Esophageal CancerPhase 2NCT06123338
A Study of Pembrolizumab With Trastuzumab and Chemotherapy in People With Esophagogastric Cancer
A Phase 2 study testing Pembrolizumab, Trastuzumab and Oxaliplatin in people with Esophageal Cancer and Gastric Adenocarcinoma, run by Memorial Sloan Kettering Cancer Center at 10 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Esophageal Cancer, Gastric Adenocarcinoma, HER2 Gene Mutation
- What is being tested?
- Pembrolizumab, Trastuzumab and Oxaliplatin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 49 participants
- Where
- 10 sitesUnited States
- Study dates
- 1 Feb 2024to 30 Nov 2027
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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 as defined 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
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- 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 total bilirubin 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 partial thromboplastin time (aPTT): <1.5 x ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants
- Male participants: A male participant must agree to use contraception as detailed in Section 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 from donating sperm during this period.
- Female participants: A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
- Not a woman of childbearing potential (WOCBP) as defined in section 15.3 OR
- A WOCBP who agrees to follow the contraceptive guidance in section 15.3 during the treatment period and for at least 170 days (140 days plus an additional 30 days [menstruation cycle]) after the last dose of study treatment.
Who cannot join
- 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 or echocardiogram. Patients with an ejection fraction 45-49% may be permissible in the absence of any cardiac symptoms, if cleared by a cardiologist, and per the investigator's discresion.
- Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
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- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
- Patients who have received acute, low dose, systemic immunosuppressant medications (e.g., dexamethasone containing antiemetic regimen or steroids as CT scan contrast premedication) may be enrolled.
- The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension or adrenocortical insufficiency is allowed.
- 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 (not including non-melanoma skin cancer)
- Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
- 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 laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 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 pregnancy test will be required.
- Has had an allogeneic tissue or solid organ transplant
- Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease; systemic lupus erythematosus; Wegener syndrome [granulomatosis with polyangiitis]; myasthenia gravis; Graves' disease; rheumatoid arthritis, hypophysitis, uveitis) within the past 3 years prior to the start of treatment. The following are exceptions to this criterion:
- Subjects with vitiligo or alopecia
- Subjects with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone 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 and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.
- Is unwilling to give written informed consent, unwilling to participate, or unable to comply with the protocol for the duration of the study.
Trial locations and contacts
10 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Samuel Cytryn, MD contact
10 sites in 1 country
United States10 sites, 9 recruiting
- Recruiting
Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)
Basking Ridge, New Jersey, 07920
Yelena Janjigian, MD, 646-888-4186
- Recruiting
Massachusetts General Hospital (Data Collection Only)
Boston, Massachusetts, 02114
Samuel Klempner, MD, 617-724-4000
- Recruiting
Memorial Sloan Kettering Suffolk-Commack (Limited protocol activity)
Commack, New York, 11725
Yelena Janjigian, MD, 646-888-4186
- Recruiting
Memorial Sloan Kettering Westchester (Limited Protocol Activities)
Harrison, New York, 10604
Yelena Janjigian, MD, 646-888-4186
- Recruiting
MD Anderson Cancer Center (Data Collection Only)
Houston, Texas, 77030
Jennifer Li, MD, 855-760-5921
- Recruiting
Memorial Sloan Kettering Monmouth (Limited Protocol Activities)
Middletown, New Jersey, 07748
Yelena Janjigian, MD, 646-888-4186
- Recruiting
Memorial Sloan Kettering Bergen (Limited Protocol Activities)
Montvale, New Jersey, 07645
Yelena Janjigian, MD, 646-888-4186
- Recruiting
Memorial Sloan Kettering Cancer Center (All Protocol Activities)
New York, New York, 10065
Yelena Y Janjigian, MD, 646-888-4186
- Active, not recruiting
University of Pennsylvania (Data Collection Only)
Philadelphia, Pennsylvania, 19104
- Recruiting
Memorial Sloan Kettering Nassau (Limited Protocol Activities)
Uniondale, New York, 11553
Yelena Janjigian, MD, 646-888-4186
About this study
Official title: A Single-Arm, Multicenter Phase 2 Study of Neoadjuvant Pembrolizumab With Trastuzumab and Chemotherapy in Resectable HER2+ Esophagogastric Tumors
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.
Read the detailed 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.
- Being tested
- Pembrolizumab, Trastuzumab, Oxaliplatin, Capecitabine, 5-Fluorouracil
- Keywords
- HER2+ Esophageal cancer, Esophageal Cancer, Gastric Adenocarcinoma, HER2+ GEJ cancer, HER2 IHC3+ expression, IHC 2+/FISH>2.0 expression, Esophagogastric cancer, Memorial Sloan Kettering Cancer Center, 23-124
- Medical subject headings
- Esophageal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabDrug
Pembrolizumab will be administered on an every 3-week dosing schedule
TrastuzumabDrug
Trastuzumab will be administered on an every 3-week dosing schedule
OxaliplatinDrug
Oxaliplatin every 3 weeks, +/-7 days
CapecitabineDrug
Capecitabine twice daily on days 1 to 14 every 3 weeks or 5-FU on days 1 to 5 every 3 weeks
5-FluorouracilDrug
5-Fluorouracil administered as a 24 hour IV continuous infusion once every 2 weeks
DocetaxelDrug
Docetaxel administered intravenously once every 2 weeks.
Nutrition questionnaires (optional)Other
will be collected (optionally)
stool and saliva samples (optional)Other
will be collected (optionally)
| Study group | Role | What they receive |
|---|---|---|
| Esophagogastric Cancer | Experimental | Participants will have a diagnosis of resectable HER2+ (IHC 3+ or IHC 2+/FISH ratio >2.0) esophageal, GEJ or gastric cancer. Receives: Drug: Pembrolizumab; Drug: Trastuzumab; Drug: Oxaliplatin; Drug: Capecitabine; Drug: 5-Fluorouracil; Drug: Docetaxel; Other: Nutrition questionnaires (optional); Other: stool and saliva samples (optional) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Event-free survival (EFS)
EFS is defined as the time from start of treatment to time of disease progression, recurrence, or death, whichever occurs first.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Nov 2023
- Study start1 Feb 2024
- Primary completion30 Nov 2027 (estimated)
- Study completion30 Nov 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Esophageal CancerStudies of the same condition, open and under way.
- More trials run by Memorial Sloan Kettering Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- This is a single-arm phase 2 study in which patients with resectable HER2-positive EGC will receive peri-operative trastuzumab and pembrolizumab in combination with chemotherapy.
- Masking
- None (open label)
- Enrolment
- 49 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Genentech, Inc., Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- Yelena Janjigian, MD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06123338
- Sponsor's protocol ID
- 23-124
- Status last verified
- Oct 2026
- First submitted
- 3 Nov 2023
- Last updated
- 13 Oct 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.