FDA Grants Two Fast Track Designations to Surufatinib in Pancreatic and Extrapancreatic NETs

The FDA granted two Fast Track designations to surufatinib (HMPL-012) for the treatment of both advanced and progressive pancreatic neuroendocrine tumors (NETs) and extra-pancreatic (non-pancreatic) NETs in patients who are not amenable for surgery, according to a press release from the developer, Chi-Med. The agent was previously granted Orphan Drug Designation by the FDA for this indication.¹

Treatment with surufatinib, a VEGFR, FGFR, and CSF-1R inhibitor, prolonged progression-free survival in patients with pancreatic NETs, meeting the primary end point of the pre-planned interim analysis for the phase III SANET-p trial (NCT02589821). This positive results led to early study completion, at the recommendation of the Independent Data Monitoring Committee.² The full results from the study will be presented at an upcoming medical conference.¹

According to data presented at the 2019 European Society of Medical Oncology (ESMO) Annual Meeting, the median PFS was 9.2 months for patients treated with surufatinib versus 3.8 months for patients treated given placebo (HR, 0.334; 95% CI, 0.223-0.499; P <.0001).3

SANET-p, a randomized, double-blind, multi-center trial included approximately 195 patients who were randomized 2:1 to receive surufatinib 300 mg, orally, once daily or an equivalent dose of placebo, orally, once daily. In addition to PFS, the study assessed overall response rate (ORR), disease control rate (DCR), duration of response, time to response, overall survival, and safety/tolerability.

Eligible patients had radiological documentation of progression of disease within 12 months prior to randomization, measurable lesions, and a performance status of 0 or 1. Patients were required to have an absolute neutrophil count of ≥1.5×109/L, platelet count of ≥100×109/L, and hemoglobin ≥9 g/dL; and serum total bilirubin <1.5 times the upper limit of normal (ULN). Patients could not have progressed on any more than 2 types of systemic therapies.

Earlier data from the Phase Ib/II SANET-p trial were published in Clinical Cancer Research. In the study, surufatinib elicited antitumor responses patients with histologically advanced well-differentiated, low or intermittent grade, inoperable or metastatic NETs.⁴

Median PFS was 21.2 months in patients with pancreatic NETs and 13.4 months in those with extrapancreatic NETs (95% CI, 7.6-19.3).

The overall response rate (ORR) observed was 19% (95% CI, 9-34) for patients with pancreatic NETs, which included partial responses (PRs) in 8 patients and stable disease (SD) in 30 patients. The ORR was 15% (95% CI, 6-31) for those with extrapancreatic NETs, including 6 PRs and 30 cases of SD. Also, the disease control rate in these patients was 91% (95% CI, 77-97) and 92% (95% CI, 79-98), respectively. Among the patients who achieved a PR, the median DOR in the pancreatic NETs and extrapancreatic NETs cohort, respectively was 21.1 months (95% CI 1.5-21.1)and 12.0 months (95% CI 6.8-12.9).

Tumor shrinkage from baseline was observed in most patients. Specifically, 61% of the subjects with pancreatic NETs (n = 25) and 55% of those with extrapancreatic NETs (n = 22).

In the safety analysis, surufatinib demonstrated a manageable toxicity profile with few grade 3 or higher adverse events (AEs). Of the grade ≥3 AEs observed, the most common were hypertension (33%), proteinuria (12%), hyperuricemia (10%), hypertriglyceridemia, and diarrhea (6% for each), as well as increased alanine aminotransferase (5%).

Outside of NETs, surufatinib is being studied in combination with capecitabine for the treatment of biliary tract cancer, in a phase IIb/III clinical trial (NCT03873532).

_References

1. _{Chi-Med announces surufatinib granted U.S. FDA Fast Track designations for the treatment of both pancreatic and non-pancreatic neuroendocrine tumors [news release]. London, England: Chi-Med; April 17, 2020. https://bit.ly/2VgNpfB. Accessed 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, England: Chi-Med; January 20, 2020. https://bit.ly/2VgewHG. Accessed April 17, 2020.}
3. _{Chi-Med to Discuss Surufatinib phase iii and U.S. phase I/Ib efficacy and safety data presented at the 2019 esmo annual meeting [new release]. London, England: Chi-Med; September 29, 2019. https://bit.ly/2xDmotV. Accessed April 17, 2020.}
4. _{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.}