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

Primary Purpose

Solid Tumor, Breast Cancer, Colon Cancer

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
LY3039478
Taladegib
Abemaciclib
Cisplatin
Gemcitabine
Carboplatin
LY3023414
Sponsored by
Eli Lilly and Company
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Solid Tumor focused on measuring Notch Inhibitor

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Sylvester Comprehensive Cancer Center
  • Karmanos Cancer Institute
  • Memorial Sloan Kettering Cancer Center
  • University of Texas MD Anderson Cancer Center
  • Rigshospitalet
  • Institut Bergonie
  • Centre Leon Berard
  • Gustave Roussy
  • Hospital Universitari Vall d'Hebron
  • Fundacion Jimenez Diaz
  • Hospital Madrid Norte Sanchinarro

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

LY3039478 + Taladegib

LY3039478 + LY3023414

LY3039478 + Abemaciclib

LY3039478 + Cisplatin/Gemcitabine

LY3039478 + Gemcitabine/Carboplatin

Arm Description

LY3039478 given orally 3 times per week (TIW) in combination with taladegib given orally daily on a 28 day cycle. A single dose of taladegib will also be given on day 1 during a 3-day lead-in period.

LY3039478 given orally TIW in combination with LY3023414 given orally every 12 hours on a 28-day cycle. A single dose of LY3023414 will also be given on day 1 during a 3-day lead-in period.

LY3039478 given orally TIW in combination with abemaciclib given orally every 12 hours on a 28-day cycle. A single dose of abemaciclib will also be given on day 1 during a 3-day lead-in period.

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

LY3039478 given orally TIW in combination with gemcitabine and carboplatin given as IV infusions on days 1 and 8 of a 21 day cycle.

Outcomes

Primary Outcome Measures

Maximum Tolerated Dose (MTD) of LY3039478

Secondary Outcome Measures

Pharmacokinetics (PK): Area Under the Plasma Concentration Time Curve (AUC) of LY3039478 in Combination with Taladegib, LY3023414, Abemaciclib, Cisplatin/Gemcitabine, and Gemcitabine/Carboplatin
PK: AUC of Taladegib and its Active Metabolite LSN3185556, in Combination with LY3039478
PK: AUC of LY3023414 in Combination with LY3039478
PK: AUC of Abemaciclib and its Major Active Metabolites LSN2839567 and LSN3106726, in Combination with LY3039478
Duration of Response (DoR)
Progression Free Survival (PFS)

Full Information

First Posted
May 25, 2016
Last Updated
August 13, 2020
Sponsor
Eli Lilly and Company
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1. Study Identification

Unique Protocol Identification Number
NCT02784795
Brief Title
A Study of LY3039478 in Participants With Advanced or Metastatic Solid Tumors
Official Title
A Phase 1b Study of LY3039478 in Combination With Other Anticancer Agents in Patients With Advanced or Metastatic Solid Tumors
Study Type
Interventional

2. Study Status

Record Verification Date
August 2020
Overall Recruitment Status
Completed
Study Start Date
November 4, 2016 (Actual)
Primary Completion Date
August 9, 2018 (Actual)
Study Completion Date
February 13, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eli Lilly and Company

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Solid Tumor, Breast Cancer, Colon Cancer, Cholangiocarcinoma, Soft Tissue Sarcoma
Keywords
Notch Inhibitor

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
94 (Actual)

8. Arms, Groups, and Interventions

Arm Title
LY3039478 + Taladegib
Arm Type
Experimental
Arm Description
LY3039478 given orally 3 times per week (TIW) in combination with taladegib given orally daily on a 28 day cycle. A single dose of taladegib will also be given on day 1 during a 3-day lead-in period.
Arm Title
LY3039478 + LY3023414
Arm Type
Experimental
Arm Description
LY3039478 given orally TIW in combination with LY3023414 given orally every 12 hours on a 28-day cycle. A single dose of LY3023414 will also be given on day 1 during a 3-day lead-in period.
Arm Title
LY3039478 + Abemaciclib
Arm Type
Experimental
Arm Description
LY3039478 given orally TIW in combination with abemaciclib given orally every 12 hours on a 28-day cycle. A single dose of abemaciclib will also be given on day 1 during a 3-day lead-in period.
Arm Title
LY3039478 + Cisplatin/Gemcitabine
Arm Type
Experimental
Arm Description
LY3039478 given orally TIW in combination with cisplatin and gemcitabine given as intravenous (IV) infusions on days 1 and 8 of a 21 day cycle.
Arm Title
LY3039478 + Gemcitabine/Carboplatin
Arm Type
Experimental
Arm Description
LY3039478 given orally TIW in combination with gemcitabine and carboplatin given as IV infusions on days 1 and 8 of a 21 day cycle.
Intervention Type
Drug
Intervention Name(s)
LY3039478
Intervention Description
Administered orally
Intervention Type
Drug
Intervention Name(s)
Taladegib
Other Intervention Name(s)
LY2940680
Intervention Description
Administered orally
Intervention Type
Drug
Intervention Name(s)
Abemaciclib
Other Intervention Name(s)
LY2835219
Intervention Description
Administered orally
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Intervention Description
Administered IV
Intervention Type
Drug
Intervention Name(s)
Gemcitabine
Intervention Description
Administered IV
Intervention Type
Drug
Intervention Name(s)
Carboplatin
Intervention Description
Administered IV
Intervention Type
Drug
Intervention Name(s)
LY3023414
Intervention Description
Administered orally
Primary Outcome Measure Information:
Title
Maximum Tolerated Dose (MTD) of LY3039478
Time Frame
Cycle 1 (up to 28 Days)
Secondary Outcome Measure Information:
Title
Pharmacokinetics (PK): Area Under the Plasma Concentration Time Curve (AUC) of LY3039478 in Combination with Taladegib, LY3023414, Abemaciclib, Cisplatin/Gemcitabine, and Gemcitabine/Carboplatin
Time Frame
Predose Cycle 1 Day 1 through Predose Cycle 2 Day 1 (up to 28 Day Cycles)
Title
PK: AUC of Taladegib and its Active Metabolite LSN3185556, in Combination with LY3039478
Time Frame
Predose Cycle 1 Day 1 through Predose Cycle 2 Day 1 (up to 28 Day Cycles)
Title
PK: AUC of LY3023414 in Combination with LY3039478
Time Frame
Predose Cycle 1 Day 1 through Predose Cycle 2 Day 1 (up to 28 Day Cycles)
Title
PK: AUC of Abemaciclib and its Major Active Metabolites LSN2839567 and LSN3106726, in Combination with LY3039478
Time Frame
Predose Cycle 1 Day 1 through Predose Cycle 2 Day 1 (up to 28 Day Cycles)
Title
Duration of Response (DoR)
Time Frame
Date of Complete Response (CR) or Partial Response (PR) to Date of Objective Disease Progression (Estimated up to 12 Months)
Title
Progression Free Survival (PFS)
Time Frame
Baseline to Objective Disease Progression or Death (Estimated up to 12 Months)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
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)
Organizational Affiliation
Eli Lilly and Company
Official's Role
Study Director
Facility Information:
Facility Name
Sylvester Comprehensive Cancer Center
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Karmanos Cancer Institute
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
University of Texas MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Rigshospitalet
City
Copenhagen
State/Province
København Ø
ZIP/Postal Code
2100
Country
Denmark
Facility Name
Institut Bergonie
City
Bordeaux
ZIP/Postal Code
33076
Country
France
Facility Name
Centre Leon Berard
City
Lyon Cedex 08
ZIP/Postal Code
69373
Country
France
Facility Name
Gustave Roussy
City
Villejuif Cedex
ZIP/Postal Code
94805
Country
France
Facility Name
Hospital Universitari Vall d'Hebron
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Fundacion Jimenez Diaz
City
Madrid
ZIP/Postal Code
28040
Country
Spain
Facility Name
Hospital Madrid Norte Sanchinarro
City
Madrid
ZIP/Postal Code
28050
Country
Spain

12. IPD Sharing Statement

Citations:
PubMed Identifier
36030462
Citation
Massard C, Cassier PA, Azaro A, Anderson B, Yuen E, Yu D, Oakley G 3rd, Benhadji KA, Pant S. A phase 1b study of crenigacestat (LY3039478) in combination with gemcitabine and cisplatin or gemcitabine and carboplatin in patients with advanced or metastatic solid tumors. Cancer Chemother Pharmacol. 2022 Oct;90(4):335-344. doi: 10.1007/s00280-022-04461-z. Epub 2022 Aug 28.
Results Reference
derived
PubMed Identifier
33686452
Citation
Azaro A, Massard C, Tap WD, Cassier PA, Merchan J, Italiano A, Anderson B, Yuen E, Yu D, Oakley G 3rd, Benhadji KA, Pant S. A phase 1b study of the Notch inhibitor crenigacestat (LY3039478) in combination with other anticancer target agents (taladegib, LY3023414, or abemaciclib) in patients with advanced or metastatic solid tumors. Invest New Drugs. 2021 Aug;39(4):1089-1098. doi: 10.1007/s10637-021-01094-6. Epub 2021 Mar 8.
Results Reference
derived

Learn more about this trial

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

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