NeoplasmsPhase 1NCT01695005

A Study of LY3039478 in Participants With Advanced Cancer

A Phase 1 study testing LY3039478 and Prednisone in people with Neoplasms and Neoplasm Metastasis, run by Eli Lilly and Company at 11 sites in 6 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

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. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Neoplasms, Neoplasm Metastasis, Lymphoma
What is being tested?: LY3039478 and Prednisone
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 247 participants
Where: 11 sitesin 6 countries
Study dates: Oct 2012to 26 Jun 2018
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Show all 18Show fewer

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.

Who cannot join

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.

Show all 9Show fewer

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.

Trial locations and contacts

11 sites in 6 countries.

Country

City, postcode or hospital

11 sites in 6 countries

United States5 sites

University of Michigan
Ann Arbor, Michigan, 48109
Harvard Medical School
Boston, Massachusetts, 02215
University of Miami School of Medicine
Miami, Florida, 33136
Columbia University Medical Center
New York, New York, 10032
Montefiore Medical Center
The Bronx, New York, 10461

Other trials in United States

France2 sites

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Paris, 75248
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Villejuif, 94805

Other trials in France

Denmark1 site

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Copenhagen, 2100

Other trials in Denmark

Germany1 site

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Tübingen, 72076

Other trials in Germany

Spain1 site

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Barcelona, 08035

Other trials in Spain

United Kingdom1 site

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
London, SE1 9RT

Other trials in United Kingdom

About this study

Official title: A Phase 1 Study of LY3039478 in Patients With Advanced or Metastatic Cancer

Read the detailed description

In Part A of this study, participants with advanced/metastatic cancer (including lymphoma) will receive increasing doses of LY3039478 to define the dose level for Part B, C, D and E. In Part B, C, D and E LY3039478 will be explored at a predefined fixed dose level. Participants in Part B and D must have a defined alteration in a certain molecular pathway. Enrollment of participants in Part B, C, D and E will start once Part A is completed. In Part F participants will receive increasing doses of LY3039478 in combination with prednisone to define the maximum tolerated dose level.

Conditions: Neoplasms, Neoplasm Metastasis, Lymphoma
Being tested: LY3039478, Prednisone
Medical subject headings: Neoplasms, Neoplasm Metastasis, Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

LY3039478Drug
Administered orally
PrednisoneDrug
Administered orally

Study groups in NCT01695005
Study group	Role	What they receive
LY3039478 - Dose Escalation	Experimental	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 Receives: Drug: LY3039478
LY3039478 - Cohort Expansion	Experimental	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. Receives: Drug: LY3039478
Dose 1 LY3039478 + Prednisone	Experimental	Part F1: Participants received a loading dose of 75 mg or 100 mg administered 3 times per week for 2 weeks during Cycle 1. 50 mg LY3039478 administered orally TIW (twice a week in cycle 1) for 28 day cycles. 20 mg Prednisone will be co-administered with LY3039478 for the first 2 weeks in cycle 1 only (28 day cycles). Participants receiving benefit may continue until disease progression. Receives: Drug: LY3039478; Drug: Prednisone
Dose 2 LY3039478 + Prednisone	Experimental	Part F2: Participants received a loading dose of 75 mg, 100 mg or 125 mg 2 times per week for 2 weeks during Cycle 1. 50 mg LY3039478 administered orally TIW for 28 day cycles. 20 mg Prednisone will be co-administered with LY3039478 for the first 2 weeks in cycle 1 only (28 day cycles). Participants receiving benefit may continue until disease progression. Receives: Drug: LY3039478; Drug: Prednisone

What is being measured

The primary outcome is the main question the study is designed to answer.

Part A and F: Number of Participants With Dose Limiting Toxicities (DLTs)
DLT was defined as an adverse event (AE) during Cycle 1 (Up to 28 Days) that was related to LY3039478 and fulfilled any 1 of the following criterion using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0 (NCI-CTCAE v 4.0): CTCAE Grade 3 non-hematological toxicity with a few exceptions, CTCAE Grade 4 hematological toxicity of greater than 5 days duration, any febrile neutropenia,Grade 3 thrombocytopenia with bleeding or Grade 4 thrombocytopenia, Any other significant toxicity deemed by the primary investigator and Lilly clinical research personnel to be dose limiting (for example, any toxicity that is possibly related to the study medication that requires the withdrawal of the participant from the study during Cycle 1).
Measured: Baseline through the end of Cycle 1, Up to 28 Days
Part A: Recommended Phase 2 Dose of LY3039478 : Maximum Tolerated Dose (MTD)
MTD is defined as the highest tested dose that has less than 33% probability of causing a DLT during Cycle 1.
Measured: Baseline though the end of cycle 1 (28 days cycle)
Part B, C, D and E: Recommended Phase 2 Dose of LY3039478 : Maximum Tolerated Dose (MTD)
MTD is defined as the highest tested dose that has less than 33% probability of causing a DLT during Cycle 1.
Measured: Baseline through the end of cycle 1 (28 days Cycle)
Part F1 and F2: Recommended Phase 2 Dose of LY3039478
Parts F1 and F2 compared loading dose three time per week with prednisone versus two times per week with prednisone. Even though the trial may have found an MTD, it did not identify an Recommended Phase 2 dose (RP2D).
Measured: Baseline Up to 2 Months
Part B, C, D, E and F: Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])
Objective response is complete response (CR) + partial response (PR), as classified by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST 1.1 ) guidelines. CR is disappearance of all target and non-target lesions; PR is greater than or equal to (>=) 30% decrease in sum of longest diameter of target lesions. Objective response rate is calculated as a total number of participants with CR or PR divided by the total number of participants treated multiplied by 100.
Analysis Population Description: Part D: 50 mg LY3039478 (Cohort 5) was assessed using Cheson criteria. Zero participants were analyzed for Part D: 50 mg LY3039478 (Cohort 4) because data were not collected. Data was not reported because both enrolled participants discontinued treatment early-one on Day 1 due to investigator decision and the other on Day 26 due to myocardial infarction, with no efficacy assessments performed.
Measured: Baseline to Disease Progression or Participant Discontinuation (Up To 20 Months)

Secondary outcomes (12)

Parts A, B, C, D and E: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3039478
Parts A and B: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3039478
Analysis Population Description: Per Protocol, only sparse samples were analyzed for this outcome measure. There were no Sparse Day 22 samples for Part B: 50 mg \& 75 mg LY3039478, Part C: 50 mg \&75 LY3039478, Part D: 50 mg \& 75 LY3039478 and Part E: 50 mg LY3039478
Measured: Day 1: Predose,0.5,1,2,4,6-8,8-10,24-30 hours; Day 22: Predose, 0.5,1,2,4,6-8,8-10,24-30 hours
Part F1 Cohort1 and Part F2 Cohort 1: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3039478
Part F1 Cohort 1 and Part F2 and Cohort 1: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3039478
Measured: Day 1: Predose,0.5,1,2,4,6-8,8-10,24-30 hours; Day 22: Predose, 0.5,1,2,4,6-8,8-10,24-30 hours
Parts A and B: PK: Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC[0-∞]) of LY3039478
PK: Area Under the Concentration-Time Curve From time 0 to Infinity (AUC[0-∞]) of LY3039478
Analysis Population Description: One participant assigned to the Part A: 45 mg group LY3039478 arm received 75 mg in error on Day 1 and had evaluable PK data. Therefore, this participant is included in the Part A: 75 mg LY3039478 arm PK analysis population (N=6), though only N=5 is shown in the Participant Flow module.
Measured: Day 1: Predose,0.5,1,2,4,6-8,8-10,24-30 hours
Part F1 Cohort1 and Part F2 Cohort 1: PK: Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC[0-∞]) of LY3039478
Part F1 Cohort1 and Part F2 Cohort 1: PK: Area Under the Concentration-Time Curve From time 0 to Infinity (AUC[0-∞]) of LY3039478
Measured: Day 1: Predose,0.5,1,2,4,6-8,8-10,24-30 hours
Parts A and B: PK: Area Under the Concentration-Time Curve From Time 0 to Tau (AUC[0-Tau]) of LY3039478
PK: Area Under the Concentration-Time Curve From Time 0 to Tau (AUC[0-Tau]) of LY3039478
Analysis Population Description: Per protocol, AUC0-tau was not analyzed for participants undergoing sparse PK sampling. Part B 50mg participants only underwent sparse PK sampling.
Measured: Day 22: Predose,0.5,1,2,4,6-8,8-10,24-30 hours
Part F1 Cohort1 and Part F2 Cohort 1: PK: Area Under the Concentration-Time Curve From Time 0 to Tau (AUC[0-Tau]) of LY3039478
PK: Area Under the Concentration-Time Curve From Time 0 to Tau (AUC[0-Tau]) of LY3039478
Measured: Day 22: Predose,0.5,1,2,4,6-8,8-10,24-30 hours
Parts A, B, C, D and E: PK: Time to Maximum Concentration (Tmax) of LY3039478
Pharmacokinetics: Time to Maximum Concentration (Tmax) of LY3039478
Analysis Population Description: Per Protocol, only sparse samples were analyzed for this outcome measure. There were no Sparse Day 22 samples for Part B: 50 mg \& 75 mg LY3039478, Part C: 50 mg \&75 LY3039478, Part D: 50 mg \& 75 LY3039478 and Part E: 50 mg LY3039478.
Measured: Day 1: Predose,0.5,1,2,4,6-8,8-10,24-30 hours; Day 22: Predose,0.5,1,2,4,6-8,8-10,24-30 hours
Part F1 Cohort1 and Part F2 Cohort 1: PK: Time to Maximum Concentration (Tmax) of LY3039478
Part F1 Cohort1 and Part F2 Cohort 1: PK: Time to Maximum Concentration (Tmax) of LY3039478
Measured: Day 1: Predose,0.5,1,2,4,6-8,8-10,24-30 hours; Day 22: Predose,0.5,1,2,4,6-8,8-10,24-30 hours
Part A: Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])
Objective response is complete response (CR) + partial response (PR), as classified by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST 1.1 ) guidelines. CR is disappearance of all target and non-target lesions; PR is ≥30% decrease in sum of longest diameter of target lesions. Objective response rate is calculated as a total number of participants with CR or PR divided by the total number of participants treated multiplied by 100.
Measured: Baseline to Disease Progression or Participant Discontinuation (Up To 17 Months)
Part B, C, D, E and F: Duration of Response (DoR)
The time from the date of first evidence of a confirmed complete to the date of objective progression or the date of death from any cause (whichever is earlier) as classified by RECIST 1.1 guidelines. For each participant who is not known to have died or to have had a progression of disease as of the data-inclusion cut-off date, duration of response will be censored at the date of last objective response assessment prior to the date of any subsequent systemic anticancer therapy. Progressive Disease (PD) is an increase of at least 20% in the sum of the diameters of target lesions, taking as reference the smallest sum on study (included baseline sum if that was the smallest on study). In addition, the sum must have demonstrated an absolute increase of at least 5 mm (the appearance of 1 or more new lesions was considered progression).
Measured: Date of Complete Response or Partial Response to Date of Objective Disease Progression or Death Due to Any Cause (Up To 20 Months)
Part B, C, D, E and F: Progression Free Survival (PFS)
Progression-free survival(PFS) time is defined as the time from the date of study enrollment to the first date of PD(symptomatic or objective) or death due to any cause,whichever occurs first.For participants who are not known to have died or progressed as of the data-inclusion cut-off date,PFS time will be censored at the date of the last objective progression-free disease assessment prior to the date of any subsequent systemic anticancer therapy. Progressive Disease(PD) is an increase of at least 20% in the sum of the diameters of target lesions,taking as reference the smallest sum on study(included baseline sum if that was the smallest on study).In addition, the sum must have demonstrated an absolute increase of at least 5 mm(the appearance of 1 or more new lesions was considered progression).
Analysis Population Description Continued:Part D:50 mg LY3039478(Cohort 4) and Part D:50 mg LY3039478(Cohort 5) were not assessed according to RECIST criteria due to their type of disease.
Measured: Baseline to Objective Progression or Death from Any Cause (Up To 17 Months)
Part B, C, D, E and F: Overall Survival (OS)
Overall Survival (OS) was defined as the time from the date of study enrollment to the date of death from any cause. For participants not known to have died as of the data cut-off date, OS time was censored at the last contact date the participants was known to be alive prior to the cut-off date.
Measured: Baseline to Date of Death from Any Cause (Up To 49 Months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Oct 201226 Jun 2018

First posted27 Sep 2012 (estimated)
Study startOct 2012
Primary completion26 Jun 2018
Study completion26 Jun 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (4)Papers the sponsor has linked to this study.
Other trials for NeoplasmsStudies of the same condition, open and under way.
More trials run by Eli Lilly and CompanyThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Enrolment: 247 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01695005
Sponsor's protocol ID: 14547
Other IDs: I6F-MC-JJCA
Status last verified: Dec 2025
First submitted: 24 Sep 2012
Last updated: 26 Dec 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

Michot 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.
PubMed 40756609
Azaro 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.
PubMed 32915419
Mir 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.
PubMed 30218977
Massard 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.
PubMed 30060061

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Not yet recruitingPhase 1
Hepatic Artery Infusion of Carfilzomib in Participants With Liver Metastatic Disease Previously Treated With Hepatic Artery Infusion Pump Therapy
Colorectal Neoplasms, Neoplasms
RecruitingPhase 2
Tafasitamab With Acalabrutinib and Venetoclax for the Treatment of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Chronic Lymphocytic Leukemia, Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Active, not recruitingPhase 1/2
Selumetinib in Treating Young Patients With Recurrent or Refractory Low Grade Glioma
Low Grade Glioma, Recurrent Childhood Pilocytic Astrocytoma
Enrolling by invitationPhase 2
A Single-Arm Study of Nimotuzumab Combined With NALIRIFOX as First-Line Treatment for Pancreatic Cancer
Pancreatic Cancer Metastatic
Recruiting
Methylation Profiling in Self-Samples for Identification of (Epi)Genetic Biomarkers for Gynecological Cancers
Gynaecological Cancers, Ovarian Cancer

All Neoplasms trials

Study at a glance

From the registry record, last updated by the sponsor on 26 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 1 Study of LY3039478 in Patients With Advanced or Metastatic Cancer
ClinicalTrials.gov ID: NCT01695005
Acronym / sponsor ID: 14547
Conditions: Neoplasms, Neoplasm Metastasis, Lymphoma
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 247 participants (actual)
Lead sponsor: Eli Lilly and CompanyIndustry (pharma, biotech, devices)
Study start: Oct 2012
Primary completion: 26 Jun 2018 (actual)
Study completion: 26 Jun 2018 (actual)
First posted: 27 Sep 2012 (estimated)
Results: Posted 26 Dec 2025

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Number of arms: 4

Arm	Type	Receives
LY3039478 - Dose Escalation	Experimental	Drug: LY3039478Part 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
LY3039478 - Cohort Expansion	Experimental	Drug: LY3039478Part 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.
Dose 1 LY3039478 + Prednisone	Experimental	Drug: LY3039478, Drug: PrednisonePart F1: Participants received a loading dose of 75 mg or 100 mg administered 3 times per week for 2 weeks during Cycle 1. 50 mg LY3039478 administered orally TIW (twice a week in cycle 1) for 28 day cycles. 20 mg Prednisone will be co-administered with LY3039478 for the first 2 weeks in cycle 1 only (28 day cycles). Participants receiving benefit may continue until disease progression.
Dose 2 LY3039478 + Prednisone	Experimental	Drug: LY3039478, Drug: PrednisonePart F2: Participants received a loading dose of 75 mg, 100 mg or 125 mg 2 times per week for 2 weeks during Cycle 1. 50 mg LY3039478 administered orally TIW for 28 day cycles. 20 mg Prednisone will be co-administered with LY3039478 for the first 2 weeks in cycle 1 only (28 day cycles). Participants receiving benefit may continue until disease progression.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (18 listed)

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.

Key exclusion criteria (9 listed)

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:

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
LY3039478Administered orally	Drug	Dose 1 LY3039478 + Prednisone, Dose 2 LY3039478 + Prednisone, LY3039478 - Cohort Expansion, LY3039478 - Dose Escalation
PrednisoneAdministered orally	Drug	Dose 1 LY3039478 + Prednisone, Dose 2 LY3039478 + Prednisone

Primary outcome

Part A and F: Number of Participants With Dose Limiting Toxicities (DLTs)
Time frame: Baseline through the end of Cycle 1, Up to 28 Days
DLT was defined as an adverse event (AE) during Cycle 1 (Up to 28 Days) that was related to LY3039478 and fulfilled any 1 of the following criterion using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0 (NCI-CTCAE v 4.0): CTCAE Grade 3 non-hematological toxicity with a few exceptions, CTCAE Grade 4 hematological toxicity of greater than 5 days duration, any febrile neutropenia,Grade 3 thrombocytopenia with bleeding or Grade 4 thrombocytopenia, Any other significant toxicity deemed by the primary investigator and Lilly clinical research personnel to be dose limiting (for example, any toxicity that is possibly related to the study medication that requires the withdrawal of the participant from the study during Cycle 1).
Part A: Recommended Phase 2 Dose of LY3039478 : Maximum Tolerated Dose (MTD)
Time frame: Baseline though the end of cycle 1 (28 days cycle)
MTD is defined as the highest tested dose that has less than 33% probability of causing a DLT during Cycle 1.
Part B, C, D and E: Recommended Phase 2 Dose of LY3039478 : Maximum Tolerated Dose (MTD)
Time frame: Baseline through the end of cycle 1 (28 days Cycle)
MTD is defined as the highest tested dose that has less than 33% probability of causing a DLT during Cycle 1.
Part F1 and F2: Recommended Phase 2 Dose of LY3039478
Time frame: Baseline Up to 2 Months
Parts F1 and F2 compared loading dose three time per week with prednisone versus two times per week with prednisone. Even though the trial may have found an MTD, it did not identify an Recommended Phase 2 dose (RP2D).
Part B, C, D, E and F: Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])
Time frame: Baseline to Disease Progression or Participant Discontinuation (Up To 20 Months)
Objective response is complete response (CR) + partial response (PR), as classified by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST 1.1 ) guidelines. CR is disappearance of all target and non-target lesions; PR is greater than or equal to (>=) 30% decrease in sum of longest diameter of target lesions. Objective response rate is calculated as a total number of participants with CR or PR divided by the total number of participants treated multiplied by 100. Analysis Population Description: Part D: 50 mg LY3039478 (Cohort 5) was assessed using Cheson criteria. Zero participants were analyzed for Part D: 50 mg LY3039478 (Cohort 4) because data were not collected. Data was not reported because both enrolled participants discontinued treatment early-one on Day 1 due to investigator decision and the other on Day 26 due to myocardial infarction, with no efficacy assessments performed.

12 secondary outcomes

Parts A, B, C, D and E: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3039478
Time frame: Day 1: Predose,0.5,1,2,4,6-8,8-10,24-30 hours; Day 22: Predose, 0.5,1,2,4,6-8,8-10,24-30 hours
Part F1 Cohort1 and Part F2 Cohort 1: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3039478
Time frame: Day 1: Predose,0.5,1,2,4,6-8,8-10,24-30 hours; Day 22: Predose, 0.5,1,2,4,6-8,8-10,24-30 hours
Parts A and B: PK: Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC[0-∞]) of LY3039478
Time frame: Day 1: Predose,0.5,1,2,4,6-8,8-10,24-30 hours
Part F1 Cohort1 and Part F2 Cohort 1: PK: Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC[0-∞]) of LY3039478
Time frame: Day 1: Predose,0.5,1,2,4,6-8,8-10,24-30 hours
Parts A and B: PK: Area Under the Concentration-Time Curve From Time 0 to Tau (AUC[0-Tau]) of LY3039478
Time frame: Day 22: Predose,0.5,1,2,4,6-8,8-10,24-30 hours
Part F1 Cohort1 and Part F2 Cohort 1: PK: Area Under the Concentration-Time Curve From Time 0 to Tau (AUC[0-Tau]) of LY3039478
Time frame: Day 22: Predose,0.5,1,2,4,6-8,8-10,24-30 hours
Parts A, B, C, D and E: PK: Time to Maximum Concentration (Tmax) of LY3039478
Time frame: Day 1: Predose,0.5,1,2,4,6-8,8-10,24-30 hours; Day 22: Predose,0.5,1,2,4,6-8,8-10,24-30 hours
Part F1 Cohort1 and Part F2 Cohort 1: PK: Time to Maximum Concentration (Tmax) of LY3039478
Time frame: Day 1: Predose,0.5,1,2,4,6-8,8-10,24-30 hours; Day 22: Predose,0.5,1,2,4,6-8,8-10,24-30 hours
Part A: Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])
Time frame: Baseline to Disease Progression or Participant Discontinuation (Up To 17 Months)
Part B, C, D, E and F: Duration of Response (DoR)
Time frame: Date of Complete Response or Partial Response to Date of Objective Disease Progression or Death Due to Any Cause (Up To 20 Months)
Part B, C, D, E and F: Progression Free Survival (PFS)
Time frame: Baseline to Objective Progression or Death from Any Cause (Up To 17 Months)
Part B, C, D, E and F: Overall Survival (OS)
Time frame: Baseline to Date of Death from Any Cause (Up To 49 Months)

Results and safety

Results posted to the registry on 26 Dec 2025, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Part A: 2.5 mg LY3039478	4	4
Part A: 5 mg LY3039478	3	2
Part A: 10 mg LY3039478	4	3
Part A: 20 mg LY3039478	8	6
Part A: 30 mg LY3039478	7	7
Part A: 45 mg LY3039478	5	3
Part A: 60 mg LY3039478	9	8
Part A: 75 mg LY3039478	5	3
Part A: 100 mg LY3039478	10	7
Part B: 50 mg LY3039478	30	26
Part B: 75 mg LY3039478	25	15
Part C: 50 mg LY3039478 LMS	22	16
Part C: 75 mg LY3039478 LMS	6	3
Part C: 50 mg LY3039478 Other Sarcoma	27	22
Part C: 75 mg LY3039478 Other Sarcoma	1	1
Part C: 50 mg LY3039478 GIST	13	9
Part D: 75 mg LY3039478 (Cohort 1)	1	1
Part D: 75 mg LY3039478 (Cohort 3)	2	2
Part D: 50 mg LY3039478 (Cohort 1)	3	1
Part D: 50 mg LY3039478 (Cohort 2)	3	2
Part D: 50 mg LY3039478 (Cohort 3)	7	5
Part D: 50 mg LY3039478 (Cohort 4)	2	2
Part D: 50 mg LY3039478 (Cohort 5)	6	4
Part E: LY3039478 (Cohort 1)	16	12
Part F1:Cohort1 Load75mg_50mg LY3039478 + Prednisone	7	4
Part F1:Cohort2 Load100mg_50mg LY3039478 + Prednisone	4	4
Part F2: Cohort1 Load75mg_50mg LY3039478 + Prednisone	3	3
Part F2:Cohort2 Load100mg_50mg LY3039478 + Prednisone	7	6
Part F2: Cohort3 Load125mg_50mg LY3039478 + Prednisone	7	6

Primary outcome: Part A and F: Number of Participants With Dose Limiting Toxicities (DLTs)

Time frame: Baseline through the end of Cycle 1, Up to 28 Days. Count of participants. Unit: Participants

Measure	Part A: 2.5 mg LY3039478 n = 4	Part A: 5 mg LY3039478 n = 3	Part A: 10 mg LY3039478 n = 4	Part A: 20 mg LY3039478 n = 8	Part A: 30 mg LY3039478 n = 7	Part A: 45 mg LY3039478 n = 5	Part A: 60 mg LY3039478 n = 9	Part A: 75 mg LY3039478 n = 5	Part A: 100 mg LY3039478 n = 10	Part F1:Cohort1 Load75mg_50mg LY3039478 + Prednisone n = 7	Part F1:Cohort2 Load100mg_50mg LY3039478 + Prednisone n = 4	Part F2: Cohort1 Load75mg_50mg LY3039478 + Prednisone n = 3	Part F2:Cohort2 Load100mg_50mg LY3039478 + Prednisone n = 7	Part F2: Cohort3 Load125mg_50mg LY3039478 + Prednisone n = 7
Value	0	0	0	1	1	0	2	0	2	1	2	0	0	2

Population analysed: All Part A and F participants who received at least one dose of study drug.

Primary outcome: Part A: Recommended Phase 2 Dose of LY3039478 : Maximum Tolerated Dose (MTD)

Time frame: Baseline though the end of cycle 1 (28 days cycle). Number. Unit: milligram (mg)

Measure	Part A Participants n = 55
Value	75

Population analysed: All part A participants who received at least one dose of study drug.

Primary outcome: Part B, C, D and E: Recommended Phase 2 Dose of LY3039478 : Maximum Tolerated Dose (MTD)

Time frame: Baseline through the end of cycle 1 (28 days Cycle). Number. Unit: milligram (mg)

Measure	Part B, C, D and E Participants n = 164
Value	50

Population analysed: All part B, C, D and E participants who received at least one dose of study drug.

Primary outcome: Part F1 and F2: Recommended Phase 2 Dose of LY3039478

Time frame: Baseline Up to 2 Months. Number. Unit: milligram (mg)

Measure	Part FI and F2 Participants n = 28
Value	NA

Population analysed: All Part F1 and F2 participants who received at least one dose of study drug.

12 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to 49 Months. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Part A: 2.5 mg LY3039478	1 of 4 (25%)	4 of 4 (100%)	1 of 4
Part A: 5 mg LY3039478	0 of 3 (0%)	3 of 3 (100%)	0 of 3
Part A: 10 mg LY3039478	2 of 4 (50%)	4 of 4 (100%)	2 of 4
Part A: 20 mg LY3039478	4 of 8 (50%)	8 of 8 (100%)	1 of 8
Part A: 30 mg LY3039478	5 of 7 (71.4%)	7 of 7 (100%)	1 of 7
Part A: 45 mg LY3039478	3 of 5 (60%)	5 of 5 (100%)	2 of 5
Part A: 60 mg LY3039478	5 of 9 (55.6%)	9 of 9 (100%)	4 of 9
Part A: 75 mg LY3039478	1 of 5 (20%)	5 of 5 (100%)	3 of 5
Part A: 100 mg LY3039478	5 of 10 (50%)	10 of 10 (100%)	4 of 10
Part B: 75 mg LY3039478	14 of 25 (56%)	25 of 25 (100%)	16 of 25
Part B: 50 mg LY3039478	14 of 30 (46.7%)	30 of 30 (100%)	21 of 30
Part C: 75 mg LY3039478 LMS	5 of 6 (83.3%)	6 of 6 (100%)	4 of 6
Part C: 75 LY3039478 Other Sarcoma	1 of 1 (100%)	1 of 1 (100%)	1 of 1
Part C: 50 LY3039478 GIST	8 of 13 (61.5%)	13 of 13 (100%)	7 of 13
Part C: 50 mg LY3039478 LMS	8 of 22 (36.4%)	20 of 22 (90.9%)	17 of 22
Part C: 50 LY3039478 Other Sarcoma	10 of 27 (37%)	27 of 27 (100%)	19 of 27
Part D: 75 mg LY3039478 (Cohort 1)	0 of 1 (0%)	1 of 1 (100%)	1 of 1
Part D: 75 LY3039478 (Cohort 3)	2 of 2 (100%)	2 of 2 (100%)	2 of 2
Part D: 50 LY3039478 (Cohort 1)	2 of 3 (66.7%)	2 of 3 (66.7%)	2 of 3

Limitations and caveats (from the sponsor): 1. There was no recommended phase II dose declared from Part F1 or F2. Expansion cohort was not triggered. 2. For outcome measure number 8 (Part A and B ((AUC \[0-∞\]) of LY3039478), AUC0-inf parameter cannot be calculated (per analysis plan) for Part B: 50 mg LY3039478 due to insufficient length of PK sampling to 8h for a drug half-life of around 5-6 hours.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 26 Dec 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 40756609Michot 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.
Derived from this study: PubMed 32915419Azaro 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.
Derived from this study: PubMed 30218977Mir 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.
Derived from this study: PubMed 30060061Massard 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.
Click here for more information about this study: A Study of LY3039478 in Participants with Advanced CancerLink provided by the sponsor.
Individual participant dataSharing planned: No

Related trials for Neoplasms

Not yet recruitingPhase 1
Hepatic Artery Infusion of Carfilzomib in Participants With Liver Metastatic Disease Previously Treated With Hepatic Artery Infusion Pump Therapy
Colorectal Neoplasms, Neoplasms
RecruitingPhase 2
Tafasitamab With Acalabrutinib and Venetoclax for the Treatment of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Chronic Lymphocytic Leukemia, Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Active, not recruitingPhase 1/2
Selumetinib in Treating Young Patients With Recurrent or Refractory Low Grade Glioma
Low Grade Glioma, Recurrent Childhood Pilocytic Astrocytoma
Enrolling by invitationPhase 2
A Single-Arm Study of Nimotuzumab Combined With NALIRIFOX as First-Line Treatment for Pancreatic Cancer
Pancreatic Cancer Metastatic
Recruiting
Methylation Profiling in Self-Samples for Identification of (Epi)Genetic Biomarkers for Gynecological Cancers
Gynaecological Cancers, Ovarian Cancer

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) study director

Eli Lilly and Company

11 sites in 6 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing LY3039478 and Prednisone in people with Neoplasms and Neoplasm Metastasis, run by Eli Lilly and Company at 11 sites in 6 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in United States, France, Denmark, Germany, Spain and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 26 Dec 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part A and F: Number of Participants With Dose Limiting Toxicities (DLTs) (time frame: Baseline through the end of Cycle 1, Up to 28 Days). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01695005, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Dec 2025.