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Combining pembrolizumab, trastuzumab, and chemotherapy for HER2+ esophagogastric cancer

A Single-Arm, Multicenter Phase 2 Study of Neoadjuvant Pembrolizumab With Trastuzumab and Chemotherapy in Resectable HER2+ Esophagogastric Tumors

Phase 2 Interventional Memorial Sloan Kettering Cancer Center · NCT06123338

This study is testing if adding pembrolizumab and trastuzumab to standard chemotherapy can help people with resectable HER2+ esophagogastric cancer do better in their treatment.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment49 (estimated)
Ages18 Years and up
SexAll
SponsorMemorial Sloan Kettering Cancer Center Academic / other
Drugs / interventionstrastuzumab, pembrolizumab, chemotherapy
Locations10 sites (Boston, Massachusetts and 9 other locations)
Trial IDNCT06123338 on ClinicalTrials.gov

What this trial studies

This study aims to evaluate the effectiveness of adding pembrolizumab and trastuzumab to standard chemotherapy for patients with resectable HER2+ esophagogastric cancer. Eligible participants will undergo 8 cycles of peri-operative treatment with these drugs alongside chemotherapy, followed by a year of maintenance therapy. The chemotherapy regimen includes fluoropyrimidine/oxaliplatin and may switch to FLOT (5-fluorouracil, oxaliplatin, and docetaxel) based on initial enrollment. The goal is to determine if this combination improves treatment outcomes compared to standard chemotherapy alone.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with resectable HER2+ esophageal, gastroesophageal junction, or gastric adenocarcinoma.

Not a fit: Patients with non-resectable tumors or those without HER2+ expression may not benefit from this treatment.

Why it matters

Potential benefit: If successful, this treatment could significantly improve survival rates and outcomes for patients with HER2+ esophagogastric cancer.

How similar studies have performed: Other studies have shown promising results with similar combinations of immunotherapy and chemotherapy in HER2+ cancers, indicating potential for success.

Eligibility criteria

Show full inclusion / exclusion criteria 
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 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

* 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:

  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 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.

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 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.
* 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.

Where this trial is running

Boston, Massachusetts and 9 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Esophageal CancerGastric AdenocarcinomaHER2 Gene MutationHER2+ Esophageal cancerHER2+ GEJ cancerHER2 IHC3+ expressionIHC 2+/FISH>2.0 expressionEsophagogastric cancer
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.