Cemiplimab for Colon Cancer

Recruiting at 3 trial locations

Overseen By Michael Overman, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Antiretrovirals, Chemotherapy, Immunosuppressants, others

Disqualifiers: Congestive heart failure, Angina, Arrhythmia, 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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

50 Participants Needed

Trial Summary

What is the purpose of this trial?

To learn if cemiplimab can help to control dMMR colon cancer.

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

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you are receiving other investigational agents, chemotherapy, or targeted therapy for colon cancer.

What makes the drug cemiplimab unique for colon cancer treatment?

Cemiplimab is unique because it is a monoclonal antibody that targets the PD-1 pathway, which helps the immune system recognize and attack cancer cells. This mechanism is different from traditional chemotherapy and other treatments like cetuximab, which targets the epidermal growth factor receptor. ^{1 2 3 4 5}

Research Team

Michael J Overman, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

Adults with localized colon cancer that is dMMR or MSI-H, confirmed by specific tests. They should have a certain level of physical fitness (ECOG 0-1), accessible tumors for endoscopic evaluation, and acceptable blood test results. Women of childbearing potential and men must agree to use contraception during the study and for some time after.

Inclusion Criteria

I am fully active or can carry out light work.

I am 18 years old or older.

My primary tumor can be reached with an endoscope and I agree to have multiple endoscopic exams.

Exclusion Criteria

I have not had any recent treatments within the specified timeframes.

I have recovered from previous cancer treatments, except for mild nerve issues or hair loss.

Immunocompromised patients and those known to be HIV positive without undetectable viral load

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive cemiplimab by vein over about 30 minutes on Day 1 of each 3-week study cycle, up to 8 cycles

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Long-term follow-up

Participants are assessed for organ-sparing rate and non-operative management at 1 year

1 year

Treatment Details

Interventions

• Cemiplimab

Trial Overview The trial is testing Cemiplimab's effectiveness in controlling dMMR colon cancer without surgery. Participants will receive this immunotherapy drug to see if it can manage their cancer by enhancing their immune system's ability to fight tumor cells.

Participant Groups

Group I: Cemiplimab Experimental Treatment 1 Intervention

Participants will receive cemiplimab by vein over about 30 minutes on Day 1 of each 3-week study cycle, up to 8 cycles.

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?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

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

Cetuximab, when used alongside chemotherapy, has been associated with improved survival rates in patients with metastatic colon cancer.

In a reported case, a patient with metastatic colon cancer developed a rare condition called paraneoplastic necrotizing myopathy, which showed possible improvement with cetuximab treatment, even though the cancer itself did not respond to the therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Can cetuximab affect paraneoplastic myopathy? Galani, E., Bonakis, A., Christodoulou, C., et al.[2021]

Temsirolimus enhances the effectiveness of cetuximab in treating colon cancer by reducing the levels of CIP2A, which helps cancer cells resist treatment, thus making them more susceptible to cetuximab.

The study found that temsirolimus not only inhibits CIP2A transcription but also promotes its degradation, and this mechanism is particularly effective in colon cancer cells without the K-ras codon 12 mutation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temsirolimus enhances the efficacy of cetuximab in colon cancer through a CIP2A-dependent mechanism. Wang, HW., Yang, SH., Huang, GD., et al.[2021]

Cetuximab is an effective monoclonal antibody that targets the epidermal growth factor receptor, showing significant clinical efficacy in treating colorectal cancer (CRC) either alone or in combination with chemotherapy.

The combination of cetuximab with chemotherapy is well tolerated, with minimal overlapping toxicities, making it a crucial treatment option for patients with metastatic CRC who do not respond to traditional chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synergy between cetuximab and chemotherapy in tumors of the gastrointestinal tract. Mahtani, RL., Macdonald, JS.[2022]

Pucotenlimab is a monoclonal antibody that targets PD-1, effectively blocking its interaction with PD-L1 and PD-L2, which helps restore immune cell function against various solid tumors.

In July 2022, pucotenlimab received conditional approval in China for treating advanced solid tumors with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) characteristics, particularly after previous therapies have failed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pucotenlimab: First Approval. Dhillon, S.[2022]

In a phase I/II trial involving 55 patients with metastatic colorectal cancer, the combination of napabucasin and pembrolizumab showed promising antitumor activity, particularly in patients with microsatellite instability high (MSI-H) tumors, achieving an immune-related objective response rate (irORR) of 50%.

The treatment was generally well-tolerated, with no dose-limiting toxicities observed at the recommended phase 2 dose of napabucasin (480 mg), although the overall efficacy did not meet the primary endpoint, highlighting the need for further investigation into biomarkers that may influence treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter Phase I/II Trial of Napabucasin and Pembrolizumab in Patients with Metastatic Colorectal Cancer (EPOC1503/SCOOP Trial). Kawazoe, A., Kuboki, Y., Shinozaki, E., et al.[2021]

References

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

Can cetuximab affect paraneoplastic myopathy? [2021]

2. Germany pubmed.ncbi.nlm.nih.gov

Temsirolimus enhances the efficacy of cetuximab in colon cancer through a CIP2A-dependent mechanism. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Synergy between cetuximab and chemotherapy in tumors of the gastrointestinal tract. [2022]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Pucotenlimab: First Approval. [2022]

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

Multicenter Phase I/II Trial of Napabucasin and Pembrolizumab in Patients with Metastatic Colorectal Cancer (EPOC1503/SCOOP Trial). [2021]