Botensilimab/Balstilimab Exhibits Meaningful Activity in Ovarian Cancer

The median PFS was 2.8 months in this ovarian cancer population, with respective 6- and 9-month rates of 28% and 25%.

Botensilimab plus balstilimab demonstrated deep and clinically meaningful responses among patients with ovarian cancer refractory to the previous line of treatment or for which no standard therapy was available, according to findings from the phase 1b C-800-01 trial (NCT03860272) published in The Journal for ImmunoTherapy of Cancer (JITC).1

Topline efficacy data revealed that among 35 evaluable patients, the objective response rate (ORR) was 23% (95% CI, 10%-40%), with 1 patient (3%) achieving a complete response and 7 (20%) achieving a partial response. Thirteen patients (37%) experienced stable disease as best overall response, for a disease control rate (DCR) of 60% (95% CI, 42%-76%). The clinical benefit rate (CBR) was 31% (95% CI, 17%-49%); the median duration of response (DOR) was 9.7 months (95% CI, 2.8-not reached [NR]).

Regarding survival data, the median progression-free survival (PFS) was 2.8 months (95% CI, 1.4-5.5) in this group, with respective 6- and 9-month rates of 28% (95% CI, 14%-44%) and 25% (95% CI, 11%-40%). Additionally, the median overall survival (OS) was 14.8 months (95% CI, 12.1-NR) for this patient population after a median follow-up of 9.6 months (range, 0.6-36.6). The respective 12- and 18-month OS rates were 75% (95% CI, 55%-86%) and 50% (95% CI, 28%-69%).

“These women faced some of the most treatment-resistant forms of ovarian cancer, yet several achieved meaningful and durable benefit,” Rebecca Porter, MD, PhD, translational and clinical research in the Gynecologic Oncology Program at the Dana-Farber Cancer Institute, and lead author of the study, said in a news release on the publication.2 “Seeing this level of activity in such a heavily pretreated population is encouraging and provides important insights to the field regarding therapy approaches for patients with very limited remaining options.”

The open-label, multicenter study enrolled 44 patients with treatment-refractory ovarian cancer between April 1, 2019, and November 8, 2023. Those eligible for enrollment were 18 years and older, had measurable disease per RECIST v1.1 criteria, an ECOG performance status of 0 or 1, and adequate end-organ function. Patients were permitted to enroll if they had received prior immune checkpoint inhibition.

In the dose escalation portion of the trial, botensilimab was given at escalating intravenous doses from 0.1 to 3 mg/kg in 3- or 6-week intervals, and intravenous balstilimab was given every 2 weeks at 3 mg/kg, both for a maximum of 2 years. For the dose expansion portion of the trial, botensilimab was given at 1 or 2 mg/kg in 6-week intervals, and balstilimab was given at 3 mg/kg every 2 weeks. Those receiving botensilimab monotherapy were permitted to cross over to the combination regimen following progression.

Those enrolled had a median age of 66 years (range, 37-79), with an equal number of patients having an ECOG performance status of 0 and 1 (50% each). The median number of previous lines of therapy was 3 (range, 1-14), with 66% of patients treated with at least 3 lines of prior therapy. The most common previous therapies included platinum-containing doublet chemotherapy (100%), bevacizumab (Avastin; 77%), PARP inhibition (39%), and radiotherapy (20%).

Most patients had platinum-resistant disease (55%), multiple metastatic sites (75%), and high-grade serous histology (82%). A near equal number of patients received 1 or 2 mg/kg of botensilimab (48% vs 50%), 14% of patients had liver metastases, and the most common biomarkers included mismatch-repair deficiency (100%), PD-L1 positivity (84%), and elevated CA-125 (74%).

The primary end points of the study were safety and the occurrence of dose-limiting toxicities (DLTs). To date, a maximum tolerated dose has not been found. Secondary end points included treatment-emergent adverse effects (TEAEs), ORR, DOR, DCR, PFS, and OS.

In the safety analysis set (n = 44), 2 patients experienced DLTs. Both were resolved; however, 1 patient was able to resume therapy, whereas the other was precluded from rechallenge with botensilimab. At least 1 TEAE occurred in all patients on the study, with 68% of patients experiencing at least 1 grade 3 or higher TEAE.

Treatment-related AEs (TRAEs) of any grade occurred in 89% of patients, 41% of whom experienced one at grade 3 or higher. The most common TRAEs were primarily gastrointestinal and included diarrhea/colitis (any-grade; 43%, grade 3 or higher; 16%), nausea (36%, 2%), immune-mediated enterocolitis (20%, 5%), abdominal pain (14%, 2%), and vomiting (11%, 0%). Other common TRAEs included fatigue (36%, 7%), arthralgia (18%, 0%), decreased appetite (18%, 0%), pruritus (18%, 0%), headache (16%, 0%), and maculo-papular rash (14%, 5%).

One grade 4 instance of autonomic neuropathy, acute kidney injury, and thrombocytopenia occurred, and no patients died because of study treatment. Single instances of grade 2 pneumonitis and grade 3 myocarditis occurred on trial, and hypophysis was not observed in the trial. A total of 19 patients (43%) discontinued either treatment due to a TRAE, the most common of which included immune-mediated enterocolitis in 6 patients (14%) and colitis in 5 (11%).

“These results offer a meaningful signal of clinical activity for women with platinum-refractory ovarian cancer, a group that has seen little therapeutic progress,” Steven O’Day, MD, chief medical officer of Agenus, the developers of the combination regimen, stated in the release.2 “Botensilimab’s unique immune activation profile translated into clinically significant responses in a population long considered resistant to immunotherapy. These findings strengthen our confidence in [botensilimab/balstilimab’s] potential and support moving this combination into larger, randomized studies.”

References

1. Porter R, Bockorny B, Coor BR, et al. Botensilimab (Fc-enhanced anti–CTLA-4 antibody) plus balstilimab (anti–PD-1 antibody) in patients with treatment-refractory ovarian cancer. J Immunother Cancer. 2025;13(12):e013222. doi:10.1136/jitc-2025-013222
2. Agenus reports deep, durable responses with botensilimab + balstilimab in highly refractory ovarian cancer, published in JITC. News release. Agenus. December 23, 2025. Accessed December 24, 2025. https://tinyurl.com/3n32aftw