A Study of Pembrolizumab With Trastuzumab and Chemotherapy in People With Esophagogastric Cancer

Last updated: April 16, 2025
Sponsor: Memorial Sloan Kettering Cancer Center
Overall Status: Active - Recruiting

Phase

2

Condition

Esophageal Cancer

Gastric Cancer

Digestive System Neoplasms

Treatment

Oxaliplatin

Docetaxel

5-Fluorouracil

Clinical Study ID

NCT06123338
23-124
  • Ages > 18
  • All Genders

Study Summary

The purpose of this study to find out whether adding trastuzumab and pembrolizumab to standard chemotherapy is an effective treatment for resectable HER2+ esophagogastric cancer.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Age 18 years or older at time of signing informed consent.

  • ECOG performance status 0-1.

  • HER2+ esophageal, GEJ, or gastric adenocarcinoma biopsy or resection specimen asdefined by local HER2 IHC3+ or IHC 2+/FISH>2.0 expression.

  • Complete surgical resection of the primary tumor must be achievable

  • Demonstrate adequate organ function as defined in Table 1.

Table 1 - Organ Function Requirements for Eligibility Hematological

  • Absolute neutrophil count (ANC): ≥1,500 /mcL

  • Platelets: ≥100,000 / mcL

  • Hemoglobin: ≥8 g/dL Renal

  • Creatinine clearance: ≥ 50 mL/minute Hepatic

  • Serum total bilirubin: ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with totalbilirubin levels > 1.5 ULN. Except patients with Gilbert's disease (≤3x ULN)

  • AST and ALT: ≤ 2.5 X ULN

  • Albumin: >3 mg/dL Coagulation

  • International normalized ratio (INR) OR prothrombin time (PT) Activated partialthromboplastin time (aPTT): <1.5 x ULN unless participant is receiving anticoagulanttherapy as long as PT or aPTT is within therapeutic range of intended use ofanticoagulants

  • Male participants: A male participant must agree to use contraception as detailed inSection 15.3 of this protocol during the treatment period and for at least 230 days (5 terminal half-lives of trastuzumab [140] plus an additional 90 days [spermatogenesis cycle]) after the last dose of study treatment and refrain fromdonating sperm during this period.

  • Female participants: A female participant is eligible to participate if she is notpregnant, not breastfeeding, and at least one of the following conditions applies:

  1. Not a woman of childbearing potential (WOCBP) as defined in section 15.3 OR

  2. A WOCBP who agrees to follow the contraceptive guidance in section 15.3 duringthe treatment period and for at least 170 days (140 days plus an additional 30days [menstruation cycle]) after the last dose of study treatment.

Exclusion

Exclusion Criteria:

  • Presence of metastatic or recurrent disease.

  • Has received prior treatment for esophagogastric cancer

  • Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-CTLA-4 agent.

  • Has received prior therapy with an anti-HER2 agent

  • Left ventricular ejection fraction <50% within 1 month of screening by MUGA orechocardiogram. Patients with an ejection fraction 45-49% may be permissible in theabsence of any cardiac symptoms, if cleared by a cardiologist, and per theinvestigator's discresion.

  • Is currently participating and receiving study therapy or has participated in astudy of an investigational agent and received study therapy or used aninvestigational device within 4 weeks of the first dose of treatment.

  • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or anyother form of immunosuppressive therapy within 7 days prior to the first dose oftrial treatment.

  • Patients who have received acute, low dose, systemic immunosuppressant medications (e.g., dexamethasone containing antiemetic regimen or steroids as CT scan contrastpremedication) may be enrolled.

  • The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone)for patients with orthostatic hypotension or adrenocortical insufficiency isallowed.

  • Has a known history of active TB (Bacillus tuberculosis)

  • Hypersensitivity to pembrolizumab or any of its excipients

  • Has been diagnosed or treated for another malignancy in the past 3 years (notincluding non-melanoma skin cancer)

  • Has known active central nervous system (CNS) metastases and/or carcinomatousmeningitis

  • Has known history of, or any evidence of active, non-infectious pneumonitis.

  • Has an active infection requiring systemic therapy.

  • Has a history or current evidence of any condition, therapy, or laboratoryabnormality that might confound the results of the trial, interfere with thesubject's participation for the full duration of the trial, or is not in the bestinterest of the subject to participate, in the opinion of the treating investigator.

  • Has known psychiatric or substance abuse disorders that would interfere withcooperation with the requirements of the trial.

  • Is pregnant or breastfeeding, or expecting to conceive or father children within theprojected duration of the trial, starting with the pre-screening or screening visitthrough 120 days after the last dose of trial treatment.

  • A WOCBP who has a positive urine pregnancy test within 72 hours prior to allocation.If the urine test is positive or cannot be confirmed as negative, a serum pregnancytest will be required.

  • Has had an allogeneic tissue or solid organ transplant

  • Active or prior documented autoimmune or inflammatory disorders (includinginflammatory bowel disease; systemic lupus erythematosus; Wegener syndrome [granulomatosis with polyangiitis]; myasthenia gravis; Graves' disease; rheumatoidarthritis, hypophysitis, uveitis) within the past 3 years prior to the start oftreatment. The following are exceptions to this criterion:

  • Subjects with vitiligo or alopecia

  • Subjects with hypothyroidism (e.g., following Hashimoto syndrome) stable onhormone replacement or psoriasis not requiring systemic treatment.

  • Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).

  • Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).

  • Has received a live vaccine within 30 days of planned start of study therapy. Note:Seasonal influenza vaccines for injection are generally inactivated flu vaccines andare allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are liveattenuated vaccines, and are not allowed.

  • Is unwilling to give written informed consent, unwilling to participate, or unableto comply with the protocol for the duration of the study.

Study Design

Total Participants: 49
Treatment Group(s): 6
Primary Treatment: Oxaliplatin
Phase: 2
Study Start date:
February 01, 2024
Estimated Completion Date:
November 30, 2027

Study Description

Eligible patients will receive 8 peri-operative cycles of pembrolizumab and trastuzumab with chemotherapy (fluoropyrimidine/oxaliplatin doublet for patients initially enrolled and subsequently FLOT [5-fluorouracil, oxaliplatin and docetaxel] followed by pembrolizumab and trastuzumab maintenance to complete 1 total year of therapy.

Connect with a study center

  • Johns Hopkins University (Data Collection Only)

    Baltimore, Maryland 21287
    United States

    Site Not Available

  • Massachusetts General Hospital (Data Collection Only)

    Boston, Massachusetts 02114
    United States

    Active - Recruiting

  • Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)

    Basking Ridge, New Jersey 07920
    United States

    Active - Recruiting

  • Memorial Sloan Kettering Monmouth (Limited Protocol Activities)

    Middletown, New Jersey 07748
    United States

    Active - Recruiting

  • Memorial Sloan Kettering Bergen (Limited Protocol Activities)

    Montvale, New Jersey 07645
    United States

    Active - Recruiting

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

    Commack, New York 11725
    United States

    Site Not Available

  • Memorial Sloan Kettering Suffolk-Commack (Limited protocol activity)

    Commack, New York 11725
    United States

    Active - Recruiting

  • Memorial Sloan Kettering Westchester (Limited Protocol Activities)

    Harrison, New York 10604
    United States

    Active - Recruiting

  • Memorial Sloan Kettering Cancer Center (All Protocol Activities)

    New York, New York 10065
    United States

    Active - Recruiting

  • Memorial Sloan Kettering Nassau (Limited Protocol Activities)

    Uniondale, New York 11553
    United States

    Active - Recruiting

  • University of Pennsylvania (Data Collection Only)

    Philadelphia, Pennsylvania 19104
    United States

    Active - Recruiting

  • MD Anderson Cancer Center (Data Collection Only)

    Houston, Texas 77030
    United States

    Active - Recruiting

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