A Study of LY3039478 in Participants With Advanced or Metastatic Solid Tumors

August 1, 2025 updated by: Eli Lilly and Company

A Phase 1b Study of LY3039478 in Combination With Other Anticancer Agents in Patients With Advanced or Metastatic Solid Tumors

The main purpose of this study is to evaluate the safety of the study drug known as LY3039478 in combination with other anticancer agents in participants with advanced or metastatic solid tumors.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

94

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
    • København Ø
      • Copenhagen, København Ø, Denmark, 2100
        • Rigshospitalet
  • France
      • Bordeaux, France, 33076
        • Institut Bergonie
      • Lyon Cedex 08, France, 69373
        • Centre Leon Berard
      • Villejuif Cedex, France, 94805
        • Gustave Roussy
  • Spain
      • Barcelona, Spain, 08035
        • Hospital Universitari Vall d'Hebron
      • Madrid, Spain, 28040
        • Fundación Jiménez Díaz
      • Madrid, Spain, 28050
        • Hospital Madrid Norte Sanchinarro
  • United States
    • Florida
      • Miami, Florida, United States, 33136
        • Sylvester Comprehensive Cancer Center
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Karmanos Cancer Institute
    • New York
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center
    • Texas
      • Houston, Texas, United States, 77030
        • University of Texas MD Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 for all combinations: The participant must have histological or cytological evidence of cancer, either a solid tumor or a lymphoma, which is advanced or metastatic.
    • For Part A dose confirmation: All participants must have histological evidence of advanced or metastatic soft tissue sarcoma or breast cancer. Breast cancer participants must have prescreened mutations, amplification, or gene/protein expression alterations related to Notch pathway.
    • For Part B dose confirmation: All participants must have histological evidence of advanced or metastatic colon cancer or soft tissue sarcoma. Colon cancer participants must have prescreened mutations, amplification, or gene/protein expression alterations related to Notch pathway.
    • For Part C dose confirmation: All participants must have histological evidence of advanced or metastatic breast cancer and prescreened mutations, amplification, or gene/protein expression alterations related to Notch pathway.
    • For Part D dose confirmation: All participants must have histological evidence of cholangiocarcinoma and prescreened mutations, amplification, or gene/protein expression alterations related to Notch pathway. Participants must not have received >1 line of prior systemic therapy for metastatic or resectable disease (that is, participants may have received adjuvant gemcitabine and then later gemcitabine/cisplatin for recurrent metastatic disease).
    • For Part E dose confirmation: All participants must have histological evidence of locally advanced or metastatic triple negative breast cancer (TNBC) and prescreened mutations, amplification, or gene/protein expression alterations related to Notch pathway. Participants must not have received >2 lines of systemic treatment for advanced or metastatic TNBC.
  • Have adequate organ function.
  • Have a performance status of ≤1 on the Eastern Cooperative Oncology Group (ECOG) scale.
  • Have discontinued all previous therapies for cancer.

Exclusion Criteria:

  • Have current acute leukemia.
  • Have current or recent (within 3 months of study drug administration) gastrointestinal disease with chronic or intermittent diarrhea, or disorders that increase the risk of diarrhea, such as inflammatory bowel disease.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Part A: 25 milligram (mg) LY3039478 + 200 mg Taladegib (Cohort 1)

25 mg LY3039478 given orally 3 times per week (TIW) in combination with 200 mg taladegib given orally once daily (QD) on a 28 day cycle. A single dose of 200 mg taladegib was also be given on day 1 during a 3-day lead-in period for pharmacokinetic (PK) evaluation.

Participants receiving benefit may continue until disease progression.
Drug: LY3039478
Administered orally
Drug: Taladegib
Administered orally
Other Names:
  • LY2940680
Experimental: Part B: 25 mg LY3039478 + 150 mg LY3023414 (Cohort 1 - Dose Escalation)

25 mg LY3039478 given orally TIW in combination with 150 mg LY3023414 given orally twice daily (BID) on a 28 day cycle. A single dose of 150 mg LY3023414 was also be given on day 1 during a 3-day lead-in period for PK evaluation.

Participants receiving benefit may continue until disease progression.
Drug: LY3039478
Administered orally
Drug: LY3023414
Administered orally
Experimental: Part B: 50 mg LY3039478 + 150 mg LY3023414 (Cohort 2)

50 mg LY3039478 given orally TIW in combination with 150 mg LY3023414 given orally twice daily (BID) on a 28 day cycle. A single dose of 150 mg LY3023414 was also be given on day 1 during a 3-day lead-in period for PK evaluation.

Participants receiving benefit may continue until disease progression.
Drug: LY3039478
Administered orally
Drug: LY3023414
Administered orally
Experimental: Part B: 25 mg LY3039478 + 200 mg LY3023414 (Cohort 3)

25 mg LY3039478 given orally TIW in combination with 200 mg LY3023414 given orally twice daily (BID) on a 28 day cycle. A single dose of 200 mg LY3023414 was also be given on day 1 during a 3-day lead-in period for PK evaluation.

Participants receiving benefit may continue until disease progression.
Drug: LY3039478
Administered orally
Drug: LY3023414
Administered orally
Experimental: Part B: 25 mg LY3039478 + 150 mg LY3023414 (Cohort 4 - Dose Confirmation)

25 mg LY3039478 given orally TIW in combination with 150 mg LY3023414 given orally twice daily (BID) on a 28 day cycle. A single dose of 150 mg LY3023414 was also be given on day 1 during a 3-day lead-in period for PK evaluation.

Participants receiving benefit may continue until disease progression.
Drug: LY3039478
Administered orally
Drug: LY3023414
Administered orally
Experimental: Part C: 25 mg LY3039478 + 100 mg Abemaciclib (Cohort 1)

25 mg LY3039478 given orally TIW in combination with 100 mg abemaciclib given orally BID on a 28-day cycle. A single dose of 100 mg abemaciclib was also be given on day 1 during a 3-day lead-in period for PK evaluation.

Participants receiving benefit may continue until disease progression.
Drug: Abemaciclib
Administered orally
Other Names:
  • LY2835219
Drug: LY3039478
Administered orally
Experimental: Part C: 50 mg LY3039478 + 100 mg Abemaciclib (Cohort 2)

50 mg LY3039478 given orally TIW in combination with 100 mg abemaciclib given orally BID on a 28-day cycle. A single dose of 100 mg abemaciclib was also be given on day 1 during a 3-day lead-in period for PK evaluation.

Participants receiving benefit may continue until disease progression.
Drug: Abemaciclib
Administered orally
Other Names:
  • LY2835219
Drug: LY3039478
Administered orally
Experimental: Part C: 25 mg LY3039478 + 150 mg Abemaciclib (Cohort 3)

25 mg LY3039478 given orally TIW in combination with 150 mg abemaciclib given orally BID on a 28-day cycle. A single dose of 150 mg abemaciclib was also be given on day 1 during a 3-day lead-in period for PK evaluation.

Participants receiving benefit may continue until disease progression.
Drug: Abemaciclib
Administered orally
Other Names:
  • LY2835219
Drug: LY3039478
Administered orally
Experimental: Part D:25 mg LY3039478+25 Milligram/Square Meter (mg/m2) Cisplatin+1000 mg/m2 Gemcitabine (Cohort 1)

25 mg LY3039478 given orally TIW in combination with 25 mg/m2 cisplatin and 1000 mg/m2 gemcitabine given as intravenous (IV) infusions on days 1 and 8 of a 21 day cycle.

Participants receiving benefit may continue until disease progression.
Drug: Cisplatin
Administered IV
Drug: LY3039478
Administered orally
Drug: Gemcitabine
Administered IV
Experimental: Part D: 50 mg LY3039478 + 25 mg/m2 Cisplatin + 1000 mg/m2 Gemcitabine (Cohort 2)

50 mg LY3039478 given orally TIW in combination with 25 mg/m2 cisplatin and1000 mg/m2 gemcitabine given as IV infusions on days 1 and 8 of a 21 day cycle.

Participants receiving benefit may continue until disease progression.
Drug: Cisplatin
Administered IV
Drug: LY3039478
Administered orally
Drug: Gemcitabine
Administered IV
Experimental: Part E: 25 mg LY3039478 + 1000 mg/m2 Gemcitabine + Carboplatin (Cohort 1)

25 mg LY3039478 given orally TIW in combination with 1000 mg/m2 gemcitabine and area under the plasma concentration-time curve dose of (AUC) carboplatin given as IV infusions on days 1 and 8 of a 21 day cycle.

Participants receiving benefit may continue until disease progression.
Drug: Carboplatin
Administered IV
Drug: LY3039478
Administered orally
Drug: Gemcitabine
Administered IV
Experimental: Part E: 50 mg LY3039478 + 1000 mg/m2 Gemcitabine + Carboplatin (Cohort 2)

50 mg LY3039478 given orally TIW in combination with 1000 mg/m2 gemcitabine and AUC dose of carboplatin given as IV infusions on days 1 and 8 of a 21 day cycle.

Participants receiving benefit may continue until disease progression.
Drug: Carboplatin
Administered IV
Drug: LY3039478
Administered orally
Drug: Gemcitabine
Administered IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With LY3039478 Dose-Limiting Toxicities (DLT) in Part A, B, C, D and E
Time Frame: Baseline to toxicity (up to end of Cycle 1 [1Cycle = 28 days for Part A, B and C and 21 days for Part D, E])
DLT is defined as an adverse event (AE) during Cycle 1 (28 days for Part A, B and C and 21 days for Part D, E) that was possibly related to the study drug and met 1 of the following criteria: According to the National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0: ≥Grade 3 non-hematological toxicity except nausea/vomiting, diarrhea, or constipation that can be controlled with appropriate care; Grade 3 elevations of alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) lasting fewer than 8 days (without evidence of other hepatic injury); Grade 3 rash that resolves or improves to a Grade 2 or less within 7 days; CTCAE Grade 4 hematological toxicity of >5 days duration; Grade 4 thrombocytopenia of any duration; Grade 3 thrombocytopenia with bleeding; Grade 3 febrile neutropenia.
Baseline to toxicity (up to end of Cycle 1 [1Cycle = 28 days for Part A, B and C and 21 days for Part D, E])

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pharmacokinetics (PK): Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC[0-∞]) of LY3039478 in Combination With Taladegib, LY3023414, Abemaciclib, Cisplatin/Gemcitabine, and Gemcitabine/Carboplatin in Part A, B, C, D and E
Time Frame: Parts A/B/C Day 22 (Cycle 1): pre-dose, 0.5, 1, 2, 4, 6, 8, 24-30 hours post-dose; Parts D/E Day 1 (Cycle 1) and 15 (Cycle 1): pre-dose, 0.5, 1, 2, 4, 6-8, 24-30 hours post-dose
AUC[0-∞] of LY3039478 in combination with taladegib, LY3023414, abemaciclib, cisplatin/gemcitabine, and gemcitabine/carboplatin in dose escalation parts of Part A, B, C, D and E was evaluated.
Parts A/B/C Day 22 (Cycle 1): pre-dose, 0.5, 1, 2, 4, 6, 8, 24-30 hours post-dose; Parts D/E Day 1 (Cycle 1) and 15 (Cycle 1): pre-dose, 0.5, 1, 2, 4, 6-8, 24-30 hours post-dose
PK: AUC[0-∞] of Taladegib and Its Active Metabolite LSN3185556, in Combination With LY3039478 (Part A)
Time Frame: Day -3 (Lead in) : pre-dose, 0.5, 1, 2, 4, 6, 8, 24-30, 72 hours post-dose and Day 22 (Cycle 1): pre-dose, 0.5, 1, 2, 4, 6, 8, 24 hours post-dose
AUC[0-∞] of taladegib and its active metabolite LSN3185556, in combination with LY3039478 (Part A) was evaluated.
Day -3 (Lead in) : pre-dose, 0.5, 1, 2, 4, 6, 8, 24-30, 72 hours post-dose and Day 22 (Cycle 1): pre-dose, 0.5, 1, 2, 4, 6, 8, 24 hours post-dose
PK: AUC[0-∞] of LY3023414 in Combination With LY3039478 on Day -3 (Part B)
Time Frame: Day -3 (Lead in): pre-dose, 0.5, 1, 2, 4, 6, 8, 24-30, 72 hours post-dose
AUC[0-∞] of LY3023414 in combination with LY3039478 (Part B) on day -3 was evaluated.
Day -3 (Lead in): pre-dose, 0.5, 1, 2, 4, 6, 8, 24-30, 72 hours post-dose
PK: AUC[0-∞] of LY3023414 in Combination With LY3039478 on Day 22 (Part B)
Time Frame: Day 22 (Cycle 1): pre-dose, 0.5, 1, 2, 4, 6, 8 hours post-dose
AUC[0-∞] of LY3023414 in combination with LY3039478 (Part B) on day 22 was evaluated. LY3023414 PK data is summarized only for dose escalation patients in Part B with intensive PK sampling.
Day 22 (Cycle 1): pre-dose, 0.5, 1, 2, 4, 6, 8 hours post-dose
PK: AUC[0-∞] of Abemaciclib and AUC From Time Zero to the Last Measured Concentration Value (AUC[0-tlast]) of Its Major Active Metabolites LSN2839567 and LSN3106726, in Combination With LY3039478 on Day -3 (Part C)
Time Frame: Day -3 (Lead in): pre-dose, 0.5, 1, 2, 4, 6, 8, 24-30, 72 hours post-dose
AUC[0-∞] of abemaciclib and AUC[0-tlast] of its major active metabolites LSN2839567 and LSN3106726, in combination with LY3039478 on Day 3 (Part C) was evaluated.
Day -3 (Lead in): pre-dose, 0.5, 1, 2, 4, 6, 8, 24-30, 72 hours post-dose
PK: AUC[0-∞] of Abemaciclib and AUC From Time Zero to the Last Measured Concentration Value (AUC[0-tlast]) of Its Major Active Metabolites LSN2839567 and LSN3106726, in Combination With LY3039478 on Day 22 (Part C)
Time Frame: Day 22 (Cycle 1): pre-dose, 0.5, 1, 2, 4, 6, 8 hours post-dose
AUC[0-∞] of abemaciclib and AUC[0-tlast] of its major active metabolites LSN2839567 and LSN3106726, in combination with LY3039478 on Day 22 (Part C) was evaluated.
Day 22 (Cycle 1): pre-dose, 0.5, 1, 2, 4, 6, 8 hours post-dose
Duration of Response (DoR)
Time Frame: Date of Complete Response (CR) or Partial Response (PR) to Date of Objective Disease Progression (Up To 12 Months)
DoR was the time from the date of first evidence of complete response or partial response to the date of objective progression or the date of death due to any cause, whichever is earlier. CR and PR were defined using the RECIST v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. If a responder was not known to have died or have objective progression as of the data inclusion cutoff date, duration of response was censored at the last adequate tumor assessment date.
Date of Complete Response (CR) or Partial Response (PR) to Date of Objective Disease Progression (Up To 12 Months)
Progression Free Survival (PFS) Time in Part A, B, C, D and E
Time Frame: Baseline to Objective Disease Progression or Death (Up To 1.91 Months for Part A, 7.69 Months for Part B, 11.53 Months for Part C, 19.52 Months for Part D, 7.03 Months for Part E)
PFS defined as the time from the date of randomization to the first evidence of disease progression as defined by response evaluation criteria in solid tumors (RECIST) v1.1 or death from any cause. Progressive Disease (PD) was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. If a participant does not have a complete baseline disease assessment, then the PFS time was censored at the date of randomization, regardless of whether or not objectively determined disease progression or death has been observed for the participant. If a participant was not known to have died or have objective progression as of the data inclusion cutoff date for the analysis, the PFS time was censored at the last adequate tumor assessment date. PFS time was summarized using Kaplan-Meier estimates.
Baseline to Objective Disease Progression or Death (Up To 1.91 Months for Part A, 7.69 Months for Part B, 11.53 Months for Part C, 19.52 Months for Part D, 7.03 Months for Part E)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

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

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 4, 2016

Primary Completion (Actual)

August 9, 2018

Study Completion (Actual)

February 13, 2020

Study Registration Dates

First Submitted

May 25, 2016

First Submitted That Met QC Criteria

May 25, 2016

First Posted (Estimated)

May 27, 2016

Study Record Updates

Last Update Posted (Actual)

August 21, 2025

Last Update Submitted That Met QC Criteria

August 1, 2025

Last Verified

August 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 16209
  • I6F-MC-JJCD (Other Identifier: Eli Lilly and Company)
  • 2015-004421-14 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Soft Tissue Sarcoma

Clinical Trials on Abemaciclib

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Lebanon

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe