Calliditas' survival data salvage midphase cancer trial after primary endpoint miss

Calliditas Therapeutics had a typical to-do list for its midphase head and neck cancer study. Step one, show the molecule shrinks tumors. Step two, look for early evidence of effect on survival.

The Swedish biotech fell at the first obstacle on that timeworn path, seeing no change in tumor size, but bounced back up with early evidence of an effect on progression-free (PFS) and overall survival (OS).

The double-blind, randomized phase 2 trial compared the effect of adding setanaxib or placebo to Merck & Co.’s PD-1 checkpoint inhibitor Keytruda. Setanaxib is designed to inhibit NOX1 and NOX4, enzymes expressed by cancer-associated fibroblasts (CAFs) in solid tumors. Researchers have linked high levels of CAFs to poor survival and resistance to immunotherapy.

Calliditas identified setanaxib as a way to improve the penetration of immune cells into tumors and make checkpoint inhibitors effective in more patients. The biotech put that idea to the test in a phase 2 trial of 55 people with recurrent or metastatic head and neck cancer.

Setanaxib was no better than placebo on the primary endpoint of best percentage change from baseline in tumor size. Calliditas is yet to share the response rates, a typical midphase endpoint, but did disclose that 70% of patients on setanaxib had at least stable disease, compared to 52% of people on placebo. 

The biotech focused on the PFS and OS results. Median PFS was five months in the setanaxib arm and 2.9 months in the placebo cohort. Similarly, the OS rate at nine months was 88% on setanaxib and 58% on the control. The biotech reported a similar divergence in OS rates after six months. 

Calliditas brushed over the failure to hit the primary endpoint—relegating the finding to a single line almost 300 words into its press release—but Chief Medical Officer Richard Philipson was clear about the importance of showing a reduction in tumor size on an earnings call in February.

“We think this is an important endpoint in a study at this stage of development. It’s a little bit more sensitive than just looking at response rates,” Philipson said. “Clearly, what we want to see is a significant reduction in tumor size in patients who are receiving setanaxib on top of pembrolizumab versus patients who are receiving placebo on top of pembrolizumab.”

Calliditas’ statement lacks an explanation for why patients may live longer on setanaxib if it has no effect on tumor size. The biotech plans to host an R&D day later this month to share more information on the phase 2 trial and other data supporting the mechanism of action of setanaxib. 

Investors appeared unsure what to make of the data, with Calliditas’ stock initially rising before falling back toward its opening price.