France Approves Compassionate Access for Agenus' BOT/BAL Immunotherapy in Refractory MSS Colorectal Cancer
核心洞察
France's National Agency for Medicines and Health Products Safety (ANSM (搜索)) has approved compassionate access for Agenus' botensilimab plus balstilimab combination in patients with refractory microsatellite-stable metastatic colorectal cancer (搜索).
The treatment is fully reimbursed by France's Assurance Maladie for eligible patients meeting specific criteria, including MSS status and no active liver metastases.
Clinical data from Phase 1b trials demonstrate a 20% objective response rate and median overall survival of 20.9 months in heavily pretreated MSS colorectal cancer (搜索) patients.
Agenus Inc. announced on September 9, 2025, that its investigational immunotherapy combination botensilimab plus balstilimab (BOT/BAL (搜索)) is now available to eligible patients with refractory microsatellite-stable (MSS) metastatic colorectal cancer through France's compassionate access program (Accès Compassionnel, AAC). The French National Agency for Medicines and Health Products Safety (搜索) (ANSM (搜索)) has approved hospital use of the combination for patients meeting specific criteria, including MSS status and no active liver metastases.
Addressing Critical Unmet Need
The approval addresses a significant gap in treatment options for patients with MSS colorectal cancer (搜索), which resists current immunotherapies. "This is a breakthrough for patients and their physicians. MSS colorectal cancer resists current immunotherapies, and treatment options after standard regimens are very limited," said Garo Armen, PhD, Chairman & CEO of Agenus.
Under the compassionate access framework, treatment is fully reimbursed by France's Assurance Maladie, with hospitals compensated at the purchase price outside the standard Diagnosis-related Group (DRG), known in France as "en sus du GHS." The manufacturer either provides the therapy free of charge or charges a temporary indemnity declared to the French Ministry.
Clinical Evidence Supporting Access
The compassionate access approval is supported by data from the Phase 1b C-800-01 trial, which enrolled 123 heavily pretreated patients with a median of three prior therapies. Updated results presented at ESMO GI 2025 demonstrated that the BOT/BAL (搜索) combination achieved an objective response rate (ORR) of 20%, median overall survival (OS) of 20.9 months, and a clinical benefit rate at 24 weeks of 28%, with durable responses and a manageable safety profile.
The clinical benefit appears particularly pronounced in patients without active liver metastases, a population with extremely limited treatment options. Recent data describe approximately 21-month median OS, 42% 2-year survival, and 20% ORR in expanded cohorts of this patient population.
Pivotal Phase 3 Trial on Horizon
The Phase 3 BATTMAN trial (NCT07152821) is set to launch in November 2025 and will evaluate BOT/BAL (搜索) versus Best Supportive Care in patients with chemo-refractory, unresectable MSS metastatic colorectal adenocarcinoma. Sponsored by the Canadian Cancer Trials Group, the study plans to enroll 834 patients globally with overall survival as the primary endpoint. Secondary endpoints include progression-free survival, objective response rate, safety, and quality of life.
Mechanism of Action
Botensilimab is an Fc-enhanced CTLA-4 (搜索) antibody designed to stimulate both innate and adaptive immune responses by activating T cells, reducing regulatory T cells within tumors, engaging myeloid cells, and inducing long-term immune memory. Balstilimab is a PD-1 (搜索) inhibitor that blocks the interaction between PD-1 on T cells and PD-L1 (搜索)/PD-L2 (搜索) on tumor cells. Together, the combination creates a synergistic immune effect targeting "cold" tumors that are usually resistant to standard immunotherapy.
Broader Clinical Development
The BOT/BAL (搜索) combination has demonstrated activity across multiple tumor types and treatment settings. In the Phase 2 NEOASIS study, the combination showed efficacy in the neoadjuvant setting across multiple solid tumors, with 90% of dMMR/MSI-H patients achieving pathological response and 80% of pMMR/MSS patients showing pathological responses.
The UNICORN Phase II trial, published in the Journal of Clinical Oncology in 2025, highlighted potent neoadjuvant activity in resectable, locally advanced colon cancer (搜索). In dMMR tumors, BOT plus BAL achieved 93% complete pathological response and 100% major pathological response rates.
International Access Considerations
European Union and European Economic Area patients may obtain planned care in France under Directive 2011/24/EU, usually with prior authorization for hospital or specialist care. Reimbursement is provided by the patient's home system based on national tariffs. Outside the EU, countries such as Turkey operate treatment-abroad programs on a case-by-case basis.
Approximately 1,200 patients have been treated with botensilimab and/or balstilimab in phase 1 and phase 2 clinical trials, with the combination showing clinical responses across nine metastatic, late-line cancers.