First Patient With Gastric Cancer Dosed in iNKT/CTLA-4 Inhibitor/Anti-PD-L1 Trial
A case study previously described successful immune modulation with AgenT-797 in a patient with high-risk gastric cancer leading to a partial response.
Yelena Janjigian, MD
Credit: Memorial Sloan Kettering Cancer Center
The first participant with refractory gastroesophageal cancer has been dosed in a phase 2 trial evaluating the novel combination of the company’s allogeneic invariant natural killer T (iNKT) cell therapy agenT-797 and Agenus’ botensilimab and balstilimab (BOT/BAL).1
“This study is an important step in new treatment combinations to improve outcomes for patients with refractory gastric cancers, an incurable disease with limited response to available therapies,” Yelena Janjigian, MD, Chief Gastrointestinal Oncology Service, Memorial Sloan Kettering Cancer Center, said in a statement.1 Janjigian is leading the investigator-sponsored trial at Memorial Sloan Kettering.
"AgenT-797, an off-the-shelf iNKT cell-based therapy, has shown the capacity to target cancerous cells in diseased tissues and is compatible with immune checkpoint inhibitors. This study builds upon the promising outcomes observed with iNKTs in gastric cancer and with botensilimab/balstilimab in GI cancers. By harnessing the immune-enhancing potential of agenT-797, we aspire to improve outcomes for a greater number of patients facing challenging GI cancers,” Janjigian continued.1
The phase 2 study will evaluate the clinical safety and efficacy of the combination of agent-797 with BOT/BAL, which are a novel fc-enhanced CTLA-4 inhibitor and an anti-PD-1 therapy, respectively, with ramucirumab and paclitaxel in around 38 patients with previously treated, advanced, unresectable, or metastatic esophageal, gastric, or gastro-esophageal junction (GEJ) adenocarcinoma.
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"We are thrilled to collaborate with GI cancer expert Dr. Yelena Janjigian on this Phase 2 study, furthering the development ofagenT-797 in refractory gastric cancer," Jennifer Buell, PhD, President and Chief Executive Officer, MiNK, added.1 "This study is designed to provide crucial insights into the clinical efficacy of agenT-797, while also assessing its potential synergies with chemotherapy and next-generation immune checkpoint inhibitors, botensilimab and balstilimab. This milestone underscores our unwavering commitment to advancing iNKT cell therapies to address the pressing unmet needs in cancer care and highlights the strength of our collaboration with Agenus to access these novel and exciting combinations to deliver meaningful benefits to our patients."
The announcement comes after a case study was published in Oncogene in January describing the activity of AgenT-797 in a patient with microsatellite instability-high (MSI-H) advanced gastric cancer after progression on standard chemotherapy and anti-PD-1 therapy. The therapy yielded immune modulation leading to durable tumor response in the patient.2
“Gastric cancer remains an area of high unmet need, where the majority of patients develop disease progression related to tumor resistance,” Dr. Benedito A. Carneiro, Director of Clinical Research, Director of Cancer Drug Development (Phase I), Associate Director of the Division of Hematology/Oncology, Legorreta Cancer Center, Brown University, said in a statement about the case study.3 “Novel therapeutic approaches, like allogeneic iNKT cells, are urgently needed to overcome resistance to immune checkpoint inhibitors in gastric cancers and other refractory solid tumors. The activity, tolerability, and ease of off-the-shelf administration of iNKT-based cell therapies position them as an attractive approach for overcoming cancer resistance.”
The patient had a PD-L1 positive, HER-2 negative, MSI-H adenocarcinoma with a high mutational burden (84 mut/MB) which had failed prior treatments, including single-agent anti-PD-1 pembrolizumab and a combination therapy approach involving chemotherapy (FOLFOX) and nivolumab. Following treatment with agenT-797, the patient had increased immune cell infiltration and proliferation which correlated with a radiographic partial response.
