Esophageal Adenocarcinoma

The present meta-analysis confirmed that the benefit of PD-1 blockade in GEA patients is related to PD-L1 CPS, with increased benefit observed for higher CPS cut-offs and no OS benefit in the CPS <1 subset. Overall, data indicate that PD-L1 CPS ≥5 could represent an acceptable cut-off to optimize the risk/benefit ratio of such agents. Our data suggest a potential clinical benefit of immunotherapy in selected patients within the CPS 1-4 population which needs further investigation.

miR-16-5p may promote the proliferation, migration, and invasion of ESCC through modulating AMPK/mTOR signaling pathway.

EMI-137 accumulates in dysplastic lesions within BE and in c-MET positive EAC. EMI-137 imaging has potential as a screening and surveillance tool for patients with BE and as a means to detecting dysplasia and EAC.

As a result, CASP2 contributed nothing to CCN1-induced EAC cell apoptosis. On the contrary, CCN1 promoted CASP3, not only in its transcription but also in its translation and activation, which established the basis for CCN1-induced EAC cell apoptosis.

Our findings support NED as independent predictor of OS in EAC after neoadjuvant chemoradiation. While a subset of tumours with NED expressed serotonin, this did not provide additional prognostic information.

This database analysis showed that the main type of MET mutation is amplification in malignant melanoma. MET-amplified solid tumors might be considered for targeted therapy, as MET amplification can be regarded as a risk factor affecting the prognosis of patients with tumors treated with immunotherapy.

P2, N=14, Not yet recruiting, Amsterdam UMC, location VUmc

P=N/A, N=800, Not yet recruiting, Case Comprehensive Cancer Center

P=N/A, N=51, Terminated, Columbia University | N=100 --> 51 | Suspended --> Terminated; Product recall

P2, N=126, Not yet recruiting, Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest

P2, N=82, Not yet recruiting, Shanghai Zhongshan Hospital | Trial completion date: Jul 2028 --> Dec 2028 | Initiation date: Jul 2024 --> Nov 2024 | Trial primary completion date: Jul 2027 --> Dec 2027

Liquid-liquid phase separation is potentially implicated in esophageal adenocarcinoma and works as a prognostic biomarker assessment of vulnerability to LLPS, which could help develop individualized therapies by showing how one is situated about various medications where responses vary across the body.

P1, N=36, Recruiting, Grey Wolf Therapeutics Pty Ltd | Not yet recruiting --> Recruiting

P1, N=6, Active, not recruiting, Novartis Pharmaceuticals | Recruiting --> Active, not recruiting | N=116 --> 6

P1, N=11, Active, not recruiting, University of Manitoba | Recruiting --> Active, not recruiting | Trial completion date: Jun 2026 --> Jul 2029 | Trial primary completion date: Jun 2024 --> Jul 2025

P=N/A, N=371, Completed, Memorial Sloan Kettering Cancer Center | Active, not recruiting --> Completed | Trial completion date: Sep 2025 --> Oct 2024 | Trial primary completion date: Sep 2025 --> Oct 2024

The approaches to these targets may act together, in sequence, and even synergistically to improve outcomes. Herein, we review the state of the field, including highlighting ongoing clinical trials and additional emerging agents and approaches.

Multiomics data from The Cancer Genome Atlas linked CCL28 with RUNX3-suppressed diffuse histological subtypes of non-EBV/non-MSI-high GEA. Our data suggest that a high FOXP3+/CD8+ ratio at the invasive margin might indicate tumor immune escape via CCL28, particularly in the RUNX3-methylated diffuse histological subtype.

P1, N=160, Terminated, Inhibrx Biosciences, Inc | Trial completion date: Dec 2025 --> Oct 2024 | Active, not recruiting --> Terminated | Trial primary completion date: Aug 2025 --> Oct 2024; Program terminated due to lack of meaningful efficacy signal.

DKN-01 can be safely combined with frontline fluoropyrimidine/oxaliplatin and tislelizumab and demonstrates encouraging activity independent of PD-L1 expression levels. A randomized phase II trial is ongoing (ClinicalTrials.gov identifier: NCT04363801).

In PD-L1low HER-2 negative GEAC, the benefit of first-line ICI is modest, yet significant. Further translational work is warranted to better select patients who could benefit from immunotherapy in this setting. Meanwhile, alternative therapeutic options such as zolbetuximab in Claudin18.2-positive disease must be taken into account.

Based on these observations, clinical trials with ATX-targeted drugs and standard chemotherapy regimens may benefit from selecting GEA patients based on their levels of ATX, LPA and CEA.

Seventy-four patients (81%) received nivolumab, while the remaining received pembrolizumab. Patients with advanced G/GEJ adenocarcinomas in the real world predominantly received ICIs during later lines of therapy as opposed to first line therapy. Using a CPS cutoff of ≥5 as opposed to CPS <5 predicts for improved survivals in MSS patients and patients receiving low dose ICIs have similar survival outcomes to patients receiving standard dose ICIs within the confines of a heterogenous study cohort.

P2, N=74, Active, not recruiting, Jazz Pharmaceuticals | Trial primary completion date: Aug 2024 --> Jul 2025

The discussion extends to evaluating combination therapies, spotlighting the synergy between targeted and immune-mediated treatments, and introduces the burgeoning domain of antibody-drug conjugates, bispecific antibodies, and multitarget-directed ligands. This review lies in its holistic synthesis of EC's molecular underpinnings and therapeutic interventions, fused with an outlook on future directions including overcoming resistance mechanisms, biomarker discovery, and the potential of novel drug formulations.

P1, N=245, Recruiting, Incyte Corporation | N=165 --> 245

The link between TFF1 expression and parameters of malignancy argues for a relevant biological role of TFF1 in cancer. TFF1 may represent a suitable therapeutic target due to its expression in only a few normal cell types.

Furthermore, the impact of reflux on microbiota composition and its role in esophageal carcinogenesis is evaluated. By combining epidemiological data with mechanistic understanding, this review underscores the potential to target the microbiota-immune system interplay for novel therapeutic and diagnostic strategies to prevent and treat esophageal cancer.

P1/2, N=79, 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=20, Active, not recruiting, Ludwig-Maximilians - University of Munich

P1, N=573, Active, not recruiting, Exelixis | Trial completion date: Feb 2025 --> Jul 2025

P1/2, N=263, Active, not recruiting, Salubris Biotherapeutics Inc | Recruiting --> Active, not recruiting

OAC may be subdivided into three immune-related subgroups which undergo modulation in response to neoadjuvant therapy with marked suppression of the immune microenvironment in HER2-positive/immune-high tumours.

Patients with EAC had increased expression of cIAP2 and FLIP, and PKC-δ which is associated with inhibition of apoptosis and possible progression of esophageal adenocarcinoma.

PD-1/PD-L1 inhibitors have significantly improved overall survival, and combining them with chemotherapy is more effective than monotherapy. Both CPS ≥10 and MSI-H showed an added benefit to overall survival and should be included in biomarker investigations. Clinical trials are needed for second-line treatments and esophageal adenocarcinoma.

P2, N=40, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2024 --> Dec 2026 | Trial primary completion date: Dec 2024 --> Dec 2026

Larger, well-designed Mendelian randomization studies are practical in determining the causal status of risk factors for diseases.

P2, N=180, Not yet recruiting, AbbVie

p53 mutation contributes to BE progression by increasing expansion and fitness of undifferentiated cardia progenitors and preventing their differentiation towards metaplasia.

P=N/A, N=371, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Sep 2024 --> Sep 2025 | Trial primary completion date: Sep 2024 --> Sep 2025

P1, N=18, Recruiting, Memorial Sloan Kettering Cancer Center

P2, N=138, Terminated, Sanofi | Active, not recruiting --> Terminated; Early discontinuation based on strategic sponsor decision not driven by any safety concerns.