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

Sponsor

Eli Lilly and Company (Industry)

Overall Status

Completed

CT.gov ID

NCT02784795

Collaborator

(none)

Enrollment

Locations

Arms

39.3

Actual Duration (Months)

8.5

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Solid Tumor Breast Cancer Colon Cancer Cholangiocarcinoma Soft Tissue Sarcoma	Drug: LY3039478 Drug: Taladegib Drug: Abemaciclib Drug: Cisplatin Drug: Gemcitabine Drug: Carboplatin Drug: LY3023414	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

94 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Nov 4, 2016

Actual Primary Completion Date :

Aug 9, 2018

Actual Study Completion Date :

Feb 13, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LY3039478 + Taladegib 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.	Drug: LY3039478 Administered orally Drug: Taladegib Administered orally Other Names: LY2940680
Experimental: LY3039478 + LY3023414 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.	Drug: LY3039478 Administered orally Drug: LY3023414 Administered orally
Experimental: LY3039478 + Abemaciclib 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.	Drug: LY3039478 Administered orally Drug: Abemaciclib Administered orally Other Names: LY2835219
Experimental: LY3039478 + Cisplatin/Gemcitabine 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.	Drug: LY3039478 Administered orally Drug: Cisplatin Administered IV Drug: Gemcitabine Administered IV
Experimental: LY3039478 + Gemcitabine/Carboplatin LY3039478 given orally TIW in combination with gemcitabine and carboplatin given as IV infusions on days 1 and 8 of a 21 day cycle.	Drug: LY3039478 Administered orally Drug: Gemcitabine Administered IV Drug: Carboplatin Administered IV

Outcome Measures

Primary Outcome Measures

Maximum Tolerated Dose (MTD) of LY3039478 [Cycle 1 (up to 28 Days)]

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 [Predose Cycle 1 Day 1 through Predose Cycle 2 Day 1 (up to 28 Day Cycles)]
PK: AUC of Taladegib and its Active Metabolite LSN3185556, in Combination with LY3039478 [Predose Cycle 1 Day 1 through Predose Cycle 2 Day 1 (up to 28 Day Cycles)]
PK: AUC of LY3023414 in Combination with LY3039478 [Predose Cycle 1 Day 1 through Predose Cycle 2 Day 1 (up to 28 Day Cycles)]
PK: AUC of Abemaciclib and its Major Active Metabolites LSN2839567 and LSN3106726, in Combination with LY3039478 [Predose Cycle 1 Day 1 through Predose Cycle 2 Day 1 (up to 28 Day Cycles)]
Duration of Response (DoR) [Date of Complete Response (CR) or Partial Response (PR) to Date of Objective Disease Progression (Estimated up to 12 Months)]
Progression Free Survival (PFS) [Baseline to Objective Disease Progression or Death (Estimated up to 12 Months)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sylvester Comprehensive Cancer Center	Miami	Florida	United States	33136
2	Karmanos Cancer Institute	Detroit	Michigan	United States	48201
3	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
4	University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030
5	Rigshospitalet	Copenhagen	København Ø	Denmark	2100
6	Institut Bergonie	Bordeaux		France	33076
7	Centre Leon Berard	Lyon Cedex 08		France	69373
8	Gustave Roussy	Villejuif Cedex		France	94805
9	Hospital Universitari Vall d'Hebron	Barcelona		Spain	08035
10	Fundacion Jimenez Diaz	Madrid		Spain	28040
11	Hospital Madrid Norte Sanchinarro	Madrid		Spain	28050

Sponsors and Collaborators

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