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

NCT07763171 · Status: NOT_YET_RECRUITING · Phase: PHASE3 · Type: INTERVENTIONAL · Enrollment: 244

Last updated 2026-08-13

No results posted yet for this study

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.

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.

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.

Conditions

  • Gastroesophageal Adenocarcinoma

Interventions

DRUG

FOLFOX (5-fluorouracil, Leucovorin, Oxaliplatin)

every 14 days

DRUG

CAPOX (oxaliplatin/capecitabine)

every 21 days

DRUG

CDDP, 5 Fu

every 21 days

DRUG

Tislelizumab

every 21 days

DRUG

Ramucirumab + Paclitaxel

on days 1, 8, 15 every 28 days

Sponsors & Collaborators

  • Gruppo Oncologico del Nord-Ovest

    lead OTHER

Principal Investigators

  • Filippo Pietrantonio, MD · Fondazione IRCCS Istituto Nazionale dei Tumori di Milano

Study Design

Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Model
PARALLEL

Eligibility

Min Age
18 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2026-09-01
Primary Completion
2029-09-30
Completion
2031-09-30

Countries

  • Italy

Study Locations

More Related Trials

Entities

Drugs

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT07763171 on ClinicalTrials.gov