A Study of LY2835219 (Abemaciclib) in Combination With Therapies for Breast Cancer That Has Spread

• ClinicalTrials.gov Identifier: NCT02057133
• Recruitment Status: Active, not recruiting
• First Posted: February 6, 2014
• Last Update Posted: March 25, 2024
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

Tracking Information

• First Submitted Date: February 4, 2014
• First Posted Date: February 6, 2014
• Last Update Posted Date: March 25, 2024
• Actual Study Start Date: March 10, 2014
• Actual Primary Completion Date: March 15, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 22, 2018)

Number of Participants with One or More Drug-Related Adverse Events [ Time Frame: Baseline through study completion (estimated as 12 months) ]

Number of participants with one or more drug-related adverse events

• Original Primary Outcome Measures (submitted: February 5, 2014): Number of Participants with One or More Drug-Related Adverse Events [ Time Frame: Baseline through study completion (estimated as 12 months) ]

Current Secondary Outcome Measures (submitted: April 9, 2020)

• Pharmacokinetics: Maximum Concentration (Cmax) of LY2835219, Letrozole, Anastrozole, Tamoxifen, Exemestane, Everolimus, Trastuzumab, LY3023414, Fulvestrant, and Pertuzumab [ Time Frame: Cycle 1 up to Cycle 5 (21 or 28 Day Cycle): Predose and at multiple timepoints, depending on study part. ]
  Cmax of LY2835219, letrozole, anastrozole, tamoxifen, exemestane, everolimus, trastuzumab, LY3023414, fulvestrant, and pertuzumab.
• Number of Participants with a Complete or Partial Tumor Response (Overall Response Rate) [ Time Frame: Baseline to study completion (estimated as 12 months) ]
  Number of participants with a complete or partial tumor response (overall response rate).
• Progression Free Survival (PFS) [ Time Frame: First dose to progressive disease or death of any cause (estimated as 12 months) ]
  Progression free survival
• Change in MD Anderson Symptom Inventory (MDASI) Score from Baseline [ Time Frame: Baseline, through study completion (estimated as 12 months) ]
  Change in MD Anderson (MDASI) score from baseline.
• Pharmacokinetics: Area under the Curve (AUC) of LY2835219, Letrozole, Anastrozole, Tamoxifen, Exemestane, Everolimus, Trastuzumab, LY3023414, Fulvestrant, and Pertuzumab [ Time Frame: Cycle 1 up to Cycle 5 (21 or 28 Day Cycle): Predose and at multiple timepoints, depending on study part. ]
  Pharmacokinetics: AUC of LY2835219, letrozole, anastrozole, tamoxifen, exemestane, everolimus, trastuzumab, LY3023414, fulvestrant, and pertuzumab.

Original Secondary Outcome Measures (submitted: February 5, 2014)

• Pharmacokinetics: Maximum Concentration (Cmax) of LY2835219, Letrozole, Anastrozole, Tamoxifen, Exemestane, and Everolimus [ Time Frame: Cycle 1 - Day 1: Predose through 10 hours post dose and Day 15: Predose. Cycle 2 - Day 1: Predose through 10 hours post dose ]
• Number of Participants with a Complete or Partial Tumor Response (Overall Response Rate) [ Time Frame: Baseline to study completion (estimated as 12 months) ]
• Progression Free Survival (PFS) [ Time Frame: First dose to measured progressive disease or death of any cause (estimated as 12 months) ]
• Change from Baseline to Cycle 3 in MD Anderson Symptom Inventory (MDASI) Score [ Time Frame: Baseline, Cycle 3 ]
• Pharmacokinetics: Area under the Curve (AUC) of LY2835219, Letrozole, Anastrozole, Tamoxifen, Exemestane, and Everolimus [ Time Frame: Cycle 1: Day 1 Predose through 10 hours post dose and Day 15 Predose. Cycle 2: Day 1 Predose through 10 hours post dose. ]

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

Descriptive Information

• Brief Title: A Study of LY2835219 (Abemaciclib) in Combination With Therapies for Breast Cancer That Has Spread
• Official Title: A Phase 1b Study of Abemaciclib in Combination With Therapies for Patients With Metastatic Breast Cancer
• Brief Summary: This study evaluates the safety of abemaciclib in combination therapies (letrozole, anastrozole, tamoxifen, exemestane, exemestane plus everolimus, trastuzumab, LY3023414 plus fulvestrant, pertuzumab plus trastuzumab with loperamide, or ongoing endocrine therapy) for breast cancer that has spread to other parts of the body.
• 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: Breast Neoplasms

Intervention

• Drug: LY2835219
  Administered orally.
  Other Name: Abemaciclib
• Drug: Letrozole
  Administered orally.
• Drug: Anastrozole
  Administered orally.
• Drug: Tamoxifen
  Administered orally.
• Drug: Exemestane
  Administered orally.
• Drug: Everolimus
  Administered orally.
• Drug: Trastuzumab
  Administered IV infusion.
• Drug: LY3023414
  Administered orally.
• Drug: Fulvestrant
  Administered IM.
• Drug: Pertuzumab
  Administered IV infusion.
• Drug: Loperamide
  Administered orally.
• Drug: Endocrine therapy
  Endocrine therapy administered orally.

Study Arms

• Experimental: LY2835219 + Letrozole
  LY2835219 administered orally. Letrozole administered orally. This arm is closed to enrollment.
  Interventions:

  • Drug: LY2835219
  • Drug: Letrozole
• Experimental: LY2835219 + Anastrozole
  LY2835219 administered orally. Anastrozole administered orally. This arm is closed to enrollment.
  Interventions:

  • Drug: LY2835219
  • Drug: Anastrozole
• Experimental: LY2835219 + Tamoxifen
  LY2835219 administered orally. Tamoxifen administered orally. This arm is closed to enrollment.
  Interventions:

  • Drug: LY2835219
  • Drug: Tamoxifen
• Experimental: LY2835219 + Exemestane
  LY2835219 administered orally. Exemestane administered orally. This arm is closed to enrollment.
  Interventions:

  • Drug: LY2835219
  • Drug: Exemestane
• Experimental: LY2835219 + Exemestane + Everolimus Dose Escalation
  LY2835219 administered orally. Exemestane administered orally. Everolimus administered orally. This arm is closed to enrollment.
  Interventions:

  • Drug: LY2835219
  • Drug: Exemestane
  • Drug: Everolimus
• Experimental: LY2835219 + Exemestane + Everolimus Dose Expansion
  LY2835219 administered orally. Exemestane administered orally. Everolimus administered orally. This arm is closed to enrollment.
  Interventions:

  • Drug: LY2835219
  • Drug: Exemestane
  • Drug: Everolimus
• Experimental: LY2835219+ Trastuzumab Dose Escalation
  LY2835219 administered orally. Trastuzumab administered intravenously (IV) infusion. This arm is closed to enrollment.
  Interventions:

  • Drug: LY2835219
  • Drug: Trastuzumab
• Experimental: LY2835219+ Trastuzumab Dose Expansion
  LY2835219 administered orally. Trastuzumab administered IV infusion. This arm is closed to enrollment.
  Interventions:

  • Drug: LY2835219
  • Drug: Trastuzumab
• Experimental: LY3023414 + LY2835219 + Fulvestrant Dose Escalation
  LY3023414 administered orally. LY2835219 administered orally. Fulvestrant administered intramuscularly (IM).
  Interventions:

  • Drug: LY2835219
  • Drug: LY3023414
  • Drug: Fulvestrant
• Experimental: LY3023414 + LY2835219 + Fulvestrant Dose Expansion
  LY3023414 administered orally. LY2835219 administered orally. Fulvestrant administered IM.
  Interventions:

  • Drug: LY2835219
  • Drug: LY3023414
  • Drug: Fulvestrant
• Experimental: LY2835219 +Trastuzumab +Pertuzumab +Loperamide Dose Escalation
  LY2835219 administered orally. Loperamide administered orally. Trastuzumab administered IV infusion. Pertuzumab administered IV infusion.
  Interventions:

  • Drug: LY2835219
  • Drug: Trastuzumab
  • Drug: Pertuzumab
  • Drug: Loperamide
• Experimental: LY2835219 +Trastuzumab + Pertuzumab +Loperamide Dose Expansion

  Hormone Receptor Negative (HR-): LY2835219 administered orally. Loperamide administered orally. Trastuzumab administered IV infusion. Pertuzumab administered IV infusion.

  Hormone Receptor Positive (HR+): LY2835219 administered orally. Loperamide administered orally. Trastuzumab administered IV infusion. Pertuzumab administered IV infusion. Endocrine therapy administered orally.

  Interventions:

  • Drug: LY2835219
  • Drug: Trastuzumab
  • Drug: Pertuzumab
  • Drug: Loperamide
  • Drug: Endocrine therapy
• Experimental: LY2835219 + Endocrine Therapy
  LY2835219 administered orally. Ongoing endocrine therapy administered orally.
  Interventions:

  • Drug: LY2835219
  • Drug: Endocrine therapy

Publications *

• Tolaney SM, Beeram M, Beck JT, Conlin A, Dees EC, Puhalla SL, Rexer BN, Burris HA, Jhaveri K, Helsten T, Becerra C, Kalinsky K, Moore KN, Manuel AM, Lithio A, Price GL, Chapman SC, Litchfield LM, Goetz MP. Abemaciclib in Combination With Endocrine Therapy for Patients With Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer: A Phase 1b Study. Front Oncol. 2022 Feb 10;11:810023. doi: 10.3389/fonc.2021.810023. eCollection 2021.
• Gelbert LM, Cai S, Lin X, Sanchez-Martinez C, Del Prado M, Lallena MJ, Torres R, Ajamie RT, Wishart GN, Flack RS, Neubauer BL, Young J, Chan EM, Iversen P, Cronier D, Kreklau E, de Dios A. Preclinical characterization of the CDK4/6 inhibitor LY2835219: in-vivo cell cycle-dependent/independent anti-tumor activities alone/in combination with gemcitabine. Invest New Drugs. 2014 Oct;32(5):825-37. doi: 10.1007/s10637-014-0120-7. Epub 2014 Jun 13.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: May 22, 2018): 198
• Original Estimated Enrollment (submitted: February 5, 2014): 81
• Estimated Study Completion Date: December 31, 2024
• Actual Primary Completion Date: March 15, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Have a diagnosis of hormone receptor positive (HR+), human epidermal growth factor receptor 2 (HER2) negative metastatic breast cancer for Parts A to E, G, and I.
• Have a diagnosis of human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer for Parts F and H.
• For Part A (LY2835219 + letrozole): Except for ongoing therapy with letrozole, the participant must not have received prior systemic endocrine therapy for metastatic disease.
• For Part B (LY2835219 + anastrozole): Except for ongoing therapy with anastrozole, the participant must not have received prior systemic endocrine therapy for metastatic disease.
• For Part C (LY2835219 + tamoxifen): The participant may have received prior systemic endocrine therapy for metastatic disease and may be receiving ongoing therapy with tamoxifen.
• For Part D (LY2835219 + exemestane): The participant must have received prior systemic endocrine therapy with at least one nonsteroidal aromatase inhibitor (anastrozole, letrozole) for metastatic disease and may be receiving ongoing therapy with exemestane.
• For Part E (LY2835219 + exemestane + everolimus): The participant must have received prior systemic endocrine therapy with at least one nonsteroidal aromatase inhibitor (anastrozole, letrozole) for metastatic disease and may be receiving ongoing therapy with either exemestane or exemestane + everolimus.
• For Part F (LY2835219 + trastuzumab):The participant must have received at least 1 chemotherapy regimen for metastatic disease and may be receiving ongoing therapy with trastuzumab. The participant must have an estimated left ventricular ejection fraction within the normal range by either echocardiogram or multigated acquisition (MUGA) scan
• For Part G (abemaciclib + LY3023414 + fulvestrant): The participant may have received prior systemic endocrine therapy with at least one nonsteroidal aromatase inhibitor (anastrozole, letrozole) for metastatic disease.
• For Part H: (abemaciclib + trastuzumab + pertuzumab): The participant must have received at least 1 chemotherapy regimen for metastatic disease. The participant may be receiving ongoing therapy with trastuzumab and/or pertuzumab at the time of study entry. The participant must have an estimated left ventricular ejection fraction (LVEF) within the normal range by either echocardiogram or multigated acquisition (MUGA) scan.
• For Part I (abemaciclib + endocrine therapy): The participant must have demonstrated evidence of disease progression on a Cyclin Dependent Kinase 4 (CDK4) and Cyclin Dependent Kinase 6 (CDK6) inhibitor (either palbociclib or ribociclib) plus endocrine therapy for advanced or metastatic disease as the most recent therapy immediately preceding study entry. The participant should remain on the current endocrine therapy while receiving abemaciclib.
• For Parts A, B, C, D, E, and F: Have either measureable disease or nonmeasureable but evaluable bone disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
• For Part G, H, and I: Have measureable disease as defined by RECIST 1.1.
• For all Parts except Part F and H: Participants must have either post-menopausal status or pre-menopausal status if continuing or beginning ovarian suppression with a luteinizing hormone-releasing hormone (LHRH) agonist such as goserelin.
• Parts H, and I: Must be able and willing to undergo mandatory tumor biopsies prior to study treatment and at the time of discontinuation from study treatment.

• Have adequate organ function, including:

  • Hematologic: Absolute neutrophil count (ANC) ≥1.5 x 10^9/liter (L), platelets ≥ 100 x 10^9/L, and hemoglobin ≥ 8 gram/deciliter (g/dL).
  • Hepatic: Bilirubin ≤1.5 times upper limits of normal (ULN), alanine aminotransferase (ALT) ≤ 3.0 times ULN.
  • Renal: Serum creatinine ≤ 1.5 times ULN.
• Have a performance status of ≤1 on the Eastern Cooperative Oncology Group (ECOG) scale.
• Have discontinued all previous therapies for breast cancer (including chemotherapy, radiotherapy, immunotherapy, and investigational therapy), except for ongoing corresponding combination therapy, for at least 21 days for myelosuppressive agents or 14 days for nonmyelosuppressive agents prior to receiving study drug(s), and recovered from the acute effects of therapy (until the toxicity resolves to either baseline or at least Grade 1) except for residual alopecia or peripheral neuropathy. For Part F and H: concurrent treatment with trastuzumab emtansine (T-DM1) is not allowed.

Exclusion Criteria:

• Have metastatic breast cancer with severe organ dysfunction as assessed by symptoms and signs, laboratory studies, and rapid progression of the disease.
• Have brain metastasis without prior radiotherapy.
• For Parts A, B, C, D, E, G and I: Have received prior systemic chemotherapy for metastatic disease. However, the participant may have received prior systemic chemotherapy in the neoadjuvant or adjuvant setting.
• For Parts A, B, C, D, E, F, H: Have received prior therapy with a CDK4/6 inhibitor, Part G: Have received prior therapy with fulvestrant or any PI3K and/or mTOR inhibitor (including LY3023414); Part I: Have received prior treatment with abemaciclib in any setting.
• Have serious preexisting medical conditions that, in the judgment of the investigator, would preclude participation in this study (including interstitial lung disease (ILD), severe dyspnea at rest or requiring oxygen therapy or, history of major surgical resection involving the stomach or small bowel).
• Have central nervous system (CNS) metastasis with either radiotherapy or development of neurological changes ≤14 days prior to receiving study treatment. Participants may be receiving a stable dose of corticosteroids. Screening of asymptomatic participants without history of CNS metastasis is not required. Untreated CNS metastases are not permitted.
• For Parts F and H: Cardiac disease including myocardial infarction within 6 months, unstable angina, or New York Heart Association (NYHA) Grade II or greater functional impairment.
• For Part G: Have type 1 diabetes mellitus or a history of gestational diabetes mellitus. Participants with a type 2 diabetes mellitus are eligible if adequate control of blood glucose level is obtained with oral therapy as documented by Hemoglobin A1c <7%.
• For Part G: Have a baseline electrocardiogram (obtained from Day -14 to Day -1) with any of the following abnormal findings: ventricular arrhythmia, evidence of acute myocardial ischemia, heart block (of any degree), or QTc prolongation (defined as QTcB ≥450 milliseconds).

Sex/Gender

• Sexes Eligible for Study: Female

• 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: United States

Administrative Information

• NCT Number: NCT02057133
• Other Study ID Numbers: 15252; I3Y-MC-JPBH ( Other Identifier: Eli Lilly and Company )
• 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: Not Provided

Investigators

• Study Director: Call 1-877-CTLILLY (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 2024