ArticleCancer chemotherapy and pharmacology2022
A phase 1b study of crenigacestat (LY3039478) in combination with gemcitabine and cisplatin or gemcitabine and carboplatin in patients with advanced or metastatic solid tumors.
Article in Cancer chemotherapy and pharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02784795 (A Phase 1b Study of LY3039478 in Combination With Other Anticancer Agents in Patients With Advanced or Metastatic Solid Tumors), which is not on this map. Cited by 14 papers.
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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.
A Phase 1b Study of LY3039478 in Combination With Other Anticancer Agents in Patients With Advanced or Metastatic Solid Tumors
Who cites it
14 citing papers in PubMed, 12 citations in OpenAlex.
- Notch receptors in breast cancer: context-dependent roles and therapeutic targeting.Cell communication and signaling : CCS · 2026Review
- Notch signaling in the tumor microenvironment: recent advances and targeted therapeutics.Molecular cancer · 2026Review
- Molecular Alterations and Pathways in Intrahepatic Cholangiocarcinoma: Available Evidence and New Perspectives.International journal of molecular sciences · 2025Review
- Towards directed therapy for fusion-positive rhabdomyosarcoma.Pharmacology & therapeutics · 2025Review
- Divide and Conquer-Targeted Therapy for Triple-Negative Breast Cancer.International journal of molecular sciences · 2025Review
- Role of EMT in drug resistance of breast cancer: molecular mechanisms and therapeutic strategies.Frontiers in oncology · 2025Review
- Notch signaling pathway in cancer: from mechanistic insights to targeted therapies.Signal transduction and targeted therapy · 2024Review
- Emerging Therapies in Management of Cholangiocarcinoma.Cancers · 2024Review
- Molecular pathways and targeted therapies in head and neck cancers pathogenesis.Frontiers in oncology · 2024Review
- Novel insights into Notch signaling in tumor immunity: potential targets for cancer immunotherapy.Frontiers in immunology · 2024Review
- Crosstalk between thyroid CSCs and immune cells: basic principles and clinical implications.Frontiers in immunology · 2024Review
- Modulation of Notch Signaling by Small-Molecular Compounds and Its Potential in Anticancer Studies.Cancers · 2023Review
- Phase I trial of intravenous fenretinide (4-HPR) plus safingol in advanced malignancies.Cancer chemotherapy and pharmacology · 2023Article
- The Notch signaling pathway: a potential target for cancer immunotherapy.Journal of hematology & oncology · 2023Review
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundNotch signaling plays an integral role in development and tissue homeostasis. Inhibition of Notch signaling has been identified as a reasonable target for oncotherapy. Crenigacestat (LY3039478) is a potent Notch inhibitor that decreases Notch signaling and its downstream biologic effects.
methodsI6F-MC-JJCD was a multicenter, nonrandomized, open-label, phase 1b study with 5 separate, parallel dose escalations in patients with advanced or metastatic cancer from a variety of solid tumors followed by a dose-confirmation phase in pre-specified tumor types. This manuscript reports on 2 of 5 groups. The primary objective was to determine the recommended phase 2 dose of crenigacestat combined with other anticancer agents (gemcitabine/cisplatin or gemcitabine/carboplatin). Secondary objectives included evaluation of safety, tolerability, preliminary efficacy, and pharmacokinetics.
resultsPatients (N = 31) received treatment between November 2016 and July 2019. Dose-limiting toxicities occurred in 6 patients. The recommended phase 2 dose for crenigacestat was 50 mg TIW in Part 1 (combined with gemcitabine/cisplatin) and not established in Part 2 (combined with gemcitabine/carboplatin) due to poor tolerability. Patients had at least one treatment-emergent adverse event (TEAE), and most had Grade ≥ 3 TEAEs. Over 50% of the patients experienced gastrointestinal disorders (Grade ≥ 3). No patient had complete response; 5 patients had a partial response. Disease control rates were 62.5% (Part 1) and 60.0% (Part 2).
conclusionThis study demonstrated that the Notch inhibitor, crenigacestat, combined with different anticancer agents (gemcitabine, cisplatin, and carboplatin) was poorly tolerated and resulted in disappointing clinical activity in patients with advanced or metastatic solid tumors. CLINICALTRIALS: gov Identification Number: NCT02784795.
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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.