Conditional approvals in Armenia cover botensilimab plus balstilimab indicated for patients with MSS mCRC without active liver metastases.
Armenia’s Ministry of Health has granted conditional marketing authorizations to botensilimab (Botvymo) and balstilimab (Evamplix), each approved for use with the other, for the treatment of adult patients with microsatellite-stable (MSS) metastatic colorectal cancer (mCRC) without active liver metastases who have been previously treated with available standard therapies.¹
The authorizations are the first marketing approvals for either agent in any country. Each authorization is valid for 1 year and can be renewed on the basis of annual clinical updates. Approved dosing is botensilimab at 75 mg intravenously (IV) every 6 weeks for up to 4 doses plus balstilimab at 240 mg IV every 2 weeks for up to 2 years or until progression or unacceptable toxicity. Botensilimab is an Fc-enhanced anti–CTLA-4 antibody, and balstilimab is a fully human IgG4 anti–PD-1 antibody.
Data supporting these approvals came from the phase 1b C-800-01 trial (NCT03860272) and the randomized phase 2 C-800-25 study (NCT07227636). C-800-01 was an open-label, multicenter study of botensilimab with or without balstilimab in patients with relapsed or refractory MSS mCRC.2 Patients in the expansion cohort received botensilimab at 1 or 2 mg/kg every 6 weeks plus balstilimab at 3 mg/kg every 2 weeks.
In the initial report, 148 patients were treated, and 101 patients were response evaluable with at least 6 months of follow-up and had received a median of 3 prior lines of therapy (range, 1-10). The objective response rate (ORR) was 17% (95% CI, 10%-26%), the disease control rate (DCR) was 61% (95% CI, 51%-71%), and the median overall survival (OS) was 20.9 months (95% CI, 10.6-not reached [NR]). An exploratory analysis by liver involvement shaped the approved indication: the ORR was 22% (95% CI, 13%-33%) in patients without active liver metastases (n = 77) vs 0% (95% CI, 0%-14%) in those with active liver metastases (n = 24), and the median OS values were 20.9 months (95% CI, 16.4-NR) vs 7.4 months (95% CI, 6.1-10.3), respectively. The study investigators subsequently amended the trial protocol to enroll patients without active liver metastases.
Botensilimab Plus Balstilimab in MSS Metastatic CRC Without Active Liver Metastases: Highlights
The most recent report from the trial, published in Clinical Cancer Research, included 123 patients with MSS mCRC without active liver metastases, with a data cutoff of December 13, 2025 and a median follow-up of 20.2 months (range, 0.7-62.3).³ Patients had a median age of 56 years (range, 25-82), 67% of patients had received at least 3 prior lines of therapy, 15% of patients had received prior anti–PD-(L)1 therapy with or without anti–CTLA-4 therapy, and 67% of patients tested had RAS-mutant disease.
The confirmed ORR was 21% (95% CI, 14%-29%), including 3 complete and 23 partial responses, and the DCR was 69% (95% CI, 60%-77%). The clinical benefit rate was 28% (95% CI, 20%-36%), the median duration of response was NR (95% CI, 7.3-NR), and the median progression-free survival was 4.0 months (95% CI, 2.8-4.1). The median OS was 21.2 months (95% CI, 16.2-23.8), with 24-month and 36-month OS rates of 41% (95% CI, 32%-50%) and 33% (95% CI, 24%-43%), respectively. At the last follow-up, 21 patients (17%) were alive and off therapy.
In an exploratory, post hoc subgroup analysis of 37 patients previously exposed to regorafenib (Stivarga), trifluridine/tipiracil (Lonsurf) with or without bevacizumab (Avastin), or fruquintinib (Fruzaqla), the ORR was 22% (95% CI, 10%-38%), and the median OS was 16.2 months (95% CI, 9.7-31.3).
Any-grade treatment-related adverse effects (TRAEs) occurred in 92% of patients, and grade 3 or higher TRAEs were reported in in 41% of patients. The most common any-grade and grade 3 or higher TRAEs were diarrhea (39%; 8%), fatigue (37%; 2%), and pyrexia (24%; 3%). No treatment-related deaths occurred, and 17% of patients discontinued both agents due to a TRAE. Immune-mediated AEs were reported in 59% of patients (grade ≥ 3, 30%), with diarrhea or colitis the most frequent (41%; grade ≥ 3, 15%). The rates of immune-mediated AEs were lower at the 1-mg/kg botensilimab dose (any-grade, 45%) than at the 2-mg/kg dose (72%).
