Clinical trial · Interventional
A Study of LY3039478 in Participants With Advanced Cancer
A Phase 1 Study of LY3039478 in Patients With Advanced or Metastatic Cancer
NCT01695005CI-TRIAL-00099709completedPhase 1Results postedClinicalTrials.gov clinicaltrialsProvenance
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
The purpose of this study is to find a recommended dose level of LY3039478 that can safely be taken by participants with advanced cancer or cancer that has spread to other parts of the body, including but not limited to lymphoma. The study will also explore changes to various markers in blood cells and tissue. Finally, the study will help to document any tumor activity this drug may have.
Conditions
Conditions (3)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
Interventions
Interventions (2)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| LY3039478 | Drug | — | UNRESOLVED |
| Prednisone | Drug | Prednisone | ALIAS |
Design
Arms and outcomes
Arms (4)
- type
- EXPERIMENTAL
- label
- LY3039478 - Dose Escalation
- description
- Part A: LY3039478 administered orally three times per week (TIW) at escalating doses (2.5 milligrams \[mg\], 5 mg, 10 mg, 20 mg, 30 mg, 45 mg, 60 mg, 75 mg and 100 mg) for two 28 day cycles. Participants receiving benefit may continue until disease progression
- interventionNames
- Drug: LY3039478
- type
- EXPERIMENTAL
- label
- LY3039478 - Cohort Expansion
- description
- Part B,C,D \& E:LY3039478 administered orally three times per week(TIW) at a fixed dose determined in Part A for two 28 day cycles.Participants receiving benefit may continue until disease progression.The doses administered were as follows:Part B:50 mg or 75 mg for participants(pts) who had tumors with molecular alterations related to the Notch pathway;Part C:50 mg or 75 mg for pts who had Leiomyosarcoma(LMS),50 mg or 75 mg for pts who had other Sarcoma, 50 mg for pts who had gastrointestinal stromal tumors(GIST);Part D: 75 mg for pts in the Triple Negative Breast Cancer cohort,75 mg for pts in Cholangiocarcinoma cohort,50 mg for pts in Triple Negative Breast Cancer cohort,50 mg for pts in the Hepatocellular Carcinoma cohort,50 mg for pts in the Cholangiocarcinoma cohort, 50 mg for pts in the Chronic lymphocytic leukemia(CLL) cohort, 50 mg for pts in the Mature T cell, B cell or Natural Killer(NK) cell neoplasms cohort; Part E: 50 mg for pts in the Triple Negative Breast Cancer cohort.
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
Inclusion Criteria: * For all parts: The participant must be, in the judgment of the investigator, an appropriate candidate for experimental therapy after available standard therapies have failed to provide clinical benefit for their advanced or metastatic cancer. * For Dose Escalation (Part A): The participant must have histological or cytological evidence of cancer, either a solid tumor or a lymphoma, which is advanced or metastatic. * For Part B: All participants must have a histological evidence of their advanced or metastatic cancer and prescreened alterations in a defined pathway. * For Part C: All participants must have histological evidence of advanced or metastatic specific subtypes of soft tissue sarcoma. * For Part D: All participants must have histological evidence of advanced or metastatic cancer and prescreened alterations in a defined pathway. * Cohort 1: Participants must have triple negative breast cancer. * Cohort 2: Participants must have hepatocellular carcinoma (HCC). These participants should have Child-Pugh stage A. * Cohort 3: Participants must have cholangiocarcinoma. * Cohort 4: Participants must have chronic lymphocytic leukemia. * Cohort 5: Participants must have a mature T cell, B cell, or natural killer (NK) cell neoplasm. * For Part E: Participants must have adenoid cystic carcinoma (ACC). * For Part F dose confirmation: Participants must have leiomyosarcoma and prescreened alterations in a defined pathway. * As defined by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1), the Revised Response Criteria for Malignant Lymphoma or the Response Assessment in Neuro Oncology (RANO) criteria for glioblastoma: * For Dose Escalation (Part A): Have measurable or nonmeasurable disease. * For Parts B, C, D, E and F: Have measurable disease or reliable biomarker measure. * For Parts B, C, D, E and F: Have available tumor tissue. * Have adequate organ function. * Have a performance status of less than or equal to 1 on the Eastern Cooperative Oncology Group (ECOG) scale and life expectancy of more than 12 weeks. Exclusion Criteria: * Have symptomatic or non stable central nervous system (CNS) malignancy. * Females who are pregnant or lactating. * Have active bacterial, fungal, and/or known viral infection. * Have malabsorptive syndromes, enteropathies, gastroenteritis (acute or chronic), or diarrhea (acute or chronic). * Participants with HCC that: * Have known HCC with fibro-lamellar or mixed histology. * Have presence of clinically relevant ascites. * Have had a liver transplant. * Have active or uncontrolled clinically serious hepatitis B virus or hepatitis C virus infection.
References
Publications (4)
- DERIVEDMichot JM, Balogh Z, Brown JR, Ribrag V, Hollebecque A, Bahleda R, Quivoron C, Ammari S, Scoazec JY, Benhadji KA, Massard C. 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. Ther Adv Drug Saf. 2025 Jul 31;16:20420986241311461. doi: 10.1177/20420986241311461. eCollection 2025. PMID 40756609
- DERIVEDAzaro A, Baldini C, Rodon J, Soria JC, Yuen E, Lithio A, Oakley G, Benhadji KA, Massard C. Phase 1 study of 2 high dose intensity schedules of the pan-Notch inhibitor crenigacestat (LY3039478) in combination with prednisone in patients with advanced or metastatic cancer. Invest New Drugs. 2021 Feb;39(1):193-201. doi: 10.1007/s10637-020-00944-z. Epub 2020 Sep 11. PMID 32915419
- DERIVEDMir O, Azaro A, Merchan J, Chugh R, Trent J, Rodon J, Ohnmacht U, Diener JT, Smith C, Yuen E, Oakley GJ 3rd, Le Cesne A, Soria JC, Benhadji KA, Massard C. Notch pathway inhibition with LY3039478 in soft tissue sarcoma and gastrointestinal stromal tumours. Eur J Cancer. 2018 Nov;103:88-97. doi: 10.1016/j.ejca.2018.08.012. Epub 2018 Sep 12. PMID 30218977
- DERIVEDMassard C, Azaro A, Soria JC, Lassen U, Le Tourneau C, Sarker D, Smith C, Ohnmacht U, Oakley G, Patel BKR, Yuen ESM, Benhadji KA, Rodon J. First-in-human study of LY3039478, an oral Notch signaling inhibitor in advanced or metastatic cancer. Ann Oncol. 2018 Sep 1;29(9):1911-1917. doi: 10.1093/annonc/mdy244. PMID 30060061