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Combination therapy of botensilimab (BOT) plus balstilimab (BAL) was approved Monday as an updated national treatment protocol for patients with certain ovarian cancers and soft tissue sarcomas (STS) by France’s National Agency for Medicines and Health Products Safety (ANSM).¹

BOT plus BAL was originally approved to treat microsatellite-stable (MSS) metastatic colorectal cancer without active liver metastases. The extension, now approved for STS, will help address unmet medical needs in the disease space and allow more patients with advanced solid tumors access to the dual therapy.

What Is Botensilimab Plus Balstilimab? Mechanism and Clinical Use

The inclusion of BOT plus Bal, a chemotherapy- and radiation-free immunotherapy, was based on findings from a phase 1b multicenter clinical trial (NCT03860272). While it is still being evaluated in clinical studies, it is available in a compassionate access setting authorized by ANSM. These settings refer to expanded access to investigational medical product treatments outside of clinical trials for patients with a serious or immediately life-threatening disease or condition.² BOT is a human Fc-enhanced multifunctional anti-CTLA-4 antibody designed to boost both innate and adaptive anti-tumor immune responses. It augments immune responses across a wide variety of tumor types by priming and activating T cells, downregulating intratumoral regulatory T cells, activating myeloid cells, and inducing long-term memory responses.¹

BAL is a novel, fully human monoclonal immunoglobulin G4 designed to block programmed cell death protein 1 (PD-1) from interacting with its ligands PD-L1 and PD-L2. Numerous research studies observed antitumor activity in heavily pretreated patients with BOT plus BAL therapy. These results show promise for targeting tumors that have historically demonstrated limited responsiveness to standard immunotherapy treatments.

France Expands National Access to BOT–BAL Through Early Access and Global Partnerships

Under Frances’s Autorisation d’Accès Compassionnel (AAC) framework, BOT plus BAL therapy is fully reimbursed. The AAC pathways allow patients with serious or life-threatening diseases who lack appropriate therapeutic alternatives to access hospital-based treatments. Aside from advanced or metastatic STS, the AAC reimburses BOT plus BAL therapy for MSS metastatic colorectal cancer without active liver metastases and platinum-refractory or platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer.

The implementation of a multi-tumor early access framework under one nationally standardized protocol represents an unusual level of national early access. However, this expansion of AAC reimbursement for colorectal cancer, ovarian cancer, and STS allows equitable access for patients to receive consistent hospital-based care for an investigational treatment.

In addition to expanding access across France, Agenus, a clinical-stage biotechnology company and biologic manufacturer of BOL plus BAL, recently announced its partnership with Zydus Lifesciences Ltd, an Indian pharmaceutical company, to accelerate global development.³

The $141 million collaboration has granted Zydus exclusive rights to develop and commercialize BOT plus BAL in India and Sri Lanka. The collaboration announced in June 2025 will include an upfront consideration of $75 million cash for transferring biologics manufacturing facilities; an equity investment purchased by Zydus of Agenus of $16 million; a contingent milestone payment of up to $50 million to Agenus for BOT plus Bal production orders; and an exclusive license by Zydus with the rights to develop, for which Agenus is eligible to receive a 5% royalty on net sales.

“With these foundations in place, our focus in 2026 is disciplined execution—advancing our Phase 3 program, broadening paid patient access through authorized pathways, and progressing toward regulatory submission,” Garo Armen, PhD, chairman and chief executive officer of Agenus, said in a press release.

References

1. France expands national AAC access for Agenus’ Botensilimab + Balstilimab for ovarian cancer and soft-tissue sarcomas. News release. BioSpace. January 12, 2026. Accessed January 15, 2026. https://www.biospace.com/press-releases/france-expands-national-aac-access-for-agenus-botensilimab-balstilimab-for-ovarian-cancer-and-soft-tissue-sarcomas

2. Expanded access. U.S. Food and Drug Administration. August 9, 2025. Accessed January 15, 2026. https://www.fda.gov/news-events/public-health-focus/expanded-access

3. Agenus announces closing of $141M strategic collaboration with Zydus Lifesciences to advance BOT+BAL and strengthen U.S. Manufacturing Readiness. Agenus. News release. January 15, 2026. Accessed January 15, 2026. https://investor.agenusbio.com/news/news-details/2026/Agenus-Announces-Closing-of-141M-Strategic-Collaboration-with-Zydus-Lifesciences-to-Advance-BOTBAL-and-Strengthen-U-S–Manufacturing-Readiness/default.aspx