Biliary Tract Cancer

P2, N=27, Active, not recruiting, Abramson Cancer Center at Penn Medicine | Trial completion date: Dec 2024 --> Dec 2026 | Trial primary completion date: Dec 2024 --> Dec 2026

P1, N=158, Recruiting, Avacta Life Sciences Ltd | N=80 --> 158 | Trial completion date: Jun 2023 --> Aug 2026 | Trial primary completion date: May 2023 --> Mar 2026

P1/2, N=34, Completed, University of Michigan Rogel Cancer Center | Active, not recruiting --> Completed | Trial completion date: May 2025 --> Nov 2024 | Trial primary completion date: May 2025 --> Nov 2024

Additionally, dinaciclib affects different cell growth regulators like EGFR and STAT3 on gene and protein level, thus decreasing tumor growth. In summary, our study indicates that dinaciclib acts as a promising anti-tumorigenic agent in 2D and 3D in vitro BTC models and thus encourages further investigation.

An immune/metabolism score integrating the features of six genes was developed as a predictive biomarker for immunotherapy response in multiple cohorts, allowing for the selection of patients most likely to experience positive outcomes from this therapy regimen. In conclusion, our study provides proof-of-concept data supporting the potential of SHR-1701 plus famitinib as an effective and safe subsequent-line therapy for refractory BTC and PDAC, highlighting the promise of targeting PD-L1, TGF-β, and angiogenesis pathways simultaneously.

P=N/A, N=50, Recruiting, IRCCS Azienda Ospedaliero-Universitaria di Bologna

P1/2, N=340, Recruiting, AstraZeneca | Trial completion date: Dec 2025 --> Jun 2026 | Trial primary completion date: Dec 2025 --> Jun 2026

A tendence toward a better OS was found for BRCAness patients which did not reach the statistical significance. On the other hand, BRCAness patients showed significantly higher PFS compared to no BRCAness patients This real-world analysis largely confirmed the TOPAZ-1 findings, supporting gemcitabine, cisplatin, and durvalumab as a first-line standard of care for patients with advanced BTC.

In gallbladder and biliary tract cancers, we are mainly looking for IDH1 and IDH2 mutations, FGFR2 gene fusions and mutations, HER2 amplifications or mutations, as well as mutations of BRAF or BRCA1/2. All results should be discussed within the molecular tumor board.

The adverse impact of KRAS mutations in BTC is driven by G12 alterations in patients with IHC regardless of resection status, which was not observed in GB or EHC. There are unique comutational partners in distinct BTC subsets. These differences have important clinical implications in the era of KRAS-targeted therapeutics.

P2, N=100, Active, not recruiting, Boehringer Ingelheim | Recruiting --> Active, not recruiting

P2, N=110, Active, not recruiting, Tianjin Medical University Cancer Institute and Hospital

Currently, pemigatinib and futibatinib are FDA approved FGFR-targeted therapies that have demonstrated remarkable responses. Additionally, unique side effects of FGFR inhibitors may limit their efficacy in clinical practice and can have detrimental effects on quality of life. Several novel FGFR inhibitors are currently being investigated to overcome resistance mechanisms and reduce toxicities.

A modified GLIM malcondition can be a highly useful prognostic marker for patients with resected biliary tract cancer.

P1, N=15, Recruiting, University of Maryland, Baltimore | Not yet recruiting --> Recruiting

P1/2, N=124, Not yet recruiting, Hangzhou Hanx Biopharmaceuticals, Ltd.

P3, N=452, Active, not recruiting, SWOG Cancer Research Network | Trial completion date: Oct 2024 --> Mar 2025

cfDNA in plasma implies a prognostic value for the BTC. The online version contains supplementary material available at 10.1007/s43657-024-00160-2.

Inhibition of LGALS1 reduced tumor growth and Treg prevalence in ICC mouse models. Overall, this study unveils T cell diversity across BTC subtypes at the single-cell and spatial level that could open paths for tailored immunotherapies.

In the expert opinion, we discuss the problem of the scarcity of patients eligible for target therapies and how can clinical trials be designed to overcome this challenge. We also summarize the most promising trials that have the potential to change clinical practice both for immunotherapies and target drugs.

P2, N=36, Not yet recruiting, Insel Gruppe AG, University Hospital Bern | Initiation date: Sep 2024 --> Dec 2024

P2, N=76, Not yet recruiting, Sir Run Run Shaw Hospital

For decades, the combination of gemcitabine with cisplatin (GemCis) has been the standard of care for palliative treatment. Due to the high frequency of targetable genetic alterations in BTC patients, there is a growing emphasis on obtaining tissue or liquid biopsy samples to identify markers like microsatellite instability and other actionable oncogenic driver genes. Early initiation of systemic therapies in combination with multimodal approaches is essential for maximizing survival outcomes in patients with BTC.

Collaboration between nephrologists and oncologists is crucial for optimizing treatment benefits and managing side effects. Further research is warranted to refine management strategies and to understand the clinical implications of hyperphosphatemia.

The data presented in this study are consistent with the results of TOPAZ1 trial. However about a third of patients do not respond to CHT or have a short response duration. In our experience both NLR and basal elevated AST/ALT seem to be associated with an improved mPFS and a better outcome but further studies are needed.

Among pts with EMP available, 64.2% had intrahepatic cholangiocarcinoma and 69.8% received CT1 (36.1% cisplatinum-gemcitabine). Despite a broader availability of EMP in advanced BTC in recent years, access to TT remains suboptimal even in referral Institutions. Our results demonstrate TT administration as a pivotal positive prognostic factor in a real-world setting, whilst FGFR2 or IDH1 alterations did not act as prognostic determinants per-se. Therefore, strategies aiming at improving the rate of patients receiving TT are warranted.

This report supports the clinical benefit of anti-EGFR antibodies for EGFR-amplified biliary tract cancers and the importance of genomic analysis in personalized therapy and drug resistance research.

Here, we developed a catalog of BTC PDXs which underwent comprehensive molecular profiling and therapeutic modeling. To date, this is one of the largest collections of BTC PDX models and will facilitate the development of personalized treatments for patients with these aggressive malignancies.

P1/2, N=368, Recruiting, Innovent Biologics (Suzhou) Co. Ltd. | Not yet recruiting --> Recruiting | Trial completion date: Jul 2025 --> Oct 2025 | Trial primary completion date: Oct 2024 --> Apr 2025

P3, N=68, Completed, Krankenhaus Nordwest | Recruiting --> Completed | N=300 --> 68

P2, N=27, Not yet recruiting, West China Hospital of Sichuan University; West China Hospital of Sichuan University

P2, N=38, Not yet recruiting, Shanghai Eastern Hepatobiliary Surgery Hospital; Shanghai Eastern Hepatobiliary Surgery Hospital

P2, N=54, Not yet recruiting, The second hospital of Lanzhou University; The second hospital of Lanzhou University

The most frequent grade 3 or 4 treatment-related adverse event was neutropenia (n = 4, 29%). The combination of camrelizumab, gemcitabine, and apatinib showed promising efficacy and acceptable safety in patients with advanced PD-L1-positive biliary tract cancer.

P=N/A, N=360, Recruiting, Cedars-Sinai Medical Center | Trial primary completion date: Jun 2025 --> Jan 2026

P2/3, N=206, Not yet recruiting, Sun Yat-sen University

Ferroptosis inhibitor Fer-1 administration could reverse the beneficial effects caused by Rg3 treatment while ferroptosis inducer Erastin treatment enhanced the effects...Rg3 inactivated the circFOXP1-miR-4477a-PD-L1 signaling axis to activate the immune function of CD8+ T cells, thereby inducing ferroptosis and apoptosis in GBC cells. This research recognizes the mechanism of Rg3-mediated anti-cancer effect and offers evidence for the potentiality of Rg3 in clinical application for GBC therapy.

P=N/A, N=60, Recruiting, Jiangsu Healthy Life Innovation Medical Technology Co., Ltd | Not yet recruiting --> Recruiting

P2, N=30, Not yet recruiting, Tianjin Medical University Cancer Institute and Hospital

Among patients with advanced BTC, ctDNA-based genotyping showed acceptable concordance with tissue genomic profiling. Liquid biopsy using ctDNA could be a valuable complement to tissue-based genomic analysis in BTC.

P2, N=23, Not yet recruiting, Fujian Cancer Hospital

P3, N=452, Active, not recruiting, SWOG Cancer Research Network | Trial completion date: Jul 2024 --> Oct 2024