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Stomach Cancer Stage IVPhase 2NCT07070466

Ivonescimab in Comb. With FOLFOX in Advanced HER2 Neg. GEA

A Phase 2 study testing Ivonescimab, 5-Fluorouracil and Oxaliplatin in people with Stomach Cancer Stage IV and Esophagus Cancer, run by Massachusetts General Hospital at 2 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

This is a single arm, open-label, phase II trial investigating the combination of ivonescimab with standard FOLFOX chemotherapy in 1L therapy for HER2- GEA. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Ivonescimab, 5-Fluorouracil and Oxaliplatin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
2 sitesUnited States
Study dates
10 Oct 2025to 1 Sep 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 a pathologically confirmed diagnosis of adenocarcinoma of the esophagus, gastroesophageal junction, stomach. Squamous cell tumors are excluded. Patients with locally tested HER2 positive tumors (HER2+) tumors are excluded.
  • Participants must have disease that can be evaluated radiographically. This includes disease that may be measurable or non-measurable as per RECIST version 1.1.
  • Patients may not have received prior therapy for Stage IV disease. Patients may have received prior adjuvant therapy if more than 6 months have elapsed between the end of adjuvant therapy and registration.
  • Age ≥18 years old. Because there is no dosing or adverse event data for ivonescimab with FOLFOX in participants <18 years of age, children are excluded from this study.
  • ECOG Performance status of 0-2
  • Participants must meet the following organ and marrow function as defined below:
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  • absolute neutrophil count ≥1,500/mcL
  • hemoglobin > 9.0 g/dL
  • platelets ≥100,000/mcL
  • total bilirubin ≤ 1.5x institutional upper limit of normal (ULN). For patients with liver metastases or confirmed/suspected Gilbert syndrome, TBIL ≤3 × ULN
  • AST(SGOT)/ALT(SGPT) ≤2.5 × institutional ULN. For patients with liver metastases, AST and ALT ≤ 5 × ULN
  • Creatinine ≤ institutional ULN OR glomerular filtration rate (GFR) ≥50 mL/min.
  • Urine protein < 2+ or 24-hour protein quantification < 1.0 grams.
  • Coagulation: prothrombin time (PT) or international normalized ratio (INR) ≤ 1.5 × ULN, and partial prothrombin time (PTT) or activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN (unless abnormalities are unrelated to coagulopathy) This applies only to patients who are not on therapeutic anti-coagulation. Patients receiving therapeutic anti-coagulation should be on a stable dose.
  • For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
  • Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
  • Participants with brain metastases (active brain metastases) or leptomeningeal disease are not eligible. Patients with treated brain metastases who are off systemic steroids > 2 weeks and have documented radiographic stability over 4 weeks since initial brain metastasis diagnosis may be considered in discussion with the overall principal investigator.
  • Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
  • The effects of ivonescimab on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she must inform her treating physician immediately. Contraception must continue for 9 months from the last dose of any study medication.
  • Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 9 months after completion of ivonescimab administration.
  • Ability to understand and the willingness to sign a written informed consent document.

Who cannot join

  • Prior treatment with a PD-1 or PD-L1 inhibitor is exclusionary unless this therapy was completed > 6 months prior to the time of enrollment as part of adjuvant therapy.
  • Major surgical procedures or serious trauma within 4 weeks prior to enrollment, or plans for major surgical procedures within 4 weeks after the first dose (as determined by the investigator). Minor local procedures (excluding central venous catheterization and port implantation) within 3 days prior to registration.
  • Participants who have not recovered from adverse events due to prior adjuvant anti-cancer therapy except for alopecia or peripheral neuropathy grade 1 or less.
  • Participants who are receiving any other investigational agents for this condition are not eligible.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to ivonescimab. Patients with prior oxaliplatin and/or 5FU allergic reactions during adjuvant therapy are allowed if they have undergone prior desensitization with allergy and documented tolerance at standard dosing after desensitization.
  • Pregnant women are excluded from this study because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother, breastfeeding must be discontinued if the mother is treated with ivonescimab. These potential risks may also apply to other agents used in this study.
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  • History of perforation of the gastrointestinal tract and/or fistula, history of gastrointestinal obstruction (including incomplete intestinal obstruction requiring parenteral nutrition), extensive bowel resection (partial colectomy or extensive small bowel resection) within 6 months prior to resgistration.
  • Clinically significant hypertension with systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100 mmHg after oral antihypertensive therapy.
  • History of any grade arterial thromboembolic event, venous thromboembolic event of Grade 3 and above as specified in National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) 5.0, transient ischemic attack, cerebrovascular accident, hypertensive crisis, or hypertensive encephalopathy within 12 months prior to registration.
  • Participants with a documented history of impaired wound healing are excluded.
  • Participants with a history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
  • Participants with uncontrolled intercurrent illness that would interfere with ability to participate in the opinion of the treating investigator.
  • Participants with psychiatric illness/social situations that would limit compliance with study requirements.
  • Unstable angina, myocardial infarction, congestive heart failure (New York Heart Association [NYHA] classification ≥ grade 2) or unstable vascular disease (eg, aortic aneurysm at risk of rupture, Moyamoya disease) that required hospitalization within 12 months prior to registration, or other cardiac impairment that may affect the safety evaluation of the study drug (eg, poorly controlled arrhythmias, myocardial ischemia).
  • Subjects with any condition requiring systemic treatment with either corticosteroids (>2mg daily dexamethasone equivalent) or other immunosuppressive medications within 14 days of treatment. Premedication for hypersensitivity reactions (e.g. to contrast for CT or gadolinium for MRI) is allowed.
  • Active systemic infection requiring intravenous antibiotics or intravenous monoclonal antibody treatments within 7 days of cycle 1 day 1.
  • Participants with a known history of Human Immunodeficiency Virus (HIV) infection are excluded unless they meet all of the following criteria:
  • Stable antiretroviral therapy (ART) for at least 12 weeks prior to enrollment
  • No history of AIDS-defining conditions.
  • CD4+ T-cell count ≥ 350 cells/mm³ at screening
  • HIV viral load ≤ 50 copies/mL at screening.
  • No significant comorbidities associated with HIV infection that could interfere with the safety or efficacy of the investigational treatment.
  • No concurrent use of prohibited medications that may interfere with the study drug or cancer therapy
  • History of bleeding tendencies or coagulopathy and/or clinically significant bleeding symptoms or risk within 4 weeks prior to registration, including but not limited to:
  • Hemoptysis (defined as coughing up ≥ 0.5 teaspoon of fresh blood or small blood clots). Note: transient hemoptysis associated with diagnostic bronchoscopy is allowed.
  • Nasal bleeding /epistaxis (bloody nasal discharge is allowed)
  • Current use of prophylactic or full-dose anticoagulants or anti-platelet agents for therapeutic purposes that is not stable prior to registration is not allowed. The use of full-dose anticoagulants is permitted as long as the international normalized ratio (INR) or activated partial thromboplastin time (aPTT) is within therapeutic limits according to the medical standard of the enrolling institution.
  • History of non-infectious pneumonitis requiring therapy within 4 weeks of registration.

Trial locations and contacts

2 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Samuel Klempner, MD contact

617-724-4000

sklempner@mgb.org

United States2 sites, 2 recruiting

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

    Samuel Klempner, MD, 617-724-4000, sklempner@mgb.org

    Recruiting

  • UCLA

    Santa Monica, California, 90404

    Zev A. Wainberg, MD, 310-829-5471, zwainberg@mednet.ucla.edu

    Recruiting

Other trials in United States

About this study

Official title: A Single-Arm, Phase II Study of Ivonescimab in Combination With FOLFOX in Advanced HER2 Negative Gastroesophageal Adenocarcinomas

This is a single arm, open-label, phase II trial investigating the combination of ivonescimab with standard FOLFOX chemotherapy in 1L therapy for HER2- GEA.

Read the detailed description

This is a single arm, open-label, non-randomized multi-institution phase II trial of the anti-PD-1 x VEGR bispecific antibody ivonoescimab in combination with standard 5-fluorouracil (5FU) and oxaliplatin as first line therapy in patients with locally advanced unresectable or metastatic HER2 negative (HER2-) gastroesophageal adenocarcinomas. The primary hypothesis is that the combination of dual VEGF and PD-1 targeting with standard 5FU/oxaliplatin (FOLFOX) will overcome intrinsic immunotherapy resistance and increase the objective response rate (ORR) and progression free survival (PFS) in frontline gastroesophageal adenocarcinomas (GEA). The goal is to determine the efficacy of this combination as measured by 6-month PFS rate and confirm the safety and tolerability in this target population.

Being tested
Ivonescimab, 5-Fluorouracil, Oxaliplatin, Leucovorin
Keywords
stomach cancer, esophageal cancer, Phase 2, Immunotherapy
Medical subject headings
Stomach Neoplasms, Esophageal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IvonescimabDrug

    Humanized immunoglobulin G1 monoclonal antibody

  • 5-FluorouracilDrug

    Nucleoside metabolic inhibitor

  • OxaliplatinDrug

    Platinum-based drug and organoplatinum complex

  • LeucovorinDrug

    5-formyl derivative of tetrahydrofolic acid

Study groups in NCT07070466
Study groupRoleWhat they receive
Ivonescimab plus FOLFOXExperimentalIvonescimab will be given once every 2 weeks into your vein (by intravenous infusion) over about 60 minutes. For the first treatment ivonescimab will be given alone with no chemotherapy. FOLFOX is a combination of 5-fluorouracil, oxaliplatin, and leucovorin. Starting Cycle 2 on beyond FOLFOX will be given after ivonescimab once every 2 weeks into your vein (intravenously). Some may be given over a shorter period of time (as short as approximately 1 minute) and others up to approximately 120 minutes. Ivonescimab in combination with FOLFOX will be given for up to 2 years as long as no serious side effects and disease does not worsen.
Receives: Drug: Ivonescimab; Drug: 5-Fluorouracil; Drug: Oxaliplatin; Drug: Leucovorin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 6-month progression free survival rate

    The primary endpoint is to estimate the 6-month progression free survival rate for the combination of ivonescimab in combination with FOLFOX in frontline GEA adenocarcinomas. Progression is defined as measured from the start of the treatment with ivonescimab to the date of either documentation of disease progression or death. Progression of disease is defined per RECIST 1.1 criteria.

    Measured: From the start of treatment (Cycle 1, day 1) to first documented disease progression or date of death from any cause. Status at 6-months after starting treatment will be reported.

Secondary outcomes (4)

  1. Incidence and Severity of Treatment-Emergent Adverse Events

    Assessed using NCI Common Terminology for Adverse Event (CTCAE) version 5.0. All participants will be followed and assessed for safety and tolerability of the protocol therapy.

    Measured: From baseline until up to 90-days after end of study.

  2. Objective Response Rate

    The percentage of participants that have a partial response or complete response.

    Measured: From baseline until end of study or death, whichever comes first for up to 5 years.

  3. Overall Clinical Benefit

    This is defined by stable disease (SD), complete response rate (CR), or partial response (PR) assessed by RECISTv1.1. They will be summarized using binomial proportions along with exact 95% CI.

    Measured: From the baseline start of treatment to the date to first documented disease progression or date of death from any cause, whichever comes first for up to 5 years.

  4. Median Progression Free Survival and Overall Survival

    Median progression free survival is the length of time during treatment and after treatment to disease progression or death. Overall survival is the time from start if treatment to death due to any cause. The Kaplan-Meier method will be used to estimate median progression free survival and overall survival.

    Measured: From baseline start of treatment to first documented disease progression or date of death from any cause, whichever comes first for up to 5 years.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Jul 2025
  2. Study start10 Oct 2025
  3. Primary completion1 Dec 2026 (estimated)
  4. Study completion1 Sep 2028 (estimated)

Resources

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
40 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07070466
Sponsor's protocol ID
25-327
Status last verified
Aug 2026
First submitted
14 Jun 2025
Last updated
28 Aug 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: The Dana-Farber/Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to \[sklempner@mgb.org\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ivonescimab, 5-Fluorouracil and Oxaliplatin in people with Stomach Cancer Stage IV and Esophagus Cancer, run by Massachusetts General Hospital at 2 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 21 inclusion and 28 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: looking for participants now, as of the sponsor's last update on 28 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 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?

Contact Samuel Klempner, MD (617-724-4000, sklempner@mgb.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

6-month progression free survival rate (time frame: From the start of treatment (Cycle 1, day 1) to first documented disease progression or date of death from any cause. Status at 6-months after starting treatment will be reported.). 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 NCT07070466.

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 28 Aug 2026.

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