At the AACR Annual Meeting 2026, preliminary results from the BBOpCo clinical study evaluating first-line botensilimab (BOT) and balstilimab (BAL) in patients with microsatellite stable colorectal cancer (MSS CRC) without liver, bone, or brain metastases were presented by Nicholas C. DeVito, MD, Assistant Professor of Medicine in the Division of Medical Oncology at Duke University.
The study, titled “Preliminary results of first-line botensilimab (BOT) and balstilimab (BAL) optimization in MSS CRC without liver, bone, or brain metastasis (BBOpCo)” (Abstract CT184; NCT06268015), was presented during the Phase I Clinical Trials session on April 21, 2026.
Why This Study Matters
Patients with metastatic MSS colorectal cancer are typically treated with sequential chemotherapy regimens, often experiencing disease progression and prolonged toxicities over the course of treatment. Immunotherapy has historically shown limited efficacy in MSS CRC, which is generally considered an immunologically “cold” tumor.
This study explored whether anatomical patient selection — specifically excluding patients with liver, bone, or brain metastases — could identify a subgroup more likely to benefit from immune checkpoint blockade. The strategy also aimed to delay or potentially avoid chemotherapy by using BOT and BAL in the first-line setting. The rationale was supported by prior data from a phase I/II study of BOT/BAL in pretreated MSS CRC patients, which achieved a 73% disease control rate in patients without liver metastases.
Read about Phase 3 BATTMAN Trial in MSS or pMMR Metastatic Colorectal Cancer on OncoDaily.
The BOT/BAL Combination
Botensilimab (BOT) is an Fc-enhanced multifunctional anti–CTLA-4 antibody designed to activate both innate and adaptive anti-tumor immune responses. Its mechanism is aimed at improving outcomes in immunologically “cold” tumors, which typically show limited responsiveness to conventional checkpoint inhibitors. BOT enhances immune activity by promoting T-cell priming and expansion, reducing intratumoral regulatory T cells, activating myeloid cells, and supporting the development of long-term immune memory.
Balstilimab (BAL) is a fully human monoclonal IgG4 antibody targeting PD-1. By blocking the interaction between PD-1 and its ligands PD-L1 and PD-L2, BAL restores T-cell function and enables the immune system to recognize and attack tumor cells.
Together, BOT and BAL are designed to provide a complementary and potentially synergistic immune response, combining early immune activation with sustained checkpoint inhibition. This dual mechanism may be particularly relevant in MSS colorectal cancer, a setting where standard immunotherapy approaches have historically shown limited activity.
Methodology and Patient Population
This study enrolled 15 previously untreated patients with stage IV MSS colorectal cancer without liver, bone, or brain metastases. Patients received botensilimab (75 mg every 6 weeks, up to 4 doses) and balstilimab (240 mg every 2 weeks) as first-line therapy. Patients had a median age of 50 years, and 10 patients (66.7%) were male. Sites of metastases included lymph nodes (20%), peritoneum (26.7%), lungs (33.3%), and other locations (20%). A median of three cycles of botensilimab were administered.
Tumor assessments were performed every 6 weeks using iRECIST criteria. In cases of immune-confirmed progressive disease (iCPD), standard-of-care chemotherapy (FOLFOX plus bevacizumab or panitumumab) was added while continuing balstilimab. Tumor biopsies were collected at baseline and at the time of progression to support exploratory biomarker analyses.
The primary objectives included safety, feasibility, and disease control rate (DCR) with BOT/BAL. Secondary endpoints included best overall response to BOT/BAL alone (ORR1 by iRECIST) and following chemotherapy crossover (ORR2/DCR2 by RECIST), as well as progression-free and overall survival (PFS1, PFS2, OS). Exploratory analyses focused on spatial tumor biology and immune microenvironment characterization from pre-treatment and progression biopsies.
Key Findings
As of the data cutoff of January 5, 2026, one patient (with a BRAF mutation) withdrew from treatment. At a median follow-up of 4.3 months (95% CI, 1.6–Not Estimable), 13 patients were evaluable for efficacy and 14 for safety.
The combination achieved a disease control rate of 71%, including one confirmed immune partial response (iPR) — in a patient with lung metastases and a tumor mutational burden of 1 mut/Mb — and four cases of immune stable disease (iSD) at 24 weeks. Five patients treated with BOT/BAL alone were too early to assess at the time of data cutoff.
An important clinical outcome was the median freedom from crossover to chemotherapy of 8.7 months (95% CI, 6.2–NE). Among the four patients who progressed and transitioned to standard-of-care chemotherapy at a median of 6.3 months from BOT/BAL initiation, three were evaluable for response to chemotherapy by RECIST, demonstrating a 67% disease control rate and confirming that subsequent chemotherapy performance was consistent with expectations.
Safety and Tolerability
The safety profile was consistent with the mechanism of action of checkpoint inhibitors. Among 14 patients evaluable for immune-related adverse events (irAEs), 6 patients experienced Grade 1–2 events and 7 experienced Grade 3 events. Importantly, no Grade 4 toxicities and no treatment-related deaths were reported.
Grade 3 toxicity was primarily colitis, occurring in 5 of the 7 Grade 3 cases. Categories of irAEs of any grade experienced by more than one patient included diarrhea/colitis, fatigue, rash, AST/ALT elevations, fever, hypothyroidism, and arthritis. Arthritis was effectively managed with naproxen or ibuprofen.
A proactive management strategy was implemented to address the expected risk of immune-related colitis. Patients were provided with a short course of prednisone to take home prior to starting therapy, enabling rapid self-initiation of corticosteroids at the first signs of colitis, followed by infliximab within 48 hours when needed. This proactive approach contributed to the absence of Grade 4 toxicities and treatment-related deaths.
Read about BOT/BAL and agenT-797 in PD-1 Refractory Gastroesophageal Cancer on OncoDaily.
Translational and Biomarker Insights
Exploratory analyses using multiplex immunohistochemistry revealed distinct biological differences between responders and non-responders. Patients who responded to treatment demonstrated increased infiltration of cDC1s, while non-responders exhibited higher Spp1/CXCL9 macrophage ratios.
These findings provide early insight into potential biomarkers of response and resistance and may inform future patient selection strategies.
Key Takeaways
This early-phase study demonstrates that first-line botensilimab and balstilimab is feasible and shows clinical activity in a carefully selected MSS colorectal cancer population without liver, bone, or brain metastases. The ability to delay chemotherapy, combined with maintained responsiveness to subsequent treatment and emerging biomarker insights, supports further evaluation of this approach in larger studies.
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