The CROCOBIL trial will be conducted under the leadership of Professor Cindy Neuzillet and Dr Matthieu Delaye at Institut Curie, with Unicancer acting as sponsor and with the support of the PRODIGE French intergroup for clinical research in gastrointestinal cancers. Unicancer is a French hospital network fully dedicated to oncology. The first patient is expected to be enrolled during the second quarter of XNUMX, with XNUMX patients planned across XNUMX French clinical sites. BTC is a relatively rare but highly aggressive form of gastrointestinal cancer where treatment options are limited once first-line therapy has failed.
Mitazalimab poised for broader impact
Mitazalimab, Alligator’s lead CD40-targeting antibody, is now phase III-ready and has already demonstrated unprecedented 24-month survival benefits in first-line metastatic pancreatic cancer patients in the phase II OPTIMIZE-1 trial.
According to Alligator’s CEO Søren Bregenholt the launch of the CROCOBIL trial illustrates both the strong scientific interest in mitazalimab and the relevance of targeting CD40 in BTC.
- This support by academic network of recognized experts underscores the scientific and clinical relevance of targeting CD40 in biliary tract cancer and the broader interest in mitazalimab's therapeutic potential beyond pancreatic cancer, writes Bregenholt in a press release.
The CROCOBIL study will generate data on the efficacy and tolerance of mitazalimab plus FOLFOX and will also include further ancillary work. By adding mitazalimab to standard chemotherapy, researchers will investigate if the combination treatment is able to overcome resistance to existing first-line regimens and if it can yield better results that chemotherapy on its own.
For Alligator, the new study represents another opportunity to demonstrate mitazalimab’s versatility as an immuno-oncology candidate. Positive results could pave the way for a new treatment option in BTC while reinforcing the company’s pipeline. Recent financial measures – including a renegotiated loan with Fenja Capital and subscription commitments from management – are also expected to provide additional support for its clinical progress. Fenja Capital and subscription intentions from management, are also expected to provide continued support for clinical development.
Comments from the CEO
BioStock spoke with CEO Søren Bregenholt to gain deeper insights into the CROCOBIL trial.
What does this new phase II/III study mean for mitazalimab's broader development strategy?
– The CROCOBIL study adds breadth to mitazalimab's clinical development and provides the opportunity to potentially benefit even more patients with hard-to-treat cancers. Initiating a second, randomized phase II trial in an aggressive gastrointestinal cancer, this time in advanced biliary tract cancer (BTC), we are exploring mitazalimab's potential beyond metastatic pancreatic cancer (mPDAC) and continuing to build the clinical and translational rationale for mitazalimab. Importantly, the trial is investigator-sponsored and funded by Unicancer GI Group, and Alligator's main contribution is drug supply and trial support. Thus, this approach allows us to widen the potential clinical use of mitazalimab while we are continuing ongoing partnering discussions.
Why is biliary tract cancer an important indication to explore?
– Biliary tract cancer is a rare, aggressive tumor type with very limited treatment options and a clear unmet medical need. Like pancreatic cancer, BTC is often diagnosed late, is immunologically inert, and has very poor survival rates. Moreover, there are overlaps in the chemotherapy regimen used in BTC and pancreatic cancer. Together, this makes BTC a compelling tumor type for mitazalimab, which is designed to stimulate dendritic cell-mediated T cell priming and enhance response to chemotherapy and checkpoint inhibitors.
How do collaborations with academic networks strengthen mitazalimab's development?
– Developing mitazalimab we interact closely with clinicians on a global scale, and based on these interactions we have received many suggestions for clinical trials aimed at studying mitazalimab in pancreatic cancer and beyond. The fact that leading clinicians see a potential in mitazalimab to help the patients they treat is of course a strong validation of the data that we have generated and the potential of mitazalimab. As a randomized phase II/III study, CROCOBIL may directly support development decisions or even support registration.
Looking ahead, what milestones should investors and patients watch for as the CROCOBIL study moves towards enrollment in 2026?
- The next key milestone will be regulatory and ethical approvals to initiate the study across sites in France. Enrollment of the first patient is targeted for Q2 2026, and the study aims to recruit 112 patients in total. In parallel, Alligator continues to work towards starting a pivotal phase III trial together with a partner in metastatic pancreatic cancer. We expect to announce 30-month follow-up data from the phase II study in the coming weeks, after which we will wind down the trial; we have also successfully concluded manufacturing for phase III. With the vast majority of phase II and CMC cost behind us, we will enter 2026 with a significantly reduced burn rate.
The content of BioStock's news and analysis is independent, but BioStock's operations are to some extent financed by companies in the industry. This post refers to a company from which BioStock has received funding.