Gastroesophageal Junction Adenocarcinoma

P1/2, N=18, Terminated, BioInvent International AB | Active, not recruiting --> Terminated; After the completion of phase IA, for business reasons it was decided to terminate the study.

P2, N=40, Recruiting, ImmunityBio, Inc. | Active, not recruiting --> Recruiting | N=147 --> 40

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

P2/3, N=429, Active, not recruiting, Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest | Recruiting --> Active, not recruiting | Trial completion date: Mar 2025 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

P1/2, N=36, Not yet recruiting, Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest

P1/2, N=1, Terminated, Celularity Incorporated | N=52 --> 1 | Trial completion date: Feb 2025 --> Feb 2024 | Active, not recruiting --> Terminated | Trial primary completion date: Feb 2023 --> Feb 2024; for business reasons

P3, N=524, Recruiting, Shanghai Hengrui Pharmaceutical Co., Ltd. | Not yet recruiting --> Recruiting

P2, N=110, Not yet recruiting, Qilu Hospital of Shandong University

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

P2, N=14, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jul 2024 --> Dec 2025

P2, N=31, Active, not recruiting, Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest | Phase classification: P2a --> P2

Our study highlights the critical role of dynamic changes within the tumor immune microenvironment in predicting the efficacy of neoadjuvant combined immunochemotherapy. We examined the disparities between MPR/non-MPR groups, shedding light on potential mechanisms of immune response and suppression. In addition to bolstering cytotoxic immune responses, specifically targeting Treg cells may be crucial for enhancing treatment outcomes.

Trastuzumab with chemotherapy is the standard regimen for HER2-positive GC/GEJC. While, for HER2-negative cases, chemotherapy with or without immune checkpoint inhibitors (ICIs)such as nivolumab or pembrolizumab are regarded as the standard therapy...We will highlight the previous clinical trials of zolbetuximab and provide future perspective of CLDN18.2 targeted therapy. In addition, we will introduce the ongoing development of various CLDN18.2 targeting therapies such as newer monoclonal antibodies, antibody-drug conjugates(ADCs), chimeric antigen receptor T-cell(CAR- T)therapy, and bispecific antibodies.

This case report supports the potential importance of immunotherapy in the treatment of resectable locally advanced MSI-H gastric cancer, which is currently being evaluated in clinical trials.

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.

The INFINITY study provided promising activity results of a chemo-free T300/D combination regimen as pre-operative treatment in dMMR/MSI GAC/GEJAC and the first available feasibility results of a NOM strategy in this disease setting, worth of further validation in larger cohorts.

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

In China, tislelizumab plus chemotherapy is a cost-effective first-line therapy for unresectable GC/GEJC in both ITT and TAP ≥ 5% subgroups. In the US, tislelizumab plus chemotherapy is not cost-effective.

Eligible patients will be registered and receive three cycles of oxaliplatin and S-1 (SOX) regimen in combination with cadonilimab...The results of the study may provide more evidence for neoadjuvant immunotherapy combined with chemotherapy in locally advanced G/GOJ adenocarcinoma. ClinicalTrials.gov, NCT05948449.

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

P=N/A, N=28, Recruiting, University of California, San Francisco | Trial completion date: Nov 2026 --> Nov 2027 | Trial primary completion date: Dec 2024 --> Dec 2025

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

The metabolites accounting for >10% of infigratinib were BHS697 and CQM157. The PK profiles of infigratinib and its metabolites in Chinese patients with GC or GEJ were largely consistent with known PK profiles of infigratinib from global populations.

Intraoperative determinations of tumor marker levels in peritoneal washings may be a predictive factor for a poor prognosis in patients with gastric cancer.

P1, N=254, Terminated, Sanofi | Active, not recruiting --> Terminated; Sponsor decision, The decision is not related to any safety concern.

P1/2, N=106, Active, not recruiting, Nimbus Saturn, Inc. | Recruiting --> Active, not recruiting | Trial completion date: Dec 2024 --> May 2025 | Trial primary completion date: Sep 2024 --> Feb 2025

P1/2, N=71, Completed, BeiGene | Active, not recruiting --> Completed | Trial completion date: Dec 2026 --> Oct 2024

The GLOW clinical trial showed that zolbetuximab plus capecitabine plus oxaliplatin (CAPOX) significantly prolonged these patients' overall survival (OS) and progression-free survival (PFS). Zolbetuximab plus CAPOX had 0% cost-effectiveness at the willingness-to-pay thresholds of $150,000/QALY in the United States and $38,188/QALY in China. Zolbetuximab plus CAPOX may be a cost-effective option for patients with locally advanced, unresectable, or metastatic G/GEJ adenocarcinoma when the price of zolbetuximab reduced by 83.37% ($367.7/100 mg) in the United States and 82.25% ($110.8/100 mg) in China.

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.

P3, N=507, Active, not recruiting, Amgen | Recruiting --> Active, not recruiting

P1/2, N=135, Recruiting, Phanes Therapeutics | Trial completion date: Apr 2026 --> Apr 2028 | Trial primary completion date: Dec 2025 --> Dec 2027

Paclitaxel and ramucirumab switch maintenance could be a potential treatment strategy in patients with advanced HER2-negative gastric or gastro-oesophageal junction cancer who are not eligible for immunotherapy or targeted agents.

P2, N=80, Not yet recruiting, Ruijin Hospital

P1, N=23, Terminated, Astellas Pharma Global Development, Inc. | Active, not recruiting --> Terminated; Company Strategic Reasons

P2, N=64, Recruiting, National Cancer Center Hospital East | N=37 --> 64 | Trial completion date: Mar 2025 --> Mar 2029 | Trial primary completion date: Mar 2024 --> Mar 2028

P2, N=143, Active, not recruiting, Astellas Pharma Global Development, Inc. | Recruiting --> Active, not recruiting

Neoadjuvant cadonilimab plus FLOT chemotherapy treatment exhibits promising efficacy with manageable toxicities in locally advanced G/GEJ adenocarcinoma, providing preliminary evidence for further investigation.

Factors for improved PFS include early treatment, lower T stage, fewer metastatic sites, and lower pre-IBIL, post-GLOB, and post-CA125 levels. Nomogram models can help identify patients who may benefit from immunotherapy, providing valuable clinical guidance.

However, the pooled hazard ratio for OS favoured PD-L1 inhibitors (hazard ratios - HR, 0.83, &lsqb;95% CI: 0.78-0.88] and p < 0.00001), while PFS was better after chemotherapy (HR 1.28, &lsqb;95% CI: 1.04-1.58], p = 0.02). Program death ligand-1 inhibitors improve OS, while chemotherapy enhances PFS in advanced G/GEJC, warranting further investigation into the impact of CPS on treatment outcomes.

Zolbetuximab, a monoclonal antibody targeting claudin 18.2, showed a survival benefit in first line metastatic treatment in patients with claudin 18.2 positive gastric and gastro-oesophageal junction adénocarcinoma, in two phase III studies. CAR T-cells specifically targeting this protein have also shown promising efficacy from the second line of treatment. Considering the probable impact of the expression status of claudin 18.2 in future treatment algorithms, this review aims to present the pathophysiology underlying the targeting of claudin 18.2, summarize state of the art results of anti-claudin 18.2 therapies and discuss future challenges for the management of patients with claudin 18.2 positive gastric and gastro-oesophageal junction adenocarcinoma.

Herein, we report extended follow-up data from the INTEGA trial (NCT03409848), which investigated the efficacy of the anti-PD-1 nivolumab, trastuzumab, and FOLFOX chemotherapy (FOLFOX arm) in comparison to a chemotherapy-free regimen involving nivolumab, trastuzumab, and the anti-CTLA-4 ipilimumab (Ipi arm) in the first-line setting for advanced disease...Furthermore, a low NLR characterized patients benefiting from immune- and targeted therapy without the need for additional chemotherapy. This data suggests that patient selection based on inflammatory stress-driven immune changes could help to customize first-line treatment in patients with advanced HER2-positive EGA to potentially improve long-term survival.

P2, N=43, Active, not recruiting, National Cancer Center Hospital East | Recruiting --> Active, not recruiting | Trial primary completion date: Aug 2025 --> Aug 2026