GastroEsophageal CancerPhase 2NCT06109467
Neratinib In Combination With Chemotherapy/Trastuzumab/Pembrolizumab In HER2 Gastroesophageal Cancer
A Phase 2 study testing Neratinib, Trastuzumab and Oxaliplatin in people with GastroEsophageal Cancer and Gastric Cancer, run by H. Lee Moffitt Cancer Center and Research Institute at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- GastroEsophageal Cancer, Gastric Cancer
- What is being tested?
- Neratinib, Trastuzumab and Oxaliplatin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- 12 Jan 2024to Apr 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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
- 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.
Show all 12Show fewer
- 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
Who cannot join
- 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).
Show all 17Show fewer
- 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.
- Has active or clinically significant cardiac disease including: (a.) Congestive heart failure - New York Heart Association (NYHA) > Class II. (b) Active coronary artery disease.(c) Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin.(d) Unstable angina (anginal symptoms at rest), new-onset angina within 3 months before initiation, or myocardial infarction within 6 months before initiation. (e) QTc interval >450 ms for men or >470 ms for women or known history of QTc prolongationor Torsades de Pointes.
- Patient has significant chronic gastrointestinal disorder with diarrhea as a major symptom (e.g.,Crohn's disease, malabsorption, or Grade ≥2 (NCI CTCAE v.5.0) diarrhea of any etiology at screening).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase II Study Of Neratinib In Combination With Chemotherapy/Trastuzumab/Pembrolizumab In HER2 Overexpressing Gastroesophageal Cancers
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
- Being tested
- Neratinib, Trastuzumab, Oxaliplatin, 5-Fluorouracil + leucovorin, Pembrolizumab
- Medical subject headings
- Stomach Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NeratinibDrug
Also called NERLYNX
All participants will take 240mg neratinib by mouth every day beginning cycle 1 day 1.
TrastuzumabDrug
Also called Herceptin
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.
OxaliplatinDrug
Also called Eloxatin
All participants will receive 85mg Oxaliplatin by IV infusion day 1 of each 2 week cycle.
5-Fluorouracil + leucovorinDrug
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)
PembrolizumabDrug
Also called Keytruda
All participants will receive 400mg Pembrolizumab by IV infusion day 1 of every 3rd 2 week cycle.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Neratinib; Drug: Trastuzumab; Drug: Oxaliplatin; Drug: 5-Fluorouracil + leucovorin; Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 24 months
Secondary outcomes (3)
Clinical Benefit Rate (CBR)
CBR is defined as complete response + partial response + stable disease per RECIST v1.1 criteria. CBR will be calculated through exact binomial distribution with a 2-sided 95% CI among patients who obtain at least one dose of study drug.
Measured: Up to 24 months
Duration of Response
Duration of response will be calculated from the time of first response (complete response or partial response) until disease progression or death, whichever comes first. Duration of response will be summarized descriptively using Kaplan Meier medians and quantities.
Measured: Up to 24 months
Overall Survival (OS)
OS will be calculated from start of study treatment to death due to any cause. Overall survival will be summarized descriptively using Kaplan Meier medians and quantities.
Measured: Up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Oct 2023
- Study start12 Jan 2024
- Primary completionMar 2028 (estimated)
- Study completionApr 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GastroEsophageal CancerStudies of the same condition, open and under way.
- More trials run by H. Lee Moffitt Cancer Center and Research InstituteThe 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
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Puma Biotechnology, Inc., National Comprehensive Cancer Network
- Responsible party
- Sponsor
- Investigators
- Dae Won Kim, MD, Principal investigator, Moffitt Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06109467
- Sponsor's protocol ID
- MCC-21917
- Status last verified
- Jun 2026
- First submitted
- 25 Oct 2023
- Last updated
- 12 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 12 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study Of Neratinib In Combination With Chemotherapy/Trastuzumab/Pembrolizumab In HER2 Overexpressing Gastroesophageal Cancers
- ClinicalTrials.gov ID
- NCT06109467
- Acronym / sponsor ID
- MCC-21917
- Conditions
- GastroEsophageal Cancer, Gastric Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 8 participants (actual)
- Lead sponsor
- H. Lee Moffitt Cancer Center and Research InstituteUniversity, hospital or other
- Collaborators
- Puma Biotechnology, Inc., National Comprehensive Cancer Network
- Study start
- 12 Jan 2024 (actual)
- Primary completion
- Mar 2028 (estimated)
- Study completion
- Apr 2028 (estimated)
- First posted
- 31 Oct 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment with Neratinib with Trastuzumab, Pembrolizumb and mFOLFOX | Experimental | Drug: Neratinib, Drug: Trastuzumab, Drug: Oxaliplatin, Drug: 5-Fluorouracil + leucovorin, Drug: PembrolizumabAll 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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.
Key exclusion criteria (17 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NeratinibAlso: NERLYNXAll participants will take 240mg neratinib by mouth every day beginning cycle 1 day 1. | Drug | Treatment with Neratinib with Trastuzumab, Pembrolizumb and mFOLFOX |
| TrastuzumabAlso: HerceptinAll 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. | Drug | Treatment with Neratinib with Trastuzumab, Pembrolizumb and mFOLFOX |
| OxaliplatinAlso: EloxatinAll participants will receive 85mg Oxaliplatin by IV infusion day 1 of each 2 week cycle. | Drug | Treatment with Neratinib with Trastuzumab, Pembrolizumb and mFOLFOX |
| 5-Fluorouracil + leucovorinAll 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) | Drug | Treatment with Neratinib with Trastuzumab, Pembrolizumb and mFOLFOX |
| PembrolizumabAlso: KeytrudaAll participants will receive 400mg Pembrolizumab by IV infusion day 1 of every 3rd 2 week cycle. | Drug | Treatment with Neratinib with Trastuzumab, Pembrolizumb and mFOLFOX |
Primary outcome
Objective Response Rate (ORR)
Time frame: Up to 24 months
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.
3 secondary outcomes
Clinical Benefit Rate (CBR)
Time frame: Up to 24 months
Duration of Response
Time frame: Up to 24 months
Overall Survival (OS)
Time frame: Up to 24 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jun 2026.
- Individual participant dataSharing planned: Undecided
Related trials for GastroEsophageal Cancer
RecruitingPhase 3
A Study of Neoadjuvant-adjuvant Durvalumab and FLOT Chemotherapy Followed by Adjuvant Durvalumab in Chinese Patients With Resectable GC/GEJC.
Gastric, Esophagogastric Junction
RecruitingPhase 2
At-Home Cancer Directed Therapy Versus in Clinic for the Treatment of Patients With Advanced Cancer
Advanced Anal Carcinoma, Advanced Biliary Tract Carcinoma
Active, not recruitingPhase 2
Perioperative Cadonilimab (AK104) in Locally Advanced MSI-H/dMMR Gastric or Gastroesophageal Junction and Colorectal Adenocarcinoma
MSI-H/dMMR Gastric Carcinoma and Colorectal Cancer
RecruitingPhase 1
A Study to Learn About the Study Medicine Called PF-08046876 in People With Advanced Solid Tumors
Advanced/Metastatic Solid Tumors, Bladder Cancer
RecruitingPhase 2
Candonilimab Combined With Fruquintinib and Paclitaxel Albumin-Bound as Second-Line Treatment for Advanced Gastric or Gastro-esophageal Junction Adenocarcinoma
Stomach Neoplasms
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dae Won Kim, MD principal investigator
Moffitt Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Neratinib, Trastuzumab and Oxaliplatin in people with GastroEsophageal Cancer and Gastric Cancer, run by H. Lee Moffitt Cancer Center and Research Institute at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 12 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (ORR) (time frame: Up to 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jun 2026.