At ASCO 2021, we presented a subgroup analysis of SANET-p on the relationship of Ki-67 and baseline CgA on efficacy outcomes. SANET-p had showed that surufatinib demonstrated a statistically significant and clinically meaningful improvement in PFS, and this exploratory analysis showed that surufatinib demonstrated benefit irrespective of Ki-67 expression levels or baseline CgA. Median PFS was statistically longer in the surufatinib arm versus that in the placebo arm in subgroups of Ki-67 5-10% (11.0 vs 3.7 months), Ki-67 > 10% (11.1 vs 2.8 months) and CgA > 2 × ULN (11.0 vs 3.7 months).
Surufatinib – BTC:
Phase Ib/IIa study of surufatinib monotherapy in second-line BTC (NCT02966821) – We presented data at ASCO 2021, which highlighted surufatinib’s potential in BTC. For a total of 39 BTC patients, 16-week PFS rate was 46.33% (95% CI: 24.4‒65.7), with median PFS of 3.7 months and median OS of 6.9 months. The top three Grade 3 or higher TRAEs68 included blood bilirubin increased (20.5%), hypertension (17.9%), and proteinuria (12.8%).
Phase IIb/III study of surufatinib monotherapy in second-line BTC (NCT03873532) – In March 2019, based on preliminary Phase Ib/IIa data, we initiated a Phase IIb/III study comparing surufatinib monotherapy with capecitabine in patients with unresectable or metastatic BTC. Enrollment for the Phase IIb portion (80 patients) of this study was completed in late 2020. Based on the emerging data from our Phase II cohort of the surufatinib combination plus TUOYI® in BTC (NCT04169672), we are now prioritizing the combination over surufatinib monotherapy for further development.
Surufatinib – Combinations with checkpoint inhibitors:
Surufatinib’s ability to inhibit angiogenesis, block the accumulation of tumor associated macrophages and promote infiltration of effector T cells into tumors, could help improve the anti-tumor activity of PD-1 antibodies.
TUOYI® combinations (NCT04169672) – In a Phase I dose-finding study presented at the 2020 AACR Conference, data showed that surufatinib plus TUOYI® were well tolerated with no unexpected safety signals observed, with encouraging antitumor activity in patients with advanced solid tumors, particularly in severe settings such as grade 3 NET patients or NEC patients for whom no therapies have been approved. A Phase II China study is enrolling patients in nine solid tumor indications, including NENs, BTC, gastric cancer, thyroid cancer, SCLC, soft tissue sarcoma, endometrial cancer, esophageal cancer and NSCLC.
At ASCO 2021, encouraging preliminary data were disclosed for the surufatinib and TUOYI® combination in the NEC and gastric cancer cohorts.
For the 20 patients in the NEC cohort who received an average of 5 cycles of treatments and are efficacy evaluable, ORR was 20% while DCR was 70%. Median PFS was 3.9 months (95% CI: 1.3-NR). Grade 3 or higher TRAEs occurred in 33% of patients. We are preparing to initiate a Phase III study in second-line or above NEC.
Median duration of treatment for the gastric cancer cohort was 3 months, with 15 efficacy evaluable patients at the time of the analysis. For these 15 patients, confirmed ORR was 13% and an additional 20% of patients had unconfirmed response. DCR was 73% and median PFS was 3.7 months (95% CI: 1.4-NR). Grade 3 or higher TRAEs occurred in 14% of patients. Registration design for gastric cancer is under discussion.
Tislelizumab combinations (NCT04579757) – In addition to the TUOYI® and TYVYT® combination studies in China, in March 2021 we dosed the first patient in an open-label, Phase Ib/II study of surufatinib in combination with BeiGene’s tislelizumab in the U.S. and Europe, evaluating the safety, tolerability, pharmacokinetics and efficacy in patients with advanced solid tumors, including CRC, NET, small cell lung cancer, gastric cancer and soft tissue sarcoma.
Surufatinib – Exploratory development:
We are conducting multiple Phase Ib expansion cohorts in the U.S. to explore the use of surufatinib in BTC and soft tissue sarcoma. In China, we intend to initiate multiple exploratory studies, both as a single agent and in combinations, to evaluate the efficacy of surufatinib. We are also supporting dozens of investigator-initiated studies in various tumor settings.
Fruquintinib (ELUNATE® in China)
Fruquintinib is a novel, selective, oral inhibitor of VEGFR 1/2/3 kinases that was designed to improve kinase selectivity to minimize off-target toxicity and thereby improve tolerability. Fruquintinib has been studied in over 2,800 clinical trial patients to date, both as a monotherapy and in combinations.