ArticleInvestigational new drugs2020
A phase I study of an oral selective gamma secretase (GS) inhibitor RO4929097 in combination with neoadjuvant paclitaxel and carboplatin in triple negative breast cancer.
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 21 papers, 2 of them syntheses that pooled it.
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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.
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Who cites it
21 citing papers in PubMed, 2 syntheses or guidelines pooled it, 34 citations in OpenAlex.
- Pooled it
- Signaling pathway mechanisms in pancreatic ductal adenocarcinoma tumor microenvironment and emerging targeting strategies for improved prognosis.Oncology reviews · 2026Pooled it
- Notch receptors in breast cancer: context-dependent roles and therapeutic targeting.Cell communication and signaling : CCS · 2026Review
- The role of pluripotency regulators in triple-negative breast cancer immune response.Frontiers in genetics · 2026Review
- Recent advances in targeted therapies and immunotherapies for triple-negative breast cancer.Frontiers in oncology · 2026Review
- Role of EMT in drug resistance of breast cancer: molecular mechanisms and therapeutic strategies.Frontiers in oncology · 2025Review
- Breast Cancer Stem Cells and Tumor Heterogeneity: Characteristics and Therapeutic Strategies.Cancers · 2024Review
- Molecular pathways and therapeutic targets linked to triple-negative breast cancer (TNBC).Molecular and cellular biochemistry · 2024Review
- Novel insights into Notch signaling in tumor immunity: potential targets for cancer immunotherapy.Frontiers in immunology · 2024Review
- The Efficacy of CB-103, a First-in-Class Transcriptional Notch Inhibitor, in Preclinical Models of Breast Cancer.Cancers · 2023Article
- Silencing Notch4 promotes tumorigenesis and inhibits metastasis of triple-negative breast cancer via Nanog and Cdc42.Cell death discovery · 2023Article
- Review
- Notch signaling, hypoxia, and cancer.Frontiers in oncology · 2023Review
- A γ-Secretase Inhibitor Attenuates Cell Cycle Progression and Invasion in Human Oral Squamous Cell Carcinoma: An In Vitro Study.International journal of molecular sciences · 2022Article
- Emergence of Nanotechnology as a Powerful Cavalry against Triple-Negative Breast Cancer (TNBC).Pharmaceuticals (Basel, Switzerland) · 2022Review
- Therapeutic progress and challenges for triple negative breast cancer: targeted therapy and immunotherapy.Molecular biomedicine · 2022Review
- Herbal Ingredients in the Prevention of Breast Cancer: Comprehensive Review of Potential Molecular Targets and Role of Natural Products.Oxidative medicine and cellular longevity · 2022Review
- Article
- Targeting Notch to Maximize Chemotherapeutic Benefits: Rationale, Advanced Strategies, and Future Perspectives.Cancers · 2021Review
- Investigational Drug Treatments for Triple-Negative Breast Cancer.Journal of personalized medicine · 2021Review
Corrections and comments
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Authors and funding
20 authors at 3 institutions in 1 country.
Funding
Abstract
Upregulation of Notch pathway is associated with poor prognosis in breast cancer. We present the results of a phase I study of an oral selective gamma secretase (GS) inhibitor (critical to Notch signaling), RO4929097 in combination with neoadjuvant chemotherapy for operable triple negative breast cancer. The primary objective was to determine the maximum tolerated dose (MTD) of RO4929097. Secondary objectives were to determine real-time pharmacokinetics of RO4929097 and paclitaxel, safety and pathologic (pCR) complete response to study treatment. Eligible patients, initiated carboplatin at AUC 6 administered intravenously (IV) on day 1, weekly paclitaxel at 80 mg/m2 IV and RO4929097 10 mg daily given orally (PO) on days 1-3, 8-10 and 15-17 for six 21-day cycles. RO4929097 was escalated in 10 mg increments using the 3 + 3 dose escalation design. Two DLTs were observed in 14 patients - Grade (G) 4 thrombocytopenia in dose level 1 (10 mg) and G3 hypertension in dose level 2 (20 mg). Protocol-defined MTD was not determined due to discontinuation of RO4929097 development. However, 4 of 5 patients enrolled to 20 mg dose of RO4929097 required dose reduction to 10 mg due to toxicities (including neutropenia, thrombocytopenia and hypertension) occurring during and beyond the DLT observation period. Thus, 10 mg would have been the likely dose level for further development. G3 or higher hematologic toxicities included neutropenia (N = 8, 57%) and thrombocytopenia (N = 5, 36%) patients. Six (43%) patients had G2-3 neuropathy requiring paclitaxel dose reduction. No signs of drug-drug interaction between paclitaxel and RO4929097 were evident. Five patients (36%) had pCR.
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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.