Esophagogastric CancerPhase 2NCT04757363
A Study of Nivolumab Combined With FOLFOX and Regorafenib in People Who Have HER2-Negative Esophagogastric Cancer
A Phase 2 study testing regorafenib, nivolumab and FOLFOX chemotherapy with oxaliplatin in people with Esophagogastric Cancer and HER2-Negative, run by Memorial Sloan Kettering Cancer Center at 7 sites in United States.
Trial summary
The purpose of this study is to find out whether combining nivolumab, FOLFOX, and regorafenib may be a safe and effective treatment for people who have HER2-negative metastatic esophagogastric cancer. Nivolumab is an antibody, like the proteins made by the immune system to protect the body from harm. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Esophagogastric Cancer, HER2-Negative
- What is being tested?
- regorafenib, nivolumab and FOLFOX chemotherapy with oxaliplatin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 39 participants
- Where
- 7 sitesUnited States
- Study dates
- 11 Feb 2021to Feb 2027
- 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 histologically or cytologically confirmed metastatic esophageal, gastric, or gastroesophageal junction adenocarcinoma
- Patients must have disease that can be evaluated radiographically within 28 days of the start of study treatment. This may be measurable disease or non-measurable disease per RECIST 1.1.
- Age 18 years or older
- ECOG performance status 0 to 1
- Peripheral neuropathy grade ≤1
- Available archival tissue for correlative analysis (biopsy is required if no archival tissue is available)
Show all 15Show fewer
- Adequate organ function as below:
- Absolute neutrophil count ≥1500/mcL
- Platelets ≥100,000/mcL
- Hemoglobin ≥9 g/dL
- Serum creatinine ≤1.5X ULN
- Serum total bilirubin ≤1.5X ULN OR Direct bilirubin ≤ULN for s ubjects with total bilirubin levels >1.5X ULN, except patients with Gilbert's disease (≤3X ULN)
- AST and ALT ≤2.5X ULN
- Albumin ≥3 mg/dL
- ALT, alanine aminotransferase; AST, aminotransferase; ULN, upper limit of normal.
Who cannot join
- Confirmed HER2-positive disease (IHC 3+ or 2+, fluorescence in situ hybridization HER2:CEP17 ratio ≥2)
- ° Note: Participants that are IHC 2+ but negative by FSH w ill be considered HER2- negative and eligible for trial.
- Inability to swallow oral pills
- Prior chemotherapy for metastatic disease. Patients with metastatic disease after treatment for localized esophagogastric cancer may have received prior adjuvant therapy (chemotherapy and/or chemoradiation) if >6 months have elapsed between the end of adjuvant therapy and registration
- Currently participating in a study 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
- Underwent major surgical procedure within 4 weeks of registration
Show all 25Show fewer
- Underwent radiation within 2 weeks of registration
- Received prior therapy with regorafenib
- Received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
- Diagnosis of immunodeficiency or receipt of systemic steroid therapy or any other form of immunosuppressive therapy within 7 days before the first dose of trial treatment
- A known history of active Bacillus tuberculosis
- A known active central nervous system metastases and/or carcinomatous meningitis
- A known history of or any evidence of active, noninfectious pneumonitis
- An active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease, systemic lupus erythematosus, Wegener syndrome [granulomatosis with polyangiitis], myasthenia gravis, Grave's disease, rheumatoid arthritis, hypophysitis, uveitis) within the 3 years before 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
- A known history of human immunodeficiency virus (HIV 1/2 antibodies)
- Known active hepatitis B (e.g., HBsAg reactive) or hepatitis C (e.g., HCV RNA [qualitative] is detected). Patients with HBsAg reactive on entecavir may be eligible after consultation with hepatologist and study team.
- Received a live vaccine within 30 days of planned start of study therapy
- Active or clinically significant cardiac disease, including congestive heart failure-New York Heart Association class >II, active coronary artery disease, cardiac arrhythmias requiring antiarrhythmic therapy other than beta blockers or digoxin, unstable angina (anginal symptoms at rest), new-onset angina within 3 months before initiation, or myocardial infarction within 6 months before initiation
- Uncontrolled hypertension (systolic pressure >140 mm Hg or diastolic pressure >90 mm Hg on repeated measurement) despite optimal medical management
- Evidence or history of bleeding diathesis or coagulopathy
- Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
- Pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial, starting with the prescreening or screening visit through 120 days after the last dose of trial treatment
- 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
7 sites in 1 country.
7 sites in 1 country
United States7 sites
Memorial Sloan Kettering Basking Ridge (All Protocol Activities)
Basking Ridge, New Jersey, 07920
Memorial Sloan Kettering Commack (All Protocol Activities)
Commack, New York, 11725
Memorial Sloan Kettering Westchester (All Protocol Activities)
Harrison, New York, 10604
Memorial Sloan Kettering Monmouth (All Protocol Activities)
Middletown, New Jersey, 07748
Memorial Sloan Kettering Bergen (All Protocol Activities)
Montvale, New Jersey, 07645
Memorial Sloan Kettering Cancer Center (All Protocol Activities)
New York, New York, 10065
Memorial Sloan Kettering Nassau (All Protocol Activities)
Uniondale, New York, 11553
About this study
Official title: A Phase II Study of Nivolumab in Combination With FOLFOX and Regorafenib in Patients With HER2-Negative Metastatic Esophagogastric Cancer
The purpose of this study is to find out whether combining nivolumab, FOLFOX, and regorafenib may be a safe and effective treatment for people who have HER2-negative metastatic esophagogastric cancer.
Nivolumab is an antibody, like the proteins made by the immune system to protect the body from harm. Nivolumab blocks the protein PD-1 (programmed cell death receptor-1) that usually acts as a "brake" on the immune system. Blocking this protein is like releasing the brakes, so that the immune system can target cancer cells and destroy them.
Read more
FOLFOX is a combination of three standard chemotherapy drugs (leucovorin, 5-fluorouracil, and oxaliplatin) commonly used to treat your type of cancer. The drugs work by damaging the DNA in cancer cells, which can cause the cells to stop growing and die.
Regorafenib is a type of drug called a tyrosine kinase inhibitor (TKI). This drug targets the tyrosine kinase protein found in or on the surface of cancer cells that the cells need to survive and grow. Blocking this protein may stop cancer cells from growing, or cause them to grow more slowly or to shrink.
The study researchers think that combining nivolumab, FOLFOX, and regorafenib may be a more effective treatment for HER2-negative metastatic esophagogastric cancer than the usual chemotherapy treatment(s) alone.
- Conditions
- Esophagogastric Cancer, HER2-Negative
- Being tested
- regorafenib, nivolumab, FOLFOX chemotherapy with oxaliplatin
- Keywords
- nivolumab (OPDIVO®), regorafenib (STIVARGA®), fluorouracil, leucovorin, oxaliplatin, Regorafenib, esophageal cancer, 20-540
- Medical subject headings
- Esophageal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
regorafenibDrug
regorafenib (80 mg on days 1-21 of the 28-day cycle)
nivolumabDrug
nivolumab (240 mg on days 1 and 15 of the 28-day cycle).
FOLFOX chemotherapy with oxaliplatinDrug
FOLFOX chemotherapy with oxaliplatin (85 mg/m2 IV), leucovorin (400 mg/m2 IV), 5-FU (400 mg/m2 IV bolus), and 5-FU (2400 mg/m2/day continuous IV infusion over 48 h).
| Study group | Role | What they receive |
|---|---|---|
| Nivolumab Combined With FOLFOX and Regorafenib | Experimental | Each treatment cycle consists of 28 days. Patients will initially receive induction therapy with regorafenib (80 mg on days 1-21 of the 28-day cycle) and nivolumab (240 mg on days 1 and 15 of the 28-day cycle). Starting on cycle 2, day 1, patients will also receive FOLFOX chemotherapy with oxaliplatin (85 mg/m2 IV), leucovorin (400 mg/m2 IV), 5-FU (400 mg/m2 IV bolus), and 5-FU (2400 mg/m2/day continuous IV infusion over 48 h). If the patient is not a good candidate for induction regorafenib and nivolumab (i.e. symptomatic from a large burden of disease), 5-FU and oxaliplatin can be added during cycle 1 at the treating physician's discretion. 39 Patients will continue with this regimen until disease progression, unacceptable toxicity, or development of serious intercurrent illness. Treatment will be performed on the scheduled day (±7-day treatment window). Receives: Drug: regorafenib; Drug: nivolumab; Drug: FOLFOX chemotherapy with oxaliplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
6-month progression free Survival
will be defined according to RECIST 1.1.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Feb 2021
- Study start11 Feb 2021
- Primary completionFeb 2027 (estimated)
- Study completionFeb 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Esophagogastric 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, open-label, nonrandomized, single-institution, phase II study of nivolumab in combination with FOLFOX and regorafenib as first-line therapy in patients with metastatic esophagogastric adenocarcinoma.
- Masking
- None (open label)
- Enrolment
- 39 participants (actual)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Bayer, Bristol-Myers Squibb
- Responsible party
- Sponsor
- Investigators
- Yelena Janjigian, MD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04757363
- Sponsor's protocol ID
- 20-540
- Status last verified
- Mar 2026
- First submitted
- 12 Feb 2021
- Last updated
- 4 Mar 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.
Publications
Cytryn SL, Moy RH, Cowzer D, Shah RH, Chou JF, Joshi SS, Ku GY, Maron SB, Desai A, Yang J, Sugarman R, Rao D, Goldberg Z, Charalambous C, Lapshina M, Antoine A, Socolow F, Trivedi N, Capanu M, Gerdes H, Schattner MA, Simmons M, Lacouture ME, Paroder V, Tang LH, Shia J, Ilson DH, Solit DB, Berger MF, Janjigian YY. First-line regorafenib with nivolumab and chemotherapy in advanced oesophageal, gastric, or gastro-oesophageal junction cancer in the USA: a single-arm, single-centre, phase 2 trial. Lancet Oncol. 2023 Oct;24(10):1073-1082. doi: 10.1016/S1470-2045(23)00358-3. Epub 2023 Sep 1.
PubMed 37666264
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Nivolumab in Combination With FOLFOX and Regorafenib in Patients With HER2-Negative Metastatic Esophagogastric Cancer
- ClinicalTrials.gov ID
- NCT04757363
- Acronym / sponsor ID
- 20-540
- Conditions
- Esophagogastric Cancer, HER2-Negative
- Keywords
- nivolumab (OPDIVO®), regorafenib (STIVARGA®), fluorouracil, leucovorin, oxaliplatin, Regorafenib, esophageal cancer, 20-540
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 39 participants (actual)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Collaborators
- Bayer, Bristol-Myers Squibb
- Study start
- 11 Feb 2021 (actual)
- Primary completion
- Feb 2027 (estimated)
- Study completion
- Feb 2027 (estimated)
- First posted
- 17 Feb 2021 (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 this study is to find out whether combining nivolumab, FOLFOX, and regorafenib may be a safe and effective treatment for people who have HER2-negative metastatic esophagogastric cancer.
Nivolumab is an antibody, like the proteins made by the immune system to protect the body from harm. Nivolumab blocks the protein PD-1 (programmed cell death receptor-1) that usually acts as a "brake" on the immune system. Blocking this protein is like releasing the brakes, so that the immune system can target cancer cells and destroy them.
FOLFOX is a combination of three standard chemotherapy drugs (leucovorin, 5-fluorouracil, and oxaliplatin) commonly used to treat your type of cancer. The drugs work by damaging the DNA in cancer cells, which can cause the cells to stop growing and die.
Regorafenib is a type of drug called a tyrosine kinase inhibitor (TKI). This drug targets the tyrosine kinase protein found in or on the surface of cancer cells that the cells need to survive and grow. Blocking this protein may stop cancer cells from growing, or cause them to grow more slowly or to shrink.
The study researchers think that combining nivolumab, FOLFOX, and regorafenib may be a more effective treatment for HER2-negative metastatic esophagogastric cancer than the usual chemotherapy treatment(s) alone.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This is a single-arm, open-label, nonrandomized, single-institution, phase II study of nivolumab in combination with FOLFOX and regorafenib as first-line therapy in patients with metastatic esophagogastric adenocarcinoma.
| Arm | Type | Receives |
|---|---|---|
| Nivolumab Combined With FOLFOX and Regorafenib | Experimental | Drug: regorafenib, Drug: nivolumab, Drug: FOLFOX chemotherapy with oxaliplatinEach treatment cycle consists of 28 days. Patients will initially receive induction therapy with regorafenib (80 mg on days 1-21 of the 28-day cycle) and nivolumab (240 mg on days 1 and 15 of the 28-day cycle). Starting on cycle 2, day 1, patients will also receive FOLFOX chemotherapy with oxaliplatin (85 mg/m2 IV), leucovorin (400 mg/m2 IV), 5-FU (400 mg/m2 IV bolus), and 5-FU (2400 mg/m2/day continuous IV infusion over 48 h). If the patient is not a good candidate for induction regorafenib and nivolumab (i.e. symptomatic from a large burden of disease), 5-FU and oxaliplatin can be added during cycle 1 at the treating physician's discretion. 39 Patients will continue with this regimen until disease progression, unacceptable toxicity, or development of serious intercurrent illness. Treatment will be performed on the scheduled day (±7-day treatment window). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Patients must have histologically or cytologically confirmed metastatic esophageal, gastric, or gastroesophageal junction adenocarcinoma
- Patients must have disease that can be evaluated radiographically within 28 days of the start of study treatment. This may be measurable disease or non-measurable disease per RECIST 1.1.
- Age 18 years or older
- ECOG performance status 0 to 1
- Peripheral neuropathy grade ≤1
Key exclusion criteria (25 listed)
- Confirmed HER2-positive disease (IHC 3+ or 2+, fluorescence in situ hybridization HER2:CEP17 ratio ≥2)
- ° Note: Participants that are IHC 2+ but negative by FSH w ill be considered HER2- negative and eligible for trial.
- Inability to swallow oral pills
- Prior chemotherapy for metastatic disease. Patients with metastatic disease after treatment for localized esophagogastric cancer may have received prior adjuvant therapy (chemotherapy and/or chemoradiation) if >6 months have elapsed between the end of adjuvant therapy and registration
- Currently participating in a study 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
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 |
|---|---|---|
| regorafenibregorafenib (80 mg on days 1-21 of the 28-day cycle) | Drug | Nivolumab Combined With FOLFOX and Regorafenib |
| nivolumabnivolumab (240 mg on days 1 and 15 of the 28-day cycle). | Drug | Nivolumab Combined With FOLFOX and Regorafenib |
| FOLFOX chemotherapy with oxaliplatinFOLFOX chemotherapy with oxaliplatin (85 mg/m2 IV), leucovorin (400 mg/m2 IV), 5-FU (400 mg/m2 IV bolus), and 5-FU (2400 mg/m2/day continuous IV infusion over 48 h). | Drug | Nivolumab Combined With FOLFOX and Regorafenib |
Primary outcome
6-month progression free Survival
Time frame: 6 months
will be defined according to RECIST 1.1.
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 4 Mar 2026.
- Derived from this study: PubMed 37666264Cytryn SL, Moy RH, Cowzer D, Shah RH, Chou JF, Joshi SS, Ku GY, Maron SB, Desai A, Yang J, Sugarman R, Rao D, Goldberg Z, Charalambous C, Lapshina M, Antoine A, Socolow F, Trivedi N, Capanu M, Gerdes H, Schattner MA, Simmons M, Lacouture ME, Paroder V, Tang LH, Shia J, Ilson DH, Solit DB, Berger MF, Janjigian YY. First-line regorafenib with nivolumab and chemotherapy in advanced oesophageal, gastric, or gastro-oesophageal junction cancer in the USA: a single-arm, single-centre, phase 2 trial. Lancet Oncol. 2023 Oct;24(10):1073-1082. doi: 10.1016/S1470-2045(23)00358-3. Epub 2023 Sep 1.
- Memorial Sloan Kettering Cancer CenterLink provided by the sponsor.
- Individual participant dataSharing planned: 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.
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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.
Yelena Janjigian, MD principal investigator
Memorial Sloan Kettering Cancer Center
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing regorafenib, nivolumab and FOLFOX chemotherapy with oxaliplatin in people with Esophagogastric Cancer and HER2-Negative, run by Memorial Sloan Kettering Cancer Center at 7 sites 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 15 inclusion and 25 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 4 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites 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?
6-month progression free Survival (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04757363, which also lists 1 linked publication.
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 4 Mar 2026.