The rolling submission of a new drug application to the FDA for surufatinib for the treatment of patients with pancreatic and non-pancreatic neuroendocrine tumors has been completed.
The rolling submission of a new drug application (NDA) to the FDA for surufatinib for the treatment of patients with pancreatic and non-pancreatic neuroendocrine tumors (NETs) has been completed, according to an announcement from Hutchinson China MediTech Limited.1
The application is supported by findings yielded from 2 phase 3 trials of the agent that were conducted in patients with NETs in China: SANET-p (NCT02589821) and SANET-ep (NCT02588170). The application also includes data from a study that was done in patients with pancreatic and non-pancreatic NETs in the United States.
Previously, the company had reached an agreement with the regulatory agency 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 submit a marketing authorization application with the European Medicines Agency this year. The company also shared that it would initiate an Expanded Access Protocol to ensure that surufatinib is accessible to patients who have limited therapies available to them.
“HUTCHMED is developing 6 novel oncology drug candidates internationally and this surufatinib NDA represents our first ever in the United States,” Marek Kania, MD, MBA, managing director and chief medical officer of HUTCHMED International Corporation, stated in a press release. “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 [patients with] NETs in the United States and beyond.”
In SANET-p, about 195 Chinese patients who had low- or intermediate-grade advanced pancreatic NETs for whom no effective therapy was available underwent a 2:1 randomization to receive either oral surufatinib at a daily dose of 300 mg or placebo on a 28-day treatment cycle.2
Patients had to have well-differentiated pancreatic NETs that was grade 1 or 2, locally advanced disease or have distant metastasis, documented radiologic progression within 1 year, and progression on 2 or less previous systemic treatments for advanced disease. They could not have progressed on VEGF or VEGFR inhibitor, nor could they have functional NETs that needed treatment with long-acting somatostatin analogues.
The primary objective of the trial was investigator-assessed progression-free survival, while key secondary end points comprised objective response rate (ORR), disease control rate (DCR), time to response (TTR), duration of response (DOR), and overall survival (OS), as well as safety and tolerability.
A total of 172 patients were randomized; 113 patients received surufatinib, while 59 were given placebo. The median investigator-assessed PFS in the surufatinib arm was 10.9 months (95% CI, 7.5-13.8) vs just 3.7 months (95% CI, 2.8-5.6) in the placebo arm (HR, 0.491; 95% CI, 0.319-0.755; P = .0011), meeting the superiority criteria of PFS for the trial. Moreover, PFS benefit was found to favor surufatinib across major patient subgroups evaluated.
The blinded independent image review committee (BIIRC)–assessed PFS proved to be consistent with the investigator-assessed PFS, at 13.9 months (95% CI, 11.0-24.9) in the investigative arm vs 4.6 months (95% CI, 3.6-7.4) in the control arm (HR, 0.339; 95% CI, 0.209-0.549; P < .0001).
Moreover, surufatinib elicited an ORR of 19.2% (95% CI, 12.2%-28.1%) vs 1.9% (95% CI, 0.0%-10.1%) with placebo (P = .0021). The DCR was 80.8 months vs 66.0 months with surufatinib vs placebo, respectively (P = .0774), while the TTR was 3.8 months and 7.4 months, respectively. Moreover, the DOR with surufatinib was 7.4 months. At the time of the data presentation at the 2020 ESMO Virtual Congress, OS data remained immature.
The safety profile of the agent was noted to be manageable and consistent with data from previous studies.
In the randomized, double-blind, placebo-controlled SANET-ep trial, 198 patients with unresectable or metastatic, well differentiated, extrapancreatic NETs were enrolled.3 Patients had to be at least 18 years of age, have an ECOG performance status of 0 or 1, and could not have progressed on more than 2 types of prior systemic therapies.
Patients were randomized 2:1 to receive oral surufatinib at a daily dose of 300 mg (n = 129) or matching placebo (n = 69). Stratification was based on tumor origin, pathological grade, and prior treatment received. The median follow-up for the investigative and control arms was 13.8 months and 16.6 months, respectively.
Results showed that the median investigator-assessed PFS with surufatinib was 9.2 months (95% CI, 7.4-11.1) vs 3.8 months (95% CI, 3.7-5.7) with placebo (HR, 0.33; 95% CI, 0.22-0.50; P <.0001). The median PFS per BIIRC was 7.4 months (95% CI, 5.6-9.3) with surufatinib vs 3.9 months (95% CI, 3.7-5.8) with placebo (HR, 0.66; 95% CI, 0.44-0.98; P = .037).
Additionally, surufatinib elicited an investigator-assessed ORR of 10.0% (95% CI, 5.6%-17.0%) in the interim intent-to-treat population. The DCRs were 87.0% vs 66.0% in the investigative and control arms, respectively. Moreover, the TTR was 3.7 months with surufatinib, and the DOR was 5.6 months.
Regarding safety, again, the agent demonstrated an acceptable toxicity profile. The most frequently experienced treatment-related adverse effects (TRAEs) that were grade 3 or higher were hypertension (36.0% vs 13.0% with surufatinib and placebo, respectively), proteinuria (19.0% vs 0.0%), and anemia (5.0% vs 3.0%).
A multicenter, single-arm, open-label phase 1b/2 trial also examined surufatinib in patients with histologically well-differentiated, low- or intermediate-grade, inoperable or metastatic NETs. Here, patients were stratified by subtype: pancreatic (n = 41) or non-pancreatic (n = 39).4
Data indicated that the agent elicited an ORR of 19.0% (95% CI, 9.0%-34.0%) in those with pancreatic NETs and 15.0% (95% CI, 6.0%-31.0%) in those with non-pancreatic NETs. Moreover, the median PFS was 21.2 months and 13.4 months in the investigative and control arms, respectively. The most frequently reported grade 3 or higher TRAEs with surufatinib were hypertension (33.0%), proteinuria (12.0%), hyperuricemia (10.0%), hypertriglyceridemia (6.0%), diarrhea (6.0%), and alanine aminotransferase increase (5.0%).