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trastuzumab rezatecan + retlirafusp alfa + pertuzumab

Development stage: Unknown
Lead developer: Hengrui Pharmaceutical
Modality: Fc-Fusion Proteins → Carrier/Scaffold Proteins → Recombinant Proteins and Enzymes, Cytotoxic ADCs → Antibody-Drug Conjugates (ADCs) → Antibody Conjugates → Antibody-Based Therapeutics, Monoclonal Antibodies → Antibody-Based Therapeutics
Administration: Intravenous

Overview

Trastuzumab rezatecan + retlirafusp alfa + pertuzumab is an investigational combination regimen being evaluated for the neoadjuvant treatment of HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma. The regimen consists of three distinct biologic agents: **trastuzumab rezatecan** (SHR-A1811), a HER2-targeted antibody-drug conjugate (ADC) featuring a trastuzumab-based antibody linked to a topoisomerase I inhibitor payload; **retlirafusp alfa** (SHR-1701), a bifunctional fusion protein designed to simultaneously block the PD-L1 and TGF-β pathways to enhance anti-tumor immunity; and **pertuzumab**, a monoclonal antibody that inhibits HER2 dimerization. This combination aims to provide comprehensive HER2 blockade while leveraging immune checkpoint inhibition and TGF-β signaling modulation to overcome resistance and improve pathological complete response (pCR) rates in the pre-surgical setting.

Other names: SHR-A1811 + SHR-1701 + pertuzumab biosimilar

Targets

TGFB (GARP–latent transforming growth factor beta 1 complex)CD274 (Programmed cell death protein 1 ligand 1)TOP1 (DNA Topoisomerase I)HER2 ECD subdomain II (Human epidermal growth factor receptor 2 dimerization interface)

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