Gastroesophageal Cancer

Neoadjuvant camrelizumab plus trastuzumab and chemotherapy demonstrated favorable response and tolerable safety in HER2-positive G/GEJ adenocarcinoma.

Within NSCLC, 26% of activating mutations were not included in clinical trials that led to approval of the antibody-drug conjugate trastuzumab deruxtecan (T-DXd)...We identified substantial populations of patients with diverse ERBB2/ERBB3 activating alterations, which represent unmet therapeutic needs. We demonstrate that CGP provides additional genomic information, inclusive of ERBB2 amplification and mutation status together with potential resistance/response-modifying co-alterations, allowing for more nuanced HER2 status interpretation than is possible with IHC/FISH alone.

P1, N=70, Recruiting, TORL Biotherapeutics, LLC | Trial completion date: Jan 2026 --> Feb 2027 | Trial primary completion date: Jan 2025 --> Feb 2026

P2, N=50, Not yet recruiting, Medical College of Wisconsin

P=N/A, N=2039, Not yet recruiting, Sun Yat-sen University Cancer Prevention Center(YNMT) ; Sun Yat-sen University Cancer Prevention Center(YNMT)

P2, N=3, Terminated, Baylor College of Medicine | N=50 --> 3 | Trial completion date: Jan 2029 --> Feb 2025 | Recruiting --> Terminated | Trial primary completion date: Oct 2028 --> Feb 2025; Since activation, 3 subjects were enrolled but were not able to be randomized to a treatment arm because of a positive diagnostic laparoscopy result. Given the lack of accrual the study was closed.

P=N/A, N=40, Recruiting, University Health Network, Toronto | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

P3, N=737, Active, not recruiting, Suzhou Suncadia Biopharmaceuticals Co., Ltd. | Trial completion date: Jun 2025 --> Oct 2025 | Trial primary completion date: Mar 2025 --> May 2024

In addition, the four cell lines secrete cell-line specific EVs containing microRNAs that target YAP, BRG1-AKT1, TCF8-HDAC pathways. Overall, we highlight how the immune system plays a key role in the proliferation of CTCs through EV signaling, and how CTC cell line genomic and transcriptomic alterations make these cells less visible from the immune system and likely responsible for the survival advantage in sites distant from the microenvironment of origin.

Rampac remains a valid treatment option for patients who are unable to participate in trials or do not have access to further HER2-directed therapy beyond first line.

P=N/A, N=120, Completed, University Hospital Heidelberg | Active, not recruiting --> Completed | N=40 --> 120

This included experts in medical oncology, radiation oncology, surgical oncology, nuclear medicine, and general practitioners in oncology (GPO) from across the eastern Canadian provinces who are involved in the management of patients with gastrointestinal malignancies. This consensus statement generated by the conference addresses multiple topics, including the management of localized rectal cancer, liver-limited colorectal cancer, systemic therapy for advanced biliary tract cancers, radioligand therapy for gastroenteropancreatic neuroendocrine tumors (GEP-NETs), systemic therapy for pancreatic and midgut well-differentiated NETs, and systemic therapy for HER2-positive gastroesophageal cancers.

P1/2, N=120, Completed, MedPacto, Inc. | Active, not recruiting --> Completed | Trial completion date: Jan 2025 --> May 2024

P=N/A, N=40, Recruiting, Ohio State University Comprehensive Cancer Center | Trial completion date: Dec 2025 --> Jun 2025 | Trial primary completion date: Dec 2024 --> Jun 2025

P=N/A, N=60, Recruiting, Nanchong Central Hospital | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

P2, N=10, Recruiting, University of Arizona | Trial completion date: May 2025 --> Sep 2025 | Trial primary completion date: Mar 2025 --> Sep 2025

P3, N=840, Recruiting, AstraZeneca | Not yet recruiting --> Recruiting

P2, N=39, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Feb 2025 --> Feb 2026 | Trial primary completion date: Feb 2025 --> Feb 2026

We observed TGF-β signaling in HER2-negative tumor regions, which was associated with nonresponder status. These data highlight the biology of intratumoral heterogeneity and the impact of tumor and immune cell features on clinical outcomes and may partly explain the lesser magnitude of pembrolizumab benefit in HER2+ and PD-L1-negative subgroups.

P1, N=120, Recruiting, NeoTX Therapeutics Ltd. | Active, not recruiting --> Recruiting | N=60 --> 120 | Trial completion date: Oct 2026 --> Mar 2027 | Trial primary completion date: Oct 2026 --> Mar 2027

Tislelizumab plus ICC is an effective and tolerable first-line treatment for patients with locally advanced unresectable or metastatic HER2-negative GC/GEJC with a PD-L1 TAP score ≥ 1%.

Over the past decade, therapies for metastatic or advanced GEA/ESCC have expanded, with several new therapeutic targets alongside trastuzumab for metastatic HER2-positive GEA...Experts from the Spanish Society of Pathology (SEAP) and the Spanish Society of Medical Oncology (SEOM) have formed a consensus to optimize biomarker detection and usage in clinical practice. Their recommendations aim to improve personalized treatment strategies for GEA and ESCC patients, integrating new diagnostic insights into routine care.

P2, N=258, Recruiting, Suzhou Suncadia Biopharmaceuticals Co., Ltd. | N=156 --> 258

We demonstrate that a novel CDK9 degrader, YX0597, has high potential clinical application for GEAC treatment, especially in radiation-resistant cancer. We reveal the crosstalk of CDK9 and YAP/TEAD signaling, and that co-targeting these two mediators could be a new avenue for targeting CDK9-hyperactivated GEAC primary and radiation-resistant tumors.

P1, N=80, Recruiting, Sichuan Luzhou Buchang Biopharmaceutical Co., Ltd. | Not yet recruiting --> Recruiting

Low stroma gene expression signature scores were associated with OS benefit with nivolumab-based regimens; high regulatory T cell signatures were associated with OS benefit only with nivolumab-plus-ipilimumab. Our analyses suggest that distinct and overlapping pathways contribute to the efficacy of nivolumab-based regimens in gastroesophageal adenocarcinoma.

P3, N=610, Active, not recruiting, Akeso | Trial completion date: Apr 2025 --> Oct 2025 | Trial primary completion date: Aug 2024 --> Apr 2025

P1, N=167, Completed, Novartis Pharmaceuticals | Active, not recruiting --> Completed

However, given the significant increase in the number of bariatric procedures, further studies with longer follow-up are needed. In addition, although surgical myotomy is a truly effective therapeutic option for the treatment of achalasia in the first-line setting, its impact on the risk of esophageal cancer remains uncertain and poorly studied.

P1, N=32, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Aug 2025 --> Aug 2027 | Trial primary completion date: Mar 2025 --> Mar 2027

P1, N=180, Recruiting, Novartis Pharmaceuticals | Trial completion date: Feb 2026 --> Sep 2027 | Trial primary completion date: Feb 2026 --> Sep 2027

P2, N=115, Completed, Taiho Oncology, Inc. | Active, not recruiting --> Completed | Trial completion date: Mar 2025 --> Nov 2024

Consistent with efficacy in the overall population from KEYNOTE-859, first-line pembrolizumab plus chemotherapy showed improved efficacy, versus placebo plus chemotherapy, and manageable safety in patients enrolled in mainland China.

Tucatinib, a highly selective tyrosine kinase inhibitor, demonstrated significant efficacy in combination with trastuzumab in patients with refractory mCRC, leading to its approval by the Food and Drug Administration (FDA). The future of tucatinib-based therapeutic strategies in GI malignancies depends on its integration into different treatment lines. Addressing acquired resistance using liquid biopsy-guided strategies and other TKIs like lapatinib will be paramount to improve outcomes.

The proportion of patients receiving any second-line treatment was comparable between the groups: 76%, 80%, and 71%, respectively. Our study suggests that immunotherapy has a moderate impact on improving the survival of real-world patients with HER2-negative AGC, highlighting the need for appropriate treatment strategies, including efforts to identify biomarkers and the development of other agents.

Gastric cancer (GC) has a high global incidence and mortality rate [...].

The collection of trial results presented at the 2024 ASCO and ESMO Annual Meetings denote the ongoing efforts of the medical and scientific community for optimizing GI cancer care. The ongoing efforts of the GI cancer research and patient community provide hope for continued progress toward improved patient outcomes and new standards of care.

P1/2, N=175, Terminated, Bolt Biotherapeutics, Inc. | Trial completion date: Jan 2026 --> Feb 2025 | Active, not recruiting --> Terminated | Trial primary completion date: Jan 2025 --> Oct 2024; Sponsor Decision

No abstract available

Our findings underscore a need for region-specific approaches in gastroesophageal cancer diagnosis and treatment. MUC6 emerges as a putative immune regulator that needs further investigation. Research tailored to the unique biological profiles in different global regions is crucial to effectively address the observed disparities.

P=N/A, N=100, Recruiting, Imperial College London | Initiation date: Apr 2024 --> Feb 2025

This study provides novel insights into the complex role of immune cells in the pathogenesis of EAC, revealing a dynamic interplay where certain immune phenotypes may be protective in early stages but become risk-enhancing in later stages of disease progression. These findings highlight the potential of immune cell phenotypes to serve as biomarkers for early detection and targeted therapeutic interventions across the GERD-BE-EAC continuum. Further research is warranted to validate these findings in diverse populations and to explore the underlying mechanisms driving these immune-mediated effects.