A Phase Ⅲ Study of Rilvegostomig in Combination With Fluoropyrimidine and Trastuzumab Deruxtecan as the First-line Treatment for HER2-positive Gastric Cancer

Official title

A Randomized, Phase Ⅲ Study of Rilvegostomig in Combination With Fluoropyrimidine and Trastuzumab Deruxtecan Versus Trastuzumab, Chemotherapy, and Pembrolizumab for the First Line Treatment of HER2-positive Gastric Cancer (ARTEMIDE-Gastric01)

Overview

This is a Phase Ⅲ, randomized, open-label, Sponsor-blinded, 3-arm, global, multicenter study assessing the efficacy and safety of rilvegostomig in combination with fluoropyrimidine and T-DXd (Arm A) compared to trastuzumab, chemotherapy, and pembrolizumab (Arm B) in HER2-positive locally advanced or metastatic gastric or GEJ adenocarcinoma participants whose tumors express PD L1 CPS ≥ 1. Rilvegostomig in combination with trastuzumab and chemotherapy will be evaluated in a separate arm (Arm C) to assess the contribution of each component in the experimental arm.

Detailed description

The purpose of this study is to assess the efficacy and safety of rilvegostomig in combination with fluoropyrimidine and T-DXd (Arm A) compared to trastuzumab, chemotherapy, and pembrolizumab (Arm B) in HER2-positive locally advanced or metastatic gastric or GEJ adenocarcinoma participants whose tumors express PD L1 CPS ≥ 1. Rilvegostomig in combination with trastuzumab and chemotherapy will be evaluated in a separate arm (Arm C) to assess the contribution of each component in the experimental arm.

This study will be conducted at up to 200-250 sites globally in approximately 25 countries.

Interventions

• Drug Rilvegostomig
  Q3W, intravenous infusion
• Drug Trastuzumab deruxtecan
  Q3W, intravenous infusion
• Drug Trastuzumab
  Q3W, intravenous infusion
• Drug Pembrolizumab
  Q3W, intravenous infusion
• Drug 5-fluorouracil
  Q3W, intravenous infusion
• Drug Capecitabine
  BID, oral administration
• Drug Cisplatin
  Q3W, intravenous infusion
• Drug Oxaliplatin
  Q3W, intravenous infusion

Primary outcome measures

• Progression free survival (PFS) [Time frame: Up to approximately 6 years]
• Overall Survival (OS) [Time frame: Up to approximately 6 years]

Secondary outcome measures (12)

• Objective Response Rate (ORR) [Time frame: Up to approximately 6 years]
• Duration of Response (DoR) [Time frame: Up to approximately 6 years]
• Proportion of all randomized participants alive and progression-free at 6 months (PFS6) [Time frame: Up to 6 months]
• Proportion of all randomized participants alive and progression-free at 12 months (PFS12) [Time frame: Up to 12 months]
• Time to second progression or death (PFS2) [Time frame: Up to approximately 6 years]
• Occurrence of adverse events (AEs) and serious adverse events (SAEs) [Time frame: Up to approximately 6 years]
• Pharmacokinetics (PK) of rilvegostomig, T-DXd, total anti-HER2 antibody, DXd, 5-FU, and capecitabine in serum [Time frame: Up to approximately 6 years]
• Immunogenicity of rilvegostomig and T-DXd assessed by the presence of antidrug antibodies (ADAs) for rilvegostomig and T-DXd [Time frame: Up to approximately 6 years]
• Increase in enteral feeding assistance and eating difficulties [Time frame: Up to approximately 6 years]
• Proportion of time on study intervention with high side-effect bother [Time frame: Up to approximately 6 years]
• Overall Survival at 12 months (OS12) [Time frame: Up to 12 months]
• Overall Survival at 24 months (OS24) [Time frame: Up to 24 months]

Eligibility criteria

Inclusion criteria

• HER2 positive for gastric cancer on a tumor biopsy.
• PD-L1 combined positive score (CPS) ≥ 1.
• Provision of tumor tissue sample from recent biopsy adequate for HER2 and PD-L1 testing.
• Previously untreated, unresectable, locally advanced or metastatic gastric or GEJ adenocarcinoma.
• WHO or Eastern Cooperative Oncology Group performance status of 0 or 1.
• Have measurable target disease assessed by the Investigator based on RECIST v1.1.
• Have adequate organ and bone marrow function.
• LVEF ≥ 50% within 28 days before randomization.
• Adequate treatment washout period before randomization.

Exclusion criteria

• Lack of physiological integrity of the upper gastrointestinal tract.
• Known dihydropyrimidine dehydrogenase enzyme deficiency.
• Contraindication to pembrolizumab or trastuzumab, contraindications to fluoropyrimidine (5-FU and capecitabine) or platinum (cisplatin and oxaliplatin) treatment as per local label.
• History of another primary malignancy except for malignancy treated with curative intent with no known active disease within 3 years before the first dose of study intervention and of low potential risk for recurrence.
• Persistent toxicities caused by previous anti-cancer therapy.
• Spinal cord compression or brain metastases unless asymptomatic, treated and stable and not requiring corticosteroid or anticonvulsant may be included in the study if they have recovered from the acute toxic effect of radiotherapy.
• Uncontrolled infection including tuberculosis and active hepatitis A infection.
• Uncontrolled infection requiring intravenous (IV) antibiotics, anti-virals, or antifungals.
• Recent receipt of live, attenuated vaccine.
• Chronic/active HBV or HCV infection unless controlled.
• Clinically significant cardiac or psychological conditions.
• Active or prior documented autoimmune or inflammatory disorders requiring chronic treatment with steroids or other immunosuppressive treatment.
• History of (non-infectious) ILD/pneumonitis, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
• Lung-specific intercurrent clinically significant illnesses.
• Any active non-infectious skin disease requiring systemic treatment.
• A pleural effusion, ascites or pericardial effusion that requires drainage, peritoneal shunt, or cell-free and concentrated ascites reinfusion therapy (CART).
• History of any of the following: drug-induced severe cutaneous adverse reaction.
• Any concurrent antic-ancer treatment with the exception of receptor activator of nuclear factor kappa-B ligand inhibitors.
• Have had major surgical procedure recently (excluding placement of vascular access) or recent significant traumatic injury or an anticipated need for major surgery during the study.
• Current or prior use of immunosuppressive medication within 14 days before study intervention.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

United States · 55 centers

• Research Site — Anchorage
• Research Site — Phoenix
• Research Site — Duarte
• Research Site — Glendale
• Research Site — La Jolla
• Research Site — Los Alamitos
• Research Site — Los Angeles
• Research Site — Santa Monica
• … and 47 more centers

China · 39 centers

Center list to be confirmed — check the primary protocol.

Japan · 25 centers

Center list to be confirmed — check the primary protocol.

Germany · 18 centers

Center list to be confirmed — check the primary protocol.

France · 10 centers

Center list to be confirmed — check the primary protocol.

Brazil · 9 centers

• Research Site — Barretos
• Research Site — Brasília
• Research Site — Campo Grande
• Research Site — Natal
• Research Site — Porto Alegre
• Research Site — Recife
• Research Site — Salvador
• … and 2 more centers

Canada · 9 centers

Center list to be confirmed — check the primary protocol.

South Korea · 9 centers

Center list to be confirmed — check the primary protocol.

Taiwan · 9 centers

Center list to be confirmed — check the primary protocol.

India · 8 centers

Center list to be confirmed — check the primary protocol.

Italy · 8 centers

Center list to be confirmed — check the primary protocol.

Spain · 8 centers

Center list to be confirmed — check the primary protocol.

Chile · 7 centers

Center list to be confirmed — check the primary protocol.

Hungary · 7 centers

Center list to be confirmed — check the primary protocol.

Peru · 7 centers

Center list to be confirmed — check the primary protocol.

Poland · 7 centers

Center list to be confirmed — check the primary protocol.

Thailand · 7 centers

Center list to be confirmed — check the primary protocol.

Turkey (Türkiye) · 7 centers

Center list to be confirmed — check the primary protocol.

United Kingdom · 7 centers

Center list to be confirmed — check the primary protocol.

Argentina · 6 centers

• Research Site — Buenos Aires
• Research Site — Ciudad Autónoma Buenos Aires
• Research Site — Ciudad de Buenos Aires
• Research Site — Rosario
• Research Site — Rosario
• Research Site — Viedma

Hong Kong · 5 centers

Center list to be confirmed — check the primary protocol.

Malaysia · 5 centers

Center list to be confirmed — check the primary protocol.

Vietnam · 5 centers

Center list to be confirmed — check the primary protocol.

Australia · 4 centers

• Research Site — Darlinghurst
• Research Site — Heidelberg
• Research Site — Murdoch
• Research Site — Westmead

Austria · 4 centers

• Research Site — Linz
• Research Site — Salzburg
• Research Site — Vienna
• Research Site — Wiener Neustadt

Belgium · 4 centers

• Research Site — Edegem
• Research Site — Ghent
• Research Site — Leuven
• Research Site — Liège

Netherlands · 3 centers

Center list to be confirmed — check the primary protocol.

Puerto Rico · 1 center

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT06764875 · D702AC00001 · 2024-512583-57-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗