Adagrasib + Cetuximab + Cemiplimab for Colorectal Cancer

Recruiting in Palo Alto (17 mi)

+1 other location

Overseen by Christine Parseghian

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Immunosuppressants, Corticosteroids, Proton pump inhibitors, others

Disqualifiers: Immunodeficiency, Autoimmune disease, Brain metastases, others

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

To learn if the drug combination of adagrasib, cetuximab, and cemiplimab can help to control metastatic CRC with KRAS G12C mutations.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications at least 7 days before starting the study drugs. If you are on medications that affect heart rhythm, are processed by specific liver enzymes, or are proton pump inhibitors, you may need to switch to alternatives 10 days before the study.

What data supports the effectiveness of the drug combination Adagrasib, Cetuximab, and Cemiplimab for colorectal cancer?

Research shows that Cetuximab, one of the drugs in the combination, is effective in treating metastatic colorectal cancer, especially in patients with specific genetic markers. It works by helping the immune system target and kill cancer cells, which has been shown to improve patient outcomes. ^{1 2 3 4 5}

What safety information is available for Cetuximab in treating colorectal cancer?

Cetuximab, used for treating colorectal cancer, has been found to have an acceptable level of safety with manageable side effects. Common side effects include skin reactions like acne, hand-foot syndrome, and nail infections, as well as low calcium and magnesium levels, mouth sores, and digestive issues. ^{1 2 6 7 8}

What makes the drug combination of Adagrasib, Cetuximab, and Cemiplimab unique for colorectal cancer?

This drug combination is unique because it combines Adagrasib, a KRAS inhibitor, with Cetuximab, an EGFR-targeting antibody, and Cemiplimab, an immune checkpoint inhibitor, potentially offering a multi-faceted approach to treating colorectal cancer by targeting different pathways involved in tumor growth and immune evasion. ^{2 9 10 11 12}

Research Team

Christine Parseghian

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for adults with advanced colorectal cancer that has spread, specifically those with a KRAS G12C mutation. Participants must have had at least one prior chemotherapy treatment and be able to take oral medication. They should not have serious illnesses or conditions that could affect the study's results or their ability to participate, including certain infections or autoimmune diseases.

Inclusion Criteria

My cancer cannot be removed by surgery or has spread.

Presence of measurable disease per RECIST 1.1

I have recovered from previous cancer treatment side effects, except for hair loss and nerve issues caused by oxaliplatin.

Exclusion Criteria

Any serious illness, uncontrolled inter-current illness, psychiatric illness, active or uncontrolled infection, or other medical history, including laboratory results, which, in the investigator's opinion, would be likely to interfere with the participant's participation in the study, or with the interpretation of results

Breast-feeding or planning to breast feed during the study or within 6 months after end of treatment

I have not had major surgery in the last 4 weeks.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lead-In

Participants receive adagrasib at varying doses to determine the recommended dose

4-8 weeks

Expansion

Participants receive adagrasib at the recommended dose along with cetuximab and cemiplimab

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Adagrasib (KRAS G12C Inhibitor)
• Cemiplimab (Checkpoint Inhibitor)
• Cetuximab (Monoclonal Antibodies)

Trial Overview The trial is testing a combination of three drugs: Adagrasib, Cetuximab, and Cemiplimab in patients with metastatic colorectal cancer harboring KRAS G12C mutations. The goal is to see if this drug combo can control the disease better than current treatments.

Participant Groups

Group I: Lead-In Experimental Treatment 3 Interventions

Participants enrolled in the Lead-In phase, the dose of adagrasib participants receive will depend on when the participant join this study. The first group of participants will receive the starting dose level of adagrasib. If intolerable side effects are seen, a second group of participants will be enrolled to receive a lower dose. One (1) of these 2 doses will be chosen as the recommended dose of adagrasib.

Group II: Expansion Experimental Treatment 3 Interventions

Participants enrolled in the Expansion phase, participants will receive adagrasib at the recommended dose that was found in the Lead-In phase.

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Massachusetts General Hospital Cancer Center Boston, MA

MD Anderson Cancer Center Houston, TX

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3107

Patients Recruited

1,813,000+

Findings from Research

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FcγR and EGFR polymorphisms as predictive markers of cetuximab efficacy in metastatic colorectal cancer. Inoue, Y., Hazama, S., Iwamoto, S., et al.[2021]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab, irinotecan and fluorouracile in fiRst-line treatment of immunologically-selected advanced colorectal cancer patients: the CIFRA study protocol. Ottaiano, A., Scala, S., Normanno, N., et al.[2020]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polymorphisms within Immune Regulatory Pathways Predict Cetuximab Efficacy and Survival in Metastatic Colorectal Cancer Patients. Volz, NB., Hanna, DL., Stintzing, S., et al.[2020]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Panitumumab Plus Irinotecan and Cetuximab Plus Irinotecan for KRAS Wild-type Metastatic Colorectal Cancer. Yamaguchi, T., Iwasa, S., Nagashima, K., et al.[2018]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-Density of FcγRIIIA+ (CD16+) Tumor-Associated Neutrophils in Metastases Improves the Therapeutic Response of Cetuximab in Metastatic Colorectal Cancer Patients, Independently of the HLA-E/CD94-NKG2A Axis. Denis Musquer, M., Jouand, N., Pere, M., et al.[2021]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab as salvage monotherapy in chemotherapy-refractory metastatic colorectal cancer: A single-center report. Mekata, E., Endo, Y., Sonoda, H., et al.[2021]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genome wide association study to identify predictors for severe skin toxicity in colorectal cancer patients treated with cetuximab. Baas, J., Krens, L., Bohringer, S., et al.[2020]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Japanese post-marketing surveillance of cetuximab (Erbitux®) in patients with metastatic colorectal cancer. Ishiguro, M., Watanabe, T., Yamaguchi, K., et al.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab: appraisal of a novel drug against colorectal cancer. Hildebrandt, B., le Coutre, P., Nicolaou, A., et al.[2019]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab: a guide to its use in combination with FOLFIRI in the first-line treatment of metastatic colorectal cancer in the USA. Lyseng-Williamson, KA.[2021]

Cetuximab has demonstrated significant efficacy in treating metastatic colorectal cancer, achieving a partial response in 10.8% of patients receiving it alone and 22.9% when combined with irinotecan, based on a Phase III trial involving 329 patients.

The drug is generally well tolerated, with common side effects like acnelike rash and hypersensitivity reactions, but the lack of reliable predictive markers for patient selection remains a challenge for its clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab: an epidermal growth factor receptor monoclonal antibody for the treatment of colorectal cancer. Wong, SF.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fc gamma receptor polymorphisms as predictive markers of Cetuximab efficacy in epidermal growth factor receptor downstream-mutated metastatic colorectal cancer. Rodríguez, J., Zarate, R., Bandres, E., et al.[2022]

References

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

FcγR and EGFR polymorphisms as predictive markers of cetuximab efficacy in metastatic colorectal cancer. [2021]

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

Cetuximab, irinotecan and fluorouracile in fiRst-line treatment of immunologically-selected advanced colorectal cancer patients: the CIFRA study protocol. [2020]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Polymorphisms within Immune Regulatory Pathways Predict Cetuximab Efficacy and Survival in Metastatic Colorectal Cancer Patients. [2020]

4. Greece pubmed.ncbi.nlm.nih.gov

Comparison of Panitumumab Plus Irinotecan and Cetuximab Plus Irinotecan for KRAS Wild-type Metastatic Colorectal Cancer. [2018]

5. Switzerland pubmed.ncbi.nlm.nih.gov

High-Density of FcγRIIIA+ (CD16+) Tumor-Associated Neutrophils in Metastases Improves the Therapeutic Response of Cetuximab in Metastatic Colorectal Cancer Patients, Independently of the HLA-E/CD94-NKG2A Axis. [2021]

6. Greece pubmed.ncbi.nlm.nih.gov

Cetuximab as salvage monotherapy in chemotherapy-refractory metastatic colorectal cancer: A single-center report. [2021]

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

Genome wide association study to identify predictors for severe skin toxicity in colorectal cancer patients treated with cetuximab. [2020]

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

A Japanese post-marketing surveillance of cetuximab (Erbitux®) in patients with metastatic colorectal cancer. [2022]

9. Germany pubmed.ncbi.nlm.nih.gov

Cetuximab: appraisal of a novel drug against colorectal cancer. [2019]

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

Cetuximab: a guide to its use in combination with FOLFIRI in the first-line treatment of metastatic colorectal cancer in the USA. [2021]

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

Cetuximab: an epidermal growth factor receptor monoclonal antibody for the treatment of colorectal cancer. [2022]

12. England pubmed.ncbi.nlm.nih.gov

Fc gamma receptor polymorphisms as predictive markers of Cetuximab efficacy in epidermal growth factor receptor downstream-mutated metastatic colorectal cancer. [2022]