A Study of the CD73 Inhibitor LY3475070 Alone or in Combination With Pembrolizumab in Participants With Advanced Cancer

Sponsor

Eli Lilly and Company (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT04148937

Collaborator

Merck Sharp & Dohme LLC (Industry)

150

Enrollment

Locations

Arms

29.1

Anticipated Duration (Months)

12.5

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The reason for this study is to see if the CD73 inhibitor LY3475070 alone or in combination with pembrolizumab is safe and effective in participants with advanced cancer.

Condition or Disease	Intervention/Treatment	Phase
Advanced Cancer	Drug: LY3475070 Drug: Pembrolizumab	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

150 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1 Multicenter Global First in Human Study of the CD73 Inhibitor LY3475070 as Monotherapy or in Combination With Pembrolizumab in Patients With Advanced Solid Malignancies

Actual Study Start Date :

Jan 16, 2020

Actual Primary Completion Date :

May 12, 2021

Anticipated Study Completion Date :

Jun 20, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort A LY3475070 LY3475070 administered orally.	Drug: LY3475070 Administered orally
Experimental: Cohort B LY3475070 + Pembrolizumab LY3475070 administered orally and pembrolizumab administered intravenously (IV).	Drug: LY3475070 Administered orally Drug: Pembrolizumab Administered IV
Experimental: Cohort C1 LY3475070 + Pembrolizumab LY3475070 administered orally and pembrolizumab administered IV.	Drug: LY3475070 Administered orally Drug: Pembrolizumab Administered IV
Experimental: Cohort C2 LY3475070 LY3475070 administered orally.	Drug: LY3475070 Administered orally
Experimental: Cohort D1 LY3475070 + Pembrolizumab LY3475070 administered orally and pembrolizumab administered IV.	Drug: LY3475070 Administered orally Drug: Pembrolizumab Administered IV
Experimental: Cohort D2 LY3475070 LY3475070 administered orally.	Drug: LY3475070 Administered orally
Experimental: Cohort E LY3475070 + Pembrolizumab LY3475070 administered orally and pembrolizumab administered IV.	Drug: LY3475070 Administered orally Drug: Pembrolizumab Administered IV

Outcome Measures

Primary Outcome Measures

Number of Participants with Dose Limiting Toxicity (DLT) [Up to 28 Days]
Number of Participants with DLT

Secondary Outcome Measures

Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of LY3475070 [Predose Cycle 1 Day 1 through Predose Cycle 7 Day 1 (28 Day Cycles)]
PK: AUC of LY3475070
PK: Maximum Concentration (Cmax) of LY3475070 [Predose Cycle 1 Day 1 through Predose Cycle 7 Day 1 (28 Day Cycles)]
PK: Cmax of LY3475070
PK: AUC of LY3475070 in Combination with Pembrolizumab [Predose Cycle 1 Day 1 through Predose Cycle 7 Day 1 (28 Day Cycles)]
PK: AUC of LY3475070 in Combination with Pembrolizumab
PK: Cmax of LY3475070 in Combination with Pembrolizumab [Predose Cycle 1 Day 1 through Predose Cycle 7 Day 1 (28 Day Cycles)]
PK: Cmax of LY3475070 in Combination with Pembrolizumab
Overall Response Rate (ORR): Percentage of Participants with Complete Response (CR) or Partial Response (PR) [Baseline through Disease Progression or Death (Estimated at up to 2 Years)]
ORR: Percentage of Participants with CR or PR
Disease Control Rate (DCR): Percentage of Participants with a Best Overall Response of CR, PR, and Stable Disease [Baseline through Measured Progressive Disease (Estimated at up to 2 Years)]
DCR
Progression Free Survival (PFS) [Baseline to Objective Progression or Death Due to Any Cause (Estimated at up to 2 Years)]
PFS

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Participants must have certain types of cancer such as breast cancer, pancreatic cancer, lung cancer, kidney cancer, skin cancer (melanoma), prostate cancer, and ovarian cancer
Participants must have stopped other forms of treatment for the cancer
In the expansion cohorts participants must be able and willing to provide a sample of the tumor before beginning treatment and a sample during the treatment. For certain tumor types, the result of a test on the tumor sample may exclude the participant from the study
Participants must not be pregnant, and must agree to use birth control
Participants must have progressed through or be intolerant to therapies with known clinical benefit

Exclusion Criteria:

Participants must not have a current untreated tuberculosis, lung disease, heart disease, uncontrolled HIV, autoimmune disease, active hepatitis B or C virus infection or using corticosteroids
Participant must not have cancer that has spread to the brain
Participant must not have received a vaccine within the last 30 days
Participant must not have had bowel obstruction within the last 6 months, or intestinal surgery
Participant must not have an infection that is currently being treated

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sarah Cannon Research Institute at HealthOne	Denver	Colorado	United States	80218
2	Florida Cancer Specialists ORLANDO/DDU	Lake Mary	Florida	United States	32746
3	START Midwest	Grand Rapids	Michigan	United States	49546
4	Washington University Medical School	Saint Louis	Missouri	United States	63110
5	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
6	Sarah Cannon Research Institute SCRI	Nashville	Tennessee	United States	37203
7	University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030
8	Peter MacCallum Cancer Centre	Melbourne	Victoria	Australia	3000
9	Addenbrookes Hospital	Cambridge	Cambridgeshire	United Kingdom	CB2 0QQ
10	Beatson West of Scotland Cancer Center	Glasgow	Scotland	United Kingdom	G12 0YN
11	Christie NHS Foundation Trust	Manchester		United Kingdom	M20 4 BX
12	Royal Marsden NHS Trust	Sutton		United Kingdom	SM2 5PT

Sponsors and Collaborators

Eli Lilly and Company
Merck Sharp & Dohme LLC

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