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A Study of LY3435151 in Participants With Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04099277
Recruitment Status : Terminated (Study terminated due to strategic business decision by Eli Lilly and Company.)
First Posted : September 23, 2019
Results First Posted : August 31, 2021
Last Update Posted : August 31, 2021
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
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 Drug: LY3435151 Drug: Pembrolizumab Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 2 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1a/1b Study of LY3435151 Administered to Patients With Advanced Solid Tumors
Actual Study Start Date : October 28, 2019
Actual Primary Completion Date : March 5, 2020
Actual Study Completion Date : March 5, 2020


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: LY3435151
Administered IV

Drug: Pembrolizumab
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: LY3435151
Administered IV

Drug: Pembrolizumab
Administered IV




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04099277


Locations
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United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Japan
National Cancer Center Hospital
Chuo-Ku, Tokyo, Japan, 104-0045
Sponsors and Collaborators
Eli Lilly and Company
Investigators
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Study Director: 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) Eli Lilly and Company
  Study Documents (Full-Text)

Documents provided by Eli Lilly and Company:
Study Protocol  [PDF] January 28, 2020
Statistical Analysis Plan  [PDF] October 4, 2019

Additional Information:
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Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT04099277    
Other Study ID Numbers: 17364
J1Q-MC-JZIA ( Other Identifier: Eli Lilly and Company )
First Posted: September 23, 2019    Key Record Dates
Results First Posted: August 31, 2021
Last Update Posted: August 31, 2021
Last Verified: August 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Eli Lilly and Company:
immunotherapy
CD226 agonist
Additional relevant MeSH terms:
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Carcinoma
Triple Negative Breast Neoplasms
Squamous Cell Carcinoma of Head and Neck
Leiomyosarcoma
Histiocytoma, Malignant Fibrous
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Carcinoma, Squamous Cell
Sarcoma
Neoplasms, Connective and Soft Tissue
Neoplasms by Site
Breast Neoplasms
Breast Diseases
Skin Diseases
Head and Neck Neoplasms
Neoplasms, Muscle Tissue
Histiocytoma
Neoplasms, Fibrous Tissue
Neoplasms, Connective Tissue
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents