December 30, 2020 - The China National Medical Products Administration has approved surufatinib for the treatment of patients with non-pancreatic neuroendocrine tumors.
The China National Medical Products Administration has approved surufatinib (Sulanda) for the treatment of patients with non-pancreatic neuroendocrine tumors.1
The regulatory decision was based on data from the phase 3 SANET-ep trial (NCT02589821), which showed that the agent led to a significant improvement in progression-free survival (PFS) vs placebo; the agent was also found to have a favorable risk–benefit profile in patients who had progressive, advanced, well-differentiated extrapancreatic NETs.2
“We are very pleased to have achieved this major milestone for Chi-Med. The approval of surufatinib, our first un-partnered oncology drug, is a strong testament to our in-house research and development capability,” Christian Hogg, chief executive officer of Chi-Med, stated in a press release. “Today’s approval also marks an important development for NET patients, for whom there are currently limited treatment options.”
In the double-blind, placebo-controlled phase 3 trial, a total of 198 patients were randomized 2:1 to either oral surufatinib (n = 129) at a daily dose of 300 mg or placebo (n = 69), which was administered on a 28-day treatment cycle.3
To be eligible for participation, patients had to be aged 18 years or older and have a diagnosis of unresectable or metastatic, well-differentiated NETs of pathological grade 1 or 2 per the 2010 World Health Organization classification; the disease could originate from any extrapancreatic location. Patients also had to have an expected survival of more than 12 weeks and an ECOG performance status of 0-1.
The primary end point was PFS per investigator assessment, while a supportive outcome was PFS per BIIRC assessment. Secondary end points of the trial comprised objective response rate (ORR), disease control rate (DCR), best overall response, time to response (TTR), duration of response (DOR), overall survival (OS), and safety.
As of the data cutoff of March 31, 2019, the median PFS per investigator assessment was 9.2 months for those who received surufatinib vs 3.8 months for those given placebo (HR, 0.33; 95% CI, 0.22-0.50; P <.0001); this crossed the predefined P value boundary (two-sided, P = .015) for the interim analysis.
Moreover, results from the supportive analysis of PFS per blinded independent image review committee (BIIRC), 62% (n = 80) and 59% (n = 41) of patients who received surufatinib and placebo, respectively, experienced progressive disease or died. Here, the median PFS in the investigative and control arms was 7.4 months and 3.9 months, respectively (HR, 0.66; 95% CI, 0.44-0.98; P = .037).
In the interim intention-to-treat population, the ORR per investigator assessment was 10% in the surufatinib arm vs 0% in the placebo arm; the DCR rates were 87% vs 66%, respectively (odds ratio [OR], 3.3; P = .0022). Additionally, the TTR was 3.7 months in the investigative arm with a DOR of 5.6 months. Per BIIRC assessment, the ORRs were 8% vs 0% in the surufatinib and placebo arms, respectively; the DCRs were 78% vs 67%, respectively (OR, 1.7; P = .19). Here, the TTR with surufatinib was 2.9 months and the DOR was 5.6 months.
At this timepoint, the OS data from the trial were not mature; only 18.7% OS events had been reported at the time of the data cutoff.
Regarding safety, 98% (n = 129/129) of the patients on surufatinib and 96% (n = 65/68) of those on placebo experienced at least 1 treatment-related toxicity; these effects were primarily grade 1 or 2 in severity. The most commonly experienced treatment-related adverse effects of grade 3 or higher in the investigative and control groups included hypertension (36% vs 13%, respectively), proteinuria (19% vs 0%), anemia (5% vs 3%), increased aspartate aminotransferase and increased blood pressure (4% vs 3%), protein present in urine and hyperbilirubinemia (4% vs 0%), and increased alanine aminotransferase (3% vs 0%).
Because the trial had met its predefined primary end point of PFS during the planned interim analysis, the independent Data Monitoring Committee for the trial recommended that SANET-ep be terminated early.
“Compared with other NET therapies available in the market, surufatinib has a unique mode of action by both inhibiting angiogenesis and promoting the body’s immune response against tumor cells,” Hogg added in the release. “If our second new drug application in pancreatic NET is successful, this therapy would be approved in China to address all NET patients regardless of the tumor origin.”
In the United State, the filing of a new drug application for surufatinib was initiated with the FDA on December 28, 2020 for use as as a treatment for patients with pancreatic and non-pancreatic NETs.