NuCana has seen another of its reworked chemotherapies struggle to prove itself in the clinic, halving the biotech’s stock in post-market trading.
The company had been testing NUC-3373—a new chemical entity derived from the widely used chemotherapy ingredient nucleoside analog 5-fluorouracil—in combination with leucovorin, irinotecan and bevacizumab to treat colorectal cancer in the phase 2 NuTide:323 study.
But, in a post-market release Aug. 29, the Scottish company announced that the study’s steering committee had decided the combo regimen was unlikely to demonstrate superior progression-free survival compared to the control arm of fluorouracil, leucovorin, irinotecan and bevacizumab.
NuCana had been hoping to develop NUC-3373 as a replacement for fluorouracil as a treatment for second-line colorectal cancer, according to the steering committee’s chair Josep Tabernero, M.D., Ph.D.
“The premise of this ambitious goal was based on robust non-clinical and clinical data and the NuTide:323 study team are very disappointed with this outcome,” Tabernero said in the release.
As a result, NuCana will discontinue the NuTide:323 study. CEO Hugh Griffith described the committee’s conclusion as an “unexpected outcome.”
“These results highlight the challenges associated with developing new medicines for patients with complex and heterogenous cancers such as metastatic colorectal cancer,” Griffith said. “We will leverage insights from these data to identify future potential development options for NUC-3373 in colorectal cancer.”
A favorable safety profile was observed in all three arms of the study, with only 12 of the 175 patients—four patients in each arm—discontinuing treatment due to adverse events, the biotech pointed out.
NuCana has run into similar issues before. Acelarin, the company’s retooled version of Eli Lilly’s chemotherapy Gemzar, was deemed unlikely to successfully complete either a phase 3 metastatic pancreatic cancer trial in 2019 or a late-stage biliary cancer study in 2022. The candidate has since been removed from the biotech’s pipeline.
Acelarin, NUC-3373 and NuCana’s other clinical-stage candidate NUC-7738 all use the same ProTide technology, although they are based on different molecules with distinct modes of action. Data from a phase 2 trial of NUC-7738 in combination with Keytruda in patients with melanoma is due to be unveiled next month.
“The results of the NuTide:323 study do not impact the ongoing NuTide:303 study, in which NUC-3373 is being combined with either pembrolizumab in solid tumors or docetaxel in patients with lung cancer,” Griffiths added in the release. “Furthermore, we are excited about the potential of NUC-7738, a novel agent that profoundly impacts gene expression in cancer cells and targets multiple aspects of the tumor microenvironment.”
That excitement didn’t appear to be enough to reassure investors, who sent NuCana’s shares plunging 48% in the wake of the news, from $7.73 at market close on Thursday to $4 in post-market trading later that day.
“Given this was the first controlled trial with NUC-3373, we believe it will be difficult to regain investor interest in the program in other ongoing studies,” William Blair analysts concluded in a note late yesterday evening.
“The failures of the company’s phase 3 study with Acelarin and the randomized phase 2 study of NUC-3373 potentially increase perceived risk for the pipeline, and the data with NUC-3373 and NUC-7738 to date have come from single-arm studies, which have the potential to generate biased results,” the analysts added. “In addition, the long-term safety profile of NUC-3373 and other ProTides in the company’s pipeline needs to be established.”