A phase 3 trial of Deciphera Pharmaceuticals’ ripretinib in gastrointestinal stromal tumors (GIST) has hit its primary endpoint, setting the company up to file for FDA approval early next year. The data sparked a surge in Deciphera’s stock price, even though details of the results leave scope to question ripretinib’s prospects.
The headline findings are positive for Deciphera and its broad-spectrum KIT and PDGFRα inhibitor. In the 129-subject study, the cohort of fourth-line GIST patients who took ripretinib had a median progression-free survival (PFS) of 6.3 months, compared to one month in the placebo arm, resulting in the trial hitting its primary endpoint with a p value of less than 0.0001.
The low PFS seen in the placebo cohort is in line with data generated during development of Bayer’s Stivarga, which came to market in GIST after achieving a median PFS of 4.8 months in a 133-patient trial. The placebo PFS in the Stivarga trial was 0.9 months.
Other parts of the data are less positive. Deciphera missed the key secondary endpoint of objective response rate, numerically outperforming placebo by 9.4% to zero percent but falling just short statistically.
The objective response miss had implications for the overall survival analysis. Under the trial testing procedure, hypothesis testing of overall survival cannot formally be conducted unless the response endpoint is met. As such, Deciphera could only point to the numerical results and a nominal p value that suggest the drug may increase overall survival. In the treatment cohort, median overall survival was 15.1 months, compared to 6.6 months in the control group.
On the safety and tolerability front, 7% to 9% of patients in the ripretinib arm suffered grade 3 or 4 treatment-emergent anemia, abdominal pain and hypertension. Given ripretinib is being developed in fourth-line cancer patients, the safety and tolerability profile looks manageable.
Deciphera now plans to find out what regulators think of the data. The Massachusetts-based drug developer owns full rights to the asset outside of greater China and plans to file for approval in the U.S. in the first quarter of next year.
Shares in Deciphera rose more than 100% in premarket trading.