A cross-tumor perspective contrasts GC/GEJ testing and biology with the breast cancer paradigm and summarizes the importance of HER2-low expression in non-gastric malignancies. Finally, we discuss the therapeutic strategies in HER2-low GC/GEJ and highlight key safety and monitoring considerations for HER2-directed ADCs.

6 days ago

Review • Journal

HER-2 (Human epidermal growth factor receptor 2)

HER-2 positive • HER-2 overexpression • HER-2 amplification • HER-2 underexpression • HER-2 positive + HER-2 overexpression

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

Plasma PlGF as a Potential Biomarker in Ramucirumab-Based Second-Line Therapy for Advanced Gastroesophageal Adenocarcinoma: Exploratory Biomarker Analysis from the Phase II Part of the RAMIRIS Trial. (PubMed, Int J Cancer)

The phase II RAMIRIS trial compared RAM plus paclitaxel with RAM plus FOLFIRI (5-fluororuracil, leucovorin and irinotecan) in this setting...Elevated PlGF-particularly its early increase during RAM-based therapy-was associated with shortened survival and may represent a dynamic marker of unfavorable prognosis in advanced gastric/GEJ adenocarcinoma. Given the exploratory nature of this analysis, these findings should be considered hypothesis-generating and require validation in independent biomarker-driven studies.

8 days ago

P2 data • Journal

CA9 (Carbonic anhydrase 9)

paclitaxel • 5-fluorouracil • Cyramza (ramucirumab) • irinotecan • leucovorin calcium

FAZA PETMRI Gastro-Oesophageal Study (clinicaltrials.gov)

P=N/A, N=40, Recruiting, University Health Network, Toronto | Trial completion date: Dec 2025 --> Dec 2027 | Trial primary completion date: Dec 2025 --> Dec 2027

8 days ago

Trial completion date • Trial primary completion date

INTEGRATEIIb: RegoNivo vs Standard of Care Chemotherapy in AGOC (clinicaltrials.gov)

P3, N=462, Completed, Australasian Gastro-Intestinal Trials Group | Active, not recruiting --> Completed

8 days ago

Trial completion

HER-2 (Human epidermal growth factor receptor 2)

HER-2 positive

Opdivo (nivolumab) • docetaxel • albumin-bound paclitaxel • Stivarga (regorafenib) • irinotecan • Lonsurf (trifluridine/tipiracil)

13d

A Study of Cadonilimab Combined With Chemotherapy in People With Gastric or Gastroesophageal Junction Cancer (clinicaltrials.gov)

P2, N=37, Recruiting, Memorial Sloan Kettering Cancer Center

13 days ago

New P2 trial

HER-2 (Human epidermal growth factor receptor 2)

HER-2 amplification • HER-2 negative

Kaitanni (cadonilimab)

13d

Neoadjuvant Intra-tumoral RP2 and FLOT in Gastroesophageal Adenocarcinoma (clinicaltrials.gov)

P2, N=34, Not yet recruiting, Abramson Cancer Center at Penn Medicine | Initiation date: Apr 2026 --> Sep 2026

13 days ago

Trial initiation date

docetaxel • 5-fluorouracil • oxaliplatin • leucovorin calcium • Neulasta (pegfilgrastim) • Neupogen (filgrastim) • sturlimogene erparepvec (RP2)

13d

ARC-25: Study of AB598 Monotherapy and Combination Therapy in Participants With Advanced Cancers (clinicaltrials.gov)

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

13 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

13d

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

13 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)

14d

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.

14 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)

14d

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.

14 days ago

Retrospective data • Review • Journal

HER-2 (Human epidermal growth factor receptor 2)

HER-2 positive

Enhertu (fam-trastuzumab deruxtecan-nxki)