Testing ivonescimab in combination with standard chemotherapy in advanced or metastatic gastric and gastroesophageal adenocarcinoma patients

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Unicancer

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

24 Oct 2025 → ongoing

Decision date (initial)

2025-09-08

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Summit Therapeutics Global LLC.

External identifiers

EU CT number

2025-520694-39-00

ClinicalTrials.gov

NCT06846346

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To evaluate the efficacy of ivonescimab combined with chemotherapy in patients with advanced or metastatic GEAC, with and without actionable biomarker (HER2/PD-L1/claudin18.2) in terms of objective response rate (ORR) as assessed by central review according to RECIST v1.1.

Secondary objectives 3

1. To evaluate the efficacy of ivonescimab in terms of: • Objective Response Rate (ORR) as assessed by the investigator according to RECIST v1.1 • Duration of response (DoR) as per RECIST V1.1 • Progression free-survival (PFS) • Overall Survival (OS) • Time to deterioration of ECOG performance status (ECOG PS)
2. To evaluate the toxicity and safety profile of ivonescimab combined with chemotherapy
3. To evaluate the health-related quality of life (HRQoL) of patients treated with ivonescimab combined with chemotherapy using QLQ-C30 and QLQ-OG25 questionnaires

Conditions and MedDRA coding

Metastatic or locally advanced irresectable (stage IV) gastric cancer (GC) or esophagogastric junction cancer (EGJC), with and without actionable biomarker (HER2/Claudin18.2)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 16

1. Signed a written informed consent form prior to any trial specific procedures.
2. 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).
3. Coagulation: a. prothrombin time (PT) ≥ 70% b. international normalized ratio (INR) ≤ 1.5 x ULN c. partial prothrombin time (PTT) or activated partial thromboplastin time (aPTT) ≤40 seconds d. PTT ratio ≤1.2
4. 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.
5. WOCBP must have a negative serum pregnancy test performed within 3 days before inclusion and a negative urine pregnancy test on the day of first dose, prior to treatment administration.
6. 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
7. Affiliation to the Social Security System (or equivalent)
8. Histologically or cytologically proven oestrophageal, gastric cancer (GC) or esophagogastric junction cancer adenocarcinoma (EGJC)
9. Metastatic or locally advanced non resectable (stage IV) disease.
10. Presence of at least one measurable lesion as assessed by the investigator according to RECIST v1.1.
11. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
12. Age ≥18 years and < 80 years
13. Depending on the cohort: a. Cohort 1: Patients with no prior treatment for advanced disease and HER-2 and Claudin 18.2 negative. Time since completion of postoperative chemotherapy ≥12 months b. Cohort 2: Patients who had progressed after one prior line of chemotherapy +/- targeted agent (mandatory for HER-2 positive and/or Claudin 18.2 positive) for advanced disease.
14. Adequate hematological function: absolute neutrophil count (ANC) ≥1.5 × 10⁹/L, platelet count ≥100 × 10⁹/L, and hemoglobin ≥9 g/dL.
15. 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.
16. For patients ˃≥70 years, a G8 score ≥14 is mandatory

Exclusion criteria 23

1. Previous or concurrent cancer that is distinct in primary site or histology from gastroesophageal cancer within 2 years prior to study inclusion, except for curatively treated cervical cancer in situ, non-melanoma skin cancer and superficial bladder tumors [Ta (noninvasive tumor), Tis (carcinoma in situ) and T1 (lamina propria invasion)].
2. 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.
3. 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: a. Patients with a history of autoimmune-related hypothyroidism who are on thyroid replacement hormone are eligible for the study, b. Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study, c. Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met: i. Rash must cover < 10% of body surface area, ii. Disease is well controlled at baseline and requires only low-potency topical corticosteroids, iii. No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high potency or oral corticosteroids within the previous 12 months.
4. Known history of, or any evidence of, interstitial lung disease.
5. Patient with non-controlled human immunodeficiency virus (HIV) (positive HIV 1/2 antibodies) infection (patient with undetectable viral load (HIV RNA PCR) and CD4 above 350 either spontaneously or on stable anti-viral regimen).
6. Chronic hepatitis B or C infection (if hepatitis status cannot be obtained from medical records, re-testing is required)
7. In case of planned treatment with fluorouracil, proven complete deficiency of dihydropyrimidine dehydrogenase (DPD).
8. Any condition which in the Investigator’s opinion makes it undesirable for the subject to participate in the trial or which would jeopardize compliance with the protocol.
9. Pregnant or breast-feeding females.
10. Participation in another therapeutic trial within the 30 days prior to entering the study. Participation in an observational trial would be acceptable.
11. Patients with high microsatellite instability (MSI-H) or mismatched repair disease (dMMR) tumor.
12. Known history of hypersensitivity to ivonescimab, and to the other IMP planned (fluorouracil, oxaliplatin, folinic acid, irinotecan, and paclitaxel) or to any of their excipients
13. Depending on the treatment planned: a. 5-Fluorouracil: i. recent or concomitant treatment with brivudine, ii. potentially serious infection iii. patients in poor nutritional status, iv. live attenuated vaccines b. Oxaliplatin i. hypokalemia, hypomagnesemia, hypocalcemia ii. QT/QTc interval longer than 450 msec for men and longer than 470 msec for women on the inclusion ECG iii. peripheral sensory neuropathy with functional impairment prior to first treatment c. Irinotecan: i. concomitant use with St John’s Wort ii. chronic inflammatory bowel disease iii. live attenuated vaccines
14. Prior allogeneic bone marrow transplantation or prior solid organ transplantation
15. 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.
16. 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.
17. History of bleeding tendencies or coagulopathy and/or clinically significant bleeding symptoms or risk within 4 weeks prior to inclusion, including but not limited to: a. Hemoptysis (defined as coughing up ≥ 0.5 teaspoon of fresh blood or small blood clots), Note: transient hemoptysis associated with diagnostic bronchoscopy is allowed. b. Gastrointestinal (GI) bleeding c. Nasal bleeding /epistaxis (bloody nasal discharge is allowed), d. Current use of prophylactic or full-dose anticoagulants or anti-platelet agents
18. Poorly controlled hypertension with repeated systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100 mmHg after oral antihypertensive therapy.
19. History of major diseases before inclusion, specifically: a. Unstable angina, myocardial infarction, congestive heart failure (New York Heart Association classification ≥ grade 2) or unstable vascular disease (eg, aortic aneurysm at risk of rupture, Moyamoya disease) that required hospitalization within 12 months prior to inclusion, or other cardiac impairment that may affect the safety evaluation of the study drug (eg, poorly controlled arrhythmias, myocardial ischemia), b. History of esophageal gastric varices, severe ulcers, wounds that do not heal, abdominal fistula, intra-abdominal abscesses, or acute gastrointestinal bleeding within 6 months before inclusion, c. History of any grade arterial thromboembolic event, venous thromboembolic event of Grade 3 and above (including pulmonary embolism) as specified in NCI-CTCAE v5.0, transient ischemic attack, cerebrovascular accident, hypertensive crisis, or hypertensive encephalopathy within 12 months prior to inclusion, d. Acute exacerbation of chronic obstructive pulmonary disease within 4 weeks before inclusion, e. 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 inclusion.
20. Imaging during the screening period shows that the patient has: a. Radiologically documented evidence of major blood vessel invasion or encasement by cancer, b. Radiographic evidence of intra-tumor cavitation. c. Evidence of higher bleeding risk on prostheses
21. Enteral intake < 1500 kcal /d and or a weight loss > 15% of total body weight within the 6 months
22. Patients unwilling or unable to comply with the medical follow-up required by the trial because of geographic, familial, social, or psychological reasons.
23. Individuals deprived of liberty or placed under protective custody or guardianship

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. ORR defined as the proportion of patients achieving complete response (CR) or partial response (PR) as assessed by central review according to RECIST v1.1. Patients with unevaluable or unknown response status will be considered as non-responders.

Secondary endpoints 7

1. ORR defined as the proportion of patients achieving complete response (CR) or partial response (PR) as assessed by the investigator according to RECIST v1.1. Patients with unevaluable or unknown response status will be considered as non-responders.
2. Duration of response, defined as the time from first documented PR or CR (compared to baseline measurement taken at screening) until the date of PD, as assessed by the investigator and centralized review according to RECIST v1.1, or death from any cause, whichever occurs first. Patients who are alive and have not progressed at the time of the analysis will be censored at their last evaluable tumor assessment.
3. PFS, defined as the time from inclusion to the first documented progression of disease (PD) as assessed by the investigator and centralized review according to RECIST v1.1, or death from any cause, whichever occurs first. Patients who are alive and have not progressed at the time of the analysis will be censored at their last evaluable tumor assessment.
4. OS, defined as the time from inclusion to death due to any cause. Patients still alive at the cut-off date (including those lost to follow-up) will be censored at the last date at which they are known to be alive.
5. Time to deterioration of ECOG performance status, defined as the time from inclusion to the first observation of ECOG performance status ≥2.
6. Toxicity / Adverse events (AEs), occurrence of treatment-related AEs, treatment-related AEs (TRAEs) leading to dose reduction or discontinuation during treatment, serious adverse events (SAEs) and suspected unexpected serious adverse reactions (SUSARs), immune-related AEs (irAEs) graded according to NCI-CTCAE V5.0
7. HRQoL assessed using the European Organisation for Research and Treatment of Cancer (EORTC) quality of life questionnaires QLQ-C30 and QLQ- OG25

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 7

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Unicancer

Sponsor organisation

Unicancer

Address

101 Rue De Tolbiac

City

Paris

Postcode

75013

Country

France

Scientific contact point

Organisation

Unicancer

Contact name

Nourredine AIT RAHMOUNE

Public contact point

Organisation

Unicancer

Contact name

Nourredine AIT RAHMOUNE

Third parties 1

Locations

1 EU/EEA country · 17 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 16 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications