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

Advanced Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04148937
• Other study ID #: 17504
• Secondary ID: J2I-MC-JZMA2019-
• Status: Completed
• Phase: Phase 1
• Start date: January 16, 2020
• Est. completion date: June 20, 2022

Study information

• Verified date: April 2024
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 52
• Est. completion date: June 20, 2022
• Est. primary completion date: May 12, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Advanced Cancer
• Neoplasms

Intervention

Drug:
• LY3475070
Administered orally
• Pembrolizumab
Administered IV

Locations

Country	Name	City	State
Australia	Peter MacCallum Cancer Centre	Melbourne	Victoria
United Kingdom	Addenbrookes Hospital	Cambridge	Cambridgeshire
United Kingdom	Beatson West of Scotland Cancer Center	Glasgow	Scotland
United Kingdom	Christie NHS Foundation Trust	Manchester
United Kingdom	Royal Marsden NHS Trust	Sutton
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Sarah Cannon Research Institute at HealthOne	Denver	Colorado
United States	START Midwest	Grand Rapids	Michigan
United States	University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Florida Cancer Specialists ORLANDO/DDU	Lake Mary	Florida
United States	Sarah Cannon Research Institute SCRI	Nashville	Tennessee
United States	Washington University Medical School	Saint Louis	Missouri

Sponsors (2)

Lead Sponsor	Collaborator
Eli Lilly and Company	Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Australia,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)

External Links

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