Agenus Announces First Patient Enrolled in Global Phase 3 BATTMAN Trial Evaluating BOT+BAL Combination in MSS/pMMR Metastatic Colorectal Cance
Agenus Inc., a clinical-stage immuno-oncology company focused on developing novel therapies to address hard-to-treat cancers, has announced a significant milestone in its global development program: the enrollment of the first patient in its pivotal Phase 3 BATTMAN (CO.33) clinical trial (NCT07152821). The study is designed to evaluate the combination of botensilimab (BOT) and balstilimab (BAL) compared with best supportive care in patients with refractory, unresectable microsatellite stable (MSS) or mismatch repair proficient (pMMR) metastatic colorectal cancer (mCRC), a patient population that has historically shown limited responsiveness to immunotherapy.
The initiation of this registrational-enabling trial represents a critical step forward for Agenus as it seeks to establish BOT+BAL as a potential treatment option in one of the most challenging segments of colorectal cancer. MSS/pMMR metastatic colorectal cancer accounts for the majority of colorectal cancer cases, yet these tumors are typically considered “cold” tumors, meaning they lack the immunogenic characteristics that allow immune checkpoint inhibitors to be effective. As a result, patients in this subgroup often have limited therapeutic options once standard treatments fail, highlighting a significant unmet medical need.
The BATTMAN trial is being conducted as an international cooperative group study led by the Canadian Cancer Trials Group (CCTG), with participation from major academic and clinical research networks across Canada, France, Australia, and New Zealand. The study will involve more than 100 clinical sites globally, leveraging the infrastructure and collaborative strength of several prominent oncology research consortia. These include GI Cancer Trials in Australia and France’s Partenariat de Recherche en Oncologie Digestive (PRODIGE) consortium, which encompasses leading cooperative groups such as Unicancer, GERCOR, and FFCD.
By engaging such a broad network of institutions, the BATTMAN trial is positioned to enroll a diverse patient population across multiple regions, enhancing the generalizability of its findings and supporting a potentially expedited global development pathway. The trial is expected to enroll approximately 830 patients and represents a key step toward potential regulatory submissions, contingent upon successful outcomes.
According to Agenus, the trial has already generated considerable enthusiasm among investigators and clinical sites worldwide. Interest has been particularly strong among centers participating in expanded access initiatives, including paid named patient programs and France’s Autorisation d’Accès Compassionnel (AAC) framework, which allows early access to investigational therapies for patients with serious conditions who have exhausted approved treatment options. This demand reflects growing optimism within the oncology community regarding the BOT+BAL combination and its potential to address a historically difficult-to-treat disease setting.
Dr. Steven O’Day, Chief Medical Officer at Agenus, emphasized the importance of the milestone, noting that the enrollment of the first patient represents a pivotal moment for the company’s immunotherapy program. He highlighted that the BATTMAN study aligns with Agenus’ broader mission of developing effective therapies for patients with limited treatment options. He also acknowledged the collaborative efforts of the global research community, including partners such as CCTG, GI Cancer Trials, and PRODIGE, as well as the investigators, clinical staff, and patients contributing to the advancement of the study.
The scientific rationale behind combining botensilimab and balstilimab lies in their complementary mechanisms of action within the immune system. Botensilimab is an investigational CTLA-4 inhibitor designed to enhance T-cell priming and activation, while balstilimab is a PD-1 inhibitor that helps sustain T-cell activity by preventing tumor-induced immune suppression. Together, the combination aims to stimulate a more robust and sustained anti-tumor immune response than either agent could achieve alone.
Early clinical data from previous studies evaluating the BOT+BAL combination have shown encouraging signals of activity in MSS colorectal cancer, a tumor type that has historically been resistant to single-agent checkpoint inhibitors. These findings have supported the advancement of the combination into a Phase 3 setting, where its efficacy and safety will be rigorously evaluated against best supportive care, which represents the current standard approach for patients who have exhausted available treatment options.
Dr. Chris O’Callaghan, Senior Investigator at the Canadian Cancer Trials Group, noted that the collaboration with Agenus builds upon years of cooperative group research aimed at improving outcomes for patients with microsatellite-stable colorectal cancer. He pointed out that earlier studies conducted by CCTG suggested that dual immunotherapy approaches may extend survival even in so-called immunologically “cold” tumors. The observed durability and magnitude of responses associated with botensilimab and balstilimab in earlier-phase studies further support the decision to evaluate the combination in a large, randomized Phase 3 trial.
The cooperative group model employed in the BATTMAN trial underscores the importance of international collaboration in advancing cancer research, particularly for indications where patient populations are dispersed and clinical expertise is distributed across multiple regions. By leveraging established academic networks, the trial is expected to benefit from streamlined site activation, standardized protocols, and shared expertise among investigators with extensive experience in gastrointestinal malignancies.
Dr. Jonathan Loree, Study Chair for CO.33, also highlighted the rapid activation of trial sites following regulatory submission in Canada. He noted that leading centers across the country moved quickly to initiate the study, reflecting strong interest from the clinical community. This momentum is seen as a positive indicator for timely enrollment and execution of the trial across participating regions.
The BATTMAN trial’s design as a registrational-enabling study means that its results could potentially support future regulatory submissions if the primary and secondary endpoints are met. Key endpoints are expected to include overall survival, progression-free survival, objective response rate, and safety outcomes, although detailed statistical assumptions and endpoint hierarchies are typically outlined in the trial protocol.
Beyond its immediate clinical implications, the trial also represents a broader effort within the oncology field to expand the role of immunotherapy into tumor types that have traditionally been unresponsive to such approaches. While immune checkpoint inhibitors have transformed the treatment landscape for several cancers, including melanoma and non-small cell lung cancer, their impact in MSS colorectal cancer has remained limited. Combination strategies such as BOT+BAL are therefore being actively explored to overcome the immunosuppressive tumor microenvironment associated with these cancers.
If successful, the BATTMAN trial could help establish a new therapeutic paradigm for patients with refractory MSS/pMMR metastatic colorectal cancer, offering a potential alternative to existing treatment options and addressing a significant gap in care. The large-scale, global nature of the study, combined with its cooperative group framework, positions it as one of the more comprehensive efforts to evaluate immunotherapy combinations in this difficult-to-treat population.
As enrollment progresses, Agenus and its collaborators will continue to monitor site activation, patient recruitment, and early safety data. The company expects strong global participation to support timely completion of enrollment, driven by the high level of interest among investigators and the urgent clinical need for more effective therapies in this setting.
In summary, the first patient enrollment in the BATTMAN Phase 3 trial marks an important advancement for Agenus’ BOT+BAL program and represents a key milestone in the ongoing effort to bring innovative immunotherapy combinations to patients with microsatellite-stable metastatic colorectal cancer. With broad international collaboration, strong investigator engagement, and a clear focus on a population with limited treatment options, the study is poised to play a central role in shaping the future of immunotherapy in colorectal cancer.
About the BATTMAN (CO.33) Trial
The BATTMAN (CCTG CO.33) (NCT07152821) trial is a global Phase 3, randomized, controlled study evaluating botensilimab (BOT) plus balstilimab (BAL) versus best supportive care in patients with refractory, unresectable microsatellite stable (MSS)/mismatch repair proficient (pMMR) colorectal cancer. Conducted as an international cooperative group study led by the Canadian Cancer Trials Group (CCTG), the trial will enroll approximately 830 patients across more than 100 sites in Canada, France, Australia, and New Zealand.
Participating academic networks include CCTG, the GI Cancer Trials, and France’s Partenariat de Recherche en Oncologie Digestive (PRODIGE), sponsored by UNICANCER. This registrational-enabling study is designed to support potential regulatory submissions for BOT+BAL in this difficult-to-treat patient population. Patients interested in learning more about the study, including eligibility and enrollment information, can visit: https://www.ctg.queensu.ca/patients/colorectal-cancer-clinical-trial-co33.
About Agenus
Agenus is a leading immuno-oncology company targeting cancer with a comprehensive pipeline of immunological agents. The company was founded in 1994 with a mission to expand patient populations benefiting from cancer immunotherapy through combination approaches, using a broad repertoire of antibody therapeutics, adoptive cell therapies (through MiNK Therapeutics) and adjuvants. Agenus has robust end-to-end development capabilities, across commercial and clinical cGMP manufacturing facilities, research and discovery, and a global clinical operations footprint. Agenus is headquartered in Lexington, MA. For more information, visit www.agenusbio.com or @agenus_bio. Information that may be important to investors will be routinely posted on our website and social media channels.
About Canadian Cancer Trials Group (CCTG)
The Canadian Cancer Trials Group (CCTG) is a cancer clinical trials research cooperative that runs phase I–III trials to test anti-cancer and supportive therapies across Canada, and internationally. Headquartered at Queen’s University, CCTG has supported more than 700 trials enrolling 100,000 patients from 40 countries on 6 continents through a global network of 20,000 investigators and clinical trial staff. CCTG is the Canadian Coordinating Clinical Trial Network for the US NCTN and is a national program of the Canadian Cancer Society. CCTG’s aim is to improve survival and quality of life for all people with cancer. Learn more at cctg.ca.
About Botensilimab (BOT)
Botensilimab (BOT) is a human Fc enhanced multifunctional anti-CTLA-4 antibody designed to boost both innate and adaptive anti-tumor immune responses. Its novel design leverages mechanisms of action to extend immunotherapy benefits to “cold” tumors which generally respond poorly to standard of care or are refractory to conventional PD-1/CTLA-4 therapies and investigational therapies. Botensilimab augments immune responses across a wide range of tumor types by priming and activating T cells, downregulating intratumoral regulatory T cells, activating myeloid cells and inducing long-term memory responses.
Approximately 1,200 patients have been treated with botensilimab and/or balstilimab in phase 1 and phase 2 clinical trials. Botensilimab alone, or in combination with Agenus’ investigational PD-1 antibody, balstilimab, has shown clinical responses across nine metastatic, late-line cancers. For more information about botensilimab trials, visit www.clinicaltrials.gov.
About Balstilimab (BAL)
Balstilimab is a novel, fully human monoclonal immunoglobulin G4 (IgG4) designed to block PD-1 (programmed cell death protein 1) from interacting with its ligands PD-L1 and PD-L2. It has been evaluated in more than 900 patients to date and has demonstrated clinical activity and a favorable tolerability profile in several tumor types.
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