Colon CancerPhase 1NCT05722327
Phase I Trial of Adagrasib (MRTX849) in Combination With Cetuximab and Irinotecan in Patients With Colorectal Cancer
A Phase 1 study testing MRTX849, Irinotecan and Cetuximab in people with Colon Cancer and Colorectal Cancer, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
To find the recommended dose of MRTX849 that can be given in combination with cetuximab and irinotecan to patients with colorectal cancer that have a mutation (genetic change) called KRAS G12C. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colon Cancer, Colorectal Cancer
- What is being tested?
- MRTX849, Irinotecan and Cetuximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- 6 Dec 2023to 30 Sep 2027
- Phase
- Phase 1
- 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 adenocarcinoma of the colon or rectum with KRASG12C mutation. KRASG12C on ctDNA may also be used as basis of eligibility, with approval from study or site PIs.
- Unresectable or metastatic disease.
- Previously treated with at least two prior chemotherapy regimens for metastatic disease (where a regimen is defined as a unique combination of 5-FU, oxaliplatin, irinotecan, bevacizumab (or biosimilar), capecitabine). A treatment with adjuvant therapy with progression within 6 months of completing therapy would be considered a prior chemotherapy regimen.
- Presence of tumor lesions to be evaluated per RECIST 1.1patients must have measurable disease.
- 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, and because solid tumor malignancies with KRASG12C mutation is rare among patients < 18 years of age, children are excluded from this study.
- Able to take oral medications.
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- Most recent prior systemic therapy (e.g., chemotherapy, immunotherapy or, investigational agent) and radiation therapy discontinued at least 2 weeks before first dose or five half-lives whichever is shorter.
- Recovery from the 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, 109/L)
- Platelet count ≥ 100,000/mm3 (≥ 100, 109/L)
- INR/PTT ≤ 1.5 upper limit of normal (ULN)
- Hemoglobin ≥ 9 g/dL, in the absence of transfusions for at least 2 weeks
- Total bilirubin ≤ 1.5 upper limit of normal (ULN) (if associated with Gilbert's disease or UGT1A1*28 homozygosity, ≤ 3 ULN)
- Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 ULN (if associated with liver metastases ≤5 ULN)
- Estimated creatinine clearance ≥ 60 mL/min by Cockcroft-Gault or CKD-EPI.
- Women of child-bearing potential or men whose partner is a woman of child-bearing potential agree to use contraception while participating in this study, and for 6 months following termination of study treatment.
- Completed informed consent process, including signing of IRB-approved informed consent form.
- Willing and able to comply with clinical trial instructions and requirements.
Who cannot join
- Active brain metastases, unless adequately treated and patient 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).
- Prior treatment with KRASG12C inhibitor + EGFR inhibitor combo
- Patients with carcinomatous meningitis.
- History of significant hemoptysis or hemorrhage within 4 weeks of the first dose, unless resolved or stable.
- Major surgery within 4 weeks of first dose.
- History of intestinal disease or major gastric surgery likely to alter absorption of study treatment.
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- Any of the following cardiac abnormalities:
- Symptomatic or uncontrolled atrial fibrillation or other arrhythmia
- Unstable angina pectoris or myocardial infarction within the last 6 months.
- Congestive heart failure ≥ NYHA Class 3 within the last 6 months.
- QTc > 480 milliseconds.
- LVEF, if known, beyond the allowable window for single-agent MRTX849
- Ongoing need for a medication with any of the following characteristics that cannot be switched to alternative treatment prior to study entry (see Appendix 2): known risk of Torsades de Pointes or QT prolongation; substrate of CYP3A with narrow therapeutic index; strong inducer or inhibitor of CYP3A and/or P-gp; strong inhibitor of BCRP; and proton pump inhibitors.
- Known or suspected presence of another malignancy that could be mistaken for the malignancy under study.
- Known human immunodeficiency virus (HIV) seropositivity or active Hepatitis B or C. Patients treated for hepatitis C with no detectable viral load are permitted.
- 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.
- 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 patient's participation in the study, or with the interpretation of results.
Trial locations and contacts
1 site in 1 country.
About this study
To find the recommended dose of MRTX849 that can be given in combination with cetuximab and irinotecan to patients with colorectal cancer that have a mutation (genetic change) called KRAS G12C.
Read the detailed description
Primary objectives:
- To determine the optimal biological dose (OBD) of MRTX849 when used in combination with cetuximab and irinotecan.
- To evaluate the safety profile of this combination.
- To determine the antitumor activity of this combination in patients with metastatic KRASG12C colorectal cancer.
Exploratory objectives:
- To explore correlations between MRTX849 exposure and patient outcomes such as disease response, objective response rate (ORR), duration or response (DOR), progression-free survival (PFS), overall survival (OS), safety, and pharmacodynamic endpoints.
- To evaluate the utility of detecting KRASG12C mutation in plasma to identify suitable patients.
- To explore potential pharmacodynamic (PD) markers of KRASG12C and EGFR inhibition in tumor tissue and/or blood plasma.
- To explore correlations between baseline tumor biomarkers, gene alterations, and clinical activity/efficacy.
- To define mechanisms of acquired resistance to EGFR and KRASG12C inhibition and evaluate novel strategies to overcome such resistance.
- To assess pharmacokinetics of MRTX849 and irinotecan and key metabolites.
- Conditions
- Colon Cancer, Colorectal Cancer
- Being tested
- MRTX849, Irinotecan, Cetuximab
- Medical subject headings
- Colonic Neoplasms, Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MRTX849Drug
Given by PO (mouth)
IrinotecanDrug
Given by IV (vein)
CetuximabDrug
Also called C225, Erbitux™, MC-C225, MOAB C225
Given by IV (vein)
| Study group | Role | What they receive |
|---|---|---|
| Stage 1 ( MRTX849 and Irinotecan) | Experimental | Participants assigned to Stage 1, participants dose levels of MRTX849 and irinotecan will depend on when the participants joined the study. This study will also test 2 different dosing schedules: concurrent dosing or staggered dosing Receives: Drug: MRTX849; Drug: Irinotecan; Drug: Cetuximab |
| Stage 2 ( MRTX849 and Irinotecan) | Experimental | Participants assigned to Stage 2 will receive MRTX849 and irinotecan at the dose level that was recommended during Stage 1. This study will also test 2 different dosing schedules: concurrent dosing or staggered dosing Receives: Drug: MRTX849; Drug: Irinotecan; Drug: Cetuximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE)
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 posted10 Feb 2023
- Study start6 Dec 2023
- Primary completion30 Sep 2027 (estimated)
- Study completion30 Sep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colon 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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Mirati Therapeutics
- Responsible party
- Sponsor
- Investigators
- David S. Hong, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05722327
- Sponsor's protocol ID
- 2022-0374
- Other IDs
- NCI-2023-01157
- Status last verified
- Aug 2026
- First submitted
- 1 Feb 2023
- Last updated
- 14 Aug 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 14 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Trial of Adagrasib (MRTX849) in Combination With Cetuximab and Irinotecan in Patients With Colorectal Cancer
- ClinicalTrials.gov ID
- NCT05722327
- Acronym / sponsor ID
- 2022-0374
- Conditions
- Colon Cancer, Colorectal Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- Mirati Therapeutics
- Study start
- 6 Dec 2023 (actual)
- Primary completion
- 30 Sep 2027 (estimated)
- Study completion
- 30 Sep 2027 (estimated)
- First posted
- 10 Feb 2023 (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 find the recommended dose of MRTX849 that can be given in combination with cetuximab and irinotecan to patients with colorectal cancer that have a mutation (genetic change) called KRAS G12C.
Detailed description
Primary objectives:
- To determine the optimal biological dose (OBD) of MRTX849 when used in combination with cetuximab and irinotecan.
- To evaluate the safety profile of this combination.
- To determine the antitumor activity of this combination in patients with metastatic KRASG12C colorectal cancer.
Exploratory objectives:
- To explore correlations between MRTX849 exposure and patient outcomes such as disease response, objective response rate (ORR), duration or response (DOR), progression-free survival (PFS), overall survival (OS), safety, and pharmacodynamic endpoints.
- To evaluate the utility of detecting KRASG12C mutation in plasma to identify suitable patients.
- To explore potential pharmacodynamic (PD) markers of KRASG12C and EGFR inhibition in tumor tissue and/or blood plasma.
- To explore correlations between baseline tumor biomarkers, gene alterations, and clinical activity/efficacy.
- To define mechanisms of acquired resistance to EGFR and KRASG12C inhibition and evaluate novel strategies to overcome such resistance.
- To assess pharmacokinetics of MRTX849 and irinotecan and key metabolites.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Stage 1 ( MRTX849 and Irinotecan) | Experimental | Drug: MRTX849, Drug: Irinotecan, Drug: CetuximabParticipants assigned to Stage 1, participants dose levels of MRTX849 and irinotecan will depend on when the participants joined the study. This study will also test 2 different dosing schedules: concurrent dosing or staggered dosing |
| Stage 2 ( MRTX849 and Irinotecan) | Experimental | Drug: MRTX849, Drug: Irinotecan, Drug: CetuximabParticipants assigned to Stage 2 will receive MRTX849 and irinotecan at the dose level that was recommended during Stage 1. This study will also test 2 different dosing schedules: concurrent dosing or staggered dosing |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Histologically confirmed diagnosis of adenocarcinoma of the colon or rectum with KRASG12C mutation. KRASG12C on ctDNA may also be used as basis of eligibility, with approval from study or site PIs.
- Unresectable or metastatic disease.
- Previously treated with at least two prior chemotherapy regimens for metastatic disease (where a regimen is defined as a unique combination of 5-FU, oxaliplatin, irinotecan, bevacizumab (or biosimilar), capecitabine). A treatment with adjuvant therapy with progression within 6 months of completing therapy would be considered a prior chemotherapy regimen.
- Presence of tumor lesions to be evaluated per RECIST 1.1patients must have measurable disease.
- 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, and because solid tumor malignancies with KRASG12C mutation is rare among patients < 18 years of age, children are excluded from this study.
Key exclusion criteria (18 listed)
- Active brain metastases, unless adequately treated and patient 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).
- Prior treatment with KRASG12C inhibitor + EGFR inhibitor combo
- Patients with carcinomatous meningitis.
- History of significant hemoptysis or hemorrhage within 4 weeks of the first dose, unless resolved or stable.
- Major surgery within 4 weeks of first dose.
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 |
|---|---|---|
| MRTX849Given by PO (mouth) | Drug | Stage 1 ( MRTX849 and Irinotecan), Stage 2 ( MRTX849 and Irinotecan) |
| IrinotecanGiven by IV (vein) | Drug | Stage 1 ( MRTX849 and Irinotecan), Stage 2 ( MRTX849 and Irinotecan) |
| CetuximabAlso: C225, Erbitux™, MC-C225, MOAB C225Given by IV (vein) | Drug | Stage 1 ( MRTX849 and Irinotecan), Stage 2 ( MRTX849 and Irinotecan) |
Primary outcome
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE)
Time frame: through study completion; an average of 1 year.
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 14 Aug 2026.
- M D Anderson Cancer CenterLink provided by the sponsor.
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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. This study is not recruiting at the moment.
David S. Hong, MD principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing MRTX849, Irinotecan and Cetuximab in people with Colon Cancer and Colorectal Cancer, run by M.D. Anderson Cancer Center at 1 site 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 20 inclusion and 18 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: under way, not looking for participants, as of the sponsor's last update on 14 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 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.
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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) (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 14 Aug 2026.