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

Study Overview
=================
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.

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

Conditions
-----------------
Advanced Cancer

Intervention / Treatment
-----------------
* Drug: LY3475070
* Drug: Pembrolizumab


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A LY3475070<br>LY3475070 administered orally. | Drug: LY3475070<br>* Administered orally<br>|
| Experimental: Cohort B LY3475070 + Pembrolizumab<br>LY3475070 administered orally and pembrolizumab administered intravenously (IV). | Drug: LY3475070<br>* Administered orally<br>Drug: Pembrolizumab<br>* Administered IV<br>|
| Experimental: Cohort C1 LY3475070 + Pembrolizumab<br>LY3475070 administered orally and pembrolizumab administered IV. | Drug: LY3475070<br>* Administered orally<br>Drug: Pembrolizumab<br>* Administered IV<br>|
| Experimental: Cohort C2 LY3475070<br>LY3475070 administered orally. | Drug: LY3475070<br>* Administered orally<br>|
| Experimental: Cohort D1 LY3475070 + Pembrolizumab<br>LY3475070 administered orally and pembrolizumab administered IV. | Drug: LY3475070<br>* Administered orally<br>Drug: Pembrolizumab<br>* Administered IV<br>|
| Experimental: Cohort D2 LY3475070<br>LY3475070 administered orally. | Drug: LY3475070<br>* Administered orally<br>|
| Experimental: Cohort E LY3475070 + Pembrolizumab<br>LY3475070 administered orally and pembrolizumab administered IV. | Drug: LY3475070<br>* Administered orally<br>Drug: Pembrolizumab<br>* Administered IV<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Dose Limiting Toxicity (DLT) | Number of Participants with DLT | Up to 28 Days | 

Secondary Outcome Measures

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

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Triple Negative Breast Cancer, Pancreatic Cancer, Non-small Cell Lung Cancer, Renal Cell Carcinoma, Clear Cell, Cutaneous Melanoma, Castrate Resistant Prostate Cancer, Epithelial Ovarian Cancer, Metastatic Cancer