Botensilimab + Balstilimab + SBRT for Colorectal Cancer

TS
Overseen ByTheodore S. Hong, MD
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for individuals with colorectal cancer that has spread to the liver and is unresponsive to standard chemotherapy. It combines two experimental drugs, Botensilimab and Balstilimab, with a targeted radiation therapy called Stereotactic Body Radiation Therapy (SBRT). The goal is to determine if this combination is safe and effective for patients whose cancer lacks certain genetic markers. Participants should have colorectal cancer that has metastasized to the liver, has not responded to standard chemotherapy, and have at least one liver tumor untreated by radiation. As an Early Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have had chemotherapy or certain treatments within 14 days before starting the trial, and you should not be on high-dose corticosteroids or other immunosuppressive medications.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of botensilimab and balstilimab is generally safe. No new immune-related safety issues have emerged. In earlier research with patients who have microsatellite stable (MSS) colorectal cancer, 89% experienced treatment-related side effects. The most common side effects included fatigue and diarrhea. Although these side effects occur frequently, they are usually mild and manageable.

This study remains in an early phase, so researchers are still assessing the treatment's safety and tolerability. It is important to discuss with a healthcare provider to understand what this means for individual circumstances.12345

Why are researchers excited about this trial's treatments?

Researchers are excited about Botensilimab and Balstilimab because they offer a novel approach to treating colorectal cancer. While traditional treatments often focus on chemotherapy and radiation, Botensilimab and Balstilimab are immunotherapies that work by enhancing the body's own immune response to attack cancer cells. Botensilimab is a monoclonal antibody that targets the CTLA-4 protein, while Balstilimab targets the PD-1 pathway. By using these two together, they aim to unleash a more powerful immune attack on the cancer, potentially leading to better outcomes for patients. This combination could offer a new hope for those who have not responded well to standard therapies.

What evidence suggests that this trial's treatments could be effective for colorectal cancer?

Research has shown that the combination of Botensilimab and Balstilimab may hold promise for treating colorectal cancer. In this trial, participants will receive Stereotactic Body Radiation Therapy (SBRT) alongside Botensilimab and Balstilimab. One study found that patients with advanced colorectal cancer who received this combination lived for a median of about 21 months, with half living longer. Another study reported that about 70% of patients experienced stable disease or better, meaning their cancer did not worsen. Additionally, the treatment reduced cancer size by 30% in some patients. These findings suggest that the Botensilimab and Balstilimab combination could be an effective option for those with advanced colorectal cancer.13467

Who Is on the Research Team?

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Theodore S. Hong, MD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

This trial is for adults with colorectal cancer that has spread to the liver and isn't responding to standard treatments. They must have tried or be intolerant to certain chemotherapies, have a life expectancy over 3 months, good performance status, and meet specific organ function criteria. Pregnant individuals or those with autoimmune diseases, uncontrolled illnesses, recent vaccines, or certain infections cannot participate.

Inclusion Criteria

Participants must have a life expectancy of greater than 3 months
I have been treated with or cannot tolerate 5-FU, Oxaliplatin, and Irinotecan.
Participants must agree to use highly effective contraceptive measures if applicable
See 10 more

Exclusion Criteria

I have fluid buildup in my abdomen that doesn't respond to treatment.
Participants with known or suspected active autoimmune disease
I haven't had cancer treatment in the last 14 days and have recovered from any side effects.
See 15 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Participants receive standard of care SBRT for 2-3 weeks to control liver lesions

2-3 weeks
1 visit (in-person)

Treatment

Participants receive botensilimab and balstilimab for up to 24 weeks, followed by balstilimab alone for 14 additional 6-week cycles

108 weeks
Balstilimab every 2 weeks, botensilimab on Day 1 of 6-week cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

52 weeks

What Are the Treatments Tested in This Trial?

Interventions

  • Balstilimab
  • Botensilimab
  • Stereotactic Body Radiation Therapy (SBRT)
Trial Overview The study tests combining Botensilimab and Balstilimab with Stereotactic Body Radiation Therapy (SBRT) in patients whose tumors are not highly mutated (Non-MSI-H) or have normal DNA repair mechanisms (pMMR). It's a pilot study meaning it's an early phase of testing focusing on feasibility.
How Is the Trial Designed?
1Treatment groups
Experimental Treatment
Group I: Stereotactic Body Radiation Therapy (SBRT) + Botensilimab + BalstilimabExperimental Treatment3 Interventions

Find a Clinic Near You

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials
3,066
Recruited
13,430,000+

Agenus Inc.

Industry Sponsor

Trials
58
Recruited
4,900+

Citations

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 ...
Botensilimab/Balstilimab Elicits Sustained Efficacy in MSS ...The combination attained a 42% 2-year survival rate as well as a median overall survival of 20.9 months among 123 patients with MSS metastatic ...
A phase 2 study of SR-8541A in combination with ...Around 70% of patients had stable disease or better, with a 17-19% objective response rate, a 30% reduction in cancer burden, and near-complete ...
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.
Botensilimab and Balstilimab Show Durable Survival in ...Botensilimab plus balstilimab delivers 21-month overall survival in MSS colorectal cancer, per updated Phase 1b data at ESMO GI 2025.
Agenus' BOT/BAL Achieves 42% Two-Year Survival in ...Agenus' BOT/BAL Achieves 42% Two-Year Survival in Refractory MSS CRC, Advances Toward Registration with FDA Alignment on Phase 3 · ESMO‑GI ...
7.pubmed.ncbi.nlm.nih.govpubmed.ncbi.nlm.nih.gov/38871975/
Botensilimab plus balstilimab in relapsed/refractory ... - PubMedTreatment-related adverse events (TRAEs) occurred in 89% of patients with MSS mCRC (131/148), most commonly fatigue (35%, 52/148), diarrhea (32% ...
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