Gastroesophageal Cancer

P2, N=200, Recruiting, Jazz Pharmaceuticals | Not yet recruiting --> Recruiting

P2, N=180, Recruiting, AbbVie | Not yet recruiting --> Recruiting

P1/2, N=136, Active, not recruiting, AstraZeneca | Recruiting --> Active, not recruiting | N=232 --> 136 | Trial primary completion date: Aug 2026 --> Dec 2024

P2, N=73, Not yet recruiting, UNICANCER | Initiation date: Oct 2024 --> Jan 2025

P=N/A, N=500, Recruiting, Bristol-Myers Squibb | Not yet recruiting --> Recruiting | Initiation date: Aug 2024 --> Dec 2024

P3, N=726, Not yet recruiting, Daiichi Sankyo

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

P=N/A, N=115, Active, not recruiting, Bristol-Myers Squibb | Not yet recruiting --> Active, not recruiting

P1/2, N=21, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Apr 2025 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

P2, N=68, Recruiting, Fudan University

Within the subgroup of patients with EGC and favorable pathologic responses (TRG 0-1) after NAT, the presence of postoperative ctDNA identified patients with elevated recurrence risk.

P2, N=240, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting

P2, N=35, Active, not recruiting, Sanofi | Trial completion date: Jun 2024 --> Dec 2024

P1, N=87, Recruiting, Arcus Biosciences, Inc. | Trial completion date: Aug 2025 --> Mar 2026 | Trial primary completion date: Aug 2025 --> Mar 2026

P=N/A, N=100, Recruiting, Semmelweis University

Although no statistical significance was observed, a decrease in overall survival for patients with TS TP53 mutations was noted. The result is counterintuitive given that TS mutants have less severe structural destabilization and suggests TS TP53 mutations may have a unique prognostic value that warrants further investigation.

Most of AEs were grade 1-2 and manageable. Compared with chemotherapy alone, first-line ICIs combined with chemotherapy in patients with advanced GC/GEJC could greatly prolong PFS, but OS was not significantly improved, and the AEs were manageable.

P1, N=60, Completed, AstraZeneca | Active, not recruiting --> Completed | Trial completion date: Jan 2025 --> Oct 2024 | Trial primary completion date: Jan 2025 --> Oct 2024

P=N/A, N=72, Not yet recruiting, University Health Network, Toronto

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.

P2, N=37, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Jul 2024 --> Jul 2025

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.

ctDNA analysis has the potential to identify patients at elevated risk of recurrence, thus providing personalized treatment strategies for patients with resectable gastric and GEJ cancer. Further validation in larger cohorts and ctDNA-guided interventions are needed for future clinical use.

P=N/A, N=500, Recruiting, Stanford University | Trial primary completion date: May 2023 --> Dec 2025

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

The GMS utilized in this study successfully demonstrated the ability to reliably predict the survival advantage for patients with GECs undergoing ICI therapy.

More recently, the introduction of a new antibody-drug conjugate, that is trastuzumab deruxtecan, expanded the therapeutic options to low-HER2 breast and gastroesophageal tumors...Although the evidence about prognostic and predictive roles of HER2 in carcinomas other than breast and gastroesophageal has been widely increasing over the last decade, it still remains investigational, revealing a tumor site-related prognostic and predictive value of the different types of HER2 alterations. However, standardized and validated scoring system assays have not been well-established for many organs.

P=N/A, N=33, Terminated, Bristol-Myers Squibb | N=314 --> 33 | Trial completion date: Sep 2028 --> Aug 2024 | Recruiting --> Terminated | Trial primary completion date: Sep 2028 --> Aug 2024; A decision was made to terminate the study due to expected timelines associated with start-up, participant enrollment, ethics committee approval and data availability from the study.

Moreover, in scenario analysis, the results remained consistent despite variations in the model's time frame. In China, SINT + Chemo is a more cost-effective option (vs. chemotherapy) as a first-line therapy for unresectable advanced or metastatic GC/GEJC, irrespective of PD-L1 expression levels.

P2, N=73, Not yet recruiting, UNICANCER | Trial completion date: Jun 2028 --> Oct 2028 | Initiation date: Jun 2024 --> Oct 2024 | Trial primary completion date: Jun 2026 --> Oct 2026

P1, N=32, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Feb 2025 --> Aug 2025 | Trial primary completion date: Sep 2024 --> Mar 2025

Sitravatinib with/without tislelizumab was generally well tolerated and showed preliminary antitumor activity in patients with advanced HCC and GC/GEJC.

Despite the landmark ToGA trial, progress in HER2-positive gastrointestinal malignancies has been hampered by drug resistance. This review examines current HER2 expression patterns and therapies for gastroesophageal, colorectal, biliary tract, and small bowel cancers, while dissecting potential resistance mechanisms that limit treatment effectiveness.

We demonstrate HER2 protein overexpression and gene amplification in 20% and 66% of SMARCA4-d GECs, respectively. Our results suggest anti-HER2 therapy may be considered as an alternative therapeutic avenue in these aggressive carcinomas. Importantly, overexpression and amplification are not always concordant, bringing into question the utility of current HER2-testing guidelines in this context.SMARCA4-Deficient Gastroesophageal Carcinoma Findings

HER-2 expression was assessed by immunohistochemistry (IHC) based on the Trastuzumab for GAstric Cancer (ToGA) trial's scoring system...These insights can aid in selecting appropriate gastric and gastroesophageal carcinomas that warrant HER-2 testing on IHC. Identifying gastric and gastroesophageal carcinomas that show HER2 expression may highlight potential candidates for targeted therapy.

P=N/A, N=1000, Recruiting, KU Leuven | Not yet recruiting --> Recruiting

P=N/A, N=2200, Recruiting, KU Leuven | Not yet recruiting --> Recruiting

P=N/A, N=23, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Recruiting --> Active, not recruiting | Trial completion date: Jul 2024 --> Jun 2026 | Trial primary completion date: Jul 2024 --> Jun 2025

Patients in SPOTLIGHT and GLOW maintained measured HRQoL relative to baseline when treated with first-line zolbetuximab added to chemotherapy. Zolbetuximab plus chemotherapy improved PFS and OS without negatively affecting HRQoL in key PRO domains compared with placebo plus chemotherapy.

Furthermore, ongoing research into the gastric cancer microenvironment and the role of the microbiome suggests novel targets for future therapeutic interventions. The integration of targeted and immunotherapeutic agents with traditional chemotherapy represents a pivotal shift in gastric cancer treatment, moving towards more personalized and effective regimens.

P1, N=16, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Jul 2024 --> Jul 2025 | Trial primary completion date: Jul 2024 --> Jul 2025

P=N/A, N=200, Recruiting, Peter MacCallum Cancer Centre | Not yet recruiting --> Recruiting