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

NCT04148937 | Completed Phase 1 Results FDA Drug

• 4 other identifiers: 17504J2I-MC-JZMA2019-003270-64Keynote A57
• Study Type: interventional
• Target: 52
• Locations: 3 countries
• Sites: 12

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.

Conditions

Advanced Cancer

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• 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: 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: 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)

• 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)

• 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)

Study Arms (7)

Phase 1a Cohort A LY3475070 (dose escalation)

EXPERIMENTAL

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

Phase 1a Cohort B LY3475070 + Pembrolizumab (dose escalation)

EXPERIMENTAL

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: LY3475070; Drug: Pembrolizumab

Phase 1b Cohort C1 LY3475070 + Pembrolizumab (dose expansion)

EXPERIMENTAL

LY3475070 administered orally and pembrolizumab administered IV. Based on Sponsor decision, Phase 1b expansion cohorts were not initiated.

Drug: LY3475070; Drug: Pembrolizumab

Phase 1b Cohort C2 LY3475070 (dose expansion)

EXPERIMENTAL

LY3475070 administered orally. Based on Sponsor decision, Phase 1b expansion cohorts were not initiated.

Drug: LY3475070

Phase 1b Cohort D1 LY3475070 + Pembrolizumab (dose expansion)

EXPERIMENTAL

LY3475070 administered orally and pembrolizumab administered IV. Based on Sponsor decision, Phase 1b expansion cohorts were not initiated.

Drug: LY3475070; Drug: Pembrolizumab

Phase 1b Cohort D2 LY3475070 (dose expansion)

EXPERIMENTAL

LY3475070 administered orally. Based on Sponsor decision, Phase 1b expansion cohorts were not initiated.

Drug: LY3475070

Phase 1b Cohort E LY3475070 + Pembrolizumab (dose expansion)

EXPERIMENTAL

LY3475070 administered orally and pembrolizumab administered IV. Based on Sponsor decision, Phase 1b expansion cohorts were not initiated.

Drug: LY3475070; Drug: Pembrolizumab

Interventions

LY3475070 DRUG

Administered orally

Phase 1a Cohort A LY3475070 (dose escalation); Phase 1a Cohort B LY3475070 + Pembrolizumab (dose escalation); Phase 1b Cohort C1 LY3475070 + Pembrolizumab (dose expansion); Phase 1b Cohort C2 LY3475070 (dose expansion); Phase 1b Cohort D1 LY3475070 + Pembrolizumab (dose expansion); Phase 1b Cohort D2 LY3475070 (dose expansion); Phase 1b Cohort E LY3475070 + Pembrolizumab (dose expansion)

Pembrolizumab DRUG

Administered IV

Phase 1a Cohort B LY3475070 + Pembrolizumab (dose escalation); Phase 1b Cohort C1 LY3475070 + Pembrolizumab (dose expansion); Phase 1b Cohort D1 LY3475070 + Pembrolizumab (dose expansion); Phase 1b Cohort E LY3475070 + Pembrolizumab (dose expansion)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Eli Lilly and Company: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (12)

Sarah Cannon Research Institute at HealthOne

Denver, Colorado, 80218, United States

Location

Florida Cancer Specialists ORLANDO/DDU

Lake Mary, Florida, 32746, United States

Location

START Midwest

Grand Rapids, Michigan, 49546, United States

Location

Washington University Medical School

St Louis, Missouri, 63110, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Sarah Cannon Research Institute SCRI

Nashville, Tennessee, 37203, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

Location

Addenbrookes Hospital

Cambridge, Cambridgeshire, CB2 0QQ, United Kingdom

Location

Beatson West of Scotland Cancer Center

Glasgow, Scotland, G12 0YN, United Kingdom

Location

Christie NHS Foundation Trust

Manchester, M20 4 BX, United Kingdom

Location

Royal Marsden NHS Trust

Sutton, SM2 5PT, United Kingdom

Location

Related Links

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

MeSH Terms

Conditions

Triple Negative Breast Neoplasms; Pancreatic Neoplasms; Carcinoma, Non-Small-Cell Lung; Carcinoma, Renal Cell; Melanoma; Carcinoma, Ovarian Epithelial; Neoplasm Metastasis

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Ovarian Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Genital Neoplasms, Female; Genital Diseases; Gonadal Disorders; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

ClinicalTrials.gov@lilly.com

800-545-5979

Study Officials

• 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

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 31, 2019
• First Posted: November 4, 2019
• Study Start: January 16, 2020
• Primary Completion: May 12, 2021
• Study Completion: June 20, 2022
• Last Updated: April 5, 2024
• Results First Posted: April 5, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1); US (7); GB (4)