Cemiplimab + Fianlimab for Colorectal Cancer

Overseen By Joann Santmyer, RN

Age: 65+

Sex: Any

Trial Phase: Phase 2

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Must not be taking: Chronic steroids

Disqualifiers: Autoimmune disease, Heart disease, Metastatic cancer, 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: Unknown

Duration: 6 months

22 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate the safety and clinical activity of cemiplimab and the combination of cemiplimab/fianlimab in microsatellite unstable localized or locally advanced colorectal cancer diagnosed in patients age 70 or greater.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot be on chronic systemic steroids or require other cancer treatments while participating.

How is the drug Cemiplimab + Fianlimab unique for colorectal cancer?

Cemiplimab + Fianlimab is unique for colorectal cancer as it combines two immune checkpoint inhibitors, which may offer a novel approach for patients with microsatellite stable (MSS) colorectal cancer, a group that typically does not respond well to existing immune therapies. ^{1 2 3 4 5}

Research Team

Eric Christenson, MD

Principal Investigator

Sidney Kimmel Comprehensive Cancer Center Johns Hopkins Medical Institution

Eligibility Criteria

This trial is for patients aged 70 or older with localized or locally advanced colorectal cancer that's microsatellite instability-high (MSI-H). Specific eligibility details are not provided, but typically participants must be in good health aside from their cancer and meet certain lab criteria.

Inclusion Criteria

Ability to understand and willingness to sign a written informed consent document

I am 70 years old or older.

I agree to undergo endoscopic and CT scans for 2 years.

Exclusion Criteria

Conditions, including alcohol or drug dependence, intercurrent illness, or lack of sufficient peripheral venous access, that would affect the patient's ability to comply with study visits and procedures

I won't need other cancer treatments during the study.

I have been treated with specific immune therapies before my colorectal cancer diagnosis.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive cemiplimab with or without fianlimab to evaluate safety and clinical activity

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 month

Treatment Details

Interventions

• Cemiplimab
• Fianlimab

Trial Overview The study is testing the effectiveness and safety of cemiplimab alone, versus a combination of cemiplimab with fianlimab. It aims to see how well these treatments work in older adults with a specific type of colorectal cancer.

Participant Groups

Group I: Cohort B - Cemiplimab with Fianlimab Experimental Treatment 2 Interventions

Group II: Cohort A - Cemiplimab Experimental Treatment 1 Intervention

Cemiplimab is already approved in European Union, United States, Canada, Brazil for the following indications:

Approved in European Union as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)
• Non-small cell lung cancer (NSCLC)

Approved in United States as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)
• Basal cell carcinoma (BCC)
• Non-small cell lung cancer (NSCLC)

Approved in Canada as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)
• Non-small cell lung cancer (NSCLC)

Approved in Brazil as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)

Who Is Running the Clinical Trial?

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Lead Sponsor

Trials

578

Recruited

33,600+

Regeneron Pharmaceuticals

Industry Sponsor

Trials

690

Recruited

948,000+

Founded

1988

Headquarters

Tarrytown, USA

Known For

Precision medicine

Top Products

Dupixent, EYLEA, Libtayo, Praluent

Leonard Schleifer

Regeneron Pharmaceuticals

Chief Executive Officer since 1988

MD and PhD in Medicine

George Yancopoulos

Regeneron Pharmaceuticals

Chief Medical Officer since 1997

MD from Harvard Medical School

Findings from Research

Adjuvant chemotherapy is recommended for patients with stage III colon cancer after R0 resection, with FOLFOX4 or capecitabine as standard treatments, while older regimens like the Mayo scheme should be avoided due to toxicity.

For high-risk stage II colon cancer patients, adjuvant chemotherapy similar to stage III is suggested, although evidence is mainly from subgroup analyses; low-risk patients may benefit from 5-FU based treatments, as shown in the QUASAR trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Adjuvant therapy of colon carcinoma]. Trarbach, T., Kubicka, S., Hacker, U., et al.[2008]

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]

In a study of 49 patients with refractory metastatic colorectal cancer, the sequence of treatment with regorafenib (REG) followed by trifluridine/tipiracil (FTD/TPI) resulted in a median overall survival of 27 months, compared to 20 months for the reverse sequence.

The REG-to-FTD/TPI treatment sequence also demonstrated a higher disease control rate of 45.0%, indicating that this order may be more effective in stabilizing cancer growth compared to the FTD/TPI-to-REG sequence, which had a rate of 24.1%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regorafenib-to-trifluridine/tipiracil Versus the Reverse Sequence for Refractory Metastatic Colorectal Cancer Patients: A Multicenter Retrospective Real-life Experience. Signorelli, C., Gemma, D., Grande, R., et al.[2021]

Regorafenib, an oral multikinase inhibitor, shows dose-dependent growth inhibition in various colorectal cancer cell lines, including those resistant to cetuximab, an anti-EGFR therapy.

Combining regorafenib with cetuximab not only enhances antiproliferative and apoptotic effects in cetuximab-resistant cells but also significantly inhibits tumor growth and prevents metastasis in animal models, suggesting a potential strategy to overcome resistance in metastatic colorectal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Primary and Acquired Resistance of Colorectal Cancer to Anti-EGFR Monoclonal Antibody Can Be Overcome by Combined Treatment of Regorafenib with Cetuximab. Napolitano, S., Martini, G., Rinaldi, B., et al.[2022]

In a study of 33 advanced colorectal cancer patients treated with regorafenib and toripalimab, the combination showed a promising objective remission rate of 12.12% and a disease control rate of 48.48%, indicating potential efficacy in patients who had previously undergone multiple treatments.

The treatment was generally well-tolerated, with the most common adverse reactions being hand-foot syndrome and liver dysfunction, and only 9.09% of patients experienced severe (grade 3/4) adverse reactions, suggesting a manageable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Regorafenib Combined with Toripalimab in the Third-Line and beyond Treatment of Advanced Colorectal Cancer. Yu, W., Tao, Q., Zhang, Y., et al.[2022]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

[Adjuvant therapy of colon carcinoma]. [2008]

2. 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]

3. Greece pubmed.ncbi.nlm.nih.gov

Regorafenib-to-trifluridine/tipiracil Versus the Reverse Sequence for Refractory Metastatic Colorectal Cancer Patients: A Multicenter Retrospective Real-life Experience. [2021]

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

Primary and Acquired Resistance of Colorectal Cancer to Anti-EGFR Monoclonal Antibody Can Be Overcome by Combined Treatment of Regorafenib with Cetuximab. [2022]

5. Egypt pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Regorafenib Combined with Toripalimab in the Third-Line and beyond Treatment of Advanced Colorectal Cancer. [2022]