A Study of Abemaciclib (LY2835219) in Participants With Breast Cancer, Non-small Cell Lung Cancer, or Melanoma That Has Spread to the Brain
Condition: Breast Cancer; Non-small Cell Lung Cancer; Melanoma; Brain Metastases
MeSH terms: Breast Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Melanoma; Neoplasm Metastasis; Brain Neoplasms
Intervention: Abemaciclib
Intervention description: Administered orally
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 162.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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.
    

Eligibility criteria:

        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.