P1, N=40, Active, not recruiting, Arcus Biosciences, Inc. | Trial completion date: Mar 2026 --> Sep 2027 | Trial primary completion date: Mar 2026 --> Sep 2027

5 days ago

Trial completion date • Trial primary completion date

HER-2 (Human epidermal growth factor receptor 2)

HER-2 negative

5-fluorouracil • oxaliplatin • Yutuo (zimberelimab) • leucovorin calcium • AB598

MK3475-A53: Study of SBRT/Olaparib Followed by Pembrolizumab/Olaparib in Gastric Cancers (clinicaltrials.gov)

P2, N=9, Completed, University of Colorado, Denver | Active, not recruiting --> Completed | Trial completion date: Dec 2028 --> Jan 2026

5 days ago

Trial completion • Trial completion date

HER-2 (Human epidermal growth factor receptor 2) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • HRD (Homologous Recombination Deficiency) • BAP1 (BRCA1 Associated Protein 1) • KMT2D (Lysine Methyltransferase 2D) • ATRX (ATRX Chromatin Remodeler) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD50 (RAD50 Double Strand Break Repair Protein) • MLL2 (Myeloid/lymphoid or mixed-lineage leukemia 2) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • WRN (WRN RecQ Like Helicase) • FANCG (FA Complementation Group G) • ABRAXAS1 (Abraxas 1 BRCA1 A Complex Subunit 2) • SLX4 (SLX4 Structure-Specific Endonuclease Subunit)

HRD

Keytruda (pembrolizumab) • Lynparza (olaparib)

Gastroesophageal Junction Adenocarcinoma Presenting With De Novo Metastatic Disease and Ovarian Metastasis in a Young Woman With Atypical Chest Pain. (PubMed, Cureus)

The patient was treated with combination chemotherapy and immune checkpoint inhibition. This case highlights an atypical presentation of advanced gastroesophageal junction adenocarcinoma in a young adult and underscores the importance of early endoscopic evaluation in patients with persistent dysphagia, as well as recognition of uncommon metastatic patterns and the therapeutic implications of biomarker profiling.

6 days ago

Journal • PD(L)-1 Biomarker • IO biomarker

HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • CLDN18 (Claudin 18)

PD-L1 expression • HER-2 negative

Keytruda (pembrolizumab)

Efficacy and safety of trastuzumab deruxtecan in the treatment of HER2-positive advanced or metastatic gastric or gastroesophageal cancer: a meta-analysis of single-arm trials. (PubMed, Clin Transl Oncol)

T-DXd demonstrates meaningful antitumor activity and survival benefit in HER2-positive gastric and GEJ adenocarcinoma, with a clinically relevant toxicity profile requiring careful monitoring.

6 days ago

Retrospective data • Review • Journal

HER-2 (Human epidermal growth factor receptor 2)

HER-2 positive

Enhertu (fam-trastuzumab deruxtecan-nxki)

A Study Comparing BL-M05D1 With the Investigator's Choice of Treatment Regimen in Patients With Claudin (CLDN)18.2-Positive Advanced Gastric Cancer or Gastroesophageal Junction Adenocarcinoma (GC/GEJC) Who Have Received Prior First-Line Treatment (clinicaltrials.gov)

P3, N=438, Recruiting, Sichuan Baili Pharmaceutical Co., Ltd. | Not yet recruiting --> Recruiting

6 days ago

Enrollment open

paclitaxel • docetaxel • irinotecan

RESTAGE (REpurposing STAtins to Improve Outcomes in GastroEsophageal Cancer) Trial (clinicaltrials.gov)

P2, N=184, Not yet recruiting, McGill University Health Centre/Research Institute of the McGill University Health Centre

6 days ago

New P2 trial

simvastatin

A First-in-Human Study of HH160 in Patients With Advanced Solid Tumors (clinicaltrials.gov)

P1, N=56, Not yet recruiting, Huahui Health

7 days ago

New P1 trial • First-in-human

IBI343 in Combination With Sintilimab and SOX Regimen for Perioperative Treatment of Resectable, Locally Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (clinicaltrials.gov)

P2, N=90, Recruiting, Innovent Biologics (Suzhou) Co. Ltd. | Not yet recruiting --> Recruiting

8 days ago

Enrollment open

CLDN18 (Claudin 18)

CLDN18.2 expression

Tyvyt (sintilimab) • oxaliplatin • Teysuno (gimeracil/oteracil/tegafur) • arcotatug tavatecan (TAK-921)

HIPEC Priming Followed by Serplulimab Plus SOX/XELOX in Locally Advanced Gastric Cancer (clinicaltrials.gov)

P2, N=48, Not yet recruiting, Shanghai Changzheng Hospital

8 days ago

New P2 trial

docetaxel • capecitabine • oxaliplatin • Hetronifly (serplulimab) • Teysuno (gimeracil/oteracil/tegafur)

Emerging role of antibody-drug conjugates in gastrointestinal malignancies. (PubMed, Cancer)

Therapeutic agents such as trastuzumab deruxtecan and disitamab vedotin are currently approved ADCs in HER2-overexpressing GI cancers, while multiple investigational ADCs targeting novel antigens, including Claudin 18.2, Claudin 6, B7-H3, c-MET, TROP2, and EGFR, are being evaluated in ongoing clinical trials. Innovative designs-such as biparatopic and bispecific formats, dual or multipayload strategies, and the integration of novel cytotoxic modalities like radiotherapeutic agents-are under active development to address resistance mechanisms, optimize payload delivery, and minimize off-target toxicity. This review summarizes the structural components, mechanisms of action, approved agents, and evolving clinical pipeline of ADCs in GI cancers, highlighting both current challenges and emerging strategies aimed at expanding their therapeutic potential.

9 days ago

Review • Journal

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • MET (MET proto-oncogene, receptor tyrosine kinase) • CLDN18 (Claudin 18) • CD276 (CD276 Molecule) • CLDN6 (Claudin 6)

HER-2 overexpression

Enhertu (fam-trastuzumab deruxtecan-nxki) • Aidixi (disitamab vedotin)