31 Participants Needed

Adagrasib + Cetuximab + Cemiplimab for Colorectal Cancer

Recruiting at 1 trial location
CP
Overseen ByChristine Parseghian, MD
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Breakthrough TherapyThis drug has been fast-tracked for approval by the FDA given its high promise

What You Need to Know Before You Apply

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 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.12345

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.36789

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.23101112

Who Is on the Research Team?

Christine M. Parseghian | MD Anderson ...

Christine Parseghian

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

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.
See 11 more

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.
See 10 more

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

  • Adagrasib
  • Cemiplimab
  • Cetuximab
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.
How Is the Trial Designed?
2Treatment groups
Experimental Treatment
Group I: Lead-InExperimental Treatment3 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: ExpansionExperimental Treatment3 Interventions
Participants enrolled in the Expansion phase, participants will receive adagrasib at the recommended dose that was found in the Lead-In phase.

Adagrasib is already approved in United States, European Union for the following indications:

🇺🇸
Approved in United States as Krazati for:
  • KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC)
  • KRAS G12C-mutated locally advanced or metastatic colorectal cancer
🇪🇺
Approved in European Union as Krazati for:
  • KRAS G12C mutation non-small cell lung cancer

Find a Clinic Near You

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials
3,107
Recruited
1,813,000+

Published Research Related to This Trial

In a study of 57 patients with KRAS wild-type metastatic colorectal cancer, those with the EGFR CA repeat genotype of 36 or more showed a trend towards longer overall survival when treated with cetuximab and FOLFIRI, suggesting a potential genetic influence on treatment outcomes.
The presence of specific FcγR haplotypes (131H and 158V alleles) was linked to a lower response rate to cetuximab, indicating that genetic variations may affect the efficacy of this treatment in mCRC patients.
FcγR and EGFR polymorphisms as predictive markers of cetuximab efficacy in metastatic colorectal cancer.Inoue, Y., Hazama, S., Iwamoto, S., et al.[2021]
The CIFRA study is investigating the effectiveness of cetuximab combined with irinotecan and fluorouracil in patients with metastatic colorectal cancer who have a specific genetic profile (FcγRIIIa V/V), which may enhance the drug's action through a mechanism called Antibody-Dependent Cell-mediated Cytotoxicity (ADCC).
This phase II trial aims to determine if patients with the FcγRIIIa V/V genotype have a higher response rate to cetuximab, potentially improving treatment outcomes, while also assessing safety and survival metrics.
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]
In a study of 924 patients with metastatic colorectal cancer, those with the CD24 rs52812045 A/A genotype experienced significantly shorter progression-free survival (PFS) and overall survival (OS) when treated with cetuximab-based regimens, indicating that this genetic variant may predict poorer outcomes.
The findings suggest that CD24 genetic variants could be used to identify patients who are more likely to benefit from cetuximab therapy, potentially guiding personalized treatment strategies.
Polymorphisms within Immune Regulatory Pathways Predict Cetuximab Efficacy and Survival in Metastatic Colorectal Cancer Patients.Volz, NB., Hanna, DL., Stintzing, S., et al.[2020]

Citations

FcγR and EGFR polymorphisms as predictive markers of cetuximab efficacy in metastatic colorectal cancer. [2021]
Cetuximab, irinotecan and fluorouracile in fiRst-line treatment of immunologically-selected advanced colorectal cancer patients: the CIFRA study protocol. [2020]
Polymorphisms within Immune Regulatory Pathways Predict Cetuximab Efficacy and Survival in Metastatic Colorectal Cancer Patients. [2020]
Comparison of Panitumumab Plus Irinotecan and Cetuximab Plus Irinotecan for KRAS Wild-type Metastatic Colorectal Cancer. [2018]
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]
Cetuximab as salvage monotherapy in chemotherapy-refractory metastatic colorectal cancer: A single-center report. [2021]
Genome wide association study to identify predictors for severe skin toxicity in colorectal cancer patients treated with cetuximab. [2020]
A Japanese post-marketing surveillance of cetuximab (Erbitux®) in patients with metastatic colorectal cancer. [2022]
Cetuximab: appraisal of a novel drug against colorectal cancer. [2019]
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 Statespubmed.ncbi.nlm.nih.gov
Cetuximab: an epidermal growth factor receptor monoclonal antibody for the treatment of colorectal cancer. [2022]
Fc gamma receptor polymorphisms as predictive markers of Cetuximab efficacy in epidermal growth factor receptor downstream-mutated metastatic colorectal cancer. [2022]
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