Clinical trial NCT06764875: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: HER2-positive Gastric Cancer
Gastroesophageal Junction Adenocarcinoma
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2025-01-09
Enrollment: 840
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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 within 14 days before randomization.
* LVEF ≥ 55% 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.

Primary outcomes:
measure: Progression free survival (PFS)
timeFrame: Up to approximately 6 years
measure: Overall Survival (OS)
timeFrame: Up to approximately 6 years
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Up to approximately 6 years
measure: Duration of Response (DoR)
timeFrame: Up to approximately 6 years
measure: Proportion of all randomized participants alive and progression-free at 6 months (PFS6)
timeFrame: Up to 6 months
measure: Proportion of all randomized participants alive and progression-free at 12 months (PFS12)
timeFrame: Up to 12 months
measure: Time to second progression or death (PFS2)
timeFrame: Up to approximately 6 years
measure: Occurrence of adverse events (AEs) and serious adverse events (SAEs)
timeFrame: Up to approximately 6 years
measure: Pharmacokinetics (PK) of rilvegostomig, T-DXd, total anti-HER2 antibody, DXd, 5-FU, and capecitabine in serum
timeFrame: Up to approximately 6 years
measure: Immunogenicity of rilvegostomig and T-DXd assessed by the presence of antidrug antibodies (ADAs) for rilvegostomig and T-DXd
timeFrame: Up to approximately 6 years
measure: Increase in enteral feeding assistance and eating difficulties
timeFrame: Up to approximately 6 years
measure: Proportion of time on study intervention with high side-effect bother
timeFrame: Up to approximately 6 years
measure: Overall Survival at 12 months (OS12)
timeFrame: Up to 12 months
measure: Overall Survival at 24 months (OS24)
timeFrame: Up to 24 months
measure: Pharmacokinetics (PK) of rilvegostomig, T-DXd, total anti-HER2 antibody, DXd, 5-FU, and capecitabine in serum
timeFrame: Up to approximately 6 years
Other outcomes:
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country: Turkey
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country: Turkey
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city: Istanbul
country: Turkey
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city: Izmir
country: Turkey
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city: Mezitli
country: Turkey
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country: United Kingdom
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country: United Kingdom
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city: Dundee
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city: London
country: United Kingdom
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city: London
country: United Kingdom
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city: Manchester
country: United Kingdom
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city: Sutton
country: United Kingdom
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city: Hanoi
country: Vietnam
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city: Ho Chi Minh city
country: Vietnam
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city: Vinh
country: Vietnam
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Study officials:
References: