A Study of the CD73 Inhibitor LY3475070 Alone or in Combination With Pembrolizumab in Participants With Advanced Cancer
- Registration Number
- NCT04148937
- Lead Sponsor
- Eli Lilly and Company
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 52
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Phase 1a Cohort A LY3475070 (dose escalation) LY3475070 Participants received 150 milligram (mg) once daily or 300 mg once daily or 300mg twice daily or 600mg once daily oral LY3475070 on a 21-day cycle until progressive disease, unacceptable toxicity or other criterion for study discontinuation is met. Phase 1a Cohort B LY3475070 + Pembrolizumab (dose escalation) LY3475070 Participants received 150 mg once daily or 150 mg twice daily or 300 mg once daily or 300mg twice daily oral LY3475070 on a 21-day cycle in combination with an intravenous infusion of 200mg pembrolizumab on day 1 until progressive disease, unacceptable toxicity or other criterion for study discontinuation is met. Phase 1b Cohort C1 LY3475070 + Pembrolizumab (dose expansion) LY3475070 LY3475070 administered orally and pembrolizumab administered IV. Based on Sponsor decision, Phase 1b expansion cohorts were not initiated. Phase 1b Cohort C1 LY3475070 + Pembrolizumab (dose expansion) Pembrolizumab LY3475070 administered orally and pembrolizumab administered IV. Based on Sponsor decision, Phase 1b expansion cohorts were not initiated. Phase 1b Cohort C2 LY3475070 (dose expansion) LY3475070 LY3475070 administered orally. Based on Sponsor decision, Phase 1b expansion cohorts were not initiated. Phase 1b Cohort D1 LY3475070 + Pembrolizumab (dose expansion) LY3475070 LY3475070 administered orally and pembrolizumab administered IV. Based on Sponsor decision, Phase 1b expansion cohorts were not initiated. Phase 1b Cohort D1 LY3475070 + Pembrolizumab (dose expansion) Pembrolizumab LY3475070 administered orally and pembrolizumab administered IV. Based on Sponsor decision, Phase 1b expansion cohorts were not initiated. Phase 1b Cohort D2 LY3475070 (dose expansion) LY3475070 LY3475070 administered orally. Based on Sponsor decision, Phase 1b expansion cohorts were not initiated. Phase 1b Cohort E LY3475070 + Pembrolizumab (dose expansion) LY3475070 LY3475070 administered orally and pembrolizumab administered IV. Based on Sponsor decision, Phase 1b expansion cohorts were not initiated. Phase 1b Cohort E LY3475070 + Pembrolizumab (dose expansion) Pembrolizumab LY3475070 administered orally and pembrolizumab administered IV. Based on Sponsor decision, Phase 1b expansion cohorts were not initiated. Phase 1a Cohort B LY3475070 + Pembrolizumab (dose escalation) Pembrolizumab Participants received 150 mg once daily or 150 mg twice daily or 300 mg once daily or 300mg twice daily oral LY3475070 on a 21-day cycle in combination with an intravenous infusion of 200mg pembrolizumab on day 1 until progressive disease, unacceptable toxicity or other criterion for study discontinuation is met.
- Primary Outcome Measures
Name Time Method Number of Participants With Dose Limiting Toxicities (DLTs) Up to 28 days from the first dose 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.
- Secondary Outcome Measures
Name Time Method Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Eight Hours (AUC[0-8]) of LY3475070 Cycle 1 Day 1 (Pre-dose, 0.5, 1, 2, 4, 6, 8 hours post-dose) PK: AUC\[0-8\] of LY3475070.
PK: Area Under the Concentration Versus Time Curve During 1 Dosing Interval (AUCtau) of LY3475070 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: AUCtau of LY3475070
PK: Maximum Concentration (Cmax) of LY3475070 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) PK: Cmax of LY3475070
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 10.4 Months) 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.
Disease Control Rate (DCR): Percentage of Participants With a Best Overall Response of CR, PR, and Stable Disease (SD) Baseline through Measured Progressive Disease (Estimated at up to 10.4 Months) 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.
Progression-Free Survival (PFS) Baseline to Objective Progression or Death Due to Any Cause (Estimated at up to 10.4 Months) 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.
Trial Locations
- Locations (12)
Beatson West of Scotland Cancer Center
🇬🇧Glasgow, Scotland, United Kingdom
Royal Marsden NHS Trust
🇬🇧Sutton, United Kingdom
Addenbrookes Hospital
🇬🇧Cambridge, Cambridgeshire, United Kingdom
University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Peter MacCallum Cancer Centre
🇦🇺Melbourne, Victoria, Australia
Sarah Cannon Research Institute at HealthOne
🇺🇸Denver, Colorado, United States
Christie NHS Foundation Trust
🇬🇧Manchester, United Kingdom
Washington University Medical School
🇺🇸Saint Louis, Missouri, United States
Sarah Cannon Research Institute SCRI
🇺🇸Nashville, Tennessee, United States
Florida Cancer Specialists ORLANDO/DDU
🇺🇸Lake Mary, Florida, United States
Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
START Midwest
🇺🇸Grand Rapids, Michigan, United States