Dr Schlechter on the Potential Future Implications of Botensilimab and Balstilimab in MSS mCRC

“There are several [future directions with] botensilimab. Number 1 is in refractory disease, and we need to push forward with the approval of this agent through randomized trials in the refractory setting. That’s important, and it’s very compelling that there are some early trials.”

Benjamin L. Schlechter, MD, a senior physician in the Gastrointestinal Cancer Center at Dana-Farber Cancer Institute, discussed the next steps in research in terms of botensilimab (AGEN1181) for the treatment of patients with previously treated, microsatellite-stable (MSS) metastatic colorectal cancer (mCRC) with no active liver metastases in combination with balstilimab (AGEN2034).

There are several ways botensilimab can fit into the mCRC treatment paradigm in the future, Schlechter began. Of note, working towards getting botensilimab approved by the FDA is an important next step, particularly in the refractory setting, he explained. Currently, there are early trials investigating botensilimab in colorectal cancer, including the phase 2 NEST-1 (NCT05571293) and UNICORN (EU-CT 2022-501308-90-0) trials, he added. Both trials have demonstrated that in earlier stages of disease, botensilimab showed benefit, he asserted. However, he noted that this needs to be taken forward in all lines of therapy, especially because patients with the most refractory and advanced disease have achieved similar efficacy.

NEST-1 evaluated the efficacy and safety of neoadjuvant botensilimab plus balstilimab for the treatment of patients with resectable mismatch repair proficient (pMMR) and mismatch repair deficient (dMMR) colorectal cancer. At a median follow-up of 13.1 months in NEST-1 and 4.8 months in NEST-2, no patients experienced disease recurrence, and circulating tumor DNA findings were negative. Furthermore, the UNICORN study assessed perioperative botensilimab with or without balstilimab for the treatment of patients with resectable locally advanced pMMR or dMMR colon cancer.

Moving botensilimab into earlier lines of therapy could be feasible, as studies have demonstrated that the in situ primary tumor, along with in situ lymph nodes, can provide a training ground for the immune system, which is essential in promoting immune responses in earlier-stage disease, Schlechter emphasized. With this hypothesis, the idea that botensilimab and balstilimab can be given in earlier lines of therapy as a nonoperative management in patients with cold tumors is important to continue investigating, he concluded.