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

• ClinicalTrials.gov Identifier: NCT02779751
• Recruitment Status: Active, not recruiting
• First Posted: May 20, 2016
• Last Update Posted: March 25, 2024
• Sponsor: Eli Lilly and Company
• Collaborator: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Eli Lilly and Company

Tracking Information

• First Submitted Date: May 19, 2016
• First Posted Date: May 20, 2016
• Last Update Posted Date: March 25, 2024
• Actual Study Start Date: November 14, 2016
• Actual Primary Completion Date: February 3, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 19, 2016)

• 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) ]

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 15, 2019)

• 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) ]
• 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) ]
• 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) ]
• Progression Free Survival (PFS) per RECIST v1.1 [ Time Frame: Baseline to Measured Progressive Disease or Death (Approximately 10 Months) ]
• Overall Survival (OS) [ Time Frame: 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 [ Time Frame: Predose Cycle One Day One through Predose Cycle Eight Day One (21 Day Cycles) ]

Original Secondary Outcome Measures (submitted: May 19, 2016)

• Objective Response Rate (ORR): 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) ]
• Disease Control Rate (DCR): 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) ]
• Duration of Response (DoR) [ Time Frame: 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) [ Time Frame: Baseline to Measured Progressive Disease or Death (Approximately 10 Months) ]
• Overall Survival (OS) [ Time Frame: Baseline to Date of Death Due to Any Cause (Approximately 18 Months) ]
• Pharmacokinetics (PK): Mean Steady State Exposure of Abemaciclib [ Time Frame: Predose Cycle One Day One through Predose Cycle Eight Day One (21 Day Cycles) ]
• PK: Mean Steady State Exposure of Pembrolizumab [ Time Frame: Predose Cycle One Day One through Predose Cycle Eight Day One (21 Day Cycles) ]
• Change from Baseline on the MD Anderson Symptom Inventory (MDASI) [ Time Frame: Baseline, End of Study (Approximately 6 Months) ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Non Small Cell Lung Cancer
• Breast Cancer

Intervention

• Drug: Abemaciclib
  Administered orally
  Other Name: LY2835219
• Drug: Pembrolizumab
  Administered IV
• Drug: Anastrozole
  Administered orally

Study Arms

• Experimental: 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.
  Interventions:

  • Drug: Abemaciclib
  • Drug: Pembrolizumab
• Experimental: 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.
  Interventions:

  • Drug: Abemaciclib
  • Drug: Pembrolizumab
• Experimental: 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.
  Interventions:

  • Drug: Abemaciclib
  • Drug: Pembrolizumab
• Experimental: 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.
  Interventions:

  • Drug: Abemaciclib
  • Drug: Pembrolizumab
  • Drug: Anastrozole

• Publications *: Pujol JL, Vansteenkiste J, Paz-Ares Rodriguez L, Gregorc V, Mazieres J, Awad M, Janne PA, Chisamore M, Hossain AM, Chen Y, Beck JT. Abemaciclib in Combination With Pembrolizumab for Stage IV KRAS-Mutant or Squamous NSCLC: A Phase 1b Study. JTO Clin Res Rep. 2021 Sep 25;2(11):100234. doi: 10.1016/j.jtocrr.2021.100234. eCollection 2021 Nov.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: October 26, 2018): 100
• Original Estimated Enrollment (submitted: May 19, 2016): 75
• Estimated Study Completion Date: December 31, 2024
• Actual Primary Completion Date: February 3, 2020 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, France, Italy, Spain, Taiwan, Turkey, United States

Administrative Information

• NCT Number: NCT02779751
• Other Study ID Numbers: 16177; I3Y-MC-JPCE ( Other Identifier: Eli Lilly and Company ); 2015-005156-94 ( EudraCT Number ); KEYNOTE 287 ( Other Identifier: Merck )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Eli Lilly and Company
• Original Responsible Party: Same as current
• Current Study Sponsor: Eli Lilly and Company
• Original Study Sponsor: Same as current
• Collaborators: Merck Sharp & Dohme LLC

Investigators

• Study Director: Call 1-877-CTILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST); Eli Lilly and Company

• PRS Account: Eli Lilly and Company
• Verification Date: March 15, 2024