While tovecimig met the main goal of progression-free survival in a Phase 2/3 trial, it did not improve overall survival.
“Confounding” overall survival data for Compass Therapeutics’ bispecific has raised questions about whether the therapy is approvable in biliary tract cancer.
Compass’ tovecimig did not achieve the secondary endpoint of overall survival (OS), which the company attributed to “notably prolonged survival” in patients who had crossed over to receive the study drug from the control arm.
Shares of Compass fell more than 63% on the news to $1.81 apiece as the markets opened Monday morning. William Blair analysts expected the share volatility “as investors weigh the totality of the data and FDA uncertainty.”
Tovecimig did, however, meet the study’s main goal, which was a measure of progression-free survival (PFS). Patients who received Compass’ therapy achieved 4.7 months of PFS compared to 2.6 months for the control arm, which the company called a 56% reduction in the risk of progression.
“While we believe the totality of the data shows that tovecimig provides clinical benefit in this patient population, it will clearly be a review issue at the FDA,” William Blair wrote on Monday.
The Phase 2/3 COMPANION-002 study evaluated tovecimig in 168 patients with unresectable advanced, metastatic or recurrent biliary tract cancers who had previously received one chemotherapy regimen. Patients received either tovecimig plus the chemotherapy paclitaxel or just the chemotherapy.
While the endpoint at issue was secondary, many analysts on a call to discuss the Phase 2/3 results wondered about tovecimig’s future at the FDA.
CEO Thomas Schuetz attempted to explain the crossover issue during the Monday morning call. He said that 54% of patients crossed over from the paclitaxel alone control group, meaning 85% of patients ultimately received tovecimig. This group of crossover patients “lived an incredibl[y] long time,” according to the CEO. The overall survival rate for this group was 12.8 months, which matches what patients in the first line setting achieve on other treatments. Patients who did not cross over had an OS of 6.1 months.
Meanwhile, the pooled OS from the study was 8.9 months, meaning the OS endpoint was not statistically significant.
Analysts tried to discern characteristics about the crossover patients that may have made them respond better than those who initially received tovecimig. Schuetz explained that because most of the patients received a prior PD-1 blocking regimen like Merck’s Keytruda, there was no real explanation to be gleaned there.
The CEO wondered if initial treatment with paclitaxel may have primed the tumor microenvironment for tovecimig. “That’s sort of a fairly straightforward hypothesis,” he said. “We’re going to do some preclinical work on that.”
Next up, Compass will discuss the drug with the FDA during a pre-biologics license application meeting, which is expected to occur mid-year. Schuetz said the company plans to seek full approval for the drug based on the Phase 2/3 study, rather than an accelerated nod.
