Back to resultsA Study of LY3435151 in Participants With Solid Tumors
Primary Purpose
Solid Tumor, Triple-negative Breast Cancer, Gastric Adenocarcinoma
Status
Terminated
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
LY3435151
Pembrolizumab
Sponsored by
About this trial
This is an interventional treatment trial for Solid Tumor focused on measuring immunotherapy, CD226 agonist
Eligibility Criteria
Inclusion Criteria:
- Participant must have certain types of cancer, which your study doctor will discuss with you
- Participant must have stopped other forms of treatment for cancer, which your study doctor will discuss with you
- Participant must be able and willing to provide a sample of your tumor before beginning treatment and once while on treatment. For certain tumor types, the outcome of the biopsy may exclude you from the study treatment (for Phase 1b)
- Participant must agree to use birth control
- Participant must have progressed through or are intolerant to therapies with known clinical benefit, which your study doctor will discuss with you
Exclusion Criteria:
- Participant must not have a history of tuberculosis, uncontrolled HIV or uncontrolled hepatitis B or C virus infection
- Participant must not have an autoimmune disease, which your study doctor will discuss with you
- Participant must not use corticosteroids, which your study doctor will discuss with you
- Participant must not have heart disease, Crohn's disease or brain cancer
- Participant must not be pregnant or breastfeeding
Sites / Locations
- University of Texas MD Anderson Cancer Center
- National Cancer Center Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Part A: 10 milligrams (mg) LY3435151
Part B: LY3435151 + Pembrolizumab Dose Escalation
Part C: LY3435151 Dose Expansion
Part D: LY3435151 + Pembrolizumab Dose Expansion
Arm Description
Participants received intravenous (IV) push or IV bolus infusion of 10 mg LY3435151.
Pembrolizumab was not administered as study was terminated before completion of Part A of the dose escalation period.
Participants were not enrolled in to this arm, as trial was terminated in dose escalation phase.
Participants were not enrolled in to this arm, as trial was terminated in dose escalation phase.
Outcomes
Primary Outcome Measures
Number of Participants With LY3435151 Dose-Limiting Toxicities (DLTs)
A DLT is defined as an Adverse Event that is likely related to the study medication or combination, and fulfills any one of the following criteria, graded according to the National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0:
Any death not clearly due to the underlying disease or extraneous causes
Neutropenic fever 2. Any Grade ≥3 non-hematologic toxicity
Grade ≥4 neutropenia or thrombocytopenia >7 days
Grade ≥3 thrombocytopenia with bleeding
Grade ≥3 nausea/vomiting or diarrhea>72 hours with adequate antiemetic and other supportive care
Grade ≥3 fatigue ≥1 week
Grade ≥3 electrolyte abnormality that lasts>72 hours, unless the Participant has clinical symptoms, in which case all Grade 3+electrolyte abnormality regardless of duration should count as a DLT
Grade ≥3 prolongation of QT interval corrected using the Fridericia formula on 2 separate electrocardiogram readings approximately 5 min apart.
Secondary Outcome Measures
Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3435151
Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3435151.
PK: Cmax of LY3435151 in Combination With Pembrolizumab
PK: Cmax of LY3435151 in Combination with Pembrolizumab.
Overall Response Rate (ORR): Percentage of Participants With Complete Response (CR) or Partial Response (PR)
Overall response rate is the best response of complete response (CR) or partial response (PR) as classified by the independent central review 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. Overall response rate is calculated as a total number of participants with CR or PR divided by the total number of participants per cohort with at least 1 measurable lesion, multiplied by 100.
Disease Control Rate (DCR): Percentage of Participants With a Best Overall Response of CR, PR, and Stable Disease
Disease Control Rate (DCR) is the percentage of participants with a best overall response of CR, PR, or Stable Disease (SD) as per Response using RECIST v1.1 criteria. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD for target lesions, no progression of non-target lesions, and no appearance of new lesions. PD is 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.
Duration of Response (DoR)
DOR is the time from the date of first evidence of complete response or partial response to the date of objective progression or the date of death due to any cause, whichever is earlier. CR and PR defined using the RECIST v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. If a responder was not known to have died or have objective progression as of the data inclusion cutoff date, duration of response was censored at the last adequate tumor assessment date. PD was 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 to Response (TTR)
Time to response (TTR) is defined as the time from the date of start of treatment to the date measurement criteria for confirmed CR or PR (whichever is first recorded) are first met. For participants who are not known to have achieved CR or PR as of the data inclusion cut-off date, TTR will be censored at the date of the last objective disease assessment prior the date of any subsequent systematic anticancer therapy.
Progression Free Survival (PFS)
PFS time was measured from the date of randomization until the first radiographic documentation of progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, or death from any cause. Progressive Disease (PD) was 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. If a participant does not have a complete baseline disease assessment, then the PFS time was censored at the date of first dose, regardless of whether or not objectively determined disease progression or death has been observed for the participant. If a participant was not known to have died or have objective progression as of the data inclusion cutoff date for the analysis, the PFS time was censored at the last adequate tumor assessment date.
Full Information
NCT ID
NCT04099277
First Posted
September 20, 2019
Last Updated
August 4, 2021
Sponsor
Eli Lilly and Company
1. Study Identification
Unique Protocol Identification Number
NCT04099277
Brief Title
A Study of LY3435151 in Participants With Solid Tumors
Official Title
A Phase 1a/1b Study of LY3435151 Administered to Patients With Advanced Solid Tumors
Study Type
Interventional
2. Study Status
Record Verification Date
August 2021
Overall Recruitment Status
Terminated
Why Stopped
Study terminated due to strategic business decision by Eli Lilly and Company.
Study Start Date
October 28, 2019 (Actual)
Primary Completion Date
March 5, 2020 (Actual)
Study Completion Date
March 5, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eli Lilly and Company
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The reason for this study is to see if the study drug LY3435151 is safe in participants with advanced solid tumors.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Solid Tumor, Triple-negative Breast Cancer, Gastric Adenocarcinoma, Head and Neck Squamous Cell Carcinoma, Cervical Carcinoma, High Grade Serous Ovarian Carcinoma, Hepatocellular Carcinoma, Undifferentiated Pleomorphic Sarcoma, Leiomyosarcoma
Keywords
immunotherapy, CD226 agonist
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
2 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Part A: 10 milligrams (mg) LY3435151
Arm Type
Experimental
Arm Description
Participants received intravenous (IV) push or IV bolus infusion of 10 mg LY3435151.
Arm Title
Part B: LY3435151 + Pembrolizumab Dose Escalation
Arm Type
Experimental
Arm Description
Pembrolizumab was not administered as study was terminated before completion of Part A of the dose escalation period.
Arm Title
Part C: LY3435151 Dose Expansion
Arm Type
Experimental
Arm Description
Participants were not enrolled in to this arm, as trial was terminated in dose escalation phase.
Arm Title
Part D: LY3435151 + Pembrolizumab Dose Expansion
Arm Type
Experimental
Arm Description
Participants were not enrolled in to this arm, as trial was terminated in dose escalation phase.
Intervention Type
Drug
Intervention Name(s)
LY3435151
Intervention Description
Administered IV
Intervention Type
Drug
Intervention Name(s)
Pembrolizumab
Intervention Description
Administered IV
Primary Outcome Measure Information:
Title
Number of Participants With LY3435151 Dose-Limiting Toxicities (DLTs)
Description
A DLT is defined as an Adverse Event that is likely related to the study medication or combination, and fulfills any one of the following criteria, graded according to the National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0:
Any death not clearly due to the underlying disease or extraneous causes
Neutropenic fever 2. Any Grade ≥3 non-hematologic toxicity
Grade ≥4 neutropenia or thrombocytopenia >7 days
Grade ≥3 thrombocytopenia with bleeding
Grade ≥3 nausea/vomiting or diarrhea>72 hours with adequate antiemetic and other supportive care
Grade ≥3 fatigue ≥1 week
Grade ≥3 electrolyte abnormality that lasts>72 hours, unless the Participant has clinical symptoms, in which case all Grade 3+electrolyte abnormality regardless of duration should count as a DLT
Grade ≥3 prolongation of QT interval corrected using the Fridericia formula on 2 separate electrocardiogram readings approximately 5 min apart.
Time Frame
Baseline through Cycle 2 (21 Day Cycles)
Secondary Outcome Measure Information:
Title
Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3435151
Description
Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3435151.
Time Frame
Cycle 1 Day 1 (C1D1) (Predose, 1, 3 hour (hr), C1D2 (24 hr), C1D4 (72hr), C1D8 (168hr), C1D15 (336hr)
Title
PK: Cmax of LY3435151 in Combination With Pembrolizumab
Description
PK: Cmax of LY3435151 in Combination with Pembrolizumab.
Time Frame
Predose Cycle 1 Day 1 through Predose Cycle 5 Day 1 (21 Day Cycles)
Title
Overall Response Rate (ORR): Percentage of Participants With Complete Response (CR) or Partial Response (PR)
Description
Overall response rate is the best response of complete response (CR) or partial response (PR) as classified by the independent central review 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. Overall response rate is calculated as a total number of participants with CR or PR divided by the total number of participants per cohort with at least 1 measurable lesion, multiplied by 100.
Time Frame
Baseline through Disease Progression or Death (Up to 4 Months)
Title
Disease Control Rate (DCR): Percentage of Participants With a Best Overall Response of CR, PR, and Stable Disease
Description
Disease Control Rate (DCR) is the percentage of participants with a best overall response of CR, PR, or Stable Disease (SD) as per Response using RECIST v1.1 criteria. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD for target lesions, no progression of non-target lesions, and no appearance of new lesions. PD is 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 (Up to 4 Months)
Title
Duration of Response (DoR)
Description
DOR is the time from the date of first evidence of complete response or partial response to the date of objective progression or the date of death due to any cause, whichever is earlier. CR and PR defined using the RECIST v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. If a responder was not known to have died or have objective progression as of the data inclusion cutoff date, duration of response was censored at the last adequate tumor assessment date. PD was 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
Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Up to 4 Months)
Title
Time to Response (TTR)
Description
Time to response (TTR) is defined as the time from the date of start of treatment to the date measurement criteria for confirmed CR or PR (whichever is first recorded) are first met. For participants who are not known to have achieved CR or PR as of the data inclusion cut-off date, TTR will be censored at the date of the last objective disease assessment prior the date of any subsequent systematic anticancer therapy.
Time Frame
Baseline to Date of CR or PR (Up to 4 Months)
Title
Progression Free Survival (PFS)
Description
PFS time was measured from the date of randomization until the first radiographic documentation of progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, or death from any cause. Progressive Disease (PD) was 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. If a participant does not have a complete baseline disease assessment, then the PFS time was censored at the date of first dose, regardless of whether or not objectively determined disease progression or death has been observed for the participant. If a participant was not known to have died or have objective progression as of the data inclusion cutoff date for the analysis, the PFS time was censored at the last adequate tumor assessment date.
Time Frame
Baseline to Objective Progression or Death Due to Any Cause (Up to 4 Months)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Participant must have certain types of cancer, which your study doctor will discuss with you
Participant must have stopped other forms of treatment for cancer, which your study doctor will discuss with you
Participant must be able and willing to provide a sample of your tumor before beginning treatment and once while on treatment. For certain tumor types, the outcome of the biopsy may exclude you from the study treatment (for Phase 1b)
Participant must agree to use birth control
Participant must have progressed through or are intolerant to therapies with known clinical benefit, which your study doctor will discuss with you
Exclusion Criteria:
Participant must not have a history of tuberculosis, uncontrolled HIV or uncontrolled hepatitis B or C virus infection
Participant must not have an autoimmune disease, which your study doctor will discuss with you
Participant must not use corticosteroids, which your study doctor will discuss with you
Participant must not have heart disease, Crohn's disease or brain cancer
Participant must not be pregnant or breastfeeding
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
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)
Organizational Affiliation
Eli Lilly and Company
Official's Role
Study Director
Facility Information:
Facility Name
University of Texas MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
National Cancer Center Hospital
City
Chuo-Ku
State/Province
Tokyo
ZIP/Postal Code
104-0045
Country
Japan
12. IPD Sharing Statement
Plan to Share IPD
No
Links:
URL
https://www.lillytrialguide.com/en-US/studies/solid-tumor/JZIA#?postal=
Description
A Study of LY3435151 in Participants With Solid Tumors
Learn more about this trial
A Study of LY3435151 in Participants With Solid Tumors
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