Chi-Med has unveiled some phase 3 data it’s hoping will help win FDA approval for surufatinib. Tested in Chinese patients with pancreatic neuroendocrine tumors, the kinase inhibitor staved off disease progression for a median 10.9 months, compared with 3.7 months for placebo.
Chi-Med had stopped the trial early for efficacy in May, setting it up to file for an approval in China. Since then, it laid out plans to seek U.S. FDA approval later this year on the strength of data from Chinese phase 3 trials in non-pancreatic and pancreatic NET patients, and a U.S. phase 1b/2 study.
Chi-Med used the ESMO Virtual Congress 2020 to share the phase 3 pancreatic data. The median progression-free survival of 10.9 months—among the 113 patients who received 300 mg of surufatinib orally once a day—was enough for the trial to hit its primary endpoint.
A blinded independent radiology committee reached slightly different PFS figures—13.9 months for surufatinib and 4.6 months for placebo—but both results were statistically significant.
Whether they’re significant enough for Chi-Med to compete with Novartis and Pfizer is another question.
The PFS figures from this study fall short of the 21.2 months surufatinib achieved in pancreatic patients in a previous phase 1b/2 trial. Based on that earlier data, surufatinib looked to have a clear edge over Novartis’ Afinitor and Pfizer’s Sutent, which came to market after achieving median PFS of 11.0 months and 10.2 months, respectively. The control arm in the Afinitor and Sutent trials had median PFS of 4.6 months and 5.4 months.
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Efforts to compare the trials are complicated by differences in the study populations. In Novartis’ trial, 341 of the 410 patients had grade 1, well-differentiated tumors, indicating that the cancer cells look relatively normal and are multiplying slowly. The rest had more severe grade 2 tumors.
In the Chi-Med trial, the proportions were roughly reversed, meaning it enrolled a far larger group of patients with more severe disease. That could make the Chi-Med data appear more impressive than the Novartis’ results.
Yet Afinitor actually achieved a lower hazard ratio in grade 2 patients than their counterparts with well-differentiated disease, and a lower hazard ratio in Asian people than white people. The confidence intervals for grade 2 and Asian patients were relatively wide, though.
Differences in the safety profiles of the two drugs are more clear-cut. The most common grade 3 or 4 adverse event in the Afinitor arm of Novartis’ pivotal study—inflammation of the mouth and lips—affected 7% of patients. In Chi-Med’s clinical trial, 38.9% of patients on surufatinib suffered grade 3 or greater treatment-emergent hypertension, compared to 8.5% in the placebo arm.
Chi-Med saw a similar rate of hypertension in its phase 1b/2 trial. In that study, all hypertension cases were manageable with standard supportive care or dose modifications. Dropouts due to the adverse event were very rare, with more subjects discontinuing treatment due to the presence of excess proteins in the urine, a condition known as proteinuria. In the phase 3, 9.7% of patients had grade 3 or greater treatment-emergent proteinuria, compared with 1.7% in the control cohort.
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Overall, 10.6% of patients in the surufatinib arm of the phase 3 stopped treatment because of side effects, compared with 6.8% in the control group. The dropout rate was lower than in the earlier trial—when 22% of patients stopped treatment because of adverse events—and the Afinitor study. Thirteen percent of people discontinued Afinitor due to adverse events related to the study drug.
Chi-Med expects to hear what regulators make of the data in the coming months. Work is underway to file for approval in pancreatic neuroendocrine tumors in China, the U.S. and, later, the European Union. The filing plan reflects Chi-Med’s belief that the phase 3 results are highly applicable to U.S. and EU populations. So far, U.S. adverse events are at or below levels seen in China.