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

28 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase I/II trial tests how well botensilimab, balstilimab, and regorafenib works in treating patients with microsatellite stable colorectal cancer that has spread from where it first started (primary site) to other places in the body (metastatic) or that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) and who have progressed on prior chemotherapy. Immunotherapy with monoclonal antibodies, such as botensilimab and balstilimab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Regorafenib binds to and inhibits growth factor receptors, which may inhibit the growth of new blood vessels that tumors need to grow. Giving botensilimab, balstilimab, and regorafenib in combination may work better in treating patients with metastatic colorectal cancer than giving these drugs alone.

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.

What data supports the effectiveness of the drug Regorafenib in treating colorectal cancer?

Regorafenib has shown significant improvements in overall survival for patients with metastatic colorectal cancer that has progressed after standard therapies. It is FDA-approved for this use and has demonstrated survival benefits in other cancers as well. ^{1 2 3 4 5}

Is the triple therapy for colorectal cancer safe for humans?

Regorafenib, a part of the triple therapy, has been studied for safety in humans and is known to cause side effects like skin reactions, fatigue, high blood pressure, and diarrhea. These side effects can be managed with careful monitoring and adjusting the dose if needed. ^{3 6 7 8 9}

What makes the triple therapy for colorectal cancer unique?

The triple therapy for colorectal cancer is unique because it combines Balstilimab and Botensilimab, which are immune checkpoint inhibitors (drugs that help the immune system attack cancer cells), with Regorafenib, a targeted therapy that blocks cancer cell growth. This combination aims to enhance the immune response against cancer while simultaneously inhibiting tumor growth, offering a novel approach compared to standard treatments like Regorafenib or trifluridine/tipiracil alone. ^{1 2 3 10 11}

Research Team

Marwan Fakih, MD

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Phase 2 study of irinotecan plus cetuximab rechallenge as third-line treatment in KRAS wild-type metastatic colorectal cancer: JACCRO CC-08. [2023]

2. England pubmed.ncbi.nlm.nih.gov

A Systematic Review and Network Meta-Analysis of Regorafenib and TAS-102 in Refractory Metastatic Colorectal Cancer. [2020]

3. Switzerland 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. [2022]

4. Germany pubmed.ncbi.nlm.nih.gov

Regorafenib. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

Current Options for Third-Line Treatment of Metastatic Colorectal Cancer. [2022]

6. China pubmed.ncbi.nlm.nih.gov

Efficacy and safety of regorafenib and fruquintinib as third-line treatment for colorectal cancer: a narrative review. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Efficacy of Regorafenib in Metastatic Colorectal Cancer: A Multi-institutional Retrospective Study. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Dose reduction and discontinuation of standard-dose regorafenib associated with adverse drug events in cancer patients: a systematic review and meta-analysis. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Optimizing treatment outcomes with regorafenib: personalized dosing and other strategies to support patient care. [2022]

10. France pubmed.ncbi.nlm.nih.gov

Phase II Study of Third-Line Panitumumab Rechallenge in Patients with Metastatic Wild-Type KRAS Colorectal Cancer Who Obtained Clinical Benefit from First-Line Panitumumab-Based Chemotherapy: JACCRO CC-09. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

A Real-World Comparison of Regorafenib and Trifluridine/Tipiracil in Refractory Metastatic Colorectal Cancer in the United States. [2023]