A comprehensive analysis of the HER2-positive gastric cancer therapeutic landscape reveals significant momentum in drug development, with over 20 pharmaceutical and biotech companies actively pursuing more than 20 pipeline therapies to address this critical unmet medical need. The robust pipeline activity comes as gastric cancer ranks as the sixth most common cancer globally and the third leading cause of cancer-related deaths.
Recent Clinical Milestones Drive Treatment Progress
The therapeutic landscape achieved notable milestones in 2024, with Merck & Co. announcing in July that its Phase III KEYNOTE-811 trial achieved its dual primary endpoint of overall survival. The study evaluated Keytruda in combination with trastuzumab and chemotherapy containing fluoropyrimidine and platinum for the first-line treatment of patients with HER2-positive locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma.
Adding to the momentum, ENHERTU (fam-trastuzumab deruxtecan-nxki) received approval in the US in April 2024 as the first tumor-agnostic HER2-targeted therapy for patients with metastatic HER2-positive solid tumors who have undergone prior treatment.
Diverse Pipeline Spans Multiple Development Phases
The current pipeline encompasses approximately 22 products across various development stages, including late-stage Phase III products, mid-stage Phase II candidates, and early-stage Phase I therapies. The analysis also covers pre-clinical and discovery stage candidates, along with discontinued and inactive programs.
Among the most promising emerging therapies are SHR-A1811 from Jiangsu HengRui Medicine Co., Ltd., which has advanced to Phase III clinical trials representing the most advanced stage of development in the pipeline. Other notable candidates include Cinrebafusp alfa from Pieris Pharmaceuticals and BI-1607 from BioInvent International.
Targeting the HER2 Pathway in Gastric Cancer
HER2-positive gastric cancer represents a subset characterized by overexpression of the HER2 protein, which promotes tumor growth. The HER2 protein, also known as ErbB2/Neu, is a 185 kDa transmembrane glycoprotein with three key components: an extracellular ligand-binding domain, a transmembrane domain, and an intracellular tyrosine kinase domain. HER2, a member of the EGFR family, is encoded by a gene located on chromosome 17 (17q21).
Early-stage gastric cancer is often asymptomatic, with most symptoms appearing only in advanced stages. Common late-stage symptoms include unexplained weight loss, stomach pain, loss of appetite, difficulty swallowing, fatigue, nausea, vomiting, heartburn, and indigestion. While HER2-positive cancers can benefit from targeted therapies that inhibit the HER2 protein, only a minority of patients achieve a cure through surgical resection, with many experiencing recurrence.
Industry Leaders Drive Innovation
Key companies actively developing HER2-positive gastric cancer therapies include established pharmaceutical giants and emerging biotech firms. The landscape features Jiangsu HengRui Medicine Co., Ltd., Pieris Pharmaceuticals, BioInvent International, Daiichi Sankyo, AstraZeneca, Shanghai JMT-Bio Inc., Acepodia Biotech, Inc., Klus Pharma Inc., Carisma Therapeutics Inc, Novartis Pharmaceuticals, Celularity Incorporated, Hoffmann-La Roche, DualityBio Inc., Shanghai Miracogen Inc., and Bavarian Nordic.
Therapeutic Diversity Across Multiple Modalities
The pipeline demonstrates significant diversity in therapeutic approaches, with products categorized across various routes of administration including intravenous, subcutaneous, oral, and intramuscular delivery methods. The molecular composition spans monoclonal antibodies, small molecules, and peptides, reflecting the industry's comprehensive approach to targeting HER2-positive gastric cancer through multiple mechanisms of action.
This robust pipeline activity addresses the critical need for more effective and targeted therapies for HER2-positive gastric cancer, which contributes significantly to global cancer morbidity and mortality. The advances in HER2-targeted treatments provide a promising approach for managing HER2-positive gastric cancers, offering hope for improved patient outcomes in this challenging therapeutic area.
