A Study of Trastuzumab Deruxtecan (T-DXd) and Cetuximab in People With Colorectal Cancer

NCT07691489 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 25-120
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 7

Brief Summary

The purpose of this study is find out whether the combination of trastuzumab deruxtecan (T-DXd) and cetuximab is an effective treatment for participants with metastatic and/or unresectable colorectal cancer that expresses low levels of HER2 and that has gotten worse after receiving standard treatment.

Conditions

Adenocarcinoma of the Colon; Adenocarcinoma of the Rectum; Colorectal Cancer

Keywords

Colorectal Cancer; Adenocarcinoma of the Colon; Adenocarcinoma of the Rectum; T-DXd; 25-120; Memorial Sloan Kettering Cancer Center

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  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.

  Up to 1 year

Study Arms (2)

Safety Lead-In

EXPERIMENTAL

This study will begin with a Safety Lead-In of 6-18 participants to assess safety/tolerability of this novel combination and to determine the RP2D.

Drug: Fam-Trastuzumab Deruxtecan-Nxki

Expansion Cohort

EXPERIMENTAL

If at least 1 out of 13 participants in the first stage has a complete or partial response (CR/PR), an additional 14 participants will be enrolled.

Drug: Fam-Trastuzumab Deruxtecan-Nxki

Interventions

Fam-Trastuzumab Deruxtecan-Nxki DRUG

The investigational study drug, fam-trastuzumab deruxtecan-nxki (ENHERTU® ), consists of an antibody component, MAAL-9001, covalently conjugated via a maleimide tetrapeptide linker, to a drug component, MAAA-1181a.

Also known as: T-DXd

Expansion Cohort; Safety Lead-In

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• System / Laboratory value
• Hematologic:
• Absolute neutrophil count (ANC) / ≥1500/mm3 (G-CSF administration is not allowed within 14 days prior to screening assessment of bone marrow function, or at any time after this day and prior to initiation of treatment with study drug) Hemoglobin / ≥9.0 g/dL (Red blood cell transfusion is not allowed within 14 days prior to screening assessment of bone marrow function, or at any time after this day and prior to initiation of treatment with study drug) Platelet count / ≥100,000/mm3 (Platelet transfusion is not allowed within 14 days prior to screening assessment of bone marrow function, or at any time after this day and prior to initiation of treatment with study drug)

You may not qualify if:

• 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:
• History of arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia), which is symptomatic or requires treatment (CTCAE v5.0 ≥ Grade 3), symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. Participants with atrial fibrillation controlled by medication are permitted.
• Congenital long QT syndrome.
• Corrected QT interval (QTcF) prolongation to \>470 msec (females) or \>450 msec (males) based on average of the screening triplicate 12-lead ECG.
• History of QT prolongation associated with other medications that required discontinuation of that medication.
• History of symptomatic congestive heart failure (CHF) (New York Heart Association Class II to IV), left ventricular systolic dysfunction, or decrease in ejection fraction.
• History of myocardial infarction, unstable angina, vascular stenting, angioplasty, or other cardiac surgery within 6 months prior to first dose of study treatment.
• Uncontrolled or poorly controlled hypertension (\>180 mmHg systolic or \>130 mmHg diastolic) despite medical treatment.
• History of non-infectious ILD/pneumonitis that required steroids, current ILD/pneumonitis, or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.
• Severe dyspnea at rest (CTCAE v5.0 ≥ Grade 3) due to complications of advanced malignancy or hypoxia requiring supplemental oxygen therapy.
• Lung-specific intercurrent clinically significant illnesses including, but not limited to, any underlying pulmonary disorder (e.g. pulmonary emboli within three months of the study enrollment, severe asthma, severe chronic obstructive pulmonary disease \[COPD\], restrictive lung disease pleural effusion, etc.).
• Any autoimmune, connective tissue, or inflammatory disorders (including Rheumatoid arthritis, Sjogren's, and sarcoidosis) where there is documented, or a suspicion of pulmonary involvement at the time of screening. Full details of the disorder should be recorded in the eCRF for participants who are included in the study.

Sponsors & Collaborators

• AstraZeneca: collaborator
• Eli Lilly and Company: collaborator
• Memorial Sloan Kettering Cancer Center: lead
• National Institutes of Health (NIH): collaborator

Study Sites (7)

Memorial Sloan Kettering at Basking Ridge (Limited Protocol Activities)

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Monmouth (Limited Protocol Activities)

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering at Bergen (Limited Protocol Activities)

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Cancer Center @ Suffolk-Commack (Limited protocol activity)

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester (Limited Protocol Activities)

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center (All Protocol Activities)

New York, New York, 10065, United States

Location

Memorial Sloan Kettering at Nassau (Limited Protocol Activities)

Uniondale, New York, 11553, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Colorectal Neoplasms; Colonic Neoplasms; Rectal Neoplasms

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Rona Yaeger, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rona Yaeger, MD

CONTACT

646-888-5109; yaegerr@mskcc.org

Andrea Cercek, MD

CONTACT

646-888-4189; cerceka@mskcc.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 2, 2026
• First Posted: July 9, 2026
• Study Start: August 1, 2026
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): June 1, 2029
• Last Updated: July 9, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share

Locations

US (7)