Trastuzumab Deruxtecan to Treat HER2 + Newly Diagnosed Metastatic GI Cancers

NCT07126561 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: IRB25-1217
• Study Type: interventional
• Target: 43
• Locations: 0 countries
• Sites: N/A

Brief Summary

Purpose: This clinical trial is designed to evaluate the safety and effectiveness of Trastuzumab Deruxtecan for patients with HER2 Positive Newly Diagnosed Metastatic Esophageal, Gastric, GEJ Cancer. The goal is to determine how well this treatment works and to identify any potential side effects. Who Can Participate: We are looking for Participants with histologically confirmed HER2 positive locally advanced unresectable and/or metastatic esophageal, gastric or GEJ adenocarcinoma with an ECOG PS of 2 and measurable disease according to RECIST 1.1 within 42 days prior to registration. Participants will be carefully screened to ensure they meet the study requirements. What to Expect: Participants will undergo 6.4mg/kg, IV infusion of Trastuzumab deruxtucan over the course of the study. They will receive detailed information about the study and will have the opportunity to ask questions before deciding to participate. Informed consent will be obtained to ensure that participants understand the study's purpose, procedures, risks, and benefits. Safety Monitoring: The health and safety of participants are our top priority. An Independent Data and Safety Monitoring Committee (DSMC) will regularly review the study data to ensure participant safety and to monitor for any adverse events. Any serious side effects will be reported and addressed promptly. Benefits and Risks: While the study aims to provide potential benefits, such as improved treatment options for HER2 Positive Newly Diagnosed Metastatic Esophageal, Gastric, GEJ Cancer there may also be risks involved. Participants will be informed of all possible risks before enrolling in the study. Confidentiality: All personal information will be kept confidential, and data will be used only for research purposes. Contact Information: For more information about this study, please contact PhaseIICRA@medicine.bsd.uchicago.edu

Conditions

HER2 Positive Newly Diagnosed Metastatic Esophageal, Gastric, GEJ Cancer Patients With an ECOG Performance Status of 2

Keywords

HER2; TRASTUZUMAB; DERUXTECAN; METASTATIC; CANCER; ESOPHAGEAL; GASTRIC; GEJ

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate

  The overall response rate (ORR) of participants with an Eastern Cooperative Oncology Group performance status (PS) of 2 who receive single-agent trastuzumab deruxtecan as determined by the treating investigator using RECIST 1.1.

  12 months

Secondary Outcomes (5)

• Percentage of Study Participants with Toxic Side Effects in Response to Trastuzumab Deruxtecan

  12 months

• Overall Survival

  12 months

• Progression Free Survival

  12 months

• Disease Control Rate

  12 months

• Duration of Response

  12 months

Study Arms (1)

multicenter single-arm phase II open label trial of Trastuzumab Deruxtecan (Enhertu, DS-8210).

EXPERIMENTAL

Drug: Trastuzumab Deruxtecan

Interventions

Trastuzumab Deruxtecan DRUG

Do not substitute trastuzumab deruxtecan with trastuzumab or ado-trastuzumab emtansine. Do not administer as an intravenous push or bolus. Trastuzumab deruxtecan is not compatible with sodium chloride 0.9% solution for infusion. During treatment, patients should be observed for infusion-related reactions (IRRs). For additional information on the management of IRRs

multicenter single-arm phase II open label trial of Trastuzumab Deruxtecan (Enhertu, DS-8210).

Eligibility Criteria

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

You may qualify if:

• Participants must agree to provide written informed consent and HIPAA authorization for release of personal health information prior to registration.
• NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
• Participants must be ≥ 18 years of age at the time of consent.
• Participants must have histologically confirmed locally advanced unresectable and/or metastatic esophageal, gastric or GEJ adenocarcinoma per AJCC, 8th edition.
• Participants must have measurable disease according to RECIST 1.1 within 42 days prior to registration.
• Participants must have an ECOG PS of Grade 2 within 28 days prior to registration.
• Participants must NOT be candidates for combination therapy per treating provider judgement.
• Participants must have HER2 protein overexpression or HER2 gene amplification in tumor tissue (preferred on tumor tissue biopsy if available) or liquid biopsy. (Note: HER2 levels considered positive Score 3+ on IHC, Score of 2+ with positive results of FISH)
• Prior definitive chemoradiation therapy for localized disease, systemic therapy including immunotherapy in the adjuvant setting is allowed.
• Prior cancer treatment in the adjuvant setting must be completed at least 3 months prior to registration and the participant must have recovered from all reversible acute toxic effects of the regimen (other than alopecia) to Grade ≤ 1 or baseline.
• Participants must demonstrate adequate organ and bone marrow function within 28 days before registration as described in the table below. Organ and bone marrow function criteria must also be met when laboratory tests are repeated within 3 days before Cycle 1 Day 1.
• Females of childbearing potential must have a negative serum pregnancy test within 7 days prior to registration. 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 and urine beta-human chorionic gonadotropin (β-HCG) pregnancy test prior to each administration of IMP.
• Women of childbearing potential are defined as those who are not surgically sterile (i.e. underwent bilateral salpingectomy, bilateral oophorectomy, or complete hysterectomy) or post-menopausal. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause.
• Females of childbearing potential who are sexually active with a male able to father a child must be willing to abstain from penile-vaginal intercourse or must use at least one highly effective method of contraception from the time of first exposure to study intervention until 7 months after the final dose. They must also refrain from breastfeeding or donating ova /retrieving ova for their own use for the same time period.
• Males able to father a child who are sexually active with female of childbearing potential must be willing to abstain from penile-vaginal intercourse or must use at least one highly effective method of contraception from the time of first exposure to study intervention until 4 months after the final dose. They must also refrain from freezing or donating sperm during the same time period.

You may not qualify if:

• Prior systemic therapy in the metastatic setting is not allowed, including no prior HER2-directed therapy. However, prior palliative radiation therapy is allowed.
• Participants who are eligible for combination therapy are excluded.
• Participants who are mismatch repair (MMR) deficient and/or MSI High as determined by institutional standards are not eligible for this study.
• Participants who have an LVEF \<50% within 28 days before first exposure to study drug are not eligible for this study.
• Participants who have unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to Grade ≤1 or baseline are excluded.
• NOTE: Participants may be enrolled with chronic, stable Grade 2 toxicities (defined as no worsening to \>Grade 2 for at least 3 months prior to first exposure to study intervention and managed with standard of care treatment) that the investigator deems related to previous anticancer therapy, including:
• Chemotherapy-induced neuropathy
• Fatigue
• Residual toxicities from prior immuno-oncology treatment: Grade 1 or Grade 2 endocrinopathies which may include:
• Hypothyroidism/hyperthyroidism
• Type 1 diabetes
• Hyperglycemia
• Adrenal insufficiency
• Adrenalitis
• Skin hypopigmentation (vitiligo)

Sponsors & Collaborators

• University of Chicago: lead

Related Publications (12)

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MeSH Terms

Conditions

Neoplasm Metastasis; Neoplasms

Interventions

trastuzumab deruxtecan

Condition Hierarchy (Ancestors)

Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Manik Amin, MD

  University of Chicago

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Manik Amin, MD

CONTACT

(773) 702-4400; PhaseIICRA@medicine.bsd.uchicago.edu

University of Chicago CTSO Quality Unit

CONTACT

1-855-702-8222; PhaseIICRA@medicine.bsd.uchicago.edu

Study Design

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

Model Details: Simon's two-stage optimal design

Study Record Dates

• First Submitted: August 11, 2025
• First Posted: August 17, 2025
• Study Start (Estimated): November 1, 2026
• Primary Completion (Estimated): November 1, 2028
• Study Completion (Estimated): November 1, 2028
• Last Updated: January 8, 2026

Record last verified: 2025-07