NCT04148937 · REGISTRY CONDITION SEARCH

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

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE1
Status at capture: COMPLETED
Registry last update: 2024-04-05

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Number of Participants With Dose Limiting Toxicities (DLTs)

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outcome · POSTED

Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Eight Hours (AUC[0-8]) of LY3475070

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outcome · POSTED

PK: Area Under the Concentration Versus Time Curve During 1 Dosing Interval (AUCtau) of LY3475070

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outcome · POSTED

PK: Maximum Concentration (Cmax) of LY3475070

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outcome · POSTED

Overall Response Rate (ORR): Percentage of Participants With Complete Response (CR) or Partial Response (PR)

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outcome · POSTED

Disease Control Rate (DCR): Percentage of Participants With a Best Overall Response of CR, PR, and Stable Disease (SD)

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outcome · POSTED

Progression-Free Survival (PFS)

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: 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
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
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.
intervention Names
Drug: LY3475070
label
Phase 1a Cohort A LY3475070 (dose escalation)
type
EXPERIMENTAL
description
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.
intervention Names
Drug: LY3475070
Drug: Pembrolizumab
label
Phase 1a Cohort B LY3475070 + Pembrolizumab (dose escalation)
type
EXPERIMENTAL
description
LY3475070 administered orally and pembrolizumab administered IV. Based on Sponsor decision, Phase 1b expansion cohorts were not initiated.
intervention Names
Drug: LY3475070
Drug: Pembrolizumab
label
Phase 1b Cohort C1 LY3475070 + Pembrolizumab (dose expansion)
type
EXPERIMENTAL
description
LY3475070 administered orally. Based on Sponsor decision, Phase 1b expansion cohorts were not initiated.
intervention Names
Drug: LY3475070
label
Phase 1b Cohort C2 LY3475070 (dose expansion)
type
EXPERIMENTAL
description
LY3475070 administered orally and pembrolizumab administered IV. Based on Sponsor decision, Phase 1b expansion cohorts were not initiated.
intervention Names
Drug: LY3475070
Drug: Pembrolizumab
label
Phase 1b Cohort D1 LY3475070 + Pembrolizumab (dose expansion)
type
EXPERIMENTAL
description
LY3475070 administered orally. Based on Sponsor decision, Phase 1b expansion cohorts were not initiated.
intervention Names
Drug: LY3475070
label
Phase 1b Cohort D2 LY3475070 (dose expansion)
type
EXPERIMENTAL
description
LY3475070 administered orally and pembrolizumab administered IV. Based on Sponsor decision, Phase 1b expansion cohorts were not initiated.
intervention Names
Drug: LY3475070
Drug: Pembrolizumab
label
Phase 1b Cohort E LY3475070 + Pembrolizumab (dose expansion)
type
EXPERIMENTAL

interventions

arm Group Labels
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)
description
Administered orally
name
LY3475070
type
DRUG
arm Group Labels
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)
description
Administered IV
name
Pembrolizumab
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 52
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
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.
measure
Number of Participants With Dose Limiting Toxicities (DLTs)
time Frame
Up to 28 days from the first dose

secondary Outcomes

description
PK: AUC\[0-8\] of LY3475070.
measure
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Eight Hours (AUC[0-8]) of LY3475070
time Frame
Cycle 1 Day 1 (Pre-dose, 0.5, 1, 2, 4, 6, 8 hours post-dose)
description
PK: AUCtau of LY3475070
measure
PK: Area Under the Concentration Versus Time Curve During 1 Dosing Interval (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)
description
PK: Cmax of LY3475070
measure
PK: Maximum Concentration (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)
description
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.
measure
Overall Response Rate (ORR): Percentage of Participants With Complete Response (CR) or Partial Response (PR)
time Frame
Baseline through Disease Progression or Death (Estimated at up to 10.4 Months)
description
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.
measure
Disease Control Rate (DCR): Percentage of Participants With a Best Overall Response of CR, PR, and Stable Disease (SD)
time Frame
Baseline through Measured Progressive Disease (Estimated at up to 10.4 Months)
description
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.
measure
Progression-Free Survival (PFS)
time Frame
Baseline to Objective Progression or Death Due to Any Cause (Estimated at up to 10.4 Months)

Full study description

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.

Source references