Description:
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.
Title
- Brief Title: A Study of Abemaciclib (LY2835219) in Participants With Non-Small Cell Lung Cancer or Breast Cancer
- Official Title: 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
Clinical Trial IDs
- ORG STUDY ID:
16177
- SECONDARY ID:
I3Y-MC-JPCE
- SECONDARY ID:
2015-005156-94
- SECONDARY ID:
KEYNOTE 287
- NCT ID:
NCT02779751
Conditions
- Non Small Cell Lung Cancer
- Breast Cancer
Interventions
Drug | Synonyms | Arms |
---|
Abemaciclib | LY2835219 | HR+, HER2- Locally Advanced or Metastatic Breast Cancer |
Pembrolizumab | | HR+, HER2- Locally Advanced or Metastatic Breast Cancer |
Anastrozole | | HR+, HER2- Locally Advanced or Metastatic Breast Cancer |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
NSCLC KRAS mt, PD-L1+ | Experimental | 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. | |
NSCLC Squamous | Experimental | 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. | |
HR+, HER2- Metastatic Breast Cancer | Experimental | 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. | |
HR+, HER2- Locally Advanced or Metastatic Breast Cancer | Experimental | 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. | - Abemaciclib
- Pembrolizumab
- Anastrozole
|
Eligibility Criteria
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.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Number of Participants with One or More Serious Adverse Event(s) (SAEs) |
Time Frame: | Baseline through Study Treatment Completion (Approximately 6 Months) |
Safety Issue: | |
Description: | |
Secondary Outcome Measures
Measure: | Objective Response Rate (ORR) per RECIST v1.1: Percentage of Participants With a Complete or Partial Response |
Time Frame: | Baseline to Measured Progressive Disease or Start of New Anti-Cancer Therapy (Approximately 6 Months) |
Safety Issue: | |
Description: | |
Measure: | Disease Control Rate (DCR) per RECIST v1.1: Percentage of Participants With a Best Overall Response of Complete Response, Partial Response, and Stable Disease |
Time Frame: | Baseline to Measured Progressive Disease or Start of New Anti-Cancer Therapy (Approximately 6 Months) |
Safety Issue: | |
Description: | |
Measure: | Duration of Response (DoR) per RECIST v1.1 |
Time Frame: | Date of Complete Response or Partial Response to Date of Objective Disease Progression or Death Due to Any Cause (Approximately 12 Months) |
Safety Issue: | |
Description: | |
Measure: | Progression Free Survival (PFS) per RECIST v1.1 |
Time Frame: | Baseline to Measured Progressive Disease or Death (Approximately 10 Months) |
Safety Issue: | |
Description: | |
Measure: | Overall Survival (OS) |
Time Frame: | Baseline to Date of Death Due to Any Cause (Approximately 18 Months) |
Safety Issue: | |
Description: | |
Measure: | Pharmacokinetics (PK): Mean Steady State Exposure of Abemaciclib in Combination with Pembrolizumab with or without Anastrozole |
Time Frame: | Predose Cycle One Day One through Predose Cycle Eight Day One (21 Day Cycles) |
Safety Issue: | |
Description: | |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Active, not recruiting |
Lead Sponsor: | Eli Lilly and Company |
Last Updated
March 4, 2021