Agenus Discontinues Phase 3 BATTMAN Trial in Metastatic MSS Colorectal Cancer

Agenus Inc. has discontinued financial support for the ongoing phase 3 CO.33/BATTMAN trial (NCT07152821) evaluating botensilimab plus balstilimab (BOT+BAL) in late-line metastatic microsatellite-stable (MSS) colorectal cancer (CRC), according to a news release from the developer.¹ The developer also reported that obligations to patients currently receiving treatment in the trial will be honored, and they will work closely with the Canadian Cancer Trials group and study investigators to manage the transition appropriately.

Why is Agenus discontinuing the BATTMAN trial?

The decision is part of a strategic prioritization toward the planned phase 3 ROBBIN trial of neoadjuvant BOT+BAL in high-risk stage II/III MSS colon cancer. The developer stated that it is redirecting resources toward the neoadjuvant field in earlier-stage MSS colon cancer, which has had no new curative-intent therapies approved in the space in over 20 years.

“Since Agenus was founded 32 years ago, our mission has been to harness the immune system to improve outcomes and, where possible, cure cancer,” stated Garo H. Armen, PhD, founder, chairman, and chief executive officer of Agenus, in the release.¹ “Our plan to prioritize neoadjuvant BOT+BAL in MSS colon cancer reflects both the strength of the emerging clinical evidence and the opportunity to bring this important combination regimen to patients where it may have the greatest impact. With ROBBIN, we are advancing a randomized global trial designed to confirm the rapid and deep activity observed across the [phase 2 NEST (NCT05571293) and UNICORN (NCT05845450)] trials.”

What is the BATTMAN trial's history in MSS colorectal cancer?

Previous coverage of the data supporting BATTMAN's design from the phase 1 C-800-01 trial (NCT03860272) showed a 42% 2-year survival rate and a median overall survival (OS) of 20.9 months among patients with MSS metastatic CRC without active liver metastases treated with BOT+BAL.² Following an FDA clinical outcomes meeting in July 2025, the agency indicated the existing data appeared to support balstilimab's contribution to the combination's activity, allowing a phase 3 trial to proceed without a botensilimab monotherapy arm. Agenus and the FDA subsequently aligned on the core phase 3 design, and BATTMAN launched in the fourth quarter of 2025 for patients with late-line metastatic MSS CRC.

Notably, at the European Society for Medical Oncology (ESMO) Gastrointestinal Cancers Congress 2026, results from the C-800-01 trial revealed a 2-year OS rate of 33% and median OS of 21.2 months in patient with refractory MSS metastatic CRC without active liver metastases. These results were in 123 patient who had received a median of 3 prior lines of therapy.³

What is the ROBBIN trial and why is it now the priority?

ROBBIN is a planned randomized, global phase 3 trial evaluating neoadjuvant BOT+BAL followed by standard of care vs standard of care alone. The developers plan to enroll 850 patients with previously untreated high-risk stage II/III MSS colon cancer, randomly assigned 1:1, with event-free survival (EFS) as the primary end point. The developers reported that it has aligned with the FDA on the patient population, experimental regimen, control arm, and interim analysis plan.

The first patient of ROBBIN is expected to be dosed in quarter 1 of 2027, with interim pathologic response data coming in the second half of 2027, interim event-free survival (EFS) data coming in the second half of 2029, and the final EFS analysis coming in the second half of 2030.

The rationale for ROBBIN draws on 2 independent phase 2 studies, NEST (NCT05571293) and UNICORN, in which neoadjuvant BOT+BAL produced approximately a 30% pathologic complete response rate, approximately a 30% major pathologic response rate, and 100% EFS after 9 to 18 months of median follow up, in 38 patients with MSS colon cancer.^4,5

“BOT was engineered to overcome [checkpoint inhibitor] resistance and has produced deep pathologic responses with no recurrences reported in the NEST and UNICORN studies,” stated Steven O'Day, MD, chief medical officer of Agenus, in the press release.¹ “With the ROBBIN trial, we are bringing this regimen to patients with high-risk stage II and stage III MSS colon cancer, where treating an intact tumor gives BOT+BAL its greatest opportunity to generate a durable immune response and improve long-term outcomes.”

References

1. Agenus announces oversubscribed private placement of up to $340 million to advance registrational ROBBIN trial of neoadjuvant BOT+BAL in MSS colon cancer. News release. Agenus Inc. July 13, 2026. Accessed July 13, 2026. https://tinyurl.com/stpux5au
2. Agenus' BOT/BAL achieves 42% two-year survival in refractory MSS CRC, advances toward registration with FDA alignment on phase 3. News release. Agenus Inc. July 7, 2025. Accessed July 13, 2026. https://tinyurl.com/yxkc3atd
3. Agenus reports landmark BOT+BAL data showing 33% three-year overall survival in refractory MSS metastatic colorectal cancer without active liver metastases at ESMO GI 2026. News release. Agenus Inc. July 6, 2026. Accessed July 14, 2026. https://tinyurl.com/9949ebna
4. Hissong E, Jafari D, Khan S, et al. Neoadjuvant botensilimab (BOT) plus balstilimab (BAL) in resectable mismatch repair proficient (pMMR) and deficient (dMMR) colorectal cancer (CRC). J Clin Oncol. 2025;43(suppl 4):207. doi:10.1200/JCO.2025.43.4_suppl.207
5. Ghelardi F, Ambrosini M, Raimondi A, et al. Preoperative botensilimab (BOT) with or without balstilimab (BAL) for patients with resectable locally advanced pMMR or dMMR colon cancer: Results from the UNICORN trial by GONO. J Clin Oncol. 2025;43(suppl 4):158. doi:10.1200/JCO.2025.43.4_suppl.158