Botensilimab + Balstilimab for Colorectal Cancer

Not yet recruiting at 10 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: City of Hope Medical Center

Must not be taking: Corticosteroids, Immunosuppressants, Herbal medications

Disqualifiers: Other active malignancy, Autoimmune disease, others

Stay on Your Current Meds You can continue your current medications while participating

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 7

Duration: 5-16 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of combining two immunotherapy drugs, botensilimab and balstilimab, when administered before surgery for advanced colorectal cancer that remains operable. These drugs aim to enhance the immune system's ability to recognize and attack cancer cells, potentially shrinking tumors before surgery. Suitable candidates for this trial have been diagnosed with colorectal cancer that has not spread to distant organs and have not yet received treatment. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering participants an opportunity to contribute to significant advancements in cancer treatment.

Is there any evidence suggesting that botensilimab and balstilimab are likely to be safe for humans?

Previous studies have shown that the combination of botensilimab and balstilimab has a manageable safety profile. Most side effects were not severe and could be treated with proper care. Research indicates that common side effects included fatigue and diarrhea, affecting about one-third of patients. Importantly, no new unexpected immune-related side effects were reported.

Regarding surgery outcomes, side effects did not delay any surgeries, and no patients experienced long-lasting immune-related problems. Overall, the combination treatment has been tested in other situations and is generally well-tolerated, with manageable side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of botensilimab and balstilimab for colorectal cancer because these treatments target the immune system in a novel way. Unlike standard chemotherapy and targeted therapies, these drugs are immune checkpoint inhibitors. Botensilimab and balstilimab work together to enhance the immune system's ability to recognize and attack cancer cells. This dual approach may offer a more powerful response against tumors compared to existing treatments. The potential for improved outcomes and fewer side effects makes this combination an exciting development in colorectal cancer treatment.

What evidence suggests that botensilimab and balstilimab might be effective for colorectal cancer?

Research has shown that the combination of botensilimab and balstilimab, which participants in this trial will receive, may help treat colorectal cancer. One study found that this combination helped patients with advanced disease live for about 21 months on average. It also improved response rates in patients without cancer spread to the liver. These results suggest that botensilimab and balstilimab could effectively shrink tumors and slow cancer progression, offering hope for patients with advanced colorectal cancer. ^{1 2 3 4 6}

Who Is on the Research Team?

Pashtoon M Kasi

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

This trial is for adults with advanced colorectal cancer (colon or rectal) that has spread but can still be removed by surgery. Participants must be healthy enough for surgery and able to receive immunotherapy before their operation.

Inclusion Criteria

Agreement to allow use of tissue from past and future surgery and standard of care biopsies

I had rectal cancer surgery first, with no radiation or pre-surgery treatment.

Total bilirubin ≤ 1.5 times upper limit of normal unless Gilbert's disease with other liver function criteria met

Exclusion Criteria

I do not have uncontrolled hepatitis B infection.

Any other condition contraindicating participation due to safety concerns per investigator

Participants unable to comply with study procedures or feasibility/logistics issues per investigator judgment

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive botensilimab IV on day 1 and balstilimab IV on days 1, 15, 29, and 43, followed by standard of care resection surgery 5-16 weeks later

5-16 weeks

4 visits (in-person) for IV administration

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up visits at 2 weeks, 4 weeks, every 3 months for 2 years, then every 6 months for 1 year

3 years

Multiple visits (in-person) over 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Balstilimab
• Botensilimab

Trial Overview

The study tests two immunotherapy drugs, botensilimab and balstilimab, given before surgery to see if they help shrink tumors in advanced resectable colorectal cancer. Imaging and biospecimen collection are also part of the study.

How Is the Trial Designed?

Group I: Treatment (botensilimab and balstilimab) Experimental Treatment 5 Interventions

Patients receive botensilimab IV, over 30 minutes, on day 1 and balstilimab IV, over 30 minutes, on days 1, 15, 29 and 43 in the absence of disease progression or unacceptable toxicity. 5-16 weeks later, patients then undergo standard of care resection surgery. Patients undergo CT scan and/or MRI and blood sample collection throughout the study.

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Citations

1.

sciencedirect.com

sciencedirect.com/science/article/pii/S2590018825005180

Refractory microsatellite-stable metastatic colorectal ...

The combination of botensilimab + balstilimab demonstrated promising clinical activity in heavily pre-treated patients with microsatellite-stable metastatic ...

2.

investor.agenusbio.com

investor.agenusbio.com/news/news-details/2025/Agenus-Presents-Data-at-ASCO-GI-Demonstrating-Impact-of-BOTBAL-in-Colorectal-Cancer-Across-Neoadjuvant-and-Advanced-Disease/default.aspx

Agenus Presents Data at ASCO GI Demonstrating Impact ...

Data from five presentations underscore the transformative potential of BOT/BAL across multiple lines of therapy in colorectal cancer.

3.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05608044

NCT05608044 | A Study of Botensilimab and Balstilimab ...

This is an open-label, Phase 2, multicenter study to evaluate the efficacy, safety, tolerability, and pharmacokinetic profiles of botensilimab as monotherapy ...

4.

nature.com

nature.com/articles/s41591-024-03083-7

Botensilimab plus balstilimab in relapsed/refractory ...

The median OS was 20.9 months (95% CI, 16.4 months–NR), and the 12-month OS rate was 69% (95% CI, 56–79%), with a median follow-up of 13.0 ...

5.

cancernetwork.com

cancernetwork.com/view/botensilimab-balstilimab-elicits-sustained-efficacy-in-mss-metastatic-crc

Botensilimab/Balstilimab Elicits Sustained Efficacy in MSS ...

Specifically, the combination attained a 42% 2-year survival rate as well as a median overall survival (OS) of 20.9 months among 123 patients ...

6.

clin.larvol.com

clin.larvol.com/trial-detail/NCT05571293

Combination Immunotherapy in Colorectal Cancer

Surgical Outcomes and Safety: No surgeries were delayed due to adverse events, and no patients had unresolved immune related adverse events. Side effects were ...