A Study of LY3435151 in Participants With Solid Tumors

Phase 1

Terminated

• Conditions: Hepatocellular Carcinoma; Gastric Adenocarcinoma; Cervical Carcinoma; Solid Tumor; Triple-negative Breast Cancer; Head and Neck Squamous Cell Carcinoma; Undifferentiated Pleomorphic Sarcoma; Leiomyosarcoma; High Grade Serous Ovarian Carcinoma
• Interventions: Drug: LY3435151; Drug: Pembrolizumab

• Registration Number: NCT04099277
• Lead Sponsor: Eli Lilly and Company

Brief Summary

The reason for this study is to see if the study drug LY3435151 is safe in participants with advanced solid tumors.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2019-09-20
• Study First Submitted QC: 2019-09-20
• Study First Posted: 2019-09-23
• Study Start: 2019-10-28
• Primary Completion: 2020-03-05
• Study Completion: 2020-03-05
• Status Verified: 2021-08
• Results First Submitted: 2021-08-04
• Results First Submitted QC: 2021-08-04
• Last Update Submitted: 2021-08-04
• Results First Posted: 2021-08-31
• Last Update Posted: 2021-08-31

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 2

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Part A: 10 milligrams (mg) LY3435151	LY3435151	Participants received intravenous (IV) push or IV bolus infusion of 10 mg LY3435151.
Part B: LY3435151 + Pembrolizumab Dose Escalation	LY3435151	Pembrolizumab was not administered as study was terminated before completion of Part A of the dose escalation period.
Part C: LY3435151 Dose Expansion	LY3435151	Participants were not enrolled in to this arm, as trial was terminated in dose escalation phase.
Part D: LY3435151 + Pembrolizumab Dose Expansion	LY3435151	Participants were not enrolled in to this arm, as trial was terminated in dose escalation phase.
Part B: LY3435151 + Pembrolizumab Dose Escalation	Pembrolizumab	Pembrolizumab was not administered as study was terminated before completion of Part A of the dose escalation period.
Part D: LY3435151 + Pembrolizumab Dose Expansion	Pembrolizumab	Participants were not enrolled in to this arm, as trial was terminated in dose escalation phase.

Primary Outcome Measures

Name	Time	Method
Number of Participants With LY3435151 Dose-Limiting Toxicities (DLTs)	Baseline through Cycle 2 (21 Day Cycles)	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: 1. Any death not clearly due to the underlying disease or extraneous causes; 2. Neutropenic fever 2. Any Grade ≥3 non-hematologic toxicity; 3. Grade ≥4 neutropenia or thrombocytopenia \>7 days; 4. Grade ≥3 thrombocytopenia with bleeding; 5. Grade ≥3 nausea/vomiting or diarrhea\>72 hours with adequate antiemetic and other supportive care; 6. Grade ≥3 fatigue ≥1 week; 7. 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; 8. Grade ≥3 prolongation of QT interval corrected using the Fridericia formula on 2 separate electrocardiogram readings approximately 5 min apart.

Secondary Outcome Measures

Name	Time	Method
Progression Free Survival (PFS)	Baseline to Objective Progression or Death Due to Any Cause (Up to 4 Months)	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.
Duration of Response (DoR)	Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Up to 4 Months)	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)	Baseline to Date of CR or PR (Up to 4 Months)	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.
Disease Control Rate (DCR): Percentage of Participants With a Best Overall Response of CR, PR, and Stable Disease	Baseline through Measured Progressive Disease (Up to 4 Months)	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.
Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3435151	Cycle 1 Day 1 (C1D1) (Predose, 1, 3 hour (hr), C1D2 (24 hr), C1D4 (72hr), C1D8 (168hr), C1D15 (336hr)	Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3435151.
PK: Cmax of LY3435151 in Combination With Pembrolizumab	Predose Cycle 1 Day 1 through Predose Cycle 5 Day 1 (21 Day Cycles)	PK: Cmax of LY3435151 in Combination with Pembrolizumab.
Overall Response Rate (ORR): Percentage of Participants With Complete Response (CR) or Partial Response (PR)	Baseline through Disease Progression or Death (Up to 4 Months)	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.

Trial Locations

Locations (2)

University of Texas MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

National Cancer Center Hospital; 🇯🇵 Chuo-Ku, Tokyo, Japan