Metastatic Colorectal CancerPhase 1/2NCT06412198
A Multicenter Phase 1b/2 Study of Adagrasib, Cetuximab, and Cemiplimab for Metastatic Colorectal Cancer Harboring KRAS G12C Mutations
A Phase 1/2 study testing Cetuximab, Cemiplimab and Adagrasib in people with Metastatic Colorectal Cancer and KRAS G12C Mutations, run by M.D. Anderson Cancer Center at 2 sites in United States.
Trial summary
To learn if the drug combination of adagrasib, cetuximab, and cemiplimab can help to control metastatic CRC with KRAS G12C mutations. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Colorectal Cancer, KRAS G12C Mutations
- What is being tested?
- Cetuximab, Cemiplimab and Adagrasib
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 2 sitesUnited States
- Study dates
- 28 Aug 2024to 1 Mar 2029
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed diagnosis of advanced/metastatic microsatellite stable colorectal cancer with KRASG12C mutation with 1+ prior line(s) of therapy
- Confirmed KRASG12C mutation status. If a molecular profiling report is not available, a representative paraffin-embedded tumor block or a minimum of 10 unstained slides will be requested for retrospective KRASG12C mutation testing.
- Unresectable or metastatic disease.
- Participants must have received at least one prior line of chemotherapy for metastatic disease with progression on treatment or intolerance to therapy.
- Presence of measurable disease per RECIST 1.1
- Willingness to participate in on-study related procedures, including mandatory biopsies (one baseline and one on-treatment biopsy).
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- Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of the proposed combination in patients <18 years of age, children are excluded from this study.
- Able to take oral medications.
- Most recent prior systemic therapy (e.g., chemotherapy, immunotherapy or investigational agent) and radiation therapy discontinued at least 7 days before first dose.
- Recovery from the treatment-related adverse effects of prior therapy at the time of enrollment to ≤ Grade 1 (excluding alopecia and prior oxaliplatin-induced neuropathy).
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Laboratory values within the screening period:
- Absolute neutrophil count ≥ 1,000/mm3 (≥ 1.0 x 109/L)
- Platelet count ≥ 100,000/mm3 (≥ 100 x 109/L)
- Hemoglobin ≥ 9 g/dL, in the absence of transfusions for at least 2 weeks
- Total bilirubin ≤ 1.5x upper limit of normal (ULN) (if associated with Gilbert's disease or UGT1A1*28 homozygosity, ≤ 3x ULN)
- Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0x ULN (if associated with liver metastases ≤5x ULN)
- Calculated creatinine clearance (determined as per Cockcroft-Gault) ≥ 60mL/min at screening
- Completed informed consent process, including signing of IRB-approved informed consent form.
- Willing and able to comply with clinical trial instructions and requirements. Individuals lacking the ability, based on reasonable medical judgment, to understand and appreciate the nature and consequences of participation in this study will not be eligible for participation.
- Participants who are biologically capable of having children and sexually active must agree to use an acceptable method of contraception for the duration of the treatment period and for at least 6 months after the last dose of study treatment. The Investigator will counsel the patient on selection of contraception method and instruct the participant in its consistent and correct use. Examples of acceptable forms of contraception include:
- Oral, inserted, injected or implanted hormonal methods of contraception, provided it has been used for an adequate period of time to ensure effectiveness.
- Correctly placed copper containing intrauterine device (IUD).
- Male condom or female condom used WITH a spermicide.
- Male sterilization with confirmed absence of sperm in the post-vasectomy ejaculate.
- Bilateral tubal ligation or bilateral salpingectomy.
- The Investigator will instruct the participant to call immediately if the selected birth control method is discontinued or if pregnancy is known or suspected.
- Note: Women are considered post-menopausal and/or not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least 6 months ago. In case of any ambiguity, the reproductive status of the woman should be confirmed by hormone level assessment.
Who cannot join
- Prior PD1 or CTLA4 inhibition therapy
- Prior KRASG12C inhibition therapy
- Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
- Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
- Active brain metastases, unless adequately treated and participant is neurologically stable (except for residual symptoms of central nervous system treatment) for at least 2 weeks prior to enrollment without corticosteroids or are on a stable or decreasing dose of ≤ 10 mg daily prednisone (or equivalent)
- Ongoing need for a medication with any of the following characteristics that cannot be switched to alternative treatment within 10 days prior to study entry: known risk of QTc prolongation or Torsades de Pointes; substrate of CYP3A with a narrow therapeutic index; strong inducer or inhibitor of CYP3A and/or P-gp; strong inhibitor of BCRP; strong inhibitor or inducer of CYP2C19; and proton pump inhibitors.
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- Note: one dose of propofol, midazolam, and/or fentanyl under a monitored setting during IR guided biopsies is allowed.
- Pregnancy. Women of child-bearing potential must have a negative serum or urine pregnancy test during screening
- Breast-feeding or planning to breast feed during the study or within 6 months after end of treatment.
- Participants with symptomatic leptomeningeal disease.
- Major surgery within 4 weeks of first dose of any study drug.
- History of intestinal disease or major gastric surgery likely to alter absorption of study treatment, to be determined by the treating physician
- Known human immunodeficiency virus (HIV) infection or acute or chronic hepatitis B (HBV) or C (HCV) infection as tested in a CLIA certified lab using a positive HIV antibody test. For Hepatitis B and C, an antigen that is drawn and positive. Note that the following are permitted:
- Participants treated for HIV with no detectable viral load on current regimen for at least 1 month prior to randomization;
- Note: Please refer to exclusion criteria regarding drug-drug interactions of concomitant anti-HIV agents, and in particular CYP3A substrates.
- Participants with prior HBV infections who are:
- considered to have past or resolved HBV infection, defined as the presence of hepatitis B core antibody [HBcAb] and absence of hepatitis B surface antigen [HBsAg]; or
- considered to be in an inactive HBV carrier state, defined as HBsAg-positive with normal ALT, and HBV DNA < 2,000 IU/mL or < 10,000 copies/mL;
- Note: For participants in an inactive HBV carrier state or with a resolved HBV infection, the risk of HBV reactivation should be considered and the need for anti-HBV prophylaxis prior to randomization should be carefully assessed in accordance with local guidelines.
- Participants treated for HCV with no detectable viral load.
- 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.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites, 2 recruiting
- Recruiting
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, 02114
Ryan Corcoran, MD, 617-726-8599, rbcorcoran@mgb.org
Ryan Corcoran, MD
- Recruiting
MD Anderson Cancer Center
Houston, Texas, 77030
Christine Parseghian, MD, 713-792-2828, GIClinicalTrials@mdanderson.org
Christine Parseghian, MD
About this study
To learn if the drug combination of adagrasib, cetuximab, and cemiplimab can help to control metastatic CRC with KRAS G12C mutations.
Read the detailed description
Primary Objective
- To determine the objective response rate of the adagrasib, cetuximab, and cemiplimab combination for treatment of advanced KRAS G12C MT CRC that has progressed on at least one line of prior systemic chemotherapy.
Secondary Objectives
- To estimate duration of response (DOR), progression free survival (PFS), and overall survival (OS) for the combination of adagrasib, cetuximab, and cemiplimab in participants with advanced KRAS G12C MT CRC that has progressed on at least one line of prior systemic chemotherapy.
- To estimate the safety and tolerability of the combination of adagrasib, cetuximab, and cemiplimab in participants with advanced KRAS G12C MT CRC that has progressed on at least one line of prior systemic chemotherapy.
Exploratory Objectives
- To assess predictive biomarkers of response and resistance to the combination of adagrasib, cetuximab, plus cemiplimab.
- To assess mechanisms of tumor cell adaptation upon treatment with the combination of adagrasib, cetuximab, plus cemiplimab.
- To determine mechanisms of acquired resistance to the combination of adagrasib, cetuximab, plus cemiplimab.
- To assess the effect of the combination of adagrasib, cetuximab plus cemiplimab on the immune tumor microenvironment.
- To generate cell lines and participant derived xenograft (PDX) models from tumor samples.
- Conditions
- Metastatic Colorectal Cancer, KRAS G12C Mutations
- Being tested
- Cetuximab, Cemiplimab, Adagrasib
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CetuximabDrug
Also called ERBITUX
Given by IV
CemiplimabDrug
Given by IV
AdagrasibDrug
Given by PO
| Study group | Role | What they receive |
|---|---|---|
| Lead-In | Experimental | 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. Receives: Drug: Cetuximab; Drug: Cemiplimab; Drug: Adagrasib |
| Expansion | Experimental | Participants enrolled in the Expansion phase, participants will receive adagrasib at the recommended dose that was found in the Lead-In phase. Receives: Drug: Cetuximab; Drug: Cemiplimab; Drug: Adagrasib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and adverse events (AEs)
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
Measured: Through study completion; an average of 1 year.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 May 2024
- Study start28 Aug 2024
- Primary completion1 Mar 2029 (estimated)
- Study completion1 Mar 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Colorectal CancerStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 31 participants (estimated)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Christine Parseghian, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06412198
- Sponsor's protocol ID
- 2023-1002
- Other IDs
- NCI-2024-04127
- Status last verified
- Jun 2026
- First submitted
- 9 May 2024
- Last updated
- 26 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter Phase 1b/2 Study of Adagrasib, Cetuximab, and Cemiplimab for Metastatic Colorectal Cancer Harboring KRAS G12C Mutations
- ClinicalTrials.gov ID
- NCT06412198
- Acronym / sponsor ID
- 2023-1002
- Conditions
- Metastatic Colorectal Cancer, KRAS G12C Mutations
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 31 participants (estimated)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Study start
- 28 Aug 2024 (actual)
- Primary completion
- 1 Mar 2029 (estimated)
- Study completion
- 1 Mar 2029 (estimated)
- First posted
- 14 May 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To learn if the drug combination of adagrasib, cetuximab, and cemiplimab can help to control metastatic CRC with KRAS G12C mutations.
Detailed description
Primary Objective
- To determine the objective response rate of the adagrasib, cetuximab, and cemiplimab combination for treatment of advanced KRAS G12C MT CRC that has progressed on at least one line of prior systemic chemotherapy.
Secondary Objectives
- To estimate duration of response (DOR), progression free survival (PFS), and overall survival (OS) for the combination of adagrasib, cetuximab, and cemiplimab in participants with advanced KRAS G12C MT CRC that has progressed on at least one line of prior systemic chemotherapy.
- To estimate the safety and tolerability of the combination of adagrasib, cetuximab, and cemiplimab in participants with advanced KRAS G12C MT CRC that has progressed on at least one line of prior systemic chemotherapy.
Exploratory Objectives
- To assess predictive biomarkers of response and resistance to the combination of adagrasib, cetuximab, plus cemiplimab.
- To assess mechanisms of tumor cell adaptation upon treatment with the combination of adagrasib, cetuximab, plus cemiplimab.
- To determine mechanisms of acquired resistance to the combination of adagrasib, cetuximab, plus cemiplimab.
- To assess the effect of the combination of adagrasib, cetuximab plus cemiplimab on the immune tumor microenvironment.
- To generate cell lines and participant derived xenograft (PDX) models from tumor samples.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Lead-In | Experimental | Drug: Cetuximab, Drug: Cemiplimab, Drug: AdagrasibParticipants 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. |
| Expansion | Experimental | Drug: Cetuximab, Drug: Cemiplimab, Drug: AdagrasibParticipants enrolled in the Expansion phase, participants will receive adagrasib at the recommended dose that was found in the Lead-In phase. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (28 listed)
- Histologically confirmed diagnosis of advanced/metastatic microsatellite stable colorectal cancer with KRASG12C mutation with 1+ prior line(s) of therapy
- Confirmed KRASG12C mutation status. If a molecular profiling report is not available, a representative paraffin-embedded tumor block or a minimum of 10 unstained slides will be requested for retrospective KRASG12C mutation testing.
- Unresectable or metastatic disease.
- Participants must have received at least one prior line of chemotherapy for metastatic disease with progression on treatment or intolerance to therapy.
- Presence of measurable disease per RECIST 1.1
Key exclusion criteria (21 listed)
- Prior PD1 or CTLA4 inhibition therapy
- Prior KRASG12C inhibition therapy
- Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
- Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
- Active brain metastases, unless adequately treated and participant is neurologically stable (except for residual symptoms of central nervous system treatment) for at least 2 weeks prior to enrollment without corticosteroids or are on a stable or decreasing dose of ≤ 10 mg daily prednisone (or equivalent)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CetuximabAlso: ERBITUXGiven by IV | Drug | Expansion, Lead-In |
| CemiplimabGiven by IV | Drug | Expansion, Lead-In |
| AdagrasibGiven by PO | Drug | Expansion, Lead-In |
Primary outcome
Safety and adverse events (AEs)
Time frame: Through study completion; an average of 1 year.
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jun 2026.
- MD Anderson Cancer CenterLink provided by the sponsor.
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CRC
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Christine Parseghian, MD principal investigator
M.D. Anderson Cancer Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Cetuximab, Cemiplimab and Adagrasib in people with Metastatic Colorectal Cancer and KRAS G12C Mutations, run by M.D. Anderson Cancer Center at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 28 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 26 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Christine Parseghian, MD ((713) 792-2828, GIClinicalTrials@mdanderson.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and adverse events (AEs) (time frame: Through study completion; an average of 1 year.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jun 2026.