Cemiplimab + Fianlimab for Colorectal Cancer

Overseen By Joann Santmyer, RN

Age: 18+

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

33 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two drugs, cemiplimab (an immunotherapy drug) and fianlimab (an experimental treatment), to determine their safety and effectiveness for treating a specific type of colorectal cancer with certain genetic features (mismatch repair deficient or microsatellite unstable). The study targets individuals who are either 70 years or older or not ideal candidates for surgery. Participants should have been diagnosed with localized or locally advanced colorectal cancer and should not have received previous treatments like chemotherapy or radiation. The trial involves two groups: one receiving cemiplimab alone and another receiving both cemiplimab and fianlimab. Participants must be open to regular check-ups with endoscopies and CT scans over 24 months. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

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

Research has shown that cemiplimab is generally well-tolerated. In previous studies, most patients experienced some side effects, but these were usually manageable. Many patients responded well to the treatment, with long-lasting benefits.

Early results for the combination of cemiplimab and fianlimab suggest it is also safe and tolerable. Studies found no new safety issues with this combination, and patients, even those who had tried similar treatments before, managed it well.

Overall, while side effects can occur, current research indicates that the safety of these treatments is acceptable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Cemiplimab and Fianlimab for colorectal cancer because these treatments offer a new approach compared to existing options. Most current therapies focus on chemotherapy or targeted therapy, but Cemiplimab and Fianlimab are immunotherapies that enhance the body's immune response to fight cancer cells. Cemiplimab is a PD-1 inhibitor, which helps prevent cancer cells from evading the immune system, while Fianlimab is an LAG-3 inhibitor that further boosts immune activity against tumors. Together, they have the potential to provide a more targeted and effective treatment by leveraging the immune system's natural ability to combat cancer.

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

Research shows that cemiplimab can help treat certain types of cancer. It is often chosen for advanced cancers because it improves survival when combined with chemotherapy. Studies have found it works well for colon cancer with specific genetic changes. In this trial, some participants will receive cemiplimab alone, while others will receive a combination of cemiplimab and fianlimab. Early research on this combination suggests it enhances the body's ability to fight tumors. Specifically, it has shown better results than cemiplimab alone, increasing the number of patients who respond to treatment and extending the time during which the cancer does not worsen. Together, these treatments may effectively combat colorectal cancer. ^{4 5 6 7 8}

Who Is on the Research Team?

Eric Christenson, MD

Principal Investigator

Sidney Kimmel Comprehensive Cancer Center Johns Hopkins Medical Institution

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

Group I: Cohort C - Cemiplimab Experimental Treatment 1 Intervention

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

Group III: 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

Published Research Related to This Trial

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]

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]

Citations

1. newsroom.regeneron.com newsroom.regeneron.com/news-releases/news-release-details/libtayor-cemiplimab-plus-chemotherapy-results-five-years

Libtayo® (cemiplimab) Plus Chemotherapy Results at Five ... Late-breaking data from exploratory analyses at WCLC show Libtayo plus chemotherapy demonstrates a more than double five-year overall ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11268751/

Real-World Treatment Patterns and Outcomes of Cemiplimab ... Cemiplimab is a preferred systemic treatment option in US guidelines for patients with locally advanced, recurrent, or metastatic CSCC if curative radiation or ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.2503

A phase 1/2 study of REGN7075 in combination with ... A phase 1/2 study of REGN7075 in combination with cemiplimab (cemi) in patients (pts) with advanced solid tumors: Efficacy and safety results.

4. oncodaily.com oncodaily.com/drugs/cemiplimab-rwlc-libtayo

Cemiplimab-rwlc (Libtayo) Updates 2025: Uses in cancer, ... These findings confirm that cemiplimab combined with platinum-based chemotherapy significantly improves survival outcomes compared to ...

5. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-05749

Cemiplimab for the Treatment of Localized dMMR Colon ... This phase II trial tests how well cemiplimab works in treating colon cancer that has not spread to other parts of the body (localized) with mutations.

6. newsroom.regeneron.com newsroom.regeneron.com/news-releases/news-release-details/updated-libtayor-cemiplimab-rwlc-results-reinforce-durable-and

Updated Libtayo® (cemiplimab-rwlc) Results Reinforce ... "The data presented at this meeting offer longer-term results in more than twice as many patients as initially reported for the Phase 2 trial at ASCO last year, ...

7. libtayo.com libtayo.com/high-risk-cscc/study-results

LIBTAYO® (cemiplimab-rwlc) Study Results | High-Risk CSCC Discover study results and possible side effects of the adjuvant treatment of LIBTAYO® (cemiplimab-rwlc) in adults with high-risk CSCC.

8. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK603385/

Clinical Review - Cemiplimab (Libtayo) - NCBI Bookshelf As of the data cut-off date, 88.2% of patients in the cemiplimab arm and 94.2% of patients in the chemotherapy arm had experienced at least 1 treatment-emergent ...