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A Study of LY3039478 in Participants With Advanced Cancer

NCT ID: NCT01695005

Last Updated: 2025-12-26

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

247 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-10-31

Study Completion Date

2018-06-26

Brief Summary

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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.

Detailed Description

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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

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Neoplasms Neoplasm Metastasis Lymphoma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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LY3039478 - Dose Escalation

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

Group Type EXPERIMENTAL

LY3039478

Intervention Type DRUG

Administered orally

LY3039478 - Cohort Expansion

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.

Group Type EXPERIMENTAL

LY3039478

Intervention Type DRUG

Administered orally

Dose 1 LY3039478 + Prednisone

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.

Group Type EXPERIMENTAL

LY3039478

Intervention Type DRUG

Administered orally

Prednisone

Intervention Type DRUG

Administered orally

Dose 2 LY3039478 + Prednisone

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.

Group Type EXPERIMENTAL

LY3039478

Intervention Type DRUG

Administered orally

Prednisone

Intervention Type DRUG

Administered orally

Interventions

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LY3039478

Administered orally

Intervention Type DRUG

Prednisone

Administered orally

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Eli Lilly and Company

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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

Role: STUDY_DIRECTOR

Eli Lilly and Company

Locations

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University of Miami School of Medicine

Miami, Florida, United States

Site Status

Harvard Medical School

Boston, Massachusetts, United States

Site Status

University of Michigan

Ann Arbor, Michigan, United States

Site Status

Columbia University Medical Center

New York, New York, United States

Site Status

Montefiore Medical Center

The Bronx, New York, United States

Site Status

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, , Denmark

Site Status

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, , France

Site Status

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, , France

Site Status

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, , Germany

Site Status

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, , Spain

Site Status

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, , United Kingdom

Site Status

Countries

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United States Denmark France Germany Spain United Kingdom

References

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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.

Reference Type DERIVED
PMID: 40756609 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32915419 (View on PubMed)

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.

Reference Type DERIVED
PMID: 30218977 (View on PubMed)

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.

Reference Type DERIVED
PMID: 30060061 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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https://www.lillytrialguide.com/en-US/studies/solid-tumor/JJCA#?postal=

Click here for more information about this study: A Study of LY3039478 in Participants with Advanced Cancer

Other Identifiers

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I6F-MC-JJCA

Identifier Type: OTHER

Identifier Source: secondary_id

14547

Identifier Type: -

Identifier Source: org_study_id