Agenus to Present Phase II Data on Novel BOT+BAL and agenT-797 Combination in PD-1 Refractory Gastroesophageal Cancer at AACR 2026
Agenus a biotechnology company focused on advancing immuno-oncology therapies, has announced that new clinical data from an investigator-initiated Phase II study will be presented at the upcoming American Association for Cancer Research (AACR) Annual Meeting 2026. The meeting is scheduled to take place from April 17 to April 22, 2026, in San Diego, California.
The study highlights a novel combination immunotherapy approach designed to address one of the most challenging areas in oncology—checkpoint inhibitor–refractory cancers. Specifically, the trial evaluates the combination of botensilimab (BOT), balstilimab (BAL), and agenT-797 in patients with gastroesophageal cancer (GEC) who have not responded to prior PD-1 inhibitor treatments.
This research represents a significant step toward improving outcomes for patients with limited therapeutic options and contributes to a growing body of evidence supporting multi-mechanistic immunotherapy strategies.
Study Overview and Clinical Significance
The Phase II trial was conducted at Memorial Sloan Kettering Cancer Center, one of the leading institutions in cancer research and treatment. The study focuses on patients with PD-1 refractory gastroesophageal cancer—a population that historically shows poor response rates to existing immunotherapies.
Checkpoint inhibitors targeting PD-1 have transformed cancer care in recent years. However, a substantial proportion of patients either do not respond initially or eventually develop resistance. This creates a pressing need for new treatment approaches that can overcome immune resistance and restore anti-tumor activity.
The combination evaluated in this study brings together three distinct but complementary mechanisms:
- Botensilimab (BOT): A next-generation anti-CTLA-4 antibody designed to enhance immune activation
- Balstilimab (BAL): A PD-1 blocking antibody that prevents tumor immune evasion
- agenT-797: An allogeneic invariant natural killer T (iNKT) cell therapy aimed at boosting innate and adaptive immune responses
Together, this regimen aims to create a more robust and sustained anti-tumor immune response, particularly in tumors that are resistant to conventional checkpoint inhibition.
Presentation Details at AACR 2026
The findings from this important study will be presented during a clinical trials session at AACR 2026. Key details of the presentation are as follows:
- Abstract Title: A Phase II study of agenT-797, botensilimab (BOT), and balstilimab (BAL) in PD-1 refractory gastroesophageal cancer
- Presenter: Samuel L. Cytyrn, MD, Gastrointestinal Medical Oncologist at Memorial Sloan Kettering Cancer Center
- Session Name: Phase II and Phase III Clinical Trials
- Date and Time: April 20, 2026 | 2:00–5:00 PM PT / 5:00–8:00 PM EDT
- Poster Section: 52
- Abstract Number: CT166
This session is expected to draw significant attention from researchers, clinicians, and industry experts interested in next-generation immunotherapy combinations.
Addressing an Unmet Need in Gastroesophageal Cancer
Gastroesophageal cancer remains a difficult-to-treat disease, especially in advanced stages. While checkpoint inhibitors have improved outcomes for some patients, many eventually experience disease progression due to resistance mechanisms within the tumor microenvironment.
These “cold tumors”—tumors that lack sufficient immune cell infiltration—are particularly challenging. They often fail to respond to standard immunotherapies because the immune system is not adequately activated to recognize and attack cancer cells.
The combination of BOT, BAL, and agenT-797 is specifically designed to address these challenges by:
- Enhancing T-cell activation and proliferation
- Reducing immunosuppressive regulatory T cells within tumors
- Activating innate immune components such as myeloid cells and iNKT cells
- Promoting long-term immune memory to sustain responses
This multi-layered approach has the potential to convert immunologically “cold” tumors into “hot” tumors that are more responsive to treatment.
Botensilimab: A Next-Generation CTLA-4 Antibody
Botensilimab represents a novel class of immunotherapy engineered to go beyond traditional CTLA-4 inhibitors. Unlike earlier therapies, it incorporates an Fc-enhanced design that amplifies its ability to stimulate the immune system.
Its mechanisms of action include:
- Priming and activating T cells
- Modulating the tumor microenvironment
- Reducing suppressive immune cells
- Enhancing long-term immune memory
To date, approximately 1,200 patients have been treated with botensilimab, either alone or in combination with balstilimab, across Phase I and Phase II clinical trials. These studies have demonstrated encouraging activity across multiple metastatic cancers, including those resistant to prior treatments.
Balstilimab: Targeting the PD-1 Pathway
Balstilimab is a fully human monoclonal antibody that targets the PD-1 receptor, a key checkpoint protein used by cancer cells to evade immune detection.
By blocking interactions between PD-1 and its ligands (PD-L1 and PD-L2), balstilimab helps restore the immune system’s ability to recognize and attack tumor cells.
The therapy has been evaluated in more than 900 patients and has shown:
- Clinical activity across multiple tumor types
- A favorable safety and tolerability profile
- Compatibility with combination strategies
When used alongside botensilimab, balstilimab contributes to a dual checkpoint inhibition strategy that enhances immune activation from multiple angles.
agenT-797: Harnessing iNKT Cell Therapy
A key component of this combination is agenT-797, an innovative allogeneic iNKT cell therapy developed by MiNK Therapeutics, a subsidiary of Agenus.
Invariant natural killer T (iNKT) cells are unique immune cells that bridge innate and adaptive immunity. They can rapidly respond to tumor signals and orchestrate broader immune responses.
agenT-797 is designed to:
- Activate multiple immune pathways simultaneously
- Enhance tumor recognition
- Improve immune cell infiltration into tumors
- Support durable anti-tumor responses
Its inclusion in this combination represents a novel approach to integrating cell therapy with antibody-based immunotherapy.
Implications for Treatment Sequencing and Durability
One of the most important aspects of this study is its potential to inform future treatment strategies, particularly in terms of:
- Immune modulation: Understanding how different therapies interact to enhance immune responses
- Treatment sequencing: Determining the optimal order and timing of therapies
- Durability of response: Achieving long-lasting clinical benefits
These insights could have broad implications not only for gastroesophageal cancer but also for other hard-to-treat tumors where checkpoint resistance is a major barrier.
Agenus: A Leader in Immuno-Oncology Innovation
Founded in 1994, Agenus has built a comprehensive pipeline of immuno-oncology therapies aimed at expanding the reach of cancer immunotherapy. The company’s strategy centers on combination approaches that leverage multiple immune mechanisms.
Agenus capabilities include:
- Discovery and development of antibody therapeutics
- Advanced cell therapy platforms through MiNK Therapeutics
- Proprietary adjuvant technologies
- End-to-end manufacturing infrastructure
- Global clinical development operations
Headquartered in Lexington, Massachusetts, Agenus continues to play a key role in advancing next-generation cancer treatments.
The upcoming presentation at AACR 2026 marks an important milestone for Agenus and the broader oncology community. As researchers continue to explore innovative ways to overcome treatment resistance, combination therapies like BOT, BAL, and agenT-797 offer new hope for patients with limited options.
While further studies and regulatory evaluations will be necessary, the data from this Phase II trial could help shape the future of immunotherapy—particularly in addressing some of the most challenging cancers.
As with all clinical-stage developments, the results and future applications of these therapies are subject to ongoing research, regulatory review, and clinical validation. However, the growing evidence supporting multi-mechanistic immunotherapy approaches underscores the importance of continued innovation in this field.
By combining antibody therapies with advanced cell-based treatments, Agenus is helping to push the boundaries of what is possible in cancer care—offering the potential for more effective, durable, and personalized treatment options in the years ahead.
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 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.
