Combination Immunotherapy for Colorectal Cancer

(NEST-1 Trial)

Not currently recruiting at 2 trial locations

Overseen By Myriam Elizaire-Williams

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Weill Medical College of Cornell University

Must not be taking: Immunosuppressives

Disqualifiers: Metastatic cancer, Active infection, 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: 4-8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of two drugs to assess their impact on colorectal cancer and any side effects. The drugs, balstilimab and botensilimab, aim to enhance the immune system's ability to combat cancer. Participants will receive these drugs before undergoing surgery to remove their cancer. Individuals with colorectal cancer who do not plan to have radiation therapy before surgery might be suitable candidates, particularly if their cancer has not metastasized. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on immunosuppressive 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 the combination of botensilimab and balstilimab generally has a manageable safety profile, meaning most patients can tolerate the treatment's side effects. No new immune-related safety issues have emerged with these drugs. Earlier studies have shown promising results in patients with other types of cancer. However, since this study is in Phase 2, not all possible side effects may be known yet.

As always, discussing with the medical team is crucial to understand what this might mean personally. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of balstilimab and botensilimab for colorectal cancer because these treatments are monoclonal antibodies that specifically target cancer cells in a unique way. Unlike traditional chemotherapy, which can affect both healthy and cancerous cells, this combination aims to enhance the immune system's ability to recognize and destroy cancer cells more precisely. Additionally, botensilimab and balstilimab are administered intravenously, allowing for a more controlled delivery directly into the bloodstream. This innovative approach could offer a more targeted and potentially less toxic alternative to existing treatments like chemotherapy and radiation.

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

Research shows that the combination of botensilimab and balstilimab, which participants in this trial may receive, holds promise for treating colorectal cancer. Studies have found this treatment particularly encouraging for patients with limited options. In patients with metastatic colorectal cancer, this combination resulted in a 42% survival rate over two years and an average survival time of 20.9 months. These results suggest that the treatment can help manage the disease and improve survival rates. Additionally, the safety of this combination remains manageable, with no significant new safety concerns reported. ^{1 2 6 7 8}

Who Is on the Research Team?

Manish Shah, M.D.

Principal Investigator

Weill Medical College of Cornell University

Are You a Good Fit for This Trial?

This trial is for adults with early-stage (1-3) colorectal cancer who are planning to have surgery. They must use effective contraception if they can become or get someone pregnant. It's not for those with metastatic cancer, previous immune checkpoint inhibitor treatments, active infections needing treatment, other ongoing clinical trials participation, pregnancy or breastfeeding, on immunosuppressants, or serious heart conditions.

Inclusion Criteria

If capable of becoming pregnant, or getting someone else pregnant, must be willing to use highly effective contraception from Screening period through 90 days following the last dose of study drug

I have stage 1-3 colon cancer and plan to have surgery.

Exclusion Criteria

I have been treated with drugs targeting CTLA-4, PD-1, or PD-L1.

Pregnant or breastfeeding

My cancer has spread to other parts of my body.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 2 or 4 doses of balstilimab and a single dose of botensilimab intravenously, approximately 2 weeks apart, before surgical resection

4-8 weeks

Surgical Resection

Surgical resection occurs 1-6 weeks following the last dose of balstilimab

1-6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including post-op follow-up visits

90 days

1-2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Balstilimab
• Botensilimab
• Surgical Removal of Tumor

Trial Overview The study tests a combination of two investigational drugs: balstilimab and botensilimab—both targeting the immune system—to see their effects on colorectal cancer before surgical tumor removal. Participants will receive these drugs intravenously over an 8-week period prior to surgery.

How Is the Trial Designed?

Group I: Cohort C: Experimental Treatment 2 Interventions

Botensilimab and balstilimab are both monoclonal antibodies that are administered intravenously. Four doses of balstilimab (240 mg IV), will be administered approximately 2 weeks apart. A single dose of botensilimab (75 mg IV) will be administered on the same day as the first dose of balstilimab. Surgical resection will occur 1-6 weeks following the fourth dose of balstilimab. Cohort C only includes patients with dMMR/MSI-High colorectal cancer.

Group II: Cohort B: Experimental Treatment 2 Interventions

Botensilimab and balstilimab are both monoclonal antibodies that are administered intravenously. Four doses of balstilimab (240 mg IV), will be administered approximately 2 weeks apart. A single dose of botensilimab (75 mg IV) will be administered on the same day as the first dose of balstilimab. Surgical resection will occur 1-6 weeks following the fourth dose of balstilimab.

Group III: Cohort A: Botensilimab and balstilimab (bot/bal) Experimental Treatment 2 Interventions

Botensilimab and balstilimab are both monoclonal antibodies that are administered intravenously. Two doses of balstilimab (240 mg IV), will be administered approximately 2 weeks apart. A single dose of botensilimab (75 mg IV) will be administered on the same day as the first dose of balstilimab. Surgical resection will occur 1-6 weeks following the second dose of balstilimab.

Who Is Running the Clinical Trial?

Weill Medical College of Cornell University

Lead Sponsor

Trials

1,103

Recruited

1,157,000+

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. 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. 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 ... 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 ...

5. 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 ...

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. 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 ... “These results reinforce the consistency and durability of the botensilimab plus balstilimab combination in a population that has historically ...

8. 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 ...