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

Lilly

Status and phase: Completed; Phase 2

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

Treatments: Drug: Abemaciclib

Study type: Interventional

Funder types: Industry

Identifiers

NCT02308020

15450

I3Y-MC-JPBO (Other Identifier)

2014-004010-28 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 162 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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.
• Have adequate organ function.

Exclusion criteria

• 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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162 participants in 6 patient groups

Part A Abemaciclib: HR+, HER2+ Breast Cancer

Experimental group

Description:

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.

Treatment:

Drug: Abemaciclib

Part B Abemaciclib: HR+, HER2- Breast Cancer

Experimental group

Description:

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.

Treatment:

Drug: Abemaciclib

Part C Abemaciclib: Surgical Resection

Experimental group

Description:

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.

Treatment:

Drug: Abemaciclib

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

Experimental group

Description:

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.

Treatment:

Drug: Abemaciclib

Part E Abemaciclib: Melanoma

Experimental group

Description:

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.

Treatment:

Drug: Abemaciclib

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

Experimental group

Description:

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.

Treatment:

Drug: Abemaciclib