Triple Therapy for Colorectal Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: City of Hope Medical Center

Must not be taking: Corticosteroids, Immunosuppressive drugs

Disqualifiers: Autoimmune disease, Uncontrolled hypertension, Cardiovascular disease, Active brain metastases, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effectiveness of a combination of three treatments—botensilimab, balstilimab, and regorafenib—for individuals with a specific type of metastatic colorectal cancer. The first two treatments are immunotherapies that enhance the immune system's ability to fight cancer, while regorafenib inhibits tumor growth by blocking the formation of new blood vessels. Individuals with advanced colorectal cancer, whose disease has progressed despite previous chemotherapy, and who can swallow tablets, might be suitable candidates for this trial. As a Phase 1, Phase 2 trial, this research aims to understand the treatment's effects and measure its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking cancer research.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are on corticosteroids or other immunosuppressive medications, you may need to stop them before starting the trial.

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

Research shows that the combination of botensilimab, balstilimab, and regorafenib is under study for safety and effectiveness in treating advanced colorectal cancer. Previous patients demonstrated that this combination may be well-tolerated. For example, studies have examined how these drugs work together and suggest they might be safe to use.

Botensilimab and balstilimab are types of immunotherapy, helping the body's immune system fight cancer. Regorafenib stops the growth of blood vessels that tumors need to grow. These drugs have been tested in different settings and have shown promise in being safe for patients.

Since this trial is in its early stages, researchers are still collecting data on patient tolerance. They are carefully monitoring any side effects and how patients feel during the trial.

Overall, evidence so far suggests that this combination could be a safe option for treating advanced colorectal cancer, but ongoing research will provide more detailed answers. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this triple therapy for colorectal cancer because it combines three powerful agents: Balstilimab, Botensilimab, and Regorafenib. Unlike traditional treatments that often focus solely on chemotherapy, this regimen leverages immunotherapy with Balstilimab and Botensilimab, which helps the body's immune system better recognize and attack cancer cells. Regorafenib, taken orally, adds another layer by inhibiting cancer cell growth and cutting off their blood supply. This combined approach not only targets the cancer more effectively but also holds promise for improved patient outcomes and potentially fewer side effects compared to standard chemotherapy alone.

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

Research shows that combining the drugs botensilimab and balstilimab may help treat colorectal cancer. Recent findings indicate that patients using these drugs have lived for about 21 months on average. This is promising for those with microsatellite stable (MSS) colorectal cancer, which usually doesn't respond well to standard treatments. In this trial, participants will receive botensilimab, balstilimab, and regorafenib. When combined with regorafenib, which cuts off the tumor's blood supply, patients lived for an average of 5.3 months without their cancer worsening. Overall, this combination of three treatments has the potential to improve outcomes for patients with advanced stages of this cancer. ^{4 6 7 8 9}

Who Is on the Research Team?

Marwan Fakih, MD

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

This trial is for adults with advanced colorectal cancer that's spread and hasn't responded to previous chemotherapy. Participants must be in good physical condition, able to take oral medication, have a life expectancy of at least 3 months, and use effective birth control if applicable. They can't join if they've had certain recent health issues or treatments, are on high-dose steroids or other immune-suppressing drugs, or have autoimmune diseases.

Inclusion Criteria

My cancer returned within 6 months after finishing chemotherapy.

Documented informed consent of the participant and/or legally authorized representative

My colon or rectum cancer is advanced, spreading, and not responsive to certain DNA repair errors.

Exclusion Criteria

Psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study

I have had COVID-19 within the specified timeframes.

I do not have an uncontrolled HIV infection or known hepatitis B or C.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase I Treatment

Dose-escalation study to identify the recommended phase 2 dose of botensilimab, balstilimab, and regorafenib

6 weeks

Regular visits for dose escalation and monitoring

Phase II Treatment

Evaluation of overall response rate and safety of botensilimab, balstilimab, and regorafenib

Up to 2 years

Regular visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Balstilimab
• Botensilimab
• Regorafenib

Trial Overview The study tests a combination of botensilimab (an immunotherapy drug), balstilimab (another immunotherapy), and regorafenib (a drug that inhibits tumor growth) in patients with metastatic colorectal cancer. The goal is to see if this combo is more effective than the standard treatment alone.

How Is the Trial Designed?

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

Patients receive botensilimab IV, balstilimab IV, and regorafenib PO on study. Patients also undergo CT and collection of blood 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+

Published Research Related to This Trial

In a study of 72 patients with microsatellite stable metastatic colorectal cancer, regorafenib or fruquintinib combined with sintilimab showed a median progression-free survival of 4.2 months and an overall survival of 10.5 months, indicating these combinations are viable third-line treatment options.

The treatment was generally well-tolerated, with only 15.3% of patients experiencing severe adverse events, and patients without liver metastasis showed better response rates and overall survival, suggesting they may benefit more from this regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Microsatellite stable metastatic colorectal cancer without liver metastasis may be preferred population for regorafenib or fruquintinib plus sintilimab as third-line or above therapy:A real-world study. Nie, C., Lv, H., Chen, B., et al.[2022]

Regorafenib and fruquintinib are effective and well-tolerated third-line treatment options for metastatic colorectal cancer (mCRC), as supported by a review of clinical studies.

Both drugs have similar survival outcomes, but regorafenib demonstrates a slightly better toxicity profile, making it a preferable choice in terms of safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of regorafenib and fruquintinib as third-line treatment for colorectal cancer: a narrative review. Xu, X., Yu, Y., Liu, M., et al.[2022]

Regorafenib is an oral multi-kinase inhibitor that has shown significant survival benefits in metastatic colorectal cancer and has been FDA approved for this use since 2012.

The drug also improves progression-free survival in patients with metastatic gastrointestinal stromal tumors and advanced hepatocellular carcinoma, leading to its FDA approval for these conditions as well.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regorafenib. Ettrich, TJ., Seufferlein, T.[2018]

Citations

1. 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 ...

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. gioncologynow.com gioncologynow.com/post/combination-therapy-of-botensilimab-balstilimab-and-regorafenib-for-patients-with-advanced-colorectal-cancer-and-liver-metastases

Combination Therapy of BOT/BAL + Rego for Patients With ... In the NLmCRC phase 2 cohort, one out of eight patients had an objective response, and the median progression-free survival was 5.3 months. “The ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11681808/

Progress of Immune Checkpoint Inhibitors Therapy for pMMR ... The Phase II REGOMUNE study is evaluating the efficacy and safety of regorafenib in combination with Avelumab in treated MSS colorectal cancer.

5. oncodaily.com oncodaily.com/oncolibrary/botensilimab-balstilimab-esmo-gi-2025

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.

6. careacross.com careacross.com/clinical-trials/trial/NCT06575725

Botensilimab, Balstilimab and Regorafenib or ... This helps to slow or stop the spread of tumor cells. The combination of botensilimab, balstilimab and regorafenib or botensilimab and balstilimab may be a safe ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT07152821

Study Details | NCT07152821 | Botensilimab + Balstilimab ... This study is being done to find out if this approach (taking botensilimab and balstilimab) is better or worse than the usual approach for ...

8. agenusbio.com agenusbio.com/wp-content/uploads/2025/01/21Jan2024_ASCO-GI-Rapid-Oral_FINAL_For-Website.pdf

Preliminary Results From a Randomized, Open-Label Botensilimab Plus Balstilimab in Relapsed/Refractory. Microsatellite Stable Metastatic Colorectal Cancer: A Phase 1 Trial1. June 2024. *23% after the data ...

9. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2022-10069

Botensilimab, Balstilimab and Regorafenib for the ... This phase I/II trial tests how well botensilimab, balstilimab, and regorafenib works in treating patients with microsatellite stable colorectal cancer.