Another NuCana Chemotherapy Fails to Improve Survival

NuCana, a biotech company known for developing reworked chemotherapies, faced significant setbacks after revealing disappointing results from its latest clinical trial. The company's stock plummeted by half in post-market trading following the announcement.

The focus of the trial was NUC-3373, a novel chemical entity derived from the widely utilized chemotherapy drug nucleoside analog 5-fluorouracil. NuCana had been testing this drug in combination with leucovorin, irinotecan, and bevacizumab to treat colorectal cancer in its phase 2 NuTide:323 study. However, the company disclosed on August 29 that the study's steering committee had determined the combination therapy was unlikely to achieve superior progression-free survival compared to the control group, which received standard treatments of fluorouracil, leucovorin, irinotecan, and bevacizumab.

Dr. Josep Tabernero, M.D., Ph.D., chair of the steering committee, stated that the goal was to develop NUC-3373 as a substitute for fluorouracil in the treatment of second-line colorectal cancer. Despite the ambitious goal being supported by robust non-clinical and clinical data, the team was disappointed with the outcome. Consequently, NuCana will discontinue the NuTide:323 study. CEO Hugh Griffith referred to the committee’s conclusion as an "unexpected outcome," highlighting the difficulties in creating new treatments for complex and heterogeneous cancers such as metastatic colorectal cancer. Griffith expressed the company’s intention to leverage insights from the data to explore future development options for NUC-3373 in colorectal cancer.

Despite the unfavorable results, the company noted that the safety profile was favorable across all three arms of the study. Only 12 out of 175 patients, with four patients in each arm, discontinued treatment due to adverse events.

This isn't the first time NuCana has encountered such issues. For instance, Acelarin, a reworked version of Eli Lilly’s chemotherapy drug Gemzar, faced setbacks in a phase 3 metastatic pancreatic cancer trial in 2019 and a late-stage biliary cancer study in 2022. Consequently, Acelarin was removed from NuCana’s pipeline. Both Acelarin and NUC-3373 utilize NuCana's proprietary ProTide technology, although they are based on different molecules with distinct mechanisms of action.

NuCana is also developing NUC-7738, another clinical-stage candidate using the ProTide technology. Data from a phase 2 trial of NUC-7738 in combination with Keytruda for melanoma patients is expected to be released next month. Griffith emphasized that the NuTide:323 study results would not affect the ongoing NuTide:303 study, where NUC-3373 is being tested in combination with pembrolizumab for solid tumors or with docetaxel for lung cancer. Additionally, Griffith expressed optimism about NUC-7738, which has shown promising effects on gene expression in cancer cells and targets various aspects of the tumor microenvironment.

However, the optimism did little to reassure investors, causing NuCana’s shares to drop 48%, from $7.73 at market close to $4 in post-market trading.

William Blair analysts noted the challenge in regaining investor interest in the program due to these setbacks. The analysts pointed out that the negative outcomes in both the phase 3 study with Acelarin and the randomized phase 2 study of NUC-3373 could potentially increase the perceived risk for the pipeline. They also warned that data from single-arm studies, like those previously conducted for NUC-3373 and NUC-7738, could be biased. Moreover, the long-term safety profile of NUC-3373 and other ProTides in NuCana's pipeline remains to be established.

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