular endothelial growth factor receptor and the fibroblast growth factor receptor. In doing this, surufatinib has the potential to regulate tumor-associated macrophages to promote an immune response against tumors.

_References:

_{1. HUTCHMED completes rolling submission of NDA to U.S. FDA for surufatinib for the treatment of advanced neuroendocrine tumors. News release. May 3, 2021. Accessed May 3, 2021. https://bit.ly/33bmFRa}

_{2. Xu J, Shen L, Bai C, et al. Surufatinib in advanced pancreatic neuroendocrine tumours (SANET-p): a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol. 2020; 21(11): 1489-99. doi: 10.1016/S1470-2045(20)30493-9}

_{3. Xu J, Shen L, Zhou Z, et al. Surufatinib in advanced extrapancreatic neuroendocrine tumours (SANET-ep): a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol. 2020; 21(11): 1500-12. doi: 10.1016/S1470-2045(20)30496-4}