Adjuvant Trastuzumab Deruxtecan (Enhertu) & Nivolumab For Patients Who Are Disease Free After Completion of Trimodality Treatment For HER-2+ Cancers of Esophagus & Gastroesophageal Junction

NCT05480384 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: BrUOG 413
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 2

Brief Summary

An open label phase II study to determine the safety and preliminary efficacy of the combination of 1-year of adjuvant trastuzumab deruxtecan and nivolumab for patients with HER2 overexpressing esophagogastric adenocarcinoma who have completed chemoradiation followed by esophagectomy.

Conditions

Esophageal Adenocarcinoma; Esophageal Cancer; HER-2 Protein Overexpression; Gastroesophageal-junction Cancer

Outcome Measures

Primary Outcomes (1)

• Safety of the addition of adjuvant trastuzumab deruxtecan with nivolumab for patients with esophagogastric cancer who have completed trimodality treatment

  Measured by the rates of clinically significant treatment-related grade ≥3 adverse events or pneumonitis.

  First dose of study treatment, through 30-days post last dose of drug, approximately 13 months

Secondary Outcomes (1)

• Disease-free survival with adjuvant trastuzumab deruxtecan & nivolumab after completion of trimodality treatment for HER2+ esophageal cancer.

  First dose of study treatment until time of cancer recurrence or death from any cause, whichever occurs first, maximum of 36 months

Study Arms (3)

Starting Trastuzumab Deruxtecan Dose

EXPERIMENTAL

Trastuzumab deruxtecan, 6.4 mg/kg IV every 3 weeks for 17 doses (12 months)

Drug: Nivolumab; Drug: Trastuzumab deruxtecan

First Trastuzumab Deruxtecan Dose Reduction

EXPERIMENTAL

Trastuzumab deruxtecan, 5.4 mg/kg IV every 3 weeks for 17 doses (12 months)

Drug: Nivolumab; Drug: Trastuzumab deruxtecan

Second Trastuzumab Deruxtecan Dose Reduction

EXPERIMENTAL

Trastuzumab deruxtecan, 4.4 mg/kg IV every 3 weeks for 17 doses (12 months)

Drug: Nivolumab; Drug: Trastuzumab deruxtecan

Interventions

Nivolumab DRUG

Nivolumab, 360 mg IV every 3 weeks for 17 doses (12 months)

Also known as: OPDIVO

First Trastuzumab Deruxtecan Dose Reduction; Second Trastuzumab Deruxtecan Dose Reduction; Starting Trastuzumab Deruxtecan Dose

Trastuzumab deruxtecan DRUG

Given in combination with Nivolumab.

Also known as: ENHERTU

First Trastuzumab Deruxtecan Dose Reduction; Second Trastuzumab Deruxtecan Dose Reduction; Starting Trastuzumab Deruxtecan Dose

Eligibility Criteria

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

You may qualify if:

• Pathologically confirmed primary adenocarcinoma of the esophagus, esophagogastric junction or (Stomach involvement is allowed.).
• HER2 overexpression defined by immunohistochemistry (IHC) 3+ or HER2 amplification by fluorescence in situ hybridization (FISH). This may be defined by local or commercial laboratories
• Completed trimodality treatment with chemoradiation followed by esophagectomy and had an R0 resection but did not achieve a complete pathologic response.
• weeks after esophagectomy.
• Prior to trimodality treatment had stage T1N1-2 M0, T2-3N0-2 M0 disease.
• Age ≥ 18
• ECOG performance status 0-1
• For women of childbearing potential, a negative serum pregnancy test within 7 days prior to registration
• Women of childbearing potential and male participants must practice highly effective form of non-hormonal contraception throughout the study, which is defined as from study screening (ICF) through 2 months post last treatment; Non-sterilised male partners of a woman of childbearing potential must use a male condom plus spermicide (condom alone in countries where spermicides are not approved) throughout this period.
• Ability to understand and the willingness to sign a written informed consent document.
• LVEF ≥ 50% within 28 days before randomization/enrollment.
• Evidence of post-menopausal status or negative serum pregnancy test for females of childbearing potential 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 and urine beta-human chorionic gonadotropin (β-HCG) pregnancy test prior to each administration of treatment. 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.
• Female patients of childbearing potential who are sexually active with a non-sterilized male partner must use at least one highly effective method of contraception, from the time of screening and must agree to continue using such precautions for 7 months after the last dose of treatment. Not all methods of contraception are highly effective. Female patients must refrain from breastfeeding while on study and for 7 months after the last dose of treatment. Complete heterosexual abstinence for the duration of the study and drug washout period is an acceptable contraceptive method if it is line with the patient's usual lifestyle (consideration must be made to the duration of the clinical trial); however, periodic or occasional abstinence, the rhythm method, and the withdrawal method are not acceptable.
• Non-sterilized male patients who are sexually active with a female partner of childbearing potential must use a condom with spermicide from screening to 4 months after the final dose of treatment. Complete heterosexual abstinence for the duration of the study and drug washout period is an acceptable contraceptive method if it is in line with the patient's usual lifestyle (consideration must be made to the duration of the clinical trial); however, periodic or occasional abstinence, the rhythm method, and the withdrawal method are not acceptable. It is strongly recommended for the female partners of a male patient to also use at least one highly effective method of contraception throughout this period. In addition, male patients should refrain from fathering a child, or freezing or donating sperm from the time of enrollment, throughout the study and for 4 months after the last dose of treatment. Preservation of sperm should be considered prior to enrollment in this study.
• Female subjects must not donate, or retrieve for their own use, ova from the time of enrollment and throughout the study treatment period, and for at least 7 months after the final study drug administration. They should refrain from breastfeeding throughout this time. Preservation of ova may be considered prior to enrollment in this study.

You may not qualify if:

• Has substance abuse or any other medical conditions such as clinically significant cardiac or psychological conditions, that may, in the opinion of the investigator, interfere with the subject's participation in the clinical study or evaluation of the clinical study results.
• Patients with a medical history of myocardial infarction (MI) within 6 months before enrollment, symptomatic congestive heart failure (CHF) (New York Heart Association Class II to IV), Subjects with troponin levels above ULN at screening (as defined by the manufacturer), and without any myocardial related symptoms, should have a cardiologic consultation before enrollment to rule out MI.
• Corrected QT interval (QTcF) prolongation to \> 470 msec (females) or \>450 msec (males) based on average of the screening triplicate12-lead ECG.
• History of arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia), which is symptomatic or requires treatment (CTCAE Grade 3), symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia.
• History of (non-infectious) ILD / pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
• 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 COPD, restrictive lung disease, pleural effusion etc.)
• Any autoimmune, connective tissue or inflammatory disorders (e.g. Rheumatoid arthritis, Sjogren's, sarcoidosis etc.) 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 patients who are included in the study.
• Prior pneumonectomy (complete)
• Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals
• Active primary immunodeficiency, known uncontrolled active HIV infection or active hepatitis B or C infection, such as those with serologic evidence of viral infection within 28 days of Cycle 1 Day 1. Subjects with past or resolved hepatitis B virus (HBV) infection who are anti-HBc positive (+) are eligible only if they are HBsAg negative (-).
• Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
• 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 trastuzumab deruxtecan. Note: Patients, if enrolled, should not receive live vaccine during the study and up to 30 days after the last dose of treatment.
• Has unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to Grade ≤ 1 or baseline. Note: Subjects may be enrolled with chronic, stable Grade 2 toxicities (defined as no worsening to \>Grade 2 for at least 3 months prior to \[randomization/enrollment/Cycle 1 Day 1\] and managed with standard of care treatment) that the investigator deems related to previous anticancer therapy, such as:
• Chemotherapy-induced neuropathy
• Fatigue

Sponsors & Collaborators

• Brown University: lead
• AstraZeneca: collaborator

Study Sites (2)

Weill Cornell Medicine/New York-Presbyterian

New York, New York, 10021, United States

Location

Lifespan Cancer Institute

Providence, Rhode Island, 02903, United States

Location

MeSH Terms

Conditions

Adenocarcinoma Of Esophagus; Esophageal Neoplasms

Interventions

Nivolumab; trastuzumab deruxtecan

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Howard Safran, MD

  Lifespan Cancer Institute

  PRINCIPAL INVESTIGATOR

• Manish A Shah, MD

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

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 27, 2022
• First Posted: July 29, 2022
• Study Start: July 14, 2023
• Primary Completion: May 5, 2025
• Study Completion: May 1, 2026
• Last Updated: April 21, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)