ArticleInvestigational new drugs2020
Safety and clinical activity of the Notch inhibitor, crenigacestat (LY3039478), in an open-label phase I trial expansion cohort of advanced or metastatic adenoid cystic carcinoma.
Article in Investigational new drugs, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
41 citing papers in PubMed, 69 citations in OpenAlex.
- Translational insights and clinical challenges of targeting cancer stem cells.Signal transduction and targeted therapy · 2026Review
- Advanced radiotherapy and systemic therapy in head and neck adenoid cystic carcinoma: Current progress and future integrated strategies.Translational oncology · 2026Review
- Targeting the Notch1-YY1-ICAM1 Signaling Axis Enhances the Efficacy of Immunotherapy in HCC by Activating CD8Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Notch signaling in the tumor microenvironment: recent advances and targeted therapeutics.Molecular cancer · 2026Review
- Systemic Therapy for Salivary Gland Cancers: A Review of Targeted and Chemotherapeutic Approaches.Current treatment options in oncology · 2026Review
- A case report of adenoid cystic carcinoma combined with giant renal metastasis treated with robotic surgery.Discover oncology · 2025Article
- Significance of Notch Signaling in Salivary Gland Development and Diseases.Journal of clinical medicine · 2025Review
- Potentially actionable molecular alterations in particular related to poor oncologic outcomes in salivary gland carcinomas.BMC cancer · 2025Article
- Notch pathway inhibition with crenigacestat (LY3039478) in a phase I first-in-human clinical trial for patients with relapsed or refractory non-Hodgkin lymphoma and B-cell chronic lymphocytic leukemia.Therapeutic advances in drug safety · 2025Article
- A Comprehensive Review of Advances in Molecular Mechanisms and Targeted Therapies for the Specific Type of Cystic Lung Cancer.OncoTargets and therapy · 2025Review
- Comparison of postoperative radiotherapy and definitive radiotherapy for non-metastatic adenoid cystic carcinoma of the head and neck, a propensity score matching based on the SEER database.Translational cancer research · 2024Article
- Breast Cancer Stem Cells and Tumor Heterogeneity: Characteristics and Therapeutic Strategies.Cancers · 2024Review
- Notch signaling pathway in cancer: from mechanistic insights to targeted therapies.Signal transduction and targeted therapy · 2024Review
- Molecular Aspects of Mucoepidermoid Carcinoma and Adenoid Cystic Carcinoma of the Salivary Gland.Head and neck pathology · 2024Review
- Informed by Cancer Stem Cells of Solid Tumors: Advances in Treatments Targeting Tumor-Promoting Factors and Pathways.International journal of molecular sciences · 2024Review
- Circulating tumour cell clusters: isolation, biological significance and therapeutic implications.BMJ oncology · 2024Review
- Novel insights into Notch signaling in tumor immunity: potential targets for cancer immunotherapy.Frontiers in immunology · 2024Review
- Secretase promotes AD progression: simultaneously cleave Notch and APP.Frontiers in aging neuroscience · 2024Review
- Tracheal Tumors: Clinical Practice Guidelines for Palliative Treatment and Follow-Up.Oncology reviews · 2024Review
- Heterogeneous immune landscapes and macrophage dynamics in primary and lung metastatic adenoid cystic carcinoma of the head and neck.Frontiers in immunology · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background Deregulated Notch signaling is implicated in multiple cancers. The phase I trial (I6F-MC-JJCA) investigated the safety and anti-tumor activity of crenigacestat (LY3039478), a selective oral Notch inhibitor, in an expansion cohort of patients with adenoid cystic carcinoma (ACC) who received the dose-escalation-recommended phase 2 dose (RP2D), established previously (Massard C, et al., Annals Oncol 2018, 29:1911-17). Methods Patients with advanced or metastatic cancer, measurable disease, ECOG-PS ≤1, and baseline tumor tissue were enrolled. Primary objectives were to identify a safe RP2D, confirm this dose in expansion cohorts, and document anti-tumor activity. Secondary objectives included safety and progression-free survival (PFS). The ACC expansion cohort received the RP2D regimen of 50 mg crenigacestat thrice per week in a 28-day cycle until disease progression or other discontinuation criteria were met. Results Twenty-two patients with ACC were enrolled in the expansion cohort (median age of 60 years). Median treatment duration was 3 cycles with 6 patients remaining on treatment. There were no objective responses; 1 (5%) patient had an unconfirmed partial response. Disease control rate was 73% and 4 patients had stable disease ≥6 months. Median PFS was 5.3 months (95%CI: 2.4-NE)) for the 22 patients; and 7.7 months (95%CI: 4.0-NR) and 2.4 months (95%CI: 1.1-NE) in the subgroup of patients in second-line (n = 7) or ≥ third-line (n = 9), respectively. Frequent treatment-related-adverse events (all grades) included diarrhea, fatigue, vomiting, decreased appetite, dry mouth, and dry skin. There were no new safety signals. Conclusion The crenigacestat RP2D regimen induced manageable toxicity and limited clinical activity, without confirmed responses, in heavily pretreated patients with ACC.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.