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

Eli Lilly and Company52 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Advanced Cancer

Interventions

LY3475070DRUG

Administered orally

PembrolizumabDRUG

Administered IV

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (12)

Sarah Cannon Research Institute at HealthOne

Denver, Colorado, United States

Florida Cancer Specialists ORLANDO/DDU

Lake Mary, Florida, United States

START Midwest

Grand Rapids, Michigan, United States

Outcomes

Primary Outcomes

Number of Participants With Dose Limiting Toxicities (DLTs)

A DLT is defined as an adverse event that is likely related to the study medication or combination, and fulfils any one of the following criteria, graded according to the NCI-CTCAE (National Cancer Institute-Common Terminology Criteria for Adverse Events) version 5.0: * Grade 3 thrombocytopenia associated with clinically significant bleeding and requiring platelet transfusion or Grade 4 thrombocytopenia of any duration. * Grade ≥3 febrile neutropenia * Grade ≥3 anemia requiring a blood transfusion * Other Grade ≥4 toxicities, excluding few nonhematologic Toxicities * Any other significant toxicity deemed by the investigatory to be dose-limiting, such as: any toxicity that is possibly related to the study medication that requires the withdrawal of the participant from the study during 28-day DLT observation period), persistent Grade \>2 toxicities causing a delay of LY3475070 study treatment \>14 days during the 28-day DLT observation period.

Time frame: Up to 28 days from the first dose

Secondary Outcomes

Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Eight Hours (AUC[0-8]) of LY3475070

PK: AUC\[0-8\] of LY3475070.

Time frame: Cycle 1 Day 1 (Pre-dose, 0.5, 1, 2, 4, 6, 8 hours post-dose)

PK: Area Under the Concentration Versus Time Curve During 1 Dosing Interval (AUCtau) of LY3475070

PK: AUCtau of LY3475070

Time frame: Cycle 2 Day 1 (Pre-dose, 0.5, 1, 2, 4, 6, 8, 24 hours post-dose for the QD arms, Pre-dose, 0.5, 1, 2, 4, 6, 8 hours post-dose for the BID arms)

PK: Maximum Concentration (Cmax) of LY3475070

PK: Cmax of LY3475070

Time frame: Day 1 of Cycles 1 and 2 (Pre-dose, 0.5, 1, 2, 4, 6, 8, 24 hours post-dose for the QD arms; Pre-dose, 0.5, 1, 2, 4, 6, 8 hours post-dose for the BID arms)

Overall Response Rate (ORR): Percentage of Participants With Complete Response (CR) or Partial Response (PR)

Data from ClinicalTrials.gov

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Washington University Medical School

St Louis, Missouri, United States

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Sarah Cannon Research Institute SCRI

Nashville, Tennessee, United States

University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Peter MacCallum Cancer Centre

Melbourne, Victoria, Australia

Addenbrookes Hospital

Cambridge, Cambridgeshire, United Kingdom

Beatson West of Scotland Cancer Center

Glasgow, Scotland, United Kingdom

...and 2 more locations

ORR is the best overall tumor response of complete response (CR) or partial response (PR) as classified by the investigator according to the Response Evaluation Criteria In Solid Tumors (RECIST v1.1). CR is a disappearance of all target and non-target lesions and normalization of tumor marker level. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of non-target lesions or appearance of new lesions.

Time frame: Baseline through Disease Progression or Death (Estimated at up to 10.4 Months)

Disease Control Rate (DCR): Percentage of Participants With a Best Overall Response of CR, PR, and Stable Disease (SD)

DCR is the percentage of participants with a best overall response of CR, PR or SD as defined by RECIST v1.1. CR is a disappearance of all target and non-target lesions and normalization of tumor marker level. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of non-target lesions or appearance of new lesions. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD) for target lesions, no progression of non-target lesions, and no appearance of new lesions. PD is defined as 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.

Time frame: Baseline through Measured Progressive Disease (Estimated at up to 10.4 Months)

Progression-Free Survival (PFS)

PFS is defined as the time from the date of start of treatment to the first date of the observed clinical or radiologically documented progressive disease or death due to any cause, whichever occurs first, was estimated and reported for all evaluable participants. For participants who were not known to have died or progressed as of the data-inclusion cut-off date, PFS time was censored at the date of the last objective progression-free disease assessment prior to the date of any subsequent systematic anticancer therapy.

Time frame: Baseline to Objective Progression or Death Due to Any Cause (Estimated at up to 10.4 Months)