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

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

Population: All participants enrolled in the phase 1a who either completed 28 days of follow-up and at least 75% of LY3475070 treatment doses or discontinued treatment prior to 28 days due to a DLT.

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)

Population: All enrolled participants in phase1a who received at least one dose of LY3475070.

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)

Population: All enrolled participants in phase1a who received at least one dose 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)

Population: All enrolled participants in phase1a who received LY3475070 and had intensively sampled evaluable PK data on cycle 1 day 1.

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)

Population: All enrolled participants in phase1a who received LY3475070 and had intensively sampled evaluable PK data on cycle 2 day 1. For Cohort B - 300mg QD LY3475070 + pembrolizumab, the participant has not received the treatment on cycle 2 day 1, and did not meet the analysis criteria. Thus, zero participants were analysed.

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)

Population: All enrolled participants in phase1a who received LY3475070 and had intensively sampled evaluable PK data on cycle 1 day 1, cycle 2 day 1 for this outcome. For Cohort B - 300mg QD LY3475070 + pembrolizumab, the participant has not received the treatment on cycle 2 day 1, and did not meet the analysis criteria. Thus, zero participants were analysed.

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)

Population: All enrolled participants in phase1a who received at least one dose of LY3475070 (including censored). Number of participants censored: 150mg QD LY3475070=1, 300mg QD LY3475070=1, 300mg BID LY3475070=4, 600mg QD LY3475070=1, 150mg QD LY3475070 + pembrolizumab=2, 150mg BID LY3475070 + pembrolizumab=5, 300mg QD LY3475070 + pembrolizumab=1, 300mg BID LY3475070 + pembrolizumab=14.