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Ivonescimab in Comb. With FOLFOX in Advanced HER2 Neg. GEA | Clinical Trials | Clareo Health

RECRUITINGPHASE2

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

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

NCT07070466•Massachusetts General Hospital

View on ClinicalTrials.gov

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.

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.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•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:
•1. absolute neutrophil count ≥1,500/mcL
•2. hemoglobin \> 9.0 g/dL
•3. platelets ≥100,000/mcL
•4. total bilirubin ≤ 1.5x institutional upper limit of normal (ULN). For patients with liver metastases or confirmed/suspected Gilbert syndrome, TBIL ≤3 × ULN
+5 more criteria

Exclusion Criteria

•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 should inform her treating physician immediately. Contraception should 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.
•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 enrolment, 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 randomization.
•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.
•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 should be discontinued if the mother is treated with ivonescimab. These potential risks may also apply to other agents used in this study.
•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 randomization.
+21 more criteria

Locations (2)

UCLA

Santa Monica, California, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Key Dates

Start Date

October 10, 2025

Primary Completion Date

December 1, 2026

Completion Date

September 1, 2028

Last Updated

March 6, 2026

Enrollment

ESTIMATED participants

Conditions

Stomach Cancer Stage IVEsophagus CancerStomach Cancer

Interventions

Ivonescimab

DRUG

5-Fluorouracil

DRUG

Oxaliplatin

DRUG

Leucovorin

DRUG

Contacts

Samuel Klempner, MD

CONTACT

617-724-4000 sklempner@mgb.org

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: March 6, 2026Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

View ClinicalTrials.gov Terms and Conditions

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

Inclusion Criteria

Exclusion Criteria

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