A Study of LY3022855 In Participants With Breast or Prostate Cancer

Phase 1 Study to Identify the Immunomodulatory Activity of LY3022855 (IMC-CS4) in Patients With Advanced, Refractory Breast or Prostate Cancer

The main purpose of this study is to learn more about how the investigational drug, LY3022855, affects the immune system in participants with advanced breast or prostate cancer that has not responded to other treatments. Treatment may last up to 6 cycles (cycle = 6 weeks).

Study Overview

• Status: Completed
• Conditions: Neoplasms; Neoplasm Metastasis
• Intervention / Treatment: Drug: LY3022855

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90048
      • Cedars Sinai Medical Center
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Confirmed diagnosis of advanced, refractory breast or prostate cancer that is evaluable by radiologic testing. Participants must have experienced tumor progression on or treatment intolerance to at least one prior therapy and have declined or are ineligible for a standard treatment.

• For participants with metastatic castrate-resistant prostate cancer only:

  • Must continue ongoing androgen deprivation therapy with castrate levels of serum testosterone <50 nanogram/deciliter (ng/dL) determined within 4 weeks prior to starting treatment
  • If receiving an antiandrogen as part of first-line hormonal therapy, must have shown progression of disease off the antiandrogen prior to enrollment
  • Must be willing to continue androgen deprivation therapy while on study, if no prior orchiectomy

  • Must meet at least 1 of the following 3 criteria for progressive metastatic disease, according to Prostate Cancer Working Group 2 (PCWG2) criteria:

    • A rise in prostate-specific antigen (minimal value 2 ng/milliliter (mL); ≥3 consecutive rising values)
    • ≥2 new metastases on transaxial imaging or radionuclide bone scan
    • Soft tissue progression
  • Replacement hormone therapy initiated before study entry is permitted

  • For participants with breast cancer only:

    • May continue ongoing antiestrogen therapy
    • Replacement hormone therapy initiated before study entry is permitted
    • May continue ongoing trastuzumab therapy
• Have adequate organ and hematologic function, including: Hepatic: Bilirubin ≤1.5 × the upper limit of normal (ULN), and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3.0 × ULN. For participants with tumor involvement of the liver, AST and ALT ≤5.0 × ULN are acceptable. For participants with tumor involvement of the bone, alkaline phosphatase ≤5.0 × ULN is acceptable. Renal: Serum creatinine ≤2.0 × ULN. Absolute neutrophil count (ANC) ≥1.0 × 10^9/liter (L). Hemoglobin ≥9 grams per deciliter (5.58 millimoles per liter). Platelets ≥90 × 10^9/L.
• Have Eastern Cooperative Oncology Group (ECOG) performance status of ≤2.
• Have discontinued all disease-modifying therapy for the primary cancer >28 days prior to initiation of study treatment. In addition, clinically significant toxicities associated with any prior therapy for the primary cancer, including investigational treatments, have resolved or stabilized to Grade ≤1 toxicity >28 days prior to initiation of study treatment with the exception of neuropathy, which must have resolved to Grade ≤2. Continuation of a stable dose (minimum of 28 days prior to study entry) of denosumab or bisphosphonate is permitted on study.
• Willing and able to comply with study procedures including 1 baseline and 1 posttreatment tumor biopsy procedure.
• Male participants: Agree to use a reliable method of birth control and to not donate sperm during the study and for at least 12 weeks following last dose of study drug or country requirements, whichever is longer.
• Female participants: Are women of child-bearing potential who test negative for pregnancy within 7 days prior to enrollment based on a urine or serum pregnancy test and agree to use a reliable method of birth control during the study and for 12 weeks following the last dose of the study drug and also must not be breastfeeding, OR are postmenopausal women.
• Have an estimated life expectancy that, in the judgment of the investigator, will permit the patient to complete 1 cycle of treatment.
• May have received treatment with an investigational product or non-approved use of a drug (other than the study drug used in this study) or device for non-cancer indications; however, not within 28 days prior to the initial dose of study drug.

Exclusion Criteria:

• Have received treatment within 28 days prior to the initial dose of study drug with an investigational product or non-approved use of a drug or device (other than the study drug/device used in this study) for non-cancer indications or are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study.
• Have serious preexisting medical conditions (left to the discretion of the investigator).
• Have symptomatic central nervous system (CNS) malignancy or metastasis.
• Have an active fungal, bacterial, and/or known viral infection, including human immunodeficiency virus (HIV) or viral (B or C) hepatitis.

• Have any of the following cardiovascular conditions:

  • Symptomatic coronary artery disease currently or within the past 6 months,
  • Have a second active primary malignancy that, in the judgment of the investigator or sponsor, may affect the interpretation of the results.
  • Confirmed left ventricular ejection fraction ≤50% or any cardiac insufficiency > New York Heart Association (NYHA) class II currently or within the past 6 months,
  • Uncontrolled hypertension (>170/100 millimeter of mercury [mm Hg]) currently or within the past 7 days, or
  • Serious cardiac arrhythmia (well-controlled atrial fibrillation is permitted) currently or within the past 6 months.
• Have a second active primary malignancy that, in the judgment of the investigator or sponsor, may affect the interpretation of the results.
• Are unwilling or unable to participate in tumor biopsies.
• Have corrected QT interval of >500 millisecond (msec) on screening electrocardiogram (ECG).
• Have received treatment with agents specifically targeting colony stimulating factor 1 (CSF-1) or CSF-1R, including imatinib, nilotinib, and sunitinib.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LY3022855 1.25 mg/kg Q2W; 1.25 milligram per kilogram (mg/kg) LY3022855 administered intravenously (IV), once every two weeks (Q2W). Treatment is 6 week cycle. Participants may receive multiple cycles if they are deriving clinical benefit.	Drug: LY3022855; Administered IV; Other Names: IMC-CS4
Experimental: LY3022855 1.0 mg/kg WK1_2_4_5; 1.0 mg/kg LY3022855 administered IV on Weeks 1, 2, 4, and 5 of a 6-week cycle. Participants may receive multiple cycles if they are deriving clinical benefit.	Drug: LY3022855; Administered IV; Other Names: IMC-CS4
Experimental: LY3022855 100 mg Q2W; 100 mg of LY3022855 administered IV once every two weeks of a 6-week cycle. Participants may receive multiple cycles if they are deriving clinical benefit.	Drug: LY3022855; Administered IV; Other Names: IMC-CS4
Experimental: LY3022855 100 mg QW; 100 mg of LY3022855 administered IV. once a week (QW) of a 6-week cycle. Participants may receive multiple cycles if they are deriving clinical benefit.	Drug: LY3022855; Administered IV; Other Names: IMC-CS4

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage Change From Baseline in Peripheral Blood Immune Cell (PBIC) Subsets	The immunomodulatory activity of the drug was documented by examining markers that include, but are not limited to: Live-Dead, Cluster of Differentiation 3 (CD3), CD4, CD8, CD14, CD16, Foxhead Box p3 (FoxP3), PD-1, Ki-67, Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4), Human Leukocyte Antigen-D-relate (HLA-DR), T-cell immunoglobulin and mucin-3 (TIM-3), lymphocyte-activation gene 3 (LAG-3), and Inducible T-cell COStimulator (ICOS). The expression of these markers was quantified by flow cytometric analysis with an antibody panel.	Baseline to Day 8 after 1st dose
Percentage Change From Baseline in Serum Cytokines	The immunomodulatory activity of the drug was measured in participants with advanced, refractory breast or prostate cancers using serum cytokines. Serum cytokine levels was determined by MSD multiplex cytokine immunoassay technology or ELISA, and that may include but not be limited to Interleukin 6 (IL-6), IL-8, IL-10 and Tumor necrosis factor (TNF-α).	Baseline to Day 8 after 1st dose
Serum Cytokine Levels	The immunomodulatory activity of the drug was measured in participants with advanced, refractory breast or prostate cancers using serum cytokines. Serum cytokines will be determined by MSD multiplex cytokine immunoassay or ELISA. The markers to be measured using these technologies include, but are not limited to: CSF-1, IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-34, and TNF-α.	Day 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics (PK): Area Under the Concentration Curve of LY3022855	Area under the concentration versus time curve from time zero to tau (τ) of LY3022855 (AUC[0- τ]), where tau is dosing interval of (0-14 days).	0, 1, 4, 24, 48, 72 and 168 hours post dose on Day 1 and Day 29
Percentage of Participants With a Best Overall Disease Control Response (Disease Control Rate)	Disease control rate is the percentage of participants with a confirmed CR, PR or SD, as classified by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.1. CR is the disappearance of all target and non-target lesions; PR is a ≥30% decrease in sum of longest diameter of target lesions without new lesion and progression of non-target lesion; SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease. Disease control rate is calculated as a total number of participants with CR or PR or SD divided by the total number of participants treated, then multiplied by 100.	Baseline up to 6 cycles (cycle = 6 weeks)

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Investigators: 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

Publications and helpful links

General Publications

• Autio KA, Klebanoff CA, Schaer D, Kauh JSW, Slovin SF, Adamow M, Blinder VS, Brahmachary M, Carlsen M, Comen E, Danila DC, Doman TN, Durack JC, Fox JJ, Gluskin JS, Hoffman DM, Kang S, Kang P, Landa J, McAndrew PF, Modi S, Morris MJ, Novosiadly R, Rathkopf DE, Sanford R, Chapman SC, Tate CM, Yu D, Wong P, McArthur HL. Immunomodulatory Activity of a Colony-stimulating Factor-1 Receptor Inhibitor in Patients with Advanced Refractory Breast or Prostate Cancer: A Phase I Study. Clin Cancer Res. 2020 Nov 1;26(21):5609-5620. doi: 10.1158/1078-0432.CCR-20-0855. Epub 2020 Aug 26.

Helpful Links

• A Study of LY3022855 In Participants With Breast or Prostate Cancer

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2015
• Primary Completion (Actual): November 3, 2017
• Study Completion (Actual): November 3, 2017

Study Registration Dates

• First Submitted: September 24, 2014
• First Submitted That Met QC Criteria: October 10, 2014
• First Posted (Estimated): October 16, 2014

Study Record Updates

• Last Update Posted (Actual): October 28, 2024
• Last Update Submitted That Met QC Criteria: October 24, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplastic Processes; Neoplasms; Neoplasm Metastasis
• Other Study ID Numbers: 15441; I5F-MC-JSCB (Other Identifier: Eli Lilly and Company)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO