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

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

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 Overview

• Status: Completed
• Conditions: Advanced Cancer
• Intervention / Treatment: Drug: Pembrolizumab; Drug: LY3475070

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1a Cohort A LY3475070 (dose escalation); 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.	Drug: LY3475070; Administered orally
Experimental: Phase 1a Cohort B LY3475070 + Pembrolizumab (dose escalation); 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.	Drug: Pembrolizumab; Administered IV; Drug: LY3475070; Administered orally
Experimental: Phase 1b Cohort C1 LY3475070 + Pembrolizumab (dose expansion); LY3475070 administered orally and pembrolizumab administered IV. Based on Sponsor decision, Phase 1b expansion cohorts were not initiated.	Drug: Pembrolizumab; Administered IV; Drug: LY3475070; Administered orally
Experimental: Phase 1b Cohort C2 LY3475070 (dose expansion); LY3475070 administered orally. Based on Sponsor decision, Phase 1b expansion cohorts were not initiated.	Drug: LY3475070; Administered orally
Experimental: Phase 1b Cohort D1 LY3475070 + Pembrolizumab (dose expansion); LY3475070 administered orally and pembrolizumab administered IV. Based on Sponsor decision, Phase 1b expansion cohorts were not initiated.	Drug: Pembrolizumab; Administered IV; Drug: LY3475070; Administered orally
Experimental: Phase 1b Cohort D2 LY3475070 (dose expansion); LY3475070 administered orally. Based on Sponsor decision, Phase 1b expansion cohorts were not initiated.	Drug: LY3475070; Administered orally
Experimental: Phase 1b Cohort E LY3475070 + Pembrolizumab (dose expansion); LY3475070 administered orally and pembrolizumab administered IV. Based on Sponsor decision, Phase 1b expansion cohorts were not initiated.	Drug: Pembrolizumab; Administered IV; Drug: LY3475070; Administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to 28 days from the first dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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	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	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)	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.	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.	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.	Baseline to Objective Progression or Death Due to Any Cause (Estimated at up to 10.4 Months)

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Collaborators: 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

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): January 16, 2020
• Primary Completion (Actual): May 12, 2021
• Study Completion (Actual): June 20, 2022

Study Registration Dates

• First Submitted: October 31, 2019
• First Submitted That Met QC Criteria: November 1, 2019
• First Posted (Actual): November 4, 2019

Study Record Updates

• Last Update Posted (Actual): April 5, 2024
• Last Update Submitted That Met QC Criteria: April 1, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Pancreatic Cancer; Epithelial Ovarian Cancer; Triple Negative Breast Cancer; Metastatic Cancer; Non-small Cell Lung Cancer; Cutaneous Melanoma; Castrate Resistant Prostate Cancer; Renal Cell Carcinoma, Clear Cell
• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Pembrolizumab
• Other Study ID Numbers: 17504; J2I-MC-JZMA (Other Identifier: Eli Lilly and Company); 2019-003270-64 (EudraCT Number); Keynote A57 (Other Identifier: Merck)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No