A Study of LY3039478 in Japanese Participants With Advanced Solid Tumors

A Phase 1 Study of LY3039478 in Japanese Patients With Advanced Solid Tumors

The purpose of this study is to evaluate the tolerability of the study drug LY3039478 in Japanese participants with advanced solid tumors.

Study Overview

• Status: Completed
• Conditions: Advanced Solid Tumor
• Intervention / Treatment: Drug: LY3039478

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Chiba
    • Kashiwa, Chiba, Japan, 277 8577
      • 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.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histological or cytological evidence of a diagnosis of solid tumor that is advanced and/or metastatic.
• In the judgment of the investigator, participants must be appropriate candidates for experimental therapy after available standard therapies have failed or for whom standard therapy is not appropriate.
• Performance status of less than or equal to (≤) 1 on the Eastern Cooperative Oncology Group (ECOG) scale.
• Adequate organ function, including hematologic, hepatic, and renal.
• Estimated life expectancy of greater than or equal to (≥) 12 weeks.

Exclusion Criteria:

• Received previous therapy for cancer within 14 or 21 days of the initial dose of study drug for a nonmyelosuppressive or myelosuppressive agents, respectively.
• Have serious preexisting medical conditions.
• Have current or recent (within 3 months of study drug administration) gastrointestinal disease with chronic or intermittent diarrhea.
• Have an active bacterial, fungal, and/or known viral infection.
• Have known acute or chronic leukemia or current hematologic malignancies that may affect the interpretation of results.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 25 mg LY3039478; Participants received 25 milligrams (mg) of LY3039478, administered orally three times per week (TIW) in a 28-day cycle, until disease progression, development of unacceptable toxicity, or any other discontinuation criteria were met.	Drug: LY3039478; Administered orally
Experimental: 50 mg LY3039478; Participants received 50 mg of LY3039478, administered orally TIW in a 28-day cycle, until disease progression, development of unacceptable toxicity, or any other discontinuation criteria were met.	Drug: LY3039478; Administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With LY3039478 Dose-Limiting Toxicities (DLTs)	DLT was defined as an adverse event (AE) that occurred during Cycle 1 (first 28 days) related to the study drug and met one of the following criteria per the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. These criteria included: CTCAE Grade greater than or equal to (≥) 3 non-hematological toxicity, with exceptions for nausea, vomiting, or constipation, and asymptomatic electrolyte disturbances that can be controlled with standard treatment; Grade 4 hematological toxicity of greater than (>) 5 days duration; Grade ≥ 3 anemia requiring transfusion; any febrile neutropenia; neutropenia needing granulocyte-colony stimulating factors (GCSFs); Grade 3 thrombocytopenia with bleeding or requiring platelet transfusion; Grade 4 thrombocytopenia.	Cycle 1 (Up to 28 Days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR): Percentage of Participants Who Achieved a Complete Response (CR) or Partial Response (PR)	The ORR was defined as the percentage of participants achieving either a CR or PR. Tumor response was assessed based on histology: Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) was used for solid tumors, and Response Assessment in Neuro-Oncology criteria were used for glioblastoma.; CR was defined as the disappearance of all target lesions, with any pathological lymph nodes (whether target or non-target) showing a reduction in the short axis to <10 mm. Additionally, tumor marker results were required to have normalized. PR was defined as a decrease of at least 30% in the sum of the diameters of target lesions, using baseline diameters as the reference.	Baseline through Measured Progressive Disease (Up To 100 Weeks)
Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY3039478	PK: Cmax of LY3039478 was reported.	Cycle 1, Day 1 (Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, and 24 hours post-dose); Cycle 1 Day 22 (Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, and 24 hours post-dose)
PK: Area Under the Plasma Concentration-Time Curve (AUC) From 0 to 24 Hours (AUC (0-24)) of LY3039478	PK: AUC (0-24) of LY3039478 was reported.	Cycle 1, Day 1 (Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, and 24 hours post-dose); Cycle 1 Day 22 (Pre-dose, 0.5, 1, 2, 4, 6, 8, 10, and 24 hours post-dose)

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Investigators: Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Publications and helpful links

General Publications

• Doi T, Tajimi M, Mori J, Asou H, Inoue K, Benhadji KA, Naito Y. A phase 1 study of crenigacestat (LY3039478), the Notch inhibitor, in Japanese patients with advanced solid tumors. Invest New Drugs. 2021 Apr;39(2):469-476. doi: 10.1007/s10637-020-01001-5. Epub 2020 Sep 16.

Study record dates

Study Major Dates

• Study Start (Actual): September 9, 2016
• Primary Completion (Actual): July 5, 2019
• Study Completion (Actual): May 30, 2023

Study Registration Dates

• First Submitted: July 15, 2016
• First Submitted That Met QC Criteria: July 15, 2016
• First Posted (Estimated): July 19, 2016

Study Record Updates

• Last Update Posted (Actual): August 7, 2025
• Last Update Submitted That Met QC Criteria: July 22, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: notch inhibitor
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: 16191; I6F-JE-JJCC (Other Identifier: Eli Lilly and Company)