A Study of LY3023414 in Participants With Advanced Cancer

April 7, 2022 updated by: Eli Lilly and Company

A Phase 1 First-in-Human Dose Study of LY3023414 in Patients With Advanced Cancer

The purpose of this study is to find a recommended dose level and schedule of dosing LY3023414 that can safely be taken by participants with advanced or metastatic cancer. The study will also explore the changes to various markers in blood cells and potentially tumor cells. Finally, the study will help document any antitumor activity this drug may have.

In Part A of this study, participants with advanced/metastatic cancer (including lymphoma) will receive increasing doses of LY3023414. In Part B, LY3023414 will be explored in different types of cancer, including breast and lung cancer, lymphoma and mesothelioma.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

156

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

  • Italy
    • Torino
      • Orbassano, Torino, Italy, 10043
        • Azienda Ospedaliero - Universitaria S. Luigi Gonzaga
  • Puerto Rico
      • San Juan, Puerto Rico, 00927
        • Fundacion de Investigacion de Diego
  • United States
    • California
      • Los Angeles, California, United States, 90095
        • UCLA Medical Center
    • New York
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Peggy and Charles Stephenson Oklahoma Cancer Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Penn Presbyterian Medical Center
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Sarah Cannon Cancer Center
      • Nashville, Tennessee, United States, 37203
        • Tennessee Oncology PLLC

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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Parts A, A2 & B1: Participants must have pathological evidence of a diagnosis of advanced and/or metastatic cancer and must be, in the judgment of the investigator, an appropriate candidate for experimental therapy
  • Part B2: Participants must have advanced, recurrent, or metastatic breast cancer that is refractory to aromatase inhibitors (AI) with either disease recurrence or disease progression; must be hormone receptor positive (HR+) and human epidermal growth factor receptor 2 (HER2)-negative; must be of postmenopausal status or beginning ovarian suppression with a luteinizing hormone-releasing hormone (LHRH) agonist
  • Part B3 only: Participants must have malignant pleural or peritoneal mesothelioma
  • Part B4 only: Participants must have malignant pleural or peritoneal mesothelioma and appropriate candidate for treatment with cisplatin/pemetrexed; no prior systemic chemotherapy
  • Part B5 only: Participants must have histologically confirmed diagnosis of B-cell iNHL, with histological subtype; prior treatment with ≥2 prior chemotherapy- or immunotherapy-based regimens for iNHL
  • Part B6 only: Participants must have squamous NSCLC; documented evidence of an activating molecular aberration of the PI3K/mTOR pathway
  • Parts B2, B3 & B6 only: Must have adequate tumor tissue sample from archival biopsy available, or willingness to undergo a fresh tumor biopsy
  • Parts B3, B4, B5 & B6: No previous treatment with any PI3K and/or mTOR inhibitor
  • Part B7: Must have a diagnosis of HR+ and HER2- breast cancer; have locoregionally recurrent disease not amenable to resection or radiation therapy with curative intent or metastatic disease; no previous treatment or currently receiving 1 of the following treatments for locoregionally recurrent or metastatic breast cancer (chemotherapy, endocrine therapy, CDK4/6 inhibitor, and PI3K and/or mTOR inhibitor)
  • Measurable or nonmeasurable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1), modified RECIST or Revised Response Criteria for Malignant Lymphoma
  • Have adequate organ function, including: Absolute neutrophil count (ANC) at least 1.5 x 109/Liter (L), platelets at least 100 x 109/L, and hemoglobin at least 8 grams/deciliter (g/dL); bilirubin no more than 1.5 times upper limits of normal; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) no more than 2.0 times upper limits of normal; Serum creatinine no more than 1.5 times upper limits of normal or calculated creatinine clearance >45 milliliters/minute (mL/min)
  • Have a performance status of at least 1 on the Eastern Cooperative Oncology Group (ECOG) scale and life expectancy >6 months
  • Have discontinued all previous cancer therapies (except nonsteroidal aromatase inhibitors for participants in Part B2), and any agents that have not received regulatory approval for any indication, for at least 21 days or 5 half lives prior to study enrollment, whichever is shorter, and recovered from the acute effects of therapy. Participants must have discontinued mitomycin-C or nitrosourea therapy for at least 42 days
  • Are able to swallow capsules

Exclusion Criteria:

  • Have serious preexisting medical conditions
  • Have symptomatic central nervous system (CNS) malignancy (with the exception of medulloblastoma) or metastasis (screening not required).
  • Have known acute or chronic leukemia or current hematologic malignancies (except iNHL for patients in Part B5) that, in the judgment of the investigator and sponsor, may affect the interpretation of results
  • Have an active fungal, bacterial, and/or known viral infection
  • Have a second primary malignancy that in the judgment of the investigator and sponsor may affect the interpretation of results (Part B only)
  • Part B1 only: No concomitant medications that are strong inhibitors or inducers of cytochrome P450 3A4 (CYP3A4) or midazolam
  • Intolerance to any previous treatment with any phosphatidylinositol-3-kinase (PI3K) and/or mammalian target of rapamycin (mTOR) inhibitor.
  • Participants with active alcohol abuse, as determined by the investigator
  • Have a history of New York Heart Association (NYHA) Class ≥3, unstable angina, or myocardial infarction (MI) in 6 months prior to study drug administration
  • Have QT corrected interval of >450 milliseconds (msec) on screening electrocardiogram (ECG)
  • Have insulin-dependent diabetes mellitus or a history of gestational diabetes mellitus.
  • Part B only: Hypersensitivity to study drugs given in combination with LY3023414

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: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Part A: LY3023414 Once Daily
LY3023414 administered orally once daily (QD) at escalating doses for two 21 day cycles to participants with advanced/metastatic cancer (including lymphoma); participants receiving benefit may continue until disease progression or discontinuation.
Drug: LY3023414
Administered orally. Dose of 20 to 600 mg, as determined in Part A.
Experimental: Part A2: LY3023414 Twice Daily
LY3023414 administered orally twice daily (BID) at escalating doses for two 21 day cycles to participants with advanced/metastatic cancer (including lymphoma); participants receiving benefit may continue until disease progression or discontinuation.
Drug: LY3023414
Administered orally. Dose of 20 to 600 mg, as determined in Part A.
Experimental: Part B1 : LY3023414 + Midazolam
LY3023414 administered orally BID for two 21 day cycles to participants with advanced/metastatic cancer; participants receiving benefit may continue until disease progression or discontinuation. Dose based on Part A. 0.2 milligrams (mg) midazolam administered orally once before LY3023414 on Day 1 and once after LY3023414 on Day 15.
Drug: LY3023414
Administered orally. Dose of 20 to 600 mg, as determined in Part A.
Drug: Midazolam
0.2 mg administered orally once before LY3023414 on Day 1 and once after LY3023414 on Day 15.
Experimental: Part B2: LY3023414 + Fulvestrant
LY3023414 administered orally BID for two 28 day cycles to participants with advanced/metastatic breast cancer; participants receiving benefit may continue until disease progression or discontinuation. 500 mg fulvestrant administered IM once every 28 days.
Drug: LY3023414
Administered orally. Dose of 20 to 600 mg, as determined in Part A.
Drug: Fulvestrant
500 mg administered IM on Day 1 and Day 15 in cycle 1 and Day 1 every 28 days for additional cycles.
Experimental: Part B3: LY3023414
LY3023414 administered orally BID for two 21 day cycles to participants with malignant mesothelioma; participants receiving benefit may continue until disease progression or discontinuation.
Drug: LY3023414
Administered orally. Dose of 20 to 600 mg, as determined in Part A.
Experimental: Part B4: LY3023414 + pemetrexed/cisplatin
LY3023414 administered orally BID for two 21 day cycles to participants with malignant mesothelioma; participants receiving benefit may continue until disease progression or discontinuation. 500 mg/m2 pemetrexed and 75 mg/m2 administered IV once every 21 days.
Drug: LY3023414
Administered orally. Dose of 20 to 600 mg, as determined in Part A.
Drug: Pemetrexed
500 mg/m2 administered IV once on Day 1 every 21 days
Other Names:
  • Alimta
Drug: Cisplatin
75 mg/m2 administered IV once on Day 1 every 21 days
Experimental: Part B5: LY3023414
LY3023414 administered orally BID for two 21 day cycles to participants with indolent non-Hodgkin's lymphoma; participants receiving benefit may continue until disease progression or discontinuation.
Drug: LY3023414
Administered orally. Dose of 20 to 600 mg, as determined in Part A.
Experimental: Part B6: LY3023414
LY3023414 administered orally BID for two 21 day cycles to participants with squamous NSCLC; participants receiving benefit may continue until disease progression or discontinuation.
Drug: LY3023414
Administered orally. Dose of 20 to 600 mg, as determined in Part A.
Experimental: Part B7: LY3023414 + Abemaciclib + Letrozole
LY3023414 administered orally BID with abemaciclib administered orally BID and letrozole administered orally once a day for two 28 day cycles to participants with breast cancer; participants receiving benefit may continue until disease progression or discontinuation.
Drug: Abemaciclib
Administered orally
Other Names:
  • LY2835219
Drug: Letrozole
Administered orally
Drug: LY3023414
Administered orally. Dose of 20 to 600 mg, as determined in Part A.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Recommended Phase 2 dose
Time Frame: Baseline to disease progression or participant discontinuation (estimated 9 weeks)
Baseline to disease progression or participant discontinuation (estimated 9 weeks)

Secondary Outcome Measures

Outcome Measure
Time Frame
Pharmacokinetics: Maximum concentration (Cmax)
Time Frame: Predose up to 12 hours postdose
Predose up to 12 hours postdose
Pharmacokinetics: Time of maximal concentration
Time Frame: Predose up to 12 hours postdose
Predose up to 12 hours postdose
Number of participants with tumor response
Time Frame: Baseline to disease progression or participant discontinuation (estimated 9 weeks)
Baseline to disease progression or participant discontinuation (estimated 9 weeks)
Potential of LY3023414 to inhibit CYP3A4-mediated metabolism
Time Frame: Baseline through Cycle 1
Baseline through Cycle 1

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.

General Publications

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)

July 31, 2012

Primary Completion (Actual)

April 4, 2019

Study Completion (Actual)

February 2, 2022

Study Registration Dates

First Submitted

July 19, 2012

First Submitted That Met QC Criteria

July 30, 2012

First Posted (Estimate)

August 1, 2012

Study Record Updates

Last Update Posted (Actual)

April 8, 2022

Last Update Submitted That Met QC Criteria

April 7, 2022

Last Verified

April 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 13517
  • I6A-MC-CBBA (Other Identifier: Eli Lilly and Company)

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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