Gastroesophageal Cancer

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

However, high TMB was not associated with an improved survival in MSS gastric/gastroesophageal junction/esophageal adenocarcinomas (Log Rank p = 0.5). MSS Gastric/gastroesophageal junction/esophageal adenocarcinomas with TMB above 10 mutations per Mb possess a genomic landscape with increased alteration frequencies in common gastroesophageal cancer genes and pathways.

This study developed a prognostic prediction model by integrating common clinical characteristics of irAEs and G/GEJ adenocarcinoma. This model exhibits good clinical practicality and possesses accurate predictive ability for overall survival OS in patients with advanced G/GEJ adenocarcinoma.

These findings suggest that the mechanical barrier of HA is the major reason responsible for the resistance developed during prolonged anti-angiogenesis in EGC. Incorporating PEGPH20 into the existing treatment regimen is promising to improve outcomes for patients with EGC.

P1, N=16, Active, not recruiting, NRG Oncology | Recruiting --> Active, not recruiting

P1/2, N=52, Active, not recruiting, Royal Marsden NHS Foundation Trust | Recruiting --> Active, not recruiting | Trial primary completion date: May 2024 --> Dec 2024

Though belatedly, immunotherapy has entered the treatment armamentarium of breast cancer, with the approval of pembrolizumab in combination with chemotherapy in triple-negative breast cancer (TNBC) in the neoadjuvant and advanced settings, thereby paving the path for further research and integration of immune checkpoint inhibitors in other subtypes of breast cancer...Biomarkers and precise patient selection for the utilization of immunotherapy remain cardinal and are currently under investigation, with some biomarkers showing promise, such as Program Death Lignat-1 (PDL-1) Combined Positive Score, Tumor Mutation Burden (TMB), and Tumor Infiltrating Lymphocytes (TILs). This review will present the current landscape of immunotherapy, particularly checkpoint inhibitors, in different types of breast cancer.

P2, N=320, Recruiting, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) | Trial completion date: Aug 2024 --> Jul 2026 | Trial primary completion date: Aug 2024 --> Jul 2025

T-DXd induces LM responses in a subset of patients, and such responses may be associated with prolongation of survival. Prospective trials are needed to clarify the role of T-DXd in treating LM and which patients are most likely to benefit.

P1/2, N=22, Completed, University of Wisconsin, Madison | Active, not recruiting --> Completed

We report efficacy and safety after a minimum 3-yr follow up. Adults with locally advanced, nonresectable or metastatic, HER2-negative, untreated GC/GEJC were randomized (1:1) to intravenous TIS 200 mg or PBO every 3 wks + investigator-chosen CT (oxaliplatin + capecitabine or cisplatin + 5-fluorouracil). After a minimum 3-yr follow up, TIS + CT as 1L treatment for GC/GEJC continued to demonstrate clinically meaningful improvements in OS, PFS, and DoR compared with PBO + CT, with no new safety signals. These long-term data further support TIS + CT as a new 1L treatment option for advanced HER2-negative GC/GEJC. Table: 1437P aStratified.bInvestigator evaluated.

No abstract available

There was no difference between MSS-bTMB10-15 compared with MSS-bTMB-16+ in ORR, DCR, and PFS, or between MSS-bTMB10-19 compared with MSS-bTMB20+. Regardless of bTMB cutoff at 10, 16, or 20, bTMB-H did not appear to be a predictive biomarker in MSS GI tumors in this retrospective analysis.

P=N/A, N=115, Not yet recruiting, Bristol-Myers Squibb

P2/3, N=17, Completed, Seagen Inc. | Active, not recruiting --> Completed | Trial completion date: Mar 2027 --> Apr 2024 | Trial primary completion date: May 2025 --> Apr 2024

P=N/A, N=80, Recruiting, H. Lee Moffitt Cancer Center and Research Institute

CLDN18.2 was a highly prevalent biomarker in patients with HER2-negative, LA unresectable or mG/GEJ adenocarcinoma. CLDN18.2 positivity remained relatively stable over time in many patients. Biomarker testing for CLDN18.2 should be considered in standard clinical practice in these patients.

Furthermore, the patients in PD-L1 CPS ≥1 subgroup and PD-L1 CPS ≥10 subgroup appeared to benefit from pembrolizumab plus chemotherapy treatment because of higher RR and CR. However, side effects such as the treatment-related adverse events leading to discontinuation, the 3-5 treatment-related adverse events, and immune-mediated adverse events and infusion reactions deserved more attention.