A Study of Abemaciclib (LY2835219) in Participants With Breast Cancer, Non-small Cell Lung Cancer, or Melanoma That Has Spread to the Brain

NCT02308020 | Completed Phase 2 Results

• 3 other identifiers: 15450I3Y-MC-JPBO2014-004010-28
• Study Type: interventional
• Target: 162
• Locations: 8 countries
• Sites: 40

Brief Summary

The main purpose of this study is to evaluate the safety and effectiveness of the study drug known as abemaciclib in participants with hormone receptor positive breast cancer, non-small cell lung cancer (NSCLC), or melanoma that has spread to the brain.

Conditions

Breast Cancer; Non-small Cell Lung Cancer; Melanoma; Brain Metastases

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR): Objective Intracranial Response Rate (OIRR)

  OIRR is the percentage of participants with a (CR) or (PR) based on the Response Assessment in Neuro-Oncology Brain Metastasis (RANO-BM) response criteria. CR is measurable target lesions, the disappearance of all central nervous system (CNS) target lesions for at least 4 weeks; no new lesions; no corticosteroids; stable or improved clinically. PR is at least a 30% decrease in the sum longest duration (LD) of CNS target lesions, taking as reference the baseline sum LD for at least 4 weeks; no new lesions; stable to decreased corticosteroid dose; stable or improved clinically. Nontarget lesions requires disappearance CNS non-target lesions and no new CNS lesions. Stable disease (SD) is less than (\<)30% decrease relative to baseline but \<20% increase in sum LD relative to nadir. Progressive disease (PD) is greater than or equal to (≥) 20% increase in sum LD relative to nadir and a relative increase of 20%, ≥1 lesion must increase by absolute value of ≥5 millimeter (mm).

  Baseline to Objective Disease Progression (Up to 36 Months)

Secondary Outcomes (10)

• Percentage of Participants With CR, PR, Stable Disease (SD), Progressive Disease (PD), or Not Evaluable (NE): Best Overall Intracranial Response (BOIR)

  Baseline to Earliest Objective Progression or Start of New Anticancer Therapy (Up to 36 Months)

• Duration of CR or PR: Duration of Intracranial Response (DOIR)

  Date of CR or PR to Date of Objective Disease Progression or Death from Any Cause (Up to 36 Months)

• Percentage of Participants With Best Overall Intracranial Response (BOIR) of CR, PR, or SD: Intracranial Disease Control Rate (IDCR)

  Baseline to Disease Progression or Start of New Anticancer Therapy (Up to 36 Months)

• Percentage of Participants With BOIR of CR, PR, or SD With Duration of SD for at Least 6 Months: Intracranial Clinical Benefit Rate (ICBR)

  Baseline to Disease Progression or Start of New Anticancer Therapy (Up to 36 Months)

• Overall Survival (OS)

  Baseline to the Date of Death from Any Cause (Up to 5 Years)

Study Arms (6)

Part A Abemaciclib: HR+, HER2+ Breast Cancer

EXPERIMENTAL

Abemaciclib 200 milligram (mg) was administered orally once every 12 hours on days 1-21 of a 21-day cycle when administered as a single agent or in combination with endocrine therapy (ET). Participants with hormone receptor positive (HR+), HER2+ breast cancer receiving concurrent trastuzumab, 150 mg abemaciclib was given orally once every 12 hours on days 1-21 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.

Drug: Abemaciclib

Part B Abemaciclib: HR+, HER2- Breast Cancer

EXPERIMENTAL

Abemaciclib 200 mg was administered orally once every 12 hours on days 1-21 of a 21-day cycle when administered as a single agent or for participants in combination with endocrine therapy (ET). Participants may continue to receive treatment until discontinuation criteria are met.

Drug: Abemaciclib

Part C Abemaciclib: Surgical Resection

EXPERIMENTAL

Abemaciclib 200 mg was administered orally once every 12 hours on days 1-21 of a 21-day cycle when administered as a single agent or for participants with breast cancer in combination with endocrine therapy (ET). Participants with HR+, HER2+ breast cancer, NSCLC, or melanoma with intracranial lesions for which surgical resection is clinically indicated receiving concurrent trastuzumab, gemcitabine, or pemetrexed, 150 mg abemaciclib was given orally once every 12 hours for 5-14 days prior to surgical resection. Dosing may resume following wound healing on a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.

Drug: Abemaciclib

Part D Abemaciclib: Non-Small Cell Lung Cancer (NSCLC)

EXPERIMENTAL

Abemaciclib 200 mg was administered orally once every 12 hours on days 1-21 of a 21-day cycle. Participants with NSCLC receiving concurrent gemcitabine or pemetrexed, 150 mg abemaciclib was given orally once every 12 hours on days 1-21 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.

Drug: Abemaciclib

Part E Abemaciclib: Melanoma

EXPERIMENTAL

Abemaciclib 200 mg was administered orally once every 12 hours on days 1-21 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.

Drug: Abemaciclib

Part F Abemaciclib: HR+ Breast Cancer, NSCLC, or Melanoma

EXPERIMENTAL

Abemaciclib 200 mg was administered orally once every 12 hours on days 1-21 of a 21-day cycle when administered as a single agent or for participants with breast cancer in combination with endocrine therapy (ET). Participants with HR+ (either HER2+ or HER2-) breast cancer, NSCLC, or melanoma and leptomeningeal metastases received concurrent trastuzumab, gemcitabine, or pemetrexed, 150 mg abemaciclib was given orally once every 12 hours on days 1-21 of a 21-day cycle. Participants may continue to receive treatment until discontinuation criteria are met.

Drug: Abemaciclib

Interventions

Abemaciclib DRUG

Administered orally

Also known as: LY2835219

Part A Abemaciclib: HR+, HER2+ Breast Cancer; Part B Abemaciclib: HR+, HER2- Breast Cancer; Part C Abemaciclib: Surgical Resection; Part D Abemaciclib: Non-Small Cell Lung Cancer (NSCLC); Part E Abemaciclib: Melanoma; Part F Abemaciclib: HR+ Breast Cancer, NSCLC, or Melanoma

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have brain metastases secondary to hormone receptor positive breast cancer, NSCLC, or melanoma.
• Have either human epidermal growth factor receptor 2 positive (HER2+) (Study Part A) or negative HER2- (Study Part B) breast cancer.
• Participants in Study Part C must have HR+ breast cancer, NSCLC, or melanoma with brain lesions clinically indicated for surgical resection as well as consent to provide tissue for drug concentration determination after 5 to 14 days of study drug dosing.
• Participants in Part D must have NSCLC of any subtype.
• Participants in Part E must have melanoma of any subtype.
• Participants in Part F must have HR+ breast cancer, NSCLC, or melanoma with leptomeningeal metastases.
• For Parts A, B, D, and E: Must have at least 1 measurable brain lesion ≥10 millimeters (mm) in the longest diameter (LD).
• For Part C (surgical): Have metastatic brain lesion(s) for which surgical resection is clinically indicated.
• Have completed local therapy (surgical resection, whole-breast radiotherapy (WBRT), or SRS) ≥14 days prior to initiating abemaciclib and recovered from all acute effects.
• If receiving concomitant corticosteroids, must be on a stable or decreasing dose for at least 7 days prior to the baseline Gd-MRI.
• Have a Karnofsky performance status of ≥70.
• Have a life expectancy ≥12 weeks.
• For HR+ breast cancer participants in part A, B, C, and F: If currently receiving endocrine therapy, a participant may continue to receive the same endocrine therapy provided that extracranial disease is stable for at least 3 months and central nervous system (CNS) disease progression has occurred while on this endocrine therapy. If these conditions are not met, participants must discontinue endocrine therapy prior to initiation of abemaciclib.
• For HER2+ breast cancer participants in parts A, C, and F: participants may receive concurrent treatment (ongoing or initiated simultaneously with abemaciclib) with IV trastuzumab.
• For NSCLC participants in parts C, D, and F: if currently receiving gemcitabine or pemetrexed (single-agent or in combination with another therapy), a participant may continue to receive 1 of these 2 therapies provided that extracranial disease is stable for at least 6 weeks and CNS disease progression has occurred while on this therapy.

You may not qualify if:

• Require immediate local therapy, including but not limited to WBRT, SRS, or surgical resection, for treatment of brain metastases.
• Are taking concurrent enzyme-inducing antiepileptic drugs (EIAED).
• Have evidence of significant (ie, symptomatic) intracranial hemorrhage.
• For Parts A, B, C, D, E: Have evidence of leptomeningeal metastases. Note: discrete dural metastases are permitted.
• Have experienced \>2 seizures within 4 weeks prior to study entry.
• For Parts A, B, D, E, and F: Have previously received treatment with any cyclin dependent kinase 6 (CDK6) inhibitor. For Part C participants may have received prior palbociclib or ribociclib, but not abemaciclib treatment.
• Have known contraindication to Gd-MRI.
• Have a preexisting chronic condition resulting in persistent diarrhea.

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (44)

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

University of California - San Diego

La Jolla, California, 92037-0845, United States

Location

Univ of California San Francisco

San Francisco, California, 94115, United States

Location

John Wayne Cancer Institute

Santa Monica, California, 90404, United States

Location

University of Colorado

Aurora, Colorado, 80045, United States

Location

Georgetown University Medical Center

Washington D.C., District of Columbia, 20007, United States

Location

Florida Cancer Specialists

Fort Myers, Florida, 33916-2233, United States

Location

H Lee Moffitt Cancer Center

Tampa, Florida, 33612-9497, United States

Location

Kaiser Permanente Center for Health Research

Honolulu, Hawaii, 96819, United States

Location

James Graham Brown Cancer Center

Louisville, Kentucky, 40202, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Washington University Medical Center

St Louis, Missouri, 63110, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Providence Health and Services

Portland, Oregon, 97213, United States

Location

SMO Sarah Cannon Research Inst.

Nashville, Tennessee, 37203, United States

Location

Tennessee Oncology PLLC

Nashville, Tennessee, 37203, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Nedlands, 6009, Australia

Location

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Newcastle, 2298, Australia

Location

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Southport, 4215, Australia

Location

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Woolloongabba, 4102, Australia

Location

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Vienna, 1090, Austria

Location

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Brussels, 1000, Belgium

Location

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Charleroi, 6000, Belgium

Location

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Leuven, 3000, Belgium

Location

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Liège, 4000, Belgium

Location

For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician.

Ottawa, K1H 8L6, Canada

Location

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Lille, 59020, France

Location

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Lille, 59037, France

Location

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Lyon, 69373, France

Location

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Paris, 75248, France

Location

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Saint-Brieuc, 22027, France

Location

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Toulouse, 31059, France

Location

Hadassah Medical Center - Ein Karem

Jerusalem, 9112001, Israel

Location

Sheba Medical Center

Tel Litwinsky, 5265601, Israel

Location

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Cona, 44124, Italy

Location

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Genova, 16132, Italy

Location

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Padua, 35128, Italy

Location

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Roma, 00128, Italy

Location

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Barcelona, 08035, Spain

Location

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Madrid, 28034, Spain

Location

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Seville, 41013, Spain

Location

Related Publications (1)

• Tolaney SM, Sahebjam S, Le Rhun E, Bachelot T, Kabos P, Awada A, Yardley D, Chan A, Conte P, Dieras V, Lin NU, Bear M, Chapman SC, Yang Z, Chen Y, Anders CK. A Phase II Study of Abemaciclib in Patients with Brain Metastases Secondary to Hormone Receptor-Positive Breast Cancer. Clin Cancer Res. 2020 Oct 15;26(20):5310-5319. doi: 10.1158/1078-0432.CCR-20-1764. Epub 2020 Jul 21.

  PMID: 32694159 DERIVED

Related Links

• Click here for more information about this study: A Study of Abemaciclib (LY2835219) in Participants With Breast Cancer, Non-small Cell Lung Cancer, or Melanoma that has Spread to the Brain

MeSH Terms

Conditions

Breast Neoplasms; Carcinoma, Non-Small-Cell Lung; Melanoma; Brain Neoplasms

Interventions

abemaciclib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

ClinicalTrials.gov@lilly.com

(800) 545-5979

Study Officials

• Call 1-877-CTLILLY (1-877-285-459) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

  Eli Lilly and Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: December 2, 2014
• First Posted: December 4, 2014
• Study Start: April 20, 2015
• Primary Completion: November 8, 2018
• Study Completion: November 8, 2019
• Last Updated: December 19, 2020
• Results First Posted: December 19, 2019

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and European Union (EU), whichever is later. Data will be indefinitely available for requesting.
• Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.

Locations

AU (1); FR (6); IT (4); CA (1); BE (4); ES (3); US (19); IL (2)