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Gastroesophageal AdenocarcinomaPhase 3ARMANI-2NCT07763171

Paclitaxel, Ramucirumab and Tislelizumab Switch Maintenance in Advanced HER2-negative and PD-L1 TAP Score of 5 or More Advanced Gastroesophageal Adenocarcinoma

A Phase 3 study testing FOLFOX (5-fluorouracil, Leucovorin, Oxaliplatin), CAPOX (oxaliplatin/capecitabine) and CDDP, 5 Fu in people with Gastroesophageal Adenocarcinoma, run by Gruppo Oncologico del Nord-Ovest at 42 sites in 3 countries.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
Search all trials

Trial summary

ARMANI-2/ENGIC8 is a randomized, open-label, phase III trial evaluating a switch maintenance strategy in patients with previously untreated, locally advanced unresectable or metastatic, HER2-negative and PD-L1-positive gastroesophageal adenocarcinoma. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Gastroesophageal Adenocarcinoma
What is being tested?
FOLFOX (5-fluorouracil, Leucovorin, Oxaliplatin), CAPOX (oxaliplatin/capecitabine) and CDDP, 5 Fu
Could I receive a placebo?
No, everyone receives an active treatment
How many people
244 participants
Where
42 sitesin 3 countries
Study dates
1 Sep 2026to Sep 2031
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Able to provide written informed consent and can understand and agree to comply with the requirements of the study and the schedule of assessments.
  • Age ≥ 18 years on the day of signing the informed consent form.
  • Diagnosis of histologically confirmed gastroesophageal adenocarcinoma, either locally advanced unresectable or metastatic.
  • Locally assessed HER2-negative status and PD-L1 TAP score ≥5%.
  • No prior treatment for metastatic disease. Patients who received neoadjuvant, adjuvant or perioperative therapy and had disease recurrence beyond 6 months from the last dose are eligible.
  • Measurable and/or non-measurable evaluable disease according to RECIST v1.1. Note: The target lesion(s) selected have not been previously treated with local therapy OR The target lesion(s) selected that are within the field of prior local therapy have subsequently progressed as defined by RECIST v1.1.
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  • ECOG Performance Status ≤ 1.
  • Life expectancy of at least 12 weeks in the opinion of the Investigator.
  • Adequate organ function as indicated by the following laboratory values during screening:
  • Patients must not have required a blood transfusion or growth factor support ≤ 14 days before sample collection at screening for the following i. Absolute neutrophil count (ANC) ≥ 1.5 x 10⁹/L ii. Platelets ≥ 100 x 10⁹/L iii. Hemoglobin ≥ 90 g/L b. Serum creatinine ≤ 1.5 x ULN (upper limit of normal) or estimated Glomerular Filtration Rate ≥ 60 mL/min/1.73 sqm.
  • Serum total bilirubin ≤ 1.5 x ULN (total bilirubin must be < 3 x ULN for patients with Gilberts syndrome).
  • AST and/or ALT ≤ 2.5 x ULN, or ≤ 5 x ULN in case of liver metastases. e. Adequate coagulation function as defined by International Normalized Ratio (INR) ≤ 1.5, and a partial thromboplastin time (PTT) ≤ 5 seconds above the ULN (unless receiving anticoagulation therapy).
  • The patient's urinary protein is ≤ 1+ on dipstick or routine urinalysis. If urine dipstick or routine analysis indicates proteinuria ≥ 2+, then 24-hour urine must be collected and must demonstrate < 1000 mg of protein in 24 hours to allow participation in the study.
  • Women of childbearing potential must have a negative blood pregnancy test at the baseline visit. For this trial, women of childbearing potential are defined as all women after puberty, unless they are postmenopausal for at least 12 months, are surgically sterile, or are sexually inactive. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of amenorrhea, a single FSH measurement is insufficient.
  • Male subjects with female partners of childbearing potential and female subjects of childbearing potential must be willing to use adequate contraception as approved be the Investigator (barrier contraceptive measure or oral contraception), starting with the screening visit and ≥ 120 days after the last treatment dose of tislelizumab or ≥ 180 days after the last dose of chemotherapy or or ≥ 90 days after the last dose of ramucirumab.
  • Note: abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
  • Women must not be breastfeeding.
  • Archival tumor tissue (primary or metastatic) and blood samples are required for exploratory research at enrollment.

Who cannot join

  • HER2-positive disease as determined by local standards.
  • Active leptomeningeal disease or uncontrolled brain metastases. Patients with treated, asymptomatic and radiologically stable brain metastases may be eligible according to protocol-defined criteria.
  • Active autoimmune disease or history of autoimmune disease that may relapse, except for protocol-specified conditions.
  • Any active malignancy within 3 years before enrollment, except for the cancer under investigation and protocol-specified malignancies treated with curative intent.
  • Any condition requiring systemic corticosteroids (>10 mg/day prednisone or equivalent) or other immunosuppressive medications within 14 days before the first study treatment, except as specified in the protocol.
  • Uncontrolled diabetes; Grade >1 abnormalities in potassium, sodium, or corrected calcium despite standard medical management; or Grade ≥3 hypoalbuminemia within 14 days before enrollment.
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  • Child-Pugh B or worse cirrhosis, or cirrhosis of any degree with a history of hepatic encephalopathy or clinically meaningful ascites.
  • History of interstitial lung disease, non-infectious pneumonitis or uncontrolled pulmonary disease, severe dyspnea at rest, or requirement for supplemental oxygen.
  • Severe chronic or active infections requiring systemic antibacterial, antifungal, or antiviral therapy, including protocol-defined recent severe infections or antibiotic treatment.
  • Known active HIV infection, unless protocol-defined criteria for controlled HIV infection are met.
  • Acute or chronic hepatitis B, except for patients meeting protocol-defined criteria.
  • Acute or chronic hepatitis C, except for patients meeting protocol-defined criteria.
  • Any major surgical procedure requiring general anesthesia within 28 days before the first study treatment.
  • Prior allogeneic stem cell transplantation or organ transplantation.
  • Evidence of bleeding diathesis or coagulopathy.
  • Significant bleeding episodes from the gastrointestinal tract, gastrointestinal perforation and/or fistulae within 3 months before the first study treatment.
  • Serious or non-healing wound, peptic ulcer, or bone fracture within 3 months before the first study treatment.
  • Ongoing chronic therapy with NSAIDs or other antiplatelet agents. Aspirin at doses up to 325 mg/day is permitted.
  • Protocol-defined cardiovascular risk factors, including recent cardiac chest pain, Grade ≥3 venous thromboembolism, significant vascular disease, myocardial infarction, NYHA Class III-IV heart failure, Grade ≥2 ventricular arrhythmia, QTc >470 msec, cerebrovascular accident, or uncontrolled hypertension.
  • Known hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins.
  • Complete DPYD deficiency. Additional restrictions based on uracilemia apply at German sites.
  • Known allergy or hypersensitivity to any components used in the ramucirumab or tislelizumab preparations, or contraindications to protocol chemotherapy according to local prescribing information.
  • Receipt of chemotherapy, immunotherapy, or investigational therapy within 14 days or 5 half-lives, whichever is shorter, before the first study drug administration.
  • Extended-field radiation within 4 weeks or limited-field radiation within 2 weeks before the first study treatment.
  • Receipt of any herbal medicine used to control cancer within 14 days before the first study drug administration.
  • Administration of a live vaccine within 4 weeks before the first dose of study treatment.
  • Underlying medical conditions, laboratory abnormalities, or alcohol or drug abuse or dependence that could interfere with study treatment administration, interpretation of toxicity or adverse events, or compliance with study procedures.
  • Concurrent participation in another therapeutic clinical study.
  • PRE-RANDOMIZATION CHECKLIST
  • Patients must continue to meet all applicable Induction phase inclusion and exclusion criteria before randomization.
  • Completion of the 12-week Induction phase therapy.
  • No permanent discontinuation of any study treatment administered during the Induction phase.
  • CR, PR, or SD as best response to Induction therapy for patients with measurable disease, or non-PD for patients with non-measurable disease, according to RECIST v1.1.
  • No contraindications to receiving ramucirumab before randomization, including:
  • No arterial thromboembolism or Grade ≥3 venous thromboembolism within the previous 3 months.
  • No full-dose anticoagulant therapy with warfarin, LMWH, or NOACs within the previous 3 months. Low-dose prophylactic anticoagulants are permitted.
  • No significant gastrointestinal bleeding, gastrointestinal perforation, and/or fistulae within the previous 3 months.
  • No major surgical procedure requiring general anesthesia within 28 days before the first study treatment.

Trial locations and contacts

42 sites in 3 countries. Contact the study team or a site near you to ask about taking part.

Filippo Pietrantonio, MD contact

+390223903807

filippo.pietrantonio@isitutotumori.mi.it

Giovanni Randon, MD contact

giovanni.randon@istitutotumori.mi.it

42 sites in 3 countries

Italy29 sites

  • Centro Riferimento Oncologico

    Aviano

    Luisa Foltran, MD, +390434 659111, luisa.foltran@cro.it

  • IRCCS Istituto Tumori Giovanni Paolo II

    Bari

    Oronzo Brunetti, MD, +39080 555 5111, dr.oronzo.brunetti1983@gmail.com

  • IRCCS Azienda ospedaliero-universitaria di Bologna - Policlinico Sant'Orsola

    Bologna

    Karim Rihawi, MD, +39051 214 1111, karim.rihawi@aosp.bo.it

  • ASST Ospedale Maggiore di Crema

    Crema

    Gianluca Tomasello, MD, +390373 2801, gianluca.tomasello@asst-crema.it

  • ASST di Cremona

    Cremona

    Maria Bonomi, MD, +390372 405111, maria.bonomi@asst-cremona.it

  • IRCCS Ospedale Policlinico San Martino

    Genova

    Alessandro Pastorino, MD, +39010 5551, alessandro.pastorino@hsanmartino.it

  • Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - IRST IRCCS

    Meldola

    Margherita Muratore, MD, +390543 739100, margherita.muratore@irst.emr.it

  • ASST Grande Ospedale Metropolitano Niguarda

    Milan

    Katia Bencardino, MD, +39 02 64441, katiabruna.bencardino@ospedaleniguarda.it

  • Fondazione IRCCS Istituto Nazionale dei Tumori di Milano

    Milan

    Giovanni Randon, MD, +390223903841, giovanni.randon@istitutotumori.mi.it

    Roberta Fazio, MD, roberta.fazio@istitutotumori.mi.it

  • Azienda Ospedaliera Universitaria di Modena

    Modena

    Andrea Spallanzani, MD, PhD, +39059 422 2111, spallanzani.andrea@aou.mo.it

  • Azienda Ospedaliera Universitaria "Luigi Vanvitelli"

    Naples

    Ferdinando De Vita, Prof., +39081 017 6956, Ferdinando.DEVITA@unicampania.it

  • Istituto Nazionale Tumori IRCCS Fondazione G. Pascale

    Naples

    Antonio Avallone, MD, +39081 590 3111, a.avallone@istitutotumori.na.it

  • Presidio Ospedaliero Ospedale del Mare

    Naples

    Angelica Petrillo, MD, +39 081 254 1111, angelic.petrillo@gmail.com

  • Azienda Ospedaliero-Universitaria Maggiore della Carità

    Novara

    Laura Forti, MD, +390321 3731, laura.forti@maggioreosp.novara.it

  • Azienda Ospedaliera Universitaria San Luigi Gonzaga

    Orbassano, Torino

    Silvia Novello, MD, PhD, +39011 90261, silvia.novello@unito.it

  • Istituto Oncologico Veneto I.R.C.C.S

    Padova

    francesca Bergamo, MD, +39 049 821 1111, francesca.bergamo@iov.veneto.it

  • Azienda Ospedaliero-Universitaria di Parma

    Parma

    Simona Bui, MD, +390521 702111, sbui@ao.pr.it

  • Fondazione I.R.C.C.S. Policlinico San Matteo

    Pavia

    Salvatore Corallo, MD, +390382 5011, s.corallo@smatteo.pv.it

  • Azienda Sanitaria Territoriale di Pesaro e Urbino

    Pesaro

    Rita Chiari, MD, +390721 4241, rita.chiari@sanita.marche.it

  • Azienda Ospedaliero Universitaria Pisana

    Pisa

    Lorenzo Fornaro, MD, +39050 992111, lorenzo.fornaro@gmail.com

  • Prato Santo Stefano - Azienda Usl Toscana Centro

    Prato

    Samantha Di Donato, MD, +390574 801111, samantha.didonato@uslcentro.toscana.it

  • Azienda USL della Romagna

    Ravenna

    Stefano Tamberi, MD, PhD, +390544 286550, ste.tamberi@gmail.com

  • IRCCS Istituto Nazionale Tumori Regina Elena - RIN

    Roma

    Chiara manai, MD, +3906 52661, chiara.manai@ifo.it

  • Policlinico Tor Vergata

    Roma

    Vincenzo Formica, MD PhD, +3906 20901, vincenzo.formica@uniroma2.it

  • Policlinico Universitario Fondazione Agostino Gemelli - Roma

    Roma

    Antonia Strippoli, MD, +39 06 30151, antonia.strippoli@policlinicogemelli.it

  • IRCCS Istituto Clinico Humanitas Research Hospital

    Rozzano, Milano

    Alberto Puccini, MD, +3902 82241, alberto.puccini@hunimed.eu

  • Fondazione Casa Sollievo della Sofferenza

    San Giovanni Rotondo, Foggia

    Tiziana Latiano, MD, +390882 410111, latianotiziana@gmail.com

  • Pia Fondazione PANICO

    Tricase, Lecce

    Emiliano Tamburini, MD, +390833 773111, emilianotamburini@icloud.com

  • Presidio Ospedaliero Universitario Santa Maria della Misericordia

    Udine

    Silvio Ken Garattini, MD, +390432 5521, silvioken.garattini@asufc.sanita.fvg.it

Other trials in Italy

Spain9 sites

  • Vall d'Hebron Barcelona Hospital

    Barcelona

    Eduardo Terán-Brage, MD, +34 934 89 30 00, eduardoteran@vhio.net

  • Hospital General Universitario Gregorio Marañón

    Madrid

    Aitana Calvo, MD, +34 915 86 80 00, aitanacalvo@gmail.com

  • Hospital Universitario La Paz

    Madrid

    Ana Custodio Carretero, MD, +34 917 27 70 00, anabcustodio@gmail.com

  • Hospital Regional Universitario de Málaga

    Málaga

    Carolina Muriel López, MD, +34 951 29 00 00, carolinamuriellopez@hotmail.com

  • Complexo Hospitalario Universitario de Ourense - CHUO

    Ourense

    Ana Fernández Montes, MD, +34 988 38 55 00, afm1003@hotmail.com

  • Hospital Universitario de Navarra

    Pamplona

    Maria Alsina Maqueda, MD, +34 848 42 22 22, maria.alsina.maqueda@navarra.es

  • HUMV - Hospital Universitario Marqués de Valdecilla

    Santander

    Eva Martinez De Castro, MD, +34 942 20 25 20, eva.martinezde@scsalud.es

  • Hospital Clínico Universitario de Valencia

    Valencia

    Tania Fleitas, MD, +34 961 97 35 00, tfleitask@gmail.com

  • Hospital Universitario Miguel Servet

    Zaragoza

Other trials in Spain

Germany4 sites

  • Krankenhaus Nordwest

    Frankfurt

    Thorsten Götze, MD, Prof., +49 69 76011, goetze.thorsten@khnw.de

  • Universitätsklinikum Hamburg-Eppendorf

    Hamburg

    Joseph Tintelnot, MD, +49 40 74100, j.tintelnot@uke.de

  • TUM Klinikum Rechts der Isar

    München

    Sylvie Lorenzen, MD, Prof., +49 89 41400, sylvie.lorenzen@mri.tum.de

  • Universitätsklinikum Ulm

    Ulm

    Thomas Ettrich, MD, +49 731 5000, thomas.ettrich@uniklinik-ulm.de

Other trials in Germany

About this study

Official title: Paclitaxel Plus Ramucirumab and Tislelizumab as Switch Maintenance Versus Continuation of Chemotherapy and Tislelizumab in Patients With Advanced HER2-negative and PD-L1 Positive Gastroesophageal Adenocarcinoma: the ARMANI-2/ENGIC08 Trial by GONO

ARMANI-2/ENGIC8 is a randomized, open-label, phase III trial evaluating a switch maintenance strategy in patients with previously untreated, locally advanced unresectable or metastatic, HER2-negative and PD-L1-positive gastroesophageal adenocarcinoma.

The combination of platinum- and fluoropyrimidine-based chemotherapy with an anti-PD-1 agent represents a first-line treatment option for patients with advanced HER2-negative, PD-L1-positive gastroesophageal adenocarcinoma. However, disease progression remains frequent and may lead to clinical deterioration, preventing a substantial proportion of patients from receiving subsequent anticancer treatment.

Read more

The phase III ARMANI trial demonstrated that, in patients with advanced HER2-negative gastric or gastroesophageal junction adenocarcinoma who achieved disease control after 3 months of first-line oxaliplatin- and fluoropyrimidine-based chemotherapy, switching to paclitaxel plus ramucirumab significantly improved progression-free survival and overall survival compared with continuation of the initial chemotherapy. These findings support the early introduction of a non-cross-resistant treatment before the development of chemotherapy-resistant disease and clinical deterioration.

ARMANI-2 builds on this strategy in the current immunotherapy-based treatment setting. In addition, VEGF/VEGFR blockade may have immunomodulatory effects that provide a biological rationale for combining ramucirumab with PD-1 blockade.

All eligible patients will receive a 12-week induction treatment with tislelizumab combined with platinum- and fluoropyrimidine-based chemotherapy (mFOLFOX6, CAPOX, or cisplatin plus fluorouracil). Patients who complete induction without disease progression or permanent treatment discontinuation will be randomized 1:1 to receive either switch maintenance with paclitaxel, ramucirumab, and tislelizumab (Arm A) or continuation of the chemotherapy regimen used during induction in combination with tislelizumab (Arm B).

The primary objective is to determine whether switch maintenance with paclitaxel, ramucirumab, and tislelizumab improves progression-free survival compared with continuation of chemotherapy and tislelizumab. Secondary objectives include overall survival, PFS2, tumor response and disease control, safety, health-related quality of life, and attrition to subsequent anticancer therapy. Exploratory analyses will investigate clinical and translational biomarkers potentially associated with treatment efficacy and early disease progression.

Being tested
FOLFOX (5-fluorouracil, Leucovorin, Oxaliplatin), CAPOX (oxaliplatin/capecitabine), CDDP, 5 Fu, Tislelizumab, Ramucirumab + Paclitaxel
Keywords
HER2-negative, PD-L1 TAP score, switch maintenance, paclitaxel, ramucirumab, tislelizumab

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • FOLFOX (5-fluorouracil, Leucovorin, Oxaliplatin)Drug

    every 14 days

  • CAPOX (oxaliplatin/capecitabine)Drug

    every 21 days

  • CDDP, 5 FuDrug

    every 21 days

  • TislelizumabDrug

    every 21 days

  • Ramucirumab + PaclitaxelDrug

    on days 1, 8, 15 every 28 days

Study groups in NCT07763171
Study groupRoleWhat they receive
InductionOtherPatients will receive platinum and fluoropyrimidine plus tislelizumab therapy for the 12-week Induction phase
Receives: Drug: FOLFOX (5-fluorouracil, Leucovorin, Oxaliplatin); Drug: CAPOX (oxaliplatin/capecitabine); Drug: CDDP, 5 Fu; Drug: Tislelizumab
Arm AExperimentalPatients randomized to the experimental arm will receive the swith maintance regimen of paclitaxel plus ramucirumab while continuing tislelizumab
Receives: Drug: Tislelizumab; Drug: Ramucirumab + Paclitaxel
Arm BActive comparatorPatients randomized to the continuation of chemotherapy plus tislelizumab will receive the same regimen used in the Induction phase.
Receives: Drug: FOLFOX (5-fluorouracil, Leucovorin, Oxaliplatin); Drug: CAPOX (oxaliplatin/capecitabine); Drug: CDDP, 5 Fu; Drug: Tislelizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression-free survival

    Measured: 36 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Aug 2026
  2. Study start1 Sep 2026 (estimated)
  3. Primary completionSep 2029 (estimated)
  4. Study completionSep 2031 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
244 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07763171
Sponsor's protocol ID
ARMANI-2/ENGIC08
Other IDs
2025-524048-36-00, 2025
Acronym
ARMANI-2
Status last verified
Aug 2026
First submitted
10 Aug 2026
Last updated
18 Aug 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing FOLFOX (5-fluorouracil, Leucovorin, Oxaliplatin), CAPOX (oxaliplatin/capecitabine) and CDDP, 5 Fu in people with Gastroesophageal Adenocarcinoma, run by Gruppo Oncologico del Nord-Ovest at 42 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 38 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 18 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 42 sites in Italy, Spain, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Filippo Pietrantonio, MD (+390223903807, filippo.pietrantonio@isitutotumori.mi.it), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free survival (time frame: 36 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07763171.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Aug 2026.

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