The gastric cancer therapeutic landscape is experiencing unprecedented growth, with DelveInsight's 2025 pipeline report revealing over 200 active companies developing 220+ pipeline therapies for gastric cancer treatment. This robust pipeline spans from discovery-stage compounds to late-phase clinical trials, representing a significant expansion in treatment options for the world's fifth most common cancer.
Recent Clinical Milestones Drive Pipeline Momentum
Bold Therapeutics announced on August 22, 2025, the initiation of a Phase 1b/2a dose escalation study evaluating BOLD-100 in combination with FOLFOX chemotherapy in patients with advanced solid tumors. BOLD-100, an intravenously administered ruthenium-based small molecule, has demonstrated preferential reduction of GRP78 expression in tumor cells and ER-stressed cells compared to normal cells. The study will include a dose escalation cohort to establish tolerability and safety, followed by a cohort expansion phase.
Jazz Pharmaceuticals launched a Phase 2 study on September 25, 2025, investigating zanidatamab combined with chemotherapy plus or minus tislelizumab versus trastuzumab with chemotherapy in patients with advanced HER2-positive gastric and esophageal cancers. This open-label study targets patients with unresectable or metastatic disease no longer amenable to surgical intervention or chemoradiation.
Hanmi Pharmaceutical Company Limited also announced on September 25, 2025, a Phase 2 open-label study assessing FLX475 combined with pembrolizumab in patients with advanced or metastatic gastric cancer. The study will evaluate the anti-tumor activity of FLX475 at 100mg daily dosing with pembrolizumab across two distinct cohorts.
Leading Pipeline Candidates Target Diverse Mechanisms
Late-Stage Development
Catumaxomab (Linton Pharm Co. Ltd.) represents the most advanced pipeline candidate, currently in Phase III development. This bispecific antibody, previously approved by the European Medicines Agency in 2009 for malignant ascites treatment, binds to EpCAM on tumor cells and CD3 on T cells while recruiting immune accessory cells through FcγR binding. The therapy kills tumor cells through T cell and accessory cell-mediated cytotoxicity and has demonstrated potential for inducing long-term vaccinal effects in animal models.
Mid-Stage Innovations
Tislelizumab (BeiGene) is a humanized IgG4 anti-PD-1 monoclonal antibody specifically engineered to minimize binding to FcγR on macrophages. This design addresses a key limitation identified in preclinical studies, where FcγR binding compromises anti-tumor activity through antibody-dependent macrophage-mediated killing of T effector cells. The China National Medical Products Administration has approved tislelizumab for six indications, including first-line treatment of advanced NSCLC in combination with chemotherapy, though it remains unapproved outside China.
Tivumecirnon (RAPT Therapeutics), currently in Phase II development, represents a novel approach as a small molecule CCR4 antagonist designed to block regulatory T cell migration specifically into tumors while sparing healthy tissues. Regulatory T cells represent a dominant immunosuppressive pathway that correlates with poor clinical outcomes and may limit the effectiveness of checkpoint inhibitors.
DKN-01 (Leap Therapeutics) is a humanized monoclonal antibody targeting the Dickkopf-1 (DKK1) protein, a modulator of Wnt/Beta-catenin signaling frequently implicated in tumorigenesis and immune suppression. DKK1 plays a crucial role in tumor cell signaling and mediating immunosuppressive tumor microenvironments through enhanced myeloid-derived suppressor cell activity and downregulated NK ligands on tumor cells. The therapy has received Orphan Drug Designation from the FDA for gastric and gastroesophageal junction cancer treatment.
Early-Stage and Preclinical Developments
Venadaparib (Idience), currently in Phase I development, is a potent PARP inhibitor that prevents DNA single-strand break repair and promotes conversion to double-strand breaks, ultimately leading to synthetic lethality in cancer cells. The compound is being developed as both monotherapy and in combination with other anti-cancer agents across multiple solid tumors.
BDC-4182 (Bolt Biotherapeutics) represents a next-generation ISAC candidate targeting Claudin 18.2, a novel oncology target. Currently in preclinical development, this therapy is being developed for both gastric/gastroesophageal junction cancer and pancreatic cancer treatment.
Comprehensive Therapeutic Landscape
The pipeline encompasses diverse therapeutic modalities, with products categorized across multiple routes of administration including intravenous, subcutaneous, oral, and intramuscular delivery. Molecule types span monoclonal antibodies, small molecules, and peptides, reflecting the breadth of therapeutic approaches being pursued.
Leading companies in the space include BeiGene, Linton Pharm Co. Ltd., RAPT Therapeutics, Leap Therapeutics, Idience, Bolt Biotherapeutics, Hubro Therapeutics, Immunocore, Ambrx, Hangzhou DAC Biotech, Beijing Immunoah Pharma Tech, Base Therapeutics, Nanjing KAEDI Biotech, HiberCell, Transcenta Holding, Suzhou Zelgen Biopharmaceuticals, Daiichi Sankyo, Ipsen, Alligator Bioscience, Bristol Myers Squibb, Jiangsu Hengrui Medicine, Shanghai Junshi Biosciences, and ImmunoACT.
Disease Context and Unmet Need
Gastric cancer, arising from the stomach lining, represents the third leading cause of cancer-related deaths globally. The majority of cases are adenocarcinomas developing from mucus-producing cells of the stomach lining. Risk factors include chronic gastritis, Helicobacter pylori infection, smoking, high-salt diets, and genetic predispositions. The disease often presents with non-specific symptoms including weight loss, abdominal pain, nausea, vomiting, dysphagia, early satiety, and melena, frequently leading to late-stage diagnosis when treatment options are limited.
The robust pipeline development reflects the significant unmet medical need in gastric cancer treatment, with therapeutic candidates spanning discovery through Phase III development stages. The diversity of mechanisms being pursued, from immune checkpoint inhibition to novel targets like Claudin 18.2 and DKK1, suggests a comprehensive approach to addressing the complex biology of gastric cancer.
