A Study of Abemaciclib (LY2835219) in Participants With Non-Small Cell Lung Cancer or Breast Cancer

Study Overview
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Brief Summary
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The main purpose of this study is to evaluate the safety and efficacy of abemaciclib in combination with pembrolizumab in participants with advanced non-small cell lung cancer (NSCLC) or hormone receptor positive (HR+), human epidermal growth factor receptor negative (HER2-) breast cancer.

Official Title
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A Phase 1b Study of Abemaciclib in Combination With Pembrolizumab for Patients With Stage IV Non-Small Cell Lung Cancer or Hormone Receptor Positive, HER2 Negative Breast Cancer

Conditions
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Breast Cancer, Non Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Abemaciclib
* Drug: Pembrolizumab
* Drug: Anastrozole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have a Stage IV diagnosis of 1 of the following: Part A: NSCLC (Kirsten rat sarcoma mutant [KRAS mt], PD-L1+); Part B: NSCLC (squamous histology); Part C: metastatic breast cancer (HR+, HER2-); or Part D: locally advanced or metastatic breast cancer (HR+, HER2-) Part A: must be chemotherapy naïve for metastatic NSCLC Part B: must have received at least 1 prior therapy containing platinum-based chemotherapy for advanced/metastatic NSCLC Part C: must have previously received prior treatment with at least 1 but no more than 2 chemotherapy regimens in the metastatic setting Part D: cannot have received endocrine therapy or chemotherapy as treatment in the locoregionally recurrent or metastatic breast cancer disease setting. Note: Participants may be enrolled if they received prior (neo)adjuvant chemotherapy or endocrine therapy for localized disease. Are amenable to provide tumor tissue prior to treatment and provide tumor tissue after treatment initiation (both mandatory). Have presence of measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Have a performance status (PS) ≤1 on the Eastern Cooperative Oncology Group (ECOG) scale. Have discontinued all previous treatments for cancer and recovered from the acute effects of therapy. Have an estimated life expectancy of ≥12 weeks. For Part D: Have postmenopausal status due to surgical/natural menopause or chemical ovarian suppression (initiated 28 days prior to Day 1 of Cycle 1) with a gonadotropin-releasing hormone (GnRH) agonist such as goserelin or radiation-induced ovarian suppression. Exclusion Criteria: Have a personal history of any of the following conditions: syncope of either unexplained or cardiovascular etiology, ventricular arrhythmia (including but not limited to ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest. Exception: subjects with controlled atrial fibrillation for >30 days prior to study treatment are eligible. Have central nervous system (CNS) metastasis with development of associated neurological changes 14 days prior to receiving study drug. Have corrected QT interval of >470 milliseconds on screening electrocardiogram (ECG). Have history of interstitial lung disease or pneumonitis. Have history of or active autoimmune disease, or other syndrome that requires systemic steroids or autoimmune agents for the past 2 years. Have received a live vaccination within 30 days of study start. Have received prior treatment with an anti PD-1, anti-programmed death ligand 1 (PD-L1), or anti cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) agent. For Part D Only: Have initiated bisphosphonates or approved RANK ligand (RANK-L) targeted agents (for example, denosumab) <7 days prior to Cycle 1 Day 1. Are currently receiving or have previously received endocrine therapy for locoregionally recurrent or metastatic breast cancer. Note: A participant may be enrolled if she received prior (neo)adjuvant endocrine therapy (including, but not limited to anti-estrogens or aromatase inhibitors) for localized disease. Are currently receiving or have previously received chemotherapy for locoregionally recurrent or metastatic breast cancer. Note: Participants may be enrolled if they received prior (neo)adjuvant chemotherapy for localized disease.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NSCLC KRAS mt, PD-L1+<br>Abemaciclib given orally every 12 hours (Q12H) on days 1 to 21 of each 21 day cycle in combination with pembrolizumab given intravenously (IV) on day 1 of each 21 day cycle. Participants may continue to receive treatment until discontinuation criteria are met. | Drug: Abemaciclib<br>* Administered orally<br>* Other names: LY2835219;Drug: Pembrolizumab<br>* Administered IV<br>|
| Experimental: NSCLC Squamous<br>Abemaciclib given orally Q12H on days 1 to 21 of each 21 day cycle in combination with pembrolizumab given IV on day 1 of each 21 day cycle. Participants may continue to receive treatment until discontinuation criteria are met. | Drug: Abemaciclib<br>* Administered orally<br>* Other names: LY2835219;Drug: Pembrolizumab<br>* Administered IV<br>|
| Experimental: HR+, HER2- Metastatic Breast Cancer<br>Abemaciclib given orally Q12H on days 1 to 21 of each 21 day cycle in combination with pembrolizumab given IV on day 1 of each 21 day cycle. Participants may continue to receive treatment until discontinuation criteria are met. | Drug: Abemaciclib<br>* Administered orally<br>* Other names: LY2835219;Drug: Pembrolizumab<br>* Administered IV<br>|
| Experimental: HR+, HER2- Locally Advanced or Metastatic Breast Cancer<br>Abemaciclib given orally Q12H on days 1 to 21 of each 21 day cycle in combination with pembrolizumab given IV on day 1 of each 21 day cycle and anastrozole given orally Q24H on days 1 to 21 of each 21 day cycle. Participants may continue to receive treatment until discontinuation criteria are met. | Drug: Abemaciclib<br>* Administered orally<br>* Other names: LY2835219;Drug: Pembrolizumab<br>* Administered IV<br>Drug: Anastrozole<br>* Administered orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with One or More Serious Adverse Event(s) (SAEs) |  | Baseline through Study Treatment Completion (Approximately 6 Months) | 
| Number of Participants with Non-Serious Adverse Event(s) |  | Baseline through Study Treatment Completion (Approximately 6 Months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) per RECIST v1.1: Percentage of Participants With a Complete or Partial Response |  | Baseline to Measured Progressive Disease or Start of New Anti-Cancer Therapy (Approximately 6 Months) | 
| Disease Control Rate (DCR) per RECIST v1.1: Percentage of Participants With a Best Overall Response of Complete Response, Partial Response, and Stable Disease |  | Baseline to Measured Progressive Disease or Start of New Anti-Cancer Therapy (Approximately 6 Months) | 
| Duration of Response (DoR) per RECIST v1.1 |  | Date of Complete Response or Partial Response to Date of Objective Disease Progression or Death Due to Any Cause (Approximately 12 Months) | 
| Progression Free Survival (PFS) per RECIST v1.1 |  | Baseline to Measured Progressive Disease or Death (Approximately 10 Months) | 
| Overall Survival (OS) |  | Baseline to Date of Death Due to Any Cause (Approximately 18 Months) | 
| Pharmacokinetics (PK): Mean Steady State Exposure of Abemaciclib in Combination with Pembrolizumab with or without Anastrozole |  | Predose Cycle One Day One through Predose Cycle Eight Day One (21 Day Cycles) |