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

NCT07070466 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 25-327
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Stomach Cancer Stage IV; Esophagus Cancer; Stomach Cancer

Keywords

stomach cancer; esophageal cancer; Phase 2; Immunotherapy

Outcome Measures

Primary Outcomes (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.

  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)

• Incidence and Severity of Treatment-Emergent Adverse Events

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

• Objective Response Rate

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

• Overall Clinical Benefit

  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.

• Median Progression Free Survival and Overall Survival

  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.

Study Arms (1)

Ivonescimab plus FOLFOX

EXPERIMENTAL

Ivonescimab 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.

Drug: Ivonescimab; Drug: 5-Fluorouracil; Drug: Oxaliplatin; Drug: Leucovorin

Interventions

Ivonescimab DRUG

Humanized immunoglobulin G1 monoclonal antibody

Ivonescimab plus FOLFOX

5-Fluorouracil DRUG

Nucleoside metabolic inhibitor

Ivonescimab plus FOLFOX

Oxaliplatin DRUG

Platinum-based drug and organoplatinum complex

Ivonescimab plus FOLFOX

Leucovorin DRUG

5-formyl derivative of tetrahydrofolic acid

Ivonescimab plus FOLFOX

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 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:
• 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.

You may not qualify if:

• 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.
• 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 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.
• 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 randomization.
• 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 randomization, 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.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Summit Therapeutics: collaborator

Study Sites (2)

UCLA

Santa Monica, California, 90404, United States

RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

MeSH Terms

Conditions

Stomach Neoplasms; Esophageal Neoplasms

Interventions

Fluorouracil; Oxaliplatin; Leucovorin

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Head and Neck Neoplasms; Esophageal Diseases

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Coordination Complexes; Organic Chemicals; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes

Study Officials

• Samuel Klempner, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Samuel Klempner, MD

CONTACT

617-724-4000; sklempner@mgb.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 14, 2025
• First Posted: July 17, 2025
• Study Start: October 10, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): September 1, 2028
• Last Updated: March 6, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication.
• Access Criteria: Contact the Partners Innovations team at http://www.partners.org/innovation

Locations

US (2)