Botensilimab + Balstilimab and Diet + Vitamin C for Colorectal Cancer

Recruiting at 1 trial location

Overseen By Charlean Ketchens, RN

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Southern California

Must not be taking: Diabetes medications, Oral vitamin C

Disqualifiers: Diabetes, Autoimmune disease, Uncontrolled illness, others

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

Compensation: Varies

Number of Visits: 31

Duration: Up to 2 years

15 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety, side effects, and effectiveness of combining two experimental drugs, botensilimab and balstilimab, with a special diet and high-dose vitamin C to treat colorectal cancer with a specific mutation (KRAS-mutant) that has spread. The diet mimics fasting and is low in sugar, potentially enhancing the body's response to the treatment. The trial seeks participants with KRAS-mutant colorectal cancer that has spread and who have previously tried certain treatments without success or experienced side effects. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment combination.

Do I need to stop my current medications to join the trial?

The trial requires that you stop taking any medications that cannot be safely stopped during fasting periods or that cannot be safely taken without food. If you are on such medications, you may not be eligible to participate.

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

Research shows that using botensilimab and balstilimab together is generally safe. Studies have found no new immune-related safety issues with this treatment. Participants who took these drugs together did not experience unexpected side effects, indicating that the treatment is usually well-tolerated.

Although detailed information specific to this trial, which includes a fasting mimicking diet and high-dose vitamin C, is not available, existing evidence for botensilimab and balstilimab is encouraging. Previous trials with these drugs ensured safety, providing reassurance for prospective participants. ^{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 it employs a unique approach by pairing two immune-modulating drugs with a fasting-mimicking diet (FMD) and vitamin C. Unlike standard chemotherapy, which directly targets cancer cells, this treatment boosts the body's immune response to attack the cancer. Botensilimab and Balstilimab work together to enhance the immune system's ability to recognize and destroy cancer cells, while the FMD and vitamin C may further enhance this effect by creating an environment that's less favorable for cancer growth. This multi-faceted strategy could offer a new pathway for treating colorectal cancer, potentially with fewer side effects than traditional therapies.

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

Research has shown that using botensilimab and balstilimab together may help treat colorectal cancer. In earlier studies, 42% of patients with advanced colorectal cancer lived for at least two years, with an average survival time of about 21 months. In this trial, participants will receive botensilimab and balstilimab along with vitamin C and a fasting-mimicking diet (FMD). High doses of vitamin C have demonstrated anti-cancer effects in lab studies, particularly for colorectal cancer. Consuming a low-sugar diet, such as an FMD, might enhance vitamin C's ability to fight cancer cells. These treatments aim to slow or stop tumor growth in patients with a specific type of advanced colorectal cancer called KRAS-mutant metastatic colorectal cancer. ^{1 2 5 6 7}

Who Is on the Research Team?

Diana Hanna, MD

Principal Investigator

University of Southern California

Are You a Good Fit for This Trial?

This trial is for patients with metastatic colorectal cancer that has a specific mutation called KRAS. Participants should be interested in combining standard cancer treatments with dietary changes and vitamin supplements.

Inclusion Criteria

I don't have any other cancers that need treatment right now.

Platelets ≥ 75,000/mcL

Hemoglobin ≥ 8.0 g/dL

Exclusion Criteria

I don't expect to need any other cancer treatments during the trial.

I don't have any severe side effects from previous treatments, except for possible nerve issues or hair loss.

I have had a transplant of tissue or an organ from another person, except for a cornea transplant.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive botensilimab, balstilimab, and vitamin C intravenously, along with a fasting mimicking diet, in 42-day cycles for up to 2 years

Up to 2 years

Visits on days 1, 15, and 29 of each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

6 months

Follow-up at 30 days and every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Balstilimab
• Botensilimab
• Dietary Intervention
• Vitamin C

Trial Overview The trial is testing the combination of two monoclonal antibodies, Botensilimab and Balstilimab, alongside a special low-sugar diet designed to mimic fasting and high doses of Vitamin C. The goal is to see if this combo can help stop the growth and spread of cancer cells more effectively.

How Is the Trial Designed?

Group I: Treatment (botensilimab, balstilimab, FMD, vitamin C) Experimental Treatment 7 Interventions

Patients receive botensilimab IV over 30 minutes on day 1 of each cycle for up to 4 cycles. Patients receive balstilimab IV over 30 minutes and vitamin C IV over 30 minutes on days 1, 15 and 29 of each cycle. Patients undergo a FMD on days -4 to -1 of each cycle. Cycles repeat every 42 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection, CT scans and MRI throughout the study.

Who Is Running the Clinical Trial?

University of Southern California

Lead Sponsor

Trials

956

Recruited

1,609,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Recent advancements in the treatment of colorectal cancer, including the use of oxaliplatin and irinotecan alongside fluorouracil, have significantly improved patient outcomes, with over 75% of patients with localized disease remaining recurrence-free at 3 years.

Targeted therapies that focus on the vascular endothelial growth factor and epidermal growth factor pathways are now essential in treating colorectal cancer, contributing to a survival rate of up to 50% for patients with advanced unresectable disease at 2 years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Colorectal cancer. Gill, S., Blackstock, AW., Goldberg, RM.[2023]

Bioactive Food Components (BFCs) found in fruits and vegetables have shown both chemopreventive and anti-tumor properties in colorectal cancer (CRC), suggesting they can play a significant role in cancer prevention and treatment.

BFCs may enhance the effectiveness of conventional cancer treatments, but their clinical use is limited by challenges related to bioavailability and the complexity of their effects, indicating a need for further research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bioactive food components for colorectal cancer prevention and treatment: A good match. Amintas, S., Dupin, C., Boutin, J., et al.[2023]

In a phase 1 study involving 36 patients with metastatic colorectal or gastric cancer, the maximum tolerated dose of ascorbic acid (AA) was not reached, establishing a recommended phase 2 dose of 1.5 g/kg/day without any dose-limiting toxicities observed.

The combination of AA with mFOLFOX6 or FOLFIRI showed promising preliminary efficacy, with an objective response rate of 58.3% and a disease control rate of 95.8%, indicating that this treatment could be a safe and effective option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of high-dose ascorbic acid with mFOLFOX6 or FOLFIRI in patients with metastatic colorectal cancer or gastric cancer. Wang, F., He, MM., Wang, ZX., et al.[2022]

Fruquintinib, a VEGFR inhibitor, significantly improved progression-free survival (PFS) by 3.7 months in metastatic colorectal cancer patients compared to placebo, demonstrating its efficacy in treatment-refractory cases.

The safety profile of fruquintinib was consistent with other VEGFR tyrosine kinase inhibitors, with common severe side effects including hypertension and hand-foot skin reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of fruquintinib in patients with previously treated metastatic colorectal cancer: a phase Ib study and a randomized double-blind phase II study. Xu, RH., Li, J., Bai, Y., et al.[2022]

In a 4-year chemoprevention trial involving 58 patients with familial adenomatous polyposis, the combination of vitamin C and vitamin E was tested for its effects on rectal polyps, showing limited impact from high-fiber supplements when analyzed by intent to treat.

However, when accounting for patient compliance, the high-fiber supplement demonstrated a stronger benefit in reducing rectal polyps during the middle two years of the trial, suggesting that dietary grain fiber may help inhibit the development of benign large bowel neoplasia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of wheat fiber and vitamins C and E on rectal polyps in patients with familial adenomatous polyposis. DeCosse, JJ., Miller, HH., Lesser, ML.[2019]

Recent advancements in systemic therapy for advanced colorectal cancer, including new chemotherapeutic agents like irinotecan, oxaliplatin, and capecitabine, have extended median survival for patients by up to 21 months.

The emergence of targeted therapies is promising, suggesting that some patients with advanced colorectal cancer may achieve long-term survival even without surgical intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current strategies in previously untreated advanced colorectal cancer. Penland, SK., Goldberg, RM.[2018]

High doses of Vitamin C and Vitamin B3 can selectively induce cell death in colorectal cancer stem cells (CSCs) with BRAF and KRAS mutations, showing a potential therapeutic effect for advanced colorectal cancer.

At low doses, both vitamins promote the proliferation of CSCs without affecting non-stem cancer cells, highlighting the importance of dosage in cancer treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Opposing effects of low versus high concentrations of water soluble vitamins/dietary ingredients Vitamin C and niacin on colon cancer stem cells (CSCs). Sen, U., Shenoy P, S., Bose, B.[2018]

In a study of 442 patients with metastatic colorectal cancer, adding high-dose vitamin C to standard chemotherapy (FOLFOX ± bevacizumab) did not improve progression-free survival compared to chemotherapy alone, with median PFS of 8.6 months versus 8.3 months.

However, patients with RAS mutations showed a significant benefit from the addition of vitamin C, achieving a longer median PFS of 9.2 months compared to 7.8 months with chemotherapy alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized, Open-Label, Multicenter, Phase 3 Study of High-Dose Vitamin C Plus FOLFOX ± Bevacizumab versus FOLFOX ± Bevacizumab in Unresectable Untreated Metastatic Colorectal Cancer (VITALITY Study). Wang, F., He, MM., Xiao, J., et al.[2023]

Citations

1. 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.

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

Botensilimab plus balstilimab in relapsed/refractory ... However, response rates vary across tumor types, with particularly disappointing outcomes in patients with metastatic colorectal cancer (mCRC) ...

3. 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 ...

4. 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 ...

5. 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 ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06336902

NCT06336902 | Botensilimab Plus Balstilimab and Fasting ... Botensilimab and balstilimab in combination with a fasting mimicking diet and high dose vitamin C may be safe, tolerable and effective in treating patients with ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38871975/

Botensilimab plus balstilimab in relapsed/refractory ... - PubMed Botensilimab plus balstilimab in relapsed/refractory microsatellite stable metastatic colorectal cancer: a phase 1 trial. Nat Med. 2024 Sep ...