Botensilimab + Balstilimab for Colorectal Cancer

Recruiting at 6 trial locations

Overseen By Neil Segal, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Metastatic disease, Autoimmune disease, others

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: 1

Duration: 18 weeks

284 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test whether combining two drugs, botensilimab and balstilimab, can effectively treat certain types of colorectal cancer. It focuses on patients with microsatellite stable (MSS) colon cancer or colorectal liver metastases (CRLM) who have residual cancer after surgery and chemotherapy. The trial will explore different drug administration methods, including comparisons to a placebo in some cases. Suitable participants have undergone surgery and chemotherapy for stage III colon cancer or liver metastases and still have detectable cancer DNA in their blood. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

Do I have to stop taking my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications. However, you cannot be on systemic steroid therapy or any other form of immunosuppressive therapy within 7 days before starting the trial treatment. It's best to discuss your specific medications with the trial team.

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 has a manageable safety profile. Most side effects were expected and could be addressed. Importantly, no new immune-related issues emerged, reassuring those concerned about unexpected reactions.

While these treatments remain under study and more detailed safety information will emerge over time, current findings suggest that the combination is generally well-tolerated by patients with colorectal cancer. It is important to remember that further testing is underway to ensure the treatment's safety and effectiveness for a broader population. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Botensilimab and Balstilimab for colorectal cancer because these treatments offer a fresh approach compared to traditional options like chemotherapy. Unlike the standard of care, which often targets rapidly dividing cells, Botensilimab and Balstilimab work by enhancing the immune system's ability to recognize and attack cancer cells. Botensilimab is an antibody that stimulates the immune system, while Balstilimab blocks proteins that inhibit immune response, making them a powerful duo. This unique mechanism of action holds promise for more effectively targeting tumors with potentially fewer side effects than conventional therapies.

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

Research has shown that the combination of two drugs, botensilimab and balstilimab, may effectively treat microsatellite-stable (MSS) colorectal cancer. In this trial, certain cohorts will receive both botensilimab and balstilimab, while others may receive a placebo. Studies have found that this drug combination is generally safe and effective for many patients without causing new safety issues. Specifically, one study showed that patients with advanced MSS colorectal cancer lived longer, suggesting the treatment might extend their lives. This combination boosts the immune system to better fight cancer cells. Overall, these findings offer hope for people with MSS colorectal cancer. ^{1 2 3 5 6}

Who Is on the Research Team?

Neil Segal, MD, PhD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for individuals with microsatellite stable (MSS) colon cancer or colorectal liver metastases who still have measurable disease after surgery and chemotherapy. Specific details about inclusion and exclusion criteria are not provided, but typically these would involve health status, prior treatments, and other medical conditions.

Inclusion Criteria

I am fully active or restricted in physically strenuous activity but can do light work.

I agree to provide my previous biopsy samples and to have blood tests for research.

My cancer is not MSI-High as confirmed by tests.

Exclusion Criteria

I do not have active tuberculosis.

Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment

Hypersensitivity to botensilimab or balstilimab or any of its excipients

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive botensilimab and balstilimab for 42-day cycles, followed by balstilimab alone for additional cycles

18 weeks

Botensilimab IV on day 1, Balstilimab IV on days 1, 15, and 29 of each 42-day cycle

Follow-up

Participants are monitored for ctDNA clearance and recurrence-free survival

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Balstilimab
• Botensilimab

Trial Overview The study tests a combination of two drugs: Botensilimab and Balstilimab (BOT/BAL), followed by just Balstilimab to see if they're effective in treating MSS colon cancer or CRLM post standard treatment. Some participants may receive a placebo for comparison.

How Is the Trial Designed?

Group I: Cohort 2b: MSS CRLM (Botensilimab and Balstilimab vs. Placebo) Randomized Experimental Treatment 3 Interventions

All patients will receive botensilimab IV on day 1 of the 42 day cycle for 4 doses, balstilimab IV on days 1, 15, and 29 of the 42 day cycle. Patient then continues balstilimab alone for an additional two cycles IV on days 1, 15, and 29 of the 42 day cycle OR Placebo

Group II: Cohort 2a: Stage 3 MSS Colon Cancer (Botensilimab and Balstilimab vs. Placebo) Randomized Experimental Treatment 3 Interventions

All patients will receive botensilimab IV on day 1 of the 42 day cycle for 4 doses, balstilimab IV on days 1, 15, and 29 of the 42 day cycle. Patient then continues balstilimab alone for an additional two cycles IV on days 1, 15, and 29 of the 42 day cycle OR Placebo

Group III: Cohort 1b: MSS CRLM (Botensilimab and Balstilimab) Experimental Treatment 2 Interventions

All patients will receive botensilimab IV on day 1 of the 42 day cycle for 4 doses, balstilimab IV on days 1, 15, and 29 of the 42 day cycle. Patient then continues balstilimab alone for an additional two cycles IV on days 1, 15, and 29 of the 42 day cycle.

Group IV: Cohort 1a: Stage III MSS Colon Cancer (Botensilimab and Balstilimab) Experimental Treatment 2 Interventions

All patients will receive botensilimab IV on day 1 of the 42 day cycle for 4 doses, balstilimab IV on days 1, 15, and 29 of the 42 day cycle. Patient then continues balstilimab alone for an additional two cycles IV on days 1, 15, and 29 of the 42 day cycle.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Agenus Inc.

Industry Sponsor

Trials

58

Recruited

4,900+

Citations

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

Botensilimab plus balstilimab in relapsed/refractory ... The combination of BOT plus BAL demonstrated a manageable safety profile with no new immune-mediated safety signals and encouraging clinical activity with ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.4_suppl.23

Preliminary results from a randomized, open-label, phase 2 ... Here we present preliminary data from a randomized, open-label, phase 2 study in patients (pts) with MSS mCRC NLM treated with BOT ± BAL (anti-PD−1; NCT ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT07227636

A Study of Botensilimab and Balstilimab for Colorectal ... The researchers are doing this study to find out whether the combination of botensilimab and balstilimab (BOT/BAL), followed by balstilimab alone, ...

4. gioncologynow.com gioncologynow.com/post/efficacy-of-botensilimab-balstilimab-in-microsatellite-stable-metastatic-colorectal-cancer

Efficacy of Botensilimab, Balstilimab in Microsatellite Stable ... Researchers evaluated the data of 77 patients with NLM MSS CRC who received botensilimab 1 or 2 mg/kg every 6 weeks and balstilimab 3 mg/kg ...

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

Botensilimab/Balstilimab Elicits Sustained Efficacy in MSS ... The combination of botensilimab and balstilimab elicited sustained survival outcomes in patients with microsatellite-stable (MSS) metastatic colorectal cancer ...

6. investor.agenusbio.com investor.agenusbio.com/news/news-details/2025/Agenus-BOTBAL-Achieves-42-Two-Year-Survival-in-Refractory-MSS-CRC-Advances-Toward-Registration-with-FDA-Alignment-on-Phase-3/default.aspx

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 · Launch Global ...