Neratinib In Combination With Chemotherapy/Trastuzumab/Pembrolizumab In HER2 Gastroesophageal Cancer

NCT06109467 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: MCC-21917
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to test the effects, both good and bad, of the research study drug Neratinib in combination with Trastuzumab, Pembrolizumab and FOLFOX chemotherapy. This study will also look at the safety of Neratinib in combination with Trastuzumab, Pembrolizumab and FOLFOX in HER2 overexpressing Gastroesophageal cancers.

Conditions

GastroEsophageal Cancer; Gastric Cancer

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  ORR is defined as the best overall response as complete response (CR) + partial response (PR) per RECIST v1.1 criteria. As per RECIST 1.1 criteria, any evidence of response in measurable lesions will be counted toward the calculation of ORR.ORR will be calculated through exact binomial distribution with a 2-sided 95% CI among patients who obtain at least one dose of study drug.

  Up to 24 months

Secondary Outcomes (3)

• Clinical Benefit Rate (CBR)

  Up to 24 months

• Duration of Response

  Up to 24 months

• Overall Survival (OS)

  Up to 24 months

Study Arms (1)

Treatment with Neratinib with Trastuzumab, Pembrolizumb and mFOLFOX

EXPERIMENTAL

All patients will be treated with combination of neratinib with trastuzumab, pembrolizumab and mFOLFOX. All patients will receive standard dose 5FU/oxaliplatin/trastuzumab every 2 weeks. Pembrolizumab 400 mg intravenously will be administered once every 6 weeks. Neratinib will be dosed 240 mg orally daily

Drug: Neratinib; Drug: Trastuzumab; Drug: Oxaliplatin; Drug: 5-Fluorouracil + leucovorin; Drug: Pembrolizumab

Interventions

Neratinib DRUG

All participants will take 240mg neratinib by mouth every day beginning cycle 1 day 1.

Also known as: NERLYNX

Treatment with Neratinib with Trastuzumab, Pembrolizumb and mFOLFOX

Oxaliplatin DRUG

All participants will receive 85mg Oxaliplatin by IV infusion day 1 of each 2 week cycle.

Also known as: Eloxatin

Treatment with Neratinib with Trastuzumab, Pembrolizumb and mFOLFOX

5-Fluorouracil + leucovorin DRUG

All participants will receive 400 mg/m\^2 5-Fluorouracil (5FU)+ 400 mg/m\^2 leucovorin day 1 of each 2 week cycle; 5FU continuous infusions on days 1 and 2 of each 2 week cycle. (5FU + leucovorin may be eliminated from regimen per PI discretion)

Treatment with Neratinib with Trastuzumab, Pembrolizumb and mFOLFOX

Pembrolizumab DRUG

All participants will receive 400mg Pembrolizumab by IV infusion day 1 of every 3rd 2 week cycle.

Also known as: Keytruda

Treatment with Neratinib with Trastuzumab, Pembrolizumb and mFOLFOX

Trastuzumab DRUG

All participants will receive standard dosing (6mg/kg loading dose, 4 mg/kg subsequent doses) of Trastuzumab by IV infusion day 1 of each 2 week cycle.

Also known as: Herceptin

Treatment with Neratinib with Trastuzumab, Pembrolizumb and mFOLFOX

Eligibility Criteria

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

You may qualify if:

• Patients must have pathologically or cytologically confirmed esophageal, gastric or gastroesophageal junction (GEJ) adenocarcinoma by the enrolling institution.
• Patients must have esophageal, gastric or GEJ adenocarcinoma with HER2 overexpression and/oramplification as determined by immunohistochemistry (IHC 3+) or fluorescent in situ hybridization (FISH+ as defined as HER2:CEP17 ratio ≥2.0 if IHC 2+). No central testing will be required. The testing can be performed on archival tissue that is less than 6 months old. If archival tissue is more than 6 months old, a new biopsy must be obtained to confirm HER2 status prior to enrollment.
• Patients may have received no prior chemotherapy or be treatment naïve for stage IV disease. Patients may have received prior adjuvant therapy (chemotherapy and/or chemoradiation) if more than 6 months have elapsed between the end of adjuvant therapy and expected date of treatmentstart on this study. Patients who have received maintenance nivolumab after chemoradiation and surgery would be eligible as long as the last dose of nivolumab was more than 3 months from thedate of expected date of treatment start on this study.
• Patients must have measurable disease per RECIST v1.1.
• Patients must not have active decompensated cardiomyopathy and must have a normal LVEF (≥ 53%). If a patient has a borderline LVEF (40-52%), they may be considered after consultation with cardiology and study PI.
• ECOG performance status 0 or 1.
• Demonstrate adequate organ function as outlined in protocol.
• Female patients of childbearing potential should have a negative urine or serum pregnancy within 72hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Female patients of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Patients of childbearing potential are those who have not been surgically sterilized or have not been free from menses for \> 2 years.
• Male patients should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.
• Participants with treated brain metastases are eligible if follow-up brain imaging after central nervous system- (CNS-) directed therapy shows no evidence of progression at 4-6 weeks after treatment.
• Ability to understand and the willingness to sign a written informed consent document

You may not qualify if:

• Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational treatment within 4 weeks of the first dose of treatment.
• Has had prior chemotherapy, targeted small molecule therapy, immunotherapy prior to study Day 1 for metastatic disease or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent with the exception of alopecia or immune mediated hypothyroidism.
• Note: (a) If patient received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy. (b.) If patient received radiation treatment for brain metastases, then it should have completed more than 6 weeks prior to starting Day 1 of treatment.
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
• Has active autoimmune disease that has required systemic therapy in the past 2 years (i.e. disease modifying agents, immunosuppressants or corticosteroids). Replacement therapy (i.e. thyroxine, insulin, physiologic doses of corticosteroids for adrenal or pituitary insufficiency etc.) is not considered a form of systemic therapy and is allowed.
• Has a diagnosis of immunodeficiency or receives chronic steroid therapy (in doses exceeding prednisone 10 mg/day equivalent).
• Has history of non-infectious pneumonitis that required steroids or current pneumonitis.
• Has an active infection requiring systemic therapy.
• Has baseline neuropathy \> grade 1.
• 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.
• Has had COVID-19 infection within 90 days of confirming eligibility or has sequelae of COVID-19 infection such as symptoms that cannot be explained by any other medical event or comorbidity.
• Vaccination for COVID-19 is allowed on the study unless patient had a grade 3 event after either dose of the vaccine and has not resolved to grade 1 before registration.
• Is unwilling to give written informed consent, unwillingness to participate, or inability to comply with the protocol for the duration of the study.

Sponsors & Collaborators

• Puma Biotechnology, Inc.: collaborator
• National Comprehensive Cancer Network: collaborator
• H. Lee Moffitt Cancer Center and Research Institute: lead

Study Sites (1)

Moffitt Cancer Center

Tampa, Florida, 33612, United States

RECRUITING

Related Links

• Moffitt Cancer Center's Clinical Trials website

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

neratinib; Trastuzumab; Oxaliplatin; Fluorouracil; Leucovorin; pembrolizumab

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Coordination Complexes; Organic Chemicals; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes

Study Officials

• Dae Won Kim, MD

  Moffitt Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Erin Mcewan

CONTACT

813-745-0177; Erin.Mcewan@moffitt.org

Study Design

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

Study Record Dates

• First Submitted: October 25, 2023
• First Posted: October 31, 2023
• Study Start: January 12, 2024
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): April 1, 2028
• Last Updated: February 9, 2026

Record last verified: 2026-02

Locations

US (1)