Testing Ivonescimab in Combination With Chemotherapy in Advanced or Metastatic Gastric/Gastroesophageal Adenocarcinoma

NCT06846346 | Recruiting Phase 2 DMC

• 2 other identifiers: UC-GIG-24112025-520694-39-00
• Study Type: interventional
• Target: 88
• Locations: 1 country
• Sites: 4

Brief Summary

The goal of this clinical trial is to evaluate the addition of ivonescimab to standard chemotherapy in patients with advanced or metastatic gastric and gastroesophageal adenocarcinoma. The main question it aims to answer is : Does the addition of ivonescimab increase the response to treatment ? Participants will visit the clinic every 2 weeks for checkups, treatment administration and tests for collection of adverse events.

Conditions

Advanced Esophageal Adenocarcinoma; Metastatic Gastric Adenocarcinoma; Advanced Gastric Adenocarcinoma; Metastatic Esophageal Adenocarcinoma

Keywords

Ivonescimab; Esophageal; Gastric; Adenocarcinoma; Cancer; Metastatic; Advanced; FOLFOX; Irinotecan; Paclitaxel

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate assessed by central review

  The objective response rate is defined as the percentage of patients with a complete response (CR) or a partial response (PR) for a given treatment

  Time from inclusion to disease progression, up to 3 years

Secondary Outcomes (8)

• Objective Response Rate assessed by the investigator

  Time from inclusion to disease progression, up to 3 years

• Duration of response

  Time from inclusion to disease progression or death, up to 3 years

• Progression-free survival (PFS)

  Time from inclusion to disease progression or death, up to 3 years

• Overall Survival (OS)

  From inclusion to death from any cause, up to 3 years

• Time to patient performance status deterioration >2

  From inclusion to PS deterioration >2, up to 3 years

Study Arms (2)

1st line

EXPERIMENTAL

FOLFOX combined with Ivonescimab

Drug: Ivonescimab; Drug: FOLFOX regimen

2nd line

EXPERIMENTAL

Paclitaxel or Irinotecan (at investigator discretion) combined with ivonescimab

Drug: Ivonescimab; Drug: Irinotecan; Drug: Paclitaxel

Interventions

Ivonescimab DRUG

Ivonescimab 20 mg/kg by intravenous (IV) infusion once every 2 weeks until disease progression.

Also known as: AK112

1st line; 2nd line

FOLFOX regimen DRUG

Oxaliplatin 85 mg/m2 IV, folinic acid 400 mg/m2 IV (or L-folinic acid 200 mg/m²), and fluorouracil (5-FU) 400 mg/m² IV bolus; followed by 5 FU 2400 mg/m2 as a 46 hour continuous IV infusion, every two weeks for 8 cycles followed by 5FU as maintenance therapy until disease progression.

Also known as: Oxaliplatin, folinic acid and 5-FU

1st line

Irinotecan DRUG

180 mg/ m2 IV over 90 min infusion every two weeks for a minimum of 4 cycles

Also known as: Campto

2nd line

Paclitaxel DRUG

80 mg/m2 IV at D1, D8 and D15, every four weeks (D1=D28)

Also known as: Taxol

2nd line

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed a written informed consent form prior to any trial specific procedures. Note: If the patient is physically unable to provide their written consent, a trusted person of their choice, independent of the Investigator or the Sponsor, can confirm the patients consent in writing.
• Histologically or cytologically proven gastric cancer (GC) or esophagogastric junction cancer adenocarcinoma (EGJC)
• Metastatic or locally advanced non resectable (stage IV) disease.
• Presence of at least one measurable lesion as assessed by the investigator according to RECIST v1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Age ≥18 years.
• For patients without actionable biomarker (HER2 and Claudin 18.2-negative) except for PD-L1, no prior treatment for advanced disease (cohort 1). For patients with at least one of the following actionable biomarker (PD-L1 CPS≥1, and/or HER2-positive, and/or Claudin 18.2-positive), who had received only one prior line of treatment for advanced disease (cohort 2).
• Adequate hematological function: absolute neutrophil count (ANC) ≥1.5 × 10⁹/L, platelet count ≥100 × 10⁹/L, and hemoglobin ≥9 g/dL. Note: Blood transfusion or growth factor therapy should not be performed within 7 days prior to the screening hematology analysis.
• Adequate renal function: estimated creatinine clearance ≥50 mL/min according to the Cockcroft-Gault formula, or estimated glomerular filtration rate (eGFR) value ≥50 mL/min using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, and urine protein \< 2+ or 24-hour urine protein quantification \< 1.0 g.
• Adequate liver function: total bilirubin level ≤1.5 × the upper limit of normal (ULN) range (≤3 x ULN for patients with liver metastases or confirmed/suspected Gilbert syndrome), and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels ≤2.5 × ULN (AST and ALT ≤5 x ULN when documented liver metastasis).
• Coagulation: prothrombin time (PT) or international normalized ratio (INR) ≤ 1.5 x 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.
• Women of childbearing potential (WOCBP) having sex with an unsterilized male partner and unsterilized males having sex with a female partner of childbearing potential, must agree to use an effective method of contraception for the duration of trial participation and as required after completing study treatment (120 days after the last dose of ivonescimab). Men must also agree to not donate sperm and women must agree to not donate oocytes during the specified period.
• Willing and able to comply with the protocol for the duration of the study including scheduled visits, treatment plan, laboratory tests, and other study procedures
• Affiliation to the Social Security System (or equivalent)

You may not qualify if:

• Patients with high microsatellite instability (MSI-H) or mismatched repair disease (dMMR) tumor.
• Enteral intake \< 1500 kcal /d and or a weight loss \> 15% of total body weight within the 6 months
• Toxicities from previous treatment not resolved to grade ≤ 1 (according to the version 5.0 of the National Cancer Institute - Common terminology criteria for adverse events \[NCI-CTCAE v5.0\]) before treatment start with the exception of alopecia.
• Major surgical procedures or serious trauma within 4 weeks prior to treatment start, or plans for major surgery 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 treatment start.
• 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 treatment start 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.
• Poorly controlled hypertension with repeated systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100 mmHg after oral antihypertensive therapy.
• Imaging during the screening period shows that the patient has:
• Radiologically documented evidence of major blood vessel invasion or encasement by cancer,
• Radiographic evidence of intra-tumor cavitation.
• Evidence of higher bleeding risk on prostheses
• Any immunosuppressive therapy during more than 7 days (i.e. corticosteroids \>10mg or equivalent dose) within 14 days before the planned start of study therapy. Physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency is not considered as a form of systemic treatment.
• Active autoimmune disease that has required a systemic treatment in past 2 years (i.e. corticosteroids or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin) is allowed active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis, with the following exceptions:
• Patients with a history of autoimmune-related hypothyroidism who are on thyroid replacement hormone are eligible for the study,

Sponsors & Collaborators

• UNICANCER: lead
• Summit Therapeutics: collaborator

Study Sites (4)

Centre Léon Bérard

Lyon, 69008, France

RECRUITING

Institut Paoli Calmettes

Marseille, France

NOT YET RECRUITING

Institut Jean Godinot

Reims, 51100, France

RECRUITING

Institut de Cancerologie de l'Ouest - Site René Gauducheau

Saint-Herblain, France

NOT YET RECRUITING

MeSH Terms

Conditions

Adenocarcinoma Of Esophagus; Adenocarcinoma; Neoplasms; Neoplasm Metastasis

Interventions

Folfox protocol; Oxaliplatin; Leucovorin; Fluorouracil; Irinotecan; Paclitaxel

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Camptothecin; Alkaloids; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Study Officials

• Christelle DE LA FOUCHARDIERE

  Institut Paoli-Calmettes

  PRINCIPAL INVESTIGATOR

• Judith RAIMBOURG

  ICO - Site Renée Gauducheau

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nicolas DE SOUSA CARVALHO

CONTACT

01 71 93 67 09; n-de-sousa@unicancer.fr

Laure MONARD

CONTACT

01 73 79 73 09; l-monard@unicancer.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 20, 2025
• First Posted: February 26, 2025
• Study Start: November 20, 2025
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2028
• Last Updated: April 28, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (4)