A Study of LY3435151 in Participants With Solid Tumors

August 4, 2021 updated by: Eli Lilly and Company

A Phase 1a/1b Study of LY3435151 Administered to Patients With Advanced Solid Tumors

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

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

2

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Japan
    • Tokyo
      • Chuo-Ku, Tokyo, Japan, 104-0045
        • National Cancer Center Hospital
  • United States
    • Texas
      • Houston, Texas, United States, 77030
        • University of Texas MD Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With LY3435151 Dose-Limiting Toxicities (DLTs)
Time Frame: 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.
Baseline through Cycle 2 (21 Day Cycles)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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)
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)
PK: Cmax of LY3435151 in Combination With Pembrolizumab
Time Frame: Predose Cycle 1 Day 1 through Predose Cycle 5 Day 1 (21 Day Cycles)
PK: Cmax of LY3435151 in Combination with Pembrolizumab.
Predose Cycle 1 Day 1 through Predose Cycle 5 Day 1 (21 Day Cycles)
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)
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.
Baseline through Disease Progression or Death (Up to 4 Months)
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)
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.
Baseline through Measured Progressive Disease (Up to 4 Months)
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)
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.
Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Up to 4 Months)
Time to Response (TTR)
Time Frame: 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.
Baseline to Date of CR or PR (Up to 4 Months)
Progression Free Survival (PFS)
Time Frame: 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.
Baseline to Objective Progression or Death Due to Any Cause (Up to 4 Months)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Eli Lilly and Company

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 28, 2019

Primary Completion (Actual)

March 5, 2020

Study Completion (Actual)

March 5, 2020

Study Registration Dates

First Submitted

September 20, 2019

First Submitted That Met QC Criteria

September 20, 2019

First Posted (Actual)

September 23, 2019

Study Record Updates

Last Update Posted (Actual)

August 31, 2021

Last Update Submitted That Met QC Criteria

August 4, 2021

Last Verified

August 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 17364
  • J1Q-MC-JZIA (Other Identifier: Eli Lilly and Company)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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