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Switch maintenance with paclitaxel, ramucirumab and tislelizumab versus continued chemotherapy with tislelizumab in HER2‑negative, PD‑L1‑positive gastroesophageal cancer

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What is this trial about?

A plain-language summary of the goals, design and what participants do

The study focuses on patients with advanced HER2-negative and PD-L1 positive gastroesophageal adenocarcinoma, a cancer that starts in the lining of the stomach or the lower part of the esophagus and has spread beyond the original site. This type of tumor does not have the HER2 protein and shows the PD‑L1 marker, which can affect how the disease behaves and responds to treatment.

Two treatment approaches are being compared. One group receives a combination of three drugs after an initial chemotherapy period: a taxane called paclitaxel, an antibody that blocks blood‑vessel growth named ramucirumab, and an immune‑system‑activating antibody called tislelizumab. The other group continues the standard chemotherapy regimen together with tislelizumab. Paclitaxel works by stopping cancer cells from dividing, ramucirumab stops new blood vessels that feed the tumor, and tislelizumab helps the body’s immune cells recognize and attack cancer.

The purpose of the trial is to determine whether the switch to the three‑drug combination can keep the disease from getting worse for a longer time compared with continuing the original chemotherapy. After about three months of initial therapy, participants are randomly assigned to one of the two arms and receive treatment cycles every few weeks. Tumor scans are performed roughly every two months to check for growth, and the time from random assignment until the cancer progresses or the patient dies is recorded as PFS. Safety checks and quality‑of‑life questionnaires are also completed throughout the study.

The research process

The trial runs in 10 steps – from screening to follow-up. Each step says what happens and what the team monitors.

  1. Step 1

    Randomization

    After joining the study, the patient is assigned by the investigator to one of two treatment groups. the assignment is based on a random process and cannot be predicted.

  2. Step 2

    Induction phase (12 weeks)

    The patient receives a combination of chemotherapy drugs for a period of twelve weeks. each drug is given by the specified route and dose:

    oxaliplatin: 85 mg/m² intravenous infusion (the drug is delivered into a vein; the dose is calculated from the patient's body surface area).

    capecitabine: 2000 mg/m² oral (the drug is taken by mouth; the dose is calculated from the patient's body surface area).

    fluorouracil: 800 mg/m² intravenous infusion.

    cisplatin: 80 mg/m² intravenous infusion.

    calcium folinate: 200 mg/m² intravenous infusion.

  3. Step 3

    First tumor assessment (restaging)

    At the end of the twelve‑week induction phase, imaging studies are performed to evaluate the size and spread of the tumor. the results are used to determine the next treatment step.

  4. Step 4

    Allocation to treatment arm

    Based on the randomization, the patient either continues with the same chemotherapy plus tislelizumab or switches to a maintenance regimen that includes paclitaxel, ramucirumab and tislelizumab.

  5. Step 5

    Maintenance regimen (switch arm)

    The patient receives the following drugs in each treatment cycle:

    paclitaxel: 80 mg/m² intravenous infusion.

    ramucirumab: 8 mg/kg intravenous infusion (the dose is based on the patient’s weight).

    tislelizumab: 200 mg intravenous infusion.

    Treatment cycles are repeated according to the protocol until disease progression, death, withdrawal, or the start of another anticancer therapy.

  6. Step 6

    Continuation regimen (continuation arm)

    The patient continues to receive the same chemotherapy drugs used in the induction phase together with tislelizumab 200 mg intravenous infusion.

    Treatment cycles are repeated according to the protocol until disease progression, death, withdrawal, or the start of another anticancer therapy.

  7. Step 7

    Regular tumor assessments

    After the start of the assigned treatment arm, imaging studies are performed every eight weeks to monitor tumor status. the assessments follow the RECIST v1.1 criteria, which define how tumor changes are measured.

  8. Step 8

    Patient‑reported outcome questionnaires

    The patient completes quality‑of‑life questionnaires (e.g., eortc qlq‑c30, eortc qlq‑og25, eq‑5d) after randomization and then every eight weeks. the questionnaires collect information about symptoms, daily functioning and overall well‑being.

  9. Step 9

    Monitoring of side effects

    At each visit, the investigator records any adverse events using the nci‑ctcae v5.0 grading system. serious adverse events and treatment‑emergent adverse events are reported according to the trial protocol.

  10. Step 10

    End of treatment

    Treatment stops when any of the following occurs: documented disease progression, death, patient withdrawal of consent, or initiation of a different anticancer therapy. after treatment ends, follow‑up assessments may continue as defined by the study.

Who can join the trial?

20 criteria

  • You must be able to sign a written informed consent form, meaning you understand the study and agree to follow its rules and visit schedule.
  • Your urine must show a protein level of 1+ or less on a simple dipstick test; if the test shows 2+ or more, a 24‑hour urine collection must show less than 1000 mg of protein.
  • If you are a woman who could become pregnant, you need a negative blood pregnancy test at the start of the study. Women who have not had a period for at least 12 months (and are not using hormones) are considered postmenopausal.
  • Men with partners who could become pregnant, and women who could become pregnant, must agree to use an approved method of birth control (such as condoms or oral contraceptives) from the screening visit and for the required time after the last study drug dose; choosing not to have sex is acceptable if that is your normal lifestyle.
  • Women must not be breastfeeding.
  • You must allow the study team to use a previously stored sample of your tumor tissue and a blood sample for research purposes.
  • You must be at least 18 years old on the day you sign the consent form.
  • You must have a confirmed diagnosis of gastroesophageal adenocarcinoma that is either locally advanced and cannot be removed surgically, or has spread to other parts of the body.
  • Your cancer must test HER2‑negative (meaning it does not have excess HER2 protein) and have a PD‑L1 TAP score of 5% or higher.
  • You cannot have received any treatment for cancer that has spread (metastatic disease). If you had earlier treatments before surgery (neoadjuvant, adjuvant, or peri‑operative) and the cancer came back more than 6 months after the last dose, you are still eligible.
  • Your disease must be measurable or evaluable according to the RECIST v1.1 criteria, which means doctors can track the size of tumors; selected tumors must not have been treated before, or if they were, they must have grown again.
  • Your overall health level, measured by the ECOG Performance Status, must be 0 or 1 (able to carry out normal activities with only minor limitations).
  • The doctor must believe you have a life expectancy of at least 12 weeks.
  • Your body’s organ function must be adequate, shown by lab tests taken during screening:
    • No blood transfusion or growth‑factor support in the 14 days before the tests.
    • White blood cell count (absolute neutrophil count) of at least 1.5 × 10⁹/L.
    • Platelet count of at least 100 × 10⁹/L.
    • Hemoglobin (a measure of red blood cells) of at least 90 g/L.
    • Kidney function: serum creatinine ≤ 1.5 times the normal upper limit or an estimated glomerular filtration rate (eGFR) of ≥ 60 mL/min/1.73 m².
    • Liver function: total bilirubin ≤ 1.5 times the normal upper limit (or < 3 times normal if you have Gilbert’s syndrome) and AST/ALT enzymes ≤ 2.5 times normal (or ≤ 5 times normal if you have liver metastases).
    • Blood clotting ability: INR ≤ 1.5 and partial thromboplastin time (PTT) no more than 5 seconds above the normal limit, unless you are already taking blood thinners.

Who cannot join the trial?

28 criteria

  • HER2‑positive disease – having a cancer marker called HER2 that is positive; the trial only accepts HER2‑negative disease.
  • Active HIV infection – currently having HIV that is not well‑controlled.
  • Active hepatitis B infection – testing positive for hepatitis B surface antigen; only very low‑level or treated cases are allowed.
  • Active hepatitis C infection – testing positive for hepatitis C antibodies; only those with no detectable virus after treatment are allowed.
  • Recent major surgery – any surgery with general anesthesia performed within the last 28 days.
  • Previous stem cell or organ transplant – having received an allogeneic stem cell transplant or any organ transplant.
  • Bleeding disorder – known problems with blood clotting (bleeding diathesis or coagulopathy).
  • Recent serious gastrointestinal bleeding – significant bleeding, perforation, or fistula in the stomach or intestines within the past 3 months.
  • Recent serious wound or fracture – non‑healing wound, peptic ulcer, or bone fracture that occurred within the past 3 months.
  • Ongoing use of NSAIDs or antiplatelet drugs – regular use of non‑steroidal anti‑inflammatory medicines (like ibuprofen) or blood‑thinning medicines (except low‑dose aspirin up to 325 mg/day).
  • Certain heart or blood‑vessel problems – recent chest pain, serious blood clots, major vessel disease, heart attack, advanced heart failure, significant abnormal heart rhythm, QTc interval longer than 470 ms (a heart‑electrical test), recent stroke, or high blood pressure that is not controlled.
  • Active brain disease – uncontrolled leptomeningeal disease or brain metastasis that needs steroids; stable, asymptomatic brain lesions may be allowed.
  • Allergy to antibody medicines – known hypersensitivity to chimeric or humanized antibodies or fusion proteins.
  • Complete DPYD deficiency or high uracilemia – a genetic condition (DPYD deficiency) that affects chemotherapy metabolism, or a blood test (uracilemia) ≥ 16 ng/mL.
  • Allergy to study drug ingredients – known hypersensitivity to any component of ramucirumab or tislelizumab.
  • Recent cancer treatment – having received chemotherapy, immunotherapy (such as interleukin or interferon), or any investigational therapy within 14 days (or five drug half‑lives) before the first study dose.
  • Recent radiation therapy – extensive (field) radiation within 4 weeks or limited‑field radiation within 2 weeks before enrollment.
  • Recent use of herbal cancer medicines – taking any herbal product intended to treat cancer within 14 days before the first dose.
  • Recent live vaccine – receiving a live vaccine (for example, intranasal flu vaccine) within 4 weeks before the first study dose.
  • Significant medical or substance‑use issues – underlying health problems, abnormal lab results, or alcohol/drug abuse that could affect safety or study compliance.
  • Participation in another therapeutic trial – being enrolled in any other clinical study for treatment at the same time.
  • Active autoimmune disease – an immune system disorder that could flare up; some well‑controlled conditions (like type I diabetes, hypothyroidism, celiac disease, or mild skin diseases) are exceptions.
  • Other recent cancers – any other active cancer diagnosed within the past 3 years, except the cancer being studied, or certain cured skin, bladder, or cervical cancers.
  • Need for high‑dose steroids or immunosuppressants – requiring systemic corticosteroids greater than 10 mg prednisone daily or other immune‑suppressing drugs within 14 days (low‑dose, topical, or short‑course steroids may be allowed).
  • Uncontrolled diabetes or serious lab abnormalities – diabetes that is not under control or severe irregularities in potassium, sodium, calcium, or very low albumin despite treatment.
  • Advanced liver cirrhosis – liver disease classified as Child‑Pugh B or worse, or cirrhosis with brain confusion (hepatic encephalopathy) or fluid buildup (ascites) that needs medication.
  • History of serious lung disease – interstitial lung disease, pulmonary fibrosis, severe shortness of breath at rest, or need for supplemental oxygen.
  • Severe ongoing infections – chronic or active infections that need systemic antibiotics, antifungals, or antivirals, including recent severe infection, hospitalization for infection, or antibiotics within 2 weeks before the first dose.
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Investigated drugs

  • Paclitaxel

    is a chemotherapy drug given through an IV. In this study it is used in the experimental “switch maintenance” group together with ramucirumab and tislelizumab after the initial chemotherapy has been stopped. Its purpose is to keep the cancer from growing while the patient continues on the new combination.

  • Ramucirumab

    is a targeted therapy that blocks a protein called VEGFR2, which helps tumors form new blood vessels. In the trial it is given by IV infusion along with paclitaxel and tislelizumab in the switch‑maintenance arm, aiming to slow tumor growth by cutting off its blood supply.

  • Tislelizumab

    is an immunotherapy drug that blocks the PD‑1 pathway, helping the body’s immune system recognize and attack cancer cells. It is administered by IV infusion in both the experimental arm (with paclitaxel and ramucirumab) and the control arm (continued chemotherapy), so its role is to boost immune response throughout the study.

  • Oxaliplatin

    is a platinum‑based chemotherapy given by IV infusion. It is part of the standard chemotherapy regimen used before the switch‑maintenance phase. In the trial it appears as a background or comparator drug, helping to control the disease during the initial treatment period.

  • Capecitabine

    is an oral chemotherapy pill that the body converts into fluorouracil. It is used in the standard chemotherapy backbone before the switch‑maintenance strategy. Patients take it at home, and it works to stop cancer cells from dividing.

  • Fluorouracil

    is an IV chemotherapy that interferes with DNA synthesis in cancer cells. It is included in the initial chemotherapy regimen and may be given as a continuous infusion or a rapid injection. Its role is to kill rapidly growing tumor cells early in treatment.

What is already known about the treatment

  • Oxaliplatin

    Oxaliplatin is given by intravenous infusion and belongs to the platinum‑based chemotherapy group. It is an approved drug widely used in colorectal cancer and is well described in medical literature. The medication works by attaching to DNA and preventing cancer cells from repairing it, which leads to cell death. Its main therapeutic use is as part of combination regimens for solid tumors such as colorectal and gastric cancers.

  • Capecitabine

    Capecitabine is taken as an oral tablet and is classified as an antimetabolite chemotherapy. It is an approved drug for breast and colorectal cancers and has extensive clinical data. Inside the body it is converted to 5‑fluorouracil, which blocks the building blocks needed for DNA synthesis, stopping cancer cells from growing. It is used mainly to treat solid tumors, especially when an oral option is preferred.

  • Fluorouracil

    Fluorouracil (5‑FU) is administered by intravenous infusion or rapid IV bolus and is an antimetabolite drug. It is a long‑standing, approved chemotherapy for many solid tumors such as colorectal, breast, and gastric cancers. The drug mimics a natural nucleotide and interferes with DNA and RNA production, causing cancer cells to die. It is a cornerstone of many chemotherapy regimens worldwide.

  • Cisplatin

    Cisplatin is given by intravenous infusion and is a platinum‑based chemotherapy agent. It is an approved treatment for a wide range of cancers, including testicular, lung, and head‑and‑neck cancers, with a large body of research supporting its use. The medication forms cross‑links in DNA, which prevents cancer cells from dividing and leads to their death. It is commonly used in combination with other chemotherapy drugs.

  • Paclitaxel

    Paclitaxel is administered by intravenous infusion and belongs to the taxane class of chemotherapy. It is an approved drug for breast, ovarian, lung, and gastric cancers and is well documented in clinical studies. The drug works by stabilizing microtubules, the structures that pull cells apart during division, so cancer cells cannot multiply. It is often used as a key component of combination cancer treatments.

  • Calcium Folinate

    Calcium folinate (leucovorin) is given by intravenous infusion and is a folate‑derived medication. It is approved to enhance the effect of 5‑fluorouracil and to protect normal cells from its toxicity, with extensive use in colorectal and gastric cancer regimens. The compound supplies reduced folate that helps normal cells repair DNA while boosting the anticancer activity of fluorouracil. It is classified as a folinic acid rescue agent.

Investigated diseases

Advanced HER2-negative, PD-L1-positive gastroesophageal adenocarcinoma - It is a cancer that starts in the glandular cells lining the stomach or the lower part of the esophagus. The tumor cells do not have excess HER2 protein but show the presence of PD-L1 on their surface. As the disease is advanced, the cancer has grown beyond the original site and may involve nearby lymph nodes or distant organs. The growth is typically gradual, with the tumor increasing in size and sometimes causing blockage or bleeding in the digestive tract. Over time, cancer cells can spread through the bloodstream or lymphatic system to other parts of the body.
Trial detailsLast updated 7 Oct 2026
Age18+ yearsPhasePhase IIITrial ID2025-524048-36-00Protocol codeARMANI-2/ENGIC08Estimated enrolment212 patientsSponsorFondazione GONO G.I.

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