Trastuzumab Deruxtecan and Cetuximab for Colorectal Cancer
This study is looking at whether combining two medicines, fam-trastuzumab deruxtecan-nxki (ENHERTU®) and cetuximab, can effectively treat metastatic (spread to other parts of the body) or unresectable (cannot be removed by surgery) colorectal cancer. This is for people whose cancer has low levels of HER2 and has worsened after standard treatments like fluoropyrimidine, oxaliplatin, and irinotecan. If your tumor is MSI-H/MMRd (a type of genetic change), you should have also received a PD-(L)1 directed antibody. The main goal is to see how many people respond to this treatment within one year. The study plans to enroll 27 participants, but its current status is unclear.
- Study design
- This is an interventional study, meaning participants will receive a specific treatment. It aims to enroll 27 participants.
- What's involved
- Not specified in the trial record.
- Compensation
- Not stated in the trial record.
- Follow-up
- The main goal, Overall Response Rate, will be measured for up to one year.
AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.
NCT07691489
A Study of Trastuzumab Deruxtecan (T-DXd) and Cetuximab in People With Colorectal Cancer
Not Yet Recruiting
PHASE2Ages 18+InterventionalTreatmentMemorial Sloan Kettering Cancer CenterInvestigator-initiated
~27 participants
Updated 2026-07-09 on ClinicalTrials.gov
What's tested:Fam-Trastuzumab Deruxtecan-Nxki
At a glance
Recruiting sites
0 of 7 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Overall Response Rate (ORR)
Measured over Up to 1 year
Conditions
NCT07691489
Where you'd take part
This study runs at 7 sites. They're the same protocol — you choose where, and that choice sets who your contact draft is addressed to.
Memorial Sloan Kettering at Basking Ridge (Limited Protocol Activities)
Basking Ridge, New Jerseystudy coordinator listed
Memorial Sloan Kettering at Bergen (Limited Protocol Activities)
Montvale, New Jerseystudy coordinator listed
Memorial Sloan Kettering at Nassau (Limited Protocol Activities)
Uniondale, New Yorkstudy coordinator listed
Memorial Sloan Kettering Cancer Center (All Protocol Activities)
New York, New Yorkstudy coordinator listed
Memorial Sloan Kettering Cancer Center @ Suffolk-Commack (Limited protocol activity)
Commack, New Yorkstudy coordinator listed
Memorial Sloan Kettering Monmouth (Limited Protocol Activities)
Middletown, New Jerseystudy coordinator listed
Memorial Sloan Kettering Westchester (Limited Protocol Activities)
Harrison, New Yorkstudy coordinator listed
Sites open and close at different times, so the status above is per site — it can differ from the study's overall status.
Study leadership
- Rona Yaeger, MD · PRINCIPAL_INVESTIGATOR · Memorial Sloan Kettering Cancer Center
Who to contact
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Eligibility criteria
Inclusion
Have histologically confirmed adenocarcinoma of the colon or rectum that is metastatic and/or unresectable.
Unless otherwise contraindicated, participants must have received regimens containing the following agents: fluoropyrimidine (e.g., 5-fluorouracil or capecitabine), oxaliplatin, irinotecan, and if the tumor is MSI-H/MMRd, a PD-(L)1 directed antibody. There is no maximum number of prior lines of therapy.
Prior anti-HER2 therapies other than T-DXd are allowed, with a washout period of at least 4 weeks.
Prior anti-EGFR therapies, including cetuximab, are allowed, with a washout period of at least 4 weeks.
Have progression of unresectable or metastatic CRC after last systemic therapy (as confirmed by Investigator) or be intolerant of last systemic therapy.
Participants with KRAS/NRAS or BRAF-mutant colorectal tumors are eligible.
Willing and able to undergo baseline tumor biopsy, preferably of a lesion that has progressed since the last treatment, if feasible.
Have confirmed HER2-low mCRC, defined in this study by having tumor tissue tested at a CLIA-certified laboratory as HER2 IHC 1+ or 2+, as determined by Ventana's PATHWAY anti-HER2 (clone 4B5), an FDA-approved assay following the package insert's interpretational manual for gastric cancer, regardless of amplification by FISH. Archival tissue may be used for determination of HER2 status as long as tissue was obtained after last dose of most recent HER2-targeted therapy, if applicable.
Have radiographically measurable disease according to RECIST v1.1, with at least one site of disease that is measurable and that has not been previously irradiated. If the participant has had previous radiation to the target lesion(s), there must be evidence of progression since radiation.
Age ≥18 years on the day of signing informed consent.
Have an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1.
Have parameters demonstrating adequate organ function, as defined below, obtained ≤14 days prior to the first study treatment, unless otherwise noted:
Have adequate treatment washout before enrollment (study treatment) as defined below:
Evidence of post-menopausal status or negative serum pregnancy test for females of childbearing potential (Section 6.3) who are sexually active with a non-sterilized male partner. For women of childbearing potential, a negative result for serum pregnancy test (test must have a sensitivity of at least 25 mIU/mL) must be available at the screening visit.
Male and female participants of reproductive/childbearing potential (Section 6.3) must agree to use a highly effective form of contraception or avoid intercourse during and upon completion of the study and for at least 7 months for females and 4 months for males after the last dose of study drug. Oral contraception alone is not acceptable; additional barrier methods in conjunction with spermicide must be used. Methods considered as highly effective methods of contraception include:
Male participants must not freeze or donate sperm starting at Screening and throughout the study period, and at least 4 months after the final study drug administration. Preservation of sperm should be considered prior to enrollment in this study.
Female participants must not donate, or retrieve for their own use, ova from the time of Screening and throughout the study treatment period, and for at least 7 months after the final study drug administration.
Participants who are blood donors should not donate blood during the study and for 4 months following the last dose of study drug.
Patient or legally authorized representative (LAR) willing and able to sign informed consent document that has been approved by an IRB prior to initiation of any study-related tests or procedures that are not part of standard of care for the participant's disease.
Willing and able to comply with protocol visits and procedures.
Exclusion
Involvement in the planning and/or conduct of the study (applies to both Investigator staff and/or staff at the study site).
Previous enrollment in the present study.
Currently participating in another interventional clinical trial.
Clinically significant cardiopulmonary disease, such as:
Any concomitant medications that are known to be associated with Torsades de Pointes or potent inducers of cytochrome P450 3A4 (CYP3A4).
Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals.
A pleural effusion, ascites, or pericardial effusion that requires drainage, peritoneal shunt, or Cell-free and Concentrated Ascites Reinfusion Therapy (CART).
History of severe hypersensitivity reactions to either the drug substances or inactive ingredients in the drug product(s).
History of severe hypersensitivity reactions to other monoclonal antibodies.
History of tick bite(s).
History of allergy to red meat.
Any toxicity related to prior anticancer therapies that has not resolved to ≤ Grade 1, with the following exceptions:
Clinically significant corneal disease in the opinion of the Investigator.
Spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. Participants with clinically inactive brain metastases may be included in the study. Participants with treated brain metastases that are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants may be included in the study if they have recovered from the acute toxic effect of radiotherapy. A minimum of 2 weeks must have elapsed between the end of definitive treatment (4 weeks if surgery) and study enrollment.
History of another malignancy within 3 years before the first dose of study drug, or any evidence of residual disease from a previously diagnosed malignancy. Exceptions are malignancies with a negligible risk of metastasis or death (e.g. 5-year OS ≥90%), such as adequately treated carcinoma in-situ of the cervix, adequately resected non-melanoma skin cancer, localized prostate cancer, ductal carcinoma in-situ of the breast, or stage I uterine cancer). Cases should be reviewed by the study Principal Investigator.
Substance abuse or any other medical conditions that would increase the safety risk to the participant or interfere with participation of the participant or evaluation of the clinical study in the opinion of the Investigator.
Anticipated need for major surgical procedure during the course of the study.
Positive hepatitis B surface antigen or core antibody at screening.
Known to have active hepatitis C infection (positive by polymerase chain reaction or on antiviral therapy for hepatitis C within the last 6 months). Participants who have been treated for hepatitis C infection are eligible if they have documented sustained virologic response of 12 weeks.
Known to be positive for human immunodeficiency virus (HIV). Participants should be tested for HIV prior to enrollment if required by local regulations or IRB/Ethics Committee (EC).
Prior treatment with an ADC which consists of an exatecan derivative that is a topoisomerase I inhibitor.
Receipt of live, attenuated vaccine (mRNA and replication deficient adenoviral vaccines are not considered attenuated live vaccines) within 30 days prior to the first dose of T-DXd. Note: Participants, if enrolled, should not receive live vaccine during the study and up to 30 days after the last dose of Investigational Product.
Pregnant (confirmed with positive pregnancy test), breastfeeding, or planning a pregnancy.
Social, familial, or geographical factors that would interfere with study participation or follow-up
Anyone born female who has experienced menarche and who has not undergone surgical sterilization (e.g. hysterectomy, bilateral salpingectomy, bilateral oophorectomy) or has not completed menopause. Menopause is defined clinically as 12 months of amenorrhea in a person born female over age 45 in the absence of other biological, physiological, or pharmacological causes.
Anyone born male who has testes and who has not undergone surgical sterilization (e.g. vasectomy followed by a clinical test proving that the procedure was effective).
What this trial measures
- Overall Response Rate (ORR)Up to 1 year
To determine the objective response rate (ORR), as per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1, of T-DXd + cetuximab in participants with HER2-low mCRC that has progressed on standard therapies.