Gastroesophageal Cancer

This comprehensive immune phenotype study of a large series of untreated GEACs, identified that tumors with an esophageal tumor location have more immune suppressive features compared to tumors in the gastro-esophageal junction or stomach which might explain the location-specific responses to checkpoint inhibitors in this disease. These findings provide an important rationale for stratification according to tumor location in clinical studies and the development of location-dependent immunomodulatory treatment approaches.

P2, N=25, Recruiting, University of Southampton | Not yet recruiting --> Recruiting | Trial primary completion date: Nov 2025 --> Mar 2026

P=N/A, N=300, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Nov 2024 --> Nov 2025 | Trial primary completion date: Nov 2024 --> Nov 2025

P=N/A, N=40, Recruiting, University Health Network, Toronto | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024

P=N/A, N=1000, Not yet recruiting, KU Leuven

P=N/A, N=2200, Not yet recruiting, KU Leuven

While the therapeutic implications of these observations remain unknown, these findings suggest that combination strategies targeting HER2 and PD-L1 might be directed toward distinct tumor subclones. The herein disclosed region-specific biomarker expression patterns may have important therapeutic and prognostic impacts, warranting further evaluation.

Overall, our findings suggest that DPP4 may serve as a substantial prognostic biomarker, a possible therapeutic target, as well as it can play a critical role in the regulation of immune cell invasion in patients with gastroesophageal (esophageal, gastroesophageal junction and gastric) cancer. KEY WORDS: DPP4, integrated analysis, GI cancer, gastroesophageal cancer, gastroesophageal junction, prognosis.

Additionally, the emergence of trastuzumab deruxtecan (T-DXd) highlighted the potential of new pharmaceutical technologies to extend response, particularly for patients who have advanced beyond initial HER2-targeted therapies. This review aims to navigate through both the successes and challenges encountered historically, as well as promising current trials on innovative and transformative therapeutic strategies, including promising first-in-class and novel first-in-human agents.

Patients treated with frontline programmed death 1 inhibitors who had 18F-BMS-986229 accumulation in any lesions on PET imaging had longer progression-free survival than patients without tracer accumulation in any lesions (median progression-free survival, 28.4 vs. 9.9 mo), though the small sample size prevents any definitive conclusions. PD-L1 PET imaging was safe, feasible, and concordant with pathologic evaluation and offers a potential noninvasive tool to assess PD-L1 expression.

P1, N=60, Active, not recruiting, AstraZeneca | Trial completion date: Dec 2023 --> Jan 2025 | Trial primary completion date: Dec 2023 --> Jan 2025

Our findings provide insights into the safety profile of combined PD-1 and LAG-3 blockade in gastroesophageal cancer and highlight the potential of ctDNA analysis to dynamically assess systemic tumor burden during neoadjuvant ICI that may open a therapeutic window for future intervention. ClinicalTrials.gov registration: NCT03044613 .

P2, N=39, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Feb 2024 --> Feb 2025 | Trial primary completion date: Feb 2024 --> Feb 2025

No abstract available

Other targeted agents, such as bemarituzumab and DKN-01, are under active investigation. As new agents are incorporated into the treatment continuum, the questions of biomarker overlap, tumor heterogeneity, and toxicity management will need to be addressed.

P=N/A, N=40, Recruiting, Ohio State University Comprehensive Cancer Center | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2023 --> Dec 2024

P=N/A, N=120, Recruiting, University Health Network, Toronto | Trial completion date: Nov 2021 --> Nov 2025 | Trial primary completion date: Nov 2021 --> Nov 2025

P=N/A, N=10, Completed, Memorial Sloan Kettering Cancer Center | Active, not recruiting --> Completed | Trial completion date: Nov 2024 --> Mar 2024 | Trial primary completion date: Nov 2024 --> Mar 2024

Furthermore, perioperative immunotherapy suggested a new indication with molecular biomarkers such as microsatellite status or PD-L1 status beyond the conventional tumor-lymph node-metastasis (TNM) staging system. Global studies provide the stage for discussing the future optimal indication of neoadjuvant chemotherapy, opening the door for future global collaborations to better treat patients with locally advanced G/GEJ cancer.

P2, N=36, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Jul 2024 --> Apr 2028 | Trial primary completion date: Jul 2024 --> Apr 2028

Medical records of patients with aGEC enrolled in the randomized phase II AIO-STO-0417 trial after treatment failure to first-line FOLFOX plus nivolumab and ipilimumab were retrospectively analyzed...Patients with CPS ≥1 in the RAM group showed better tumor control (ORR 25% vs 10%) and improved survival (total OS 11.5 vs 8.0 months; second-line OS 6.5 vs 3.9 months; PFS 4.5 vs 1.6 months) compared to the control. Prior exposure to first-line FOLFOX plus dual checkpoint inhibition followed by RAM plus chemotherapy shows favorable response and survival rates especially in patients with initial response and positive PD-L1 expression and has the potential to advance the treatment paradigm in aGEC.

In addition, knowing the unusual patterns of HER2 expression is also important to avoid inaccurate evaluation. In this review, we discuss the key considerations when evaluating HER2 status in solid tumours for clinical decision making, including tissue handling and preparation for HER2 biomarker testing, as well as pathologist's readout of HER2 testing results in breast carcinomas, gastroesophageal adenocarcinomas, colorectal adenocarcinomas, gynaecologic carcinomas, and non-small cell lung carcinomas.

Our findings highlighted the significant correlation between IHC and WTS, reinforcing the clinical utility of WTS. A subset with IHC-negative but WTS-positive status may benefit from specific biomarker-targeted therapies.

P=N/A, N=100, Recruiting, Imperial College London

P2, N=24, Completed, NYU Langone Health | Active, not recruiting --> Completed | Trial completion date: Sep 2023 --> Jan 2024

P2, N=25, Active, not recruiting, Henan Cancer Hospital | Unknown status --> Active, not recruiting | Trial completion date: Jun 2022 --> Dec 2026 | Trial primary completion date: Dec 2020 --> Jan 2024

The trial showed that an elevated level of IL-6 prior to treatment and C2 might be a predictor of pathological response to NAC.

This article summarizes the findings and implications of several important studies published over the past 2 years that are fundamentally changing the way we treat patients with gastroesophageal cancer.

Pranlukast treatment increased apoptosis (P<0.05). Overall, Pranlukast suppressed esophageal carcinogenesis in a rat DGER model, decreasing inflammatory cytokines such as IL-8 and VEGF.

P1, N=60, Active, not recruiting, NeoTX Therapeutics Ltd. | Phase classification: P1b --> P1 | Trial completion date: Aug 2025 --> Oct 2026 | Trial primary completion date: May 2025 --> Oct 2026

HER2 expression were enriched in patients with BrM, while it is uncommon in LMC. Patients treated with surgery followed by radiation had an improved OS in BrM and WBRT benefited patients with LMC.

P2, N=14, Completed, City of Hope Medical Center | Active, not recruiting --> Completed

Results were correlated with exposure to trastuzumab therapy, the histologic tumor type, and other demographic variables... Non-membranous overexpression of HER2 staining in GEA is rare and is secondary to the abundance of p95 HER2 isoform in the setting of polysomy rather than ERBB2 amplification. Given the lack of associated amplification, this unusual staining pattern is unlikely to be clinically relevant.

FOLFOX shown better PFS than CP. Adverse effects varied: neuropathy was more common with oxaliplatin, while thromboembolism was more frequent with cisplatin.

P1, N=715, Recruiting, Taiho Pharmaceutical Co., Ltd. | N=367 --> 715 | Trial completion date: May 2024 --> May 2026 | Trial primary completion date: May 2024 --> May 2026

P=N/A, N=10, Recruiting, Inova Health Care Services | Trial completion date: Jan 2024 --> Jan 2025 | Trial primary completion date: Dec 2023 --> Dec 2024

P2; N=46; Not yet recruiting; Sponsor:Gruppo Oncologico del Nord-Ovest

P2, N=73, Not yet recruiting, UNICANCER

MTAP alterations are found in 5%-10% of GI cancers, most frequently biliopancreatic and gastro-oesophageal. MTAP loss is the most common alteration, identified almost exclusively in MSS, CDKN2A/B loss, upper-GI cancers. Other MTAP alterations were found in colorectal cancer, but unlikely to cause protein loss and drug susceptibility.

P1, N=15, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting | Trial completion date: Jan 2024 --> Jul 2024 | Trial primary completion date: Jan 2024 --> Jul 2024

P3, N=737, Active, not recruiting, Suzhou Suncadia Biopharmaceuticals Co., Ltd. | Recruiting --> Active, not recruiting

P2, N=25, Recruiting, Memorial Sloan Kettering Cancer Center | Not yet recruiting --> Recruiting