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
Overview
- Phase
- Phase 1
- Intervention
- Pembrolizumab
- Conditions
- Non Small Cell Lung Cancer
- Sponsor
- Eli Lilly and Company
- Enrollment
- 100
- Locations
- 24
- Primary Endpoint
- Number of Participants with One or More Serious Adverse Event(s) (SAEs)
- Status
- Active, not recruiting
- Last Updated
- 3 months ago
Overview
Brief Summary
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.
Investigators
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.
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
- •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.
Arms & Interventions
NSCLC Squamous
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.
Intervention: Pembrolizumab
NSCLC KRAS mt, PD-L1+
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.
Intervention: Abemaciclib
NSCLC KRAS mt, PD-L1+
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.
Intervention: Pembrolizumab
NSCLC Squamous
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.
Intervention: Abemaciclib
HR+, HER2- Metastatic Breast Cancer
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.
Intervention: Abemaciclib
HR+, HER2- Metastatic Breast Cancer
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.
Intervention: Pembrolizumab
HR+, HER2- Locally Advanced or Metastatic Breast Cancer
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.
Intervention: Abemaciclib
HR+, HER2- Locally Advanced or Metastatic Breast Cancer
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.
Intervention: Pembrolizumab
HR+, HER2- Locally Advanced or Metastatic Breast Cancer
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.
Intervention: Anastrozole
Outcomes
Primary Outcomes
Number of Participants with One or More Serious Adverse Event(s) (SAEs)
Time Frame: Baseline through Study Treatment Completion (Approximately 6 Months)
Number of Participants with Non-Serious Adverse Event(s)
Time Frame: Baseline through Study Treatment Completion (Approximately 6 Months)
Secondary Outcomes
- 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))