Description:
The reason for this study is to see if the study drug LY3435151 is safe in participants with
advanced solid tumors.
Title
- 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
Clinical Trial IDs
- ORG STUDY ID:
17364
- SECONDARY ID:
J1Q-MC-JZIA
- NCT ID:
NCT04099277
Conditions
- 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
Interventions
Drug | Synonyms | Arms |
---|
LY3435151 | | Part A: 10 milligrams (mg) LY3435151 |
Pembrolizumab | | Part B: LY3435151 + Pembrolizumab Dose Escalation |
Purpose
The reason for this study is to see if the study drug LY3435151 is safe in participants with
advanced solid tumors.
Trial Arms
Name | Type | Description | Interventions |
---|
Part A: 10 milligrams (mg) LY3435151 | Experimental | Participants received intravenous (IV) push or IV bolus infusion of 10 mg LY3435151. | |
Part B: LY3435151 + Pembrolizumab Dose Escalation | Experimental | Pembrolizumab was not administered as study was terminated before completion of Part A of the dose escalation period. | |
Part C: LY3435151 Dose Expansion | Experimental | Participants were not enrolled in to this arm, as trial was terminated in dose escalation phase. | |
Part D: LY3435151 + Pembrolizumab Dose Expansion | Experimental | Participants were not enrolled in to this arm, as trial was terminated in dose escalation phase. | |
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
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Number of Participants With LY3435151 Dose-Limiting Toxicities (DLTs) |
Time Frame: | Baseline through Cycle 2 (21 Day Cycles) |
Safety Issue: | |
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. |
Secondary Outcome Measures
Measure: | 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) |
Safety Issue: | |
Description: | Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3435151. |
Measure: | PK: Cmax of LY3435151 in Combination With Pembrolizumab |
Time Frame: | Predose Cycle 1 Day 1 through Predose Cycle 5 Day 1 (21 Day Cycles) |
Safety Issue: | |
Description: | PK: Cmax of LY3435151 in Combination with Pembrolizumab. |
Measure: | Overall Response Rate (ORR): Percentage of Participants With Complete Response (CR) or Partial Response (PR) |
Time Frame: | Baseline through Disease Progression or Death (Up to 4 Months) |
Safety Issue: | |
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. |
Measure: | Disease Control Rate (DCR): Percentage of Participants With a Best Overall Response of CR, PR, and Stable Disease |
Time Frame: | Baseline through Measured Progressive Disease (Up to 4 Months) |
Safety Issue: | |
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. |
Measure: | Duration of Response (DoR) |
Time Frame: | Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Up to 4 Months) |
Safety Issue: | |
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. |
Measure: | Time to Response (TTR) |
Time Frame: | Baseline to Date of CR or PR (Up to 4 Months) |
Safety Issue: | |
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. |
Measure: | Progression Free Survival (PFS) |
Time Frame: | Baseline to Objective Progression or Death Due to Any Cause (Up to 4 Months) |
Safety Issue: | |
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. |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Terminated |
Lead Sponsor: | Eli Lilly and Company |
Trial Keywords
- immunotherapy
- CD226 agonist
Last Updated
August 31, 2021