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

Sponsor

Eli Lilly and Company (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT02779751

Collaborator

Merck Sharp & Dohme LLC (Industry)

100

Enrollment

Locations

Arms

82.2

Anticipated Duration (Months)

4.3

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Non Small Cell Lung Cancer Breast Cancer	Drug: Abemaciclib Drug: Pembrolizumab Drug: Anastrozole	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Nov 14, 2016

Actual Primary Completion Date :

Feb 3, 2020

Anticipated Study Completion Date :

Sep 20, 2023

Arms and Interventions

Arm	Intervention/Treatment
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.	Drug: Abemaciclib Administered orally Other Names: LY2835219 Drug: Pembrolizumab Administered IV
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.	Drug: Abemaciclib Administered orally Other Names: LY2835219 Drug: Pembrolizumab Administered IV
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.	Drug: Abemaciclib Administered orally Other Names: LY2835219 Drug: Pembrolizumab Administered IV
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.	Drug: Abemaciclib Administered orally Other Names: LY2835219 Drug: Pembrolizumab Administered IV Drug: Anastrozole Administered orally

Outcome Measures

Primary Outcome Measures

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

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)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Highlands Oncology Group	Fayetteville	Arkansas	United States	72703
2	Univ of California San Francisco	San Francisco	California	United States	94158
3	University of Colorado School of Medicine	Aurora	Colorado	United States	80045
4	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02215
5	Karmanos Cancer Institute	Detroit	Michigan	United States	48201
6	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
7	Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg	Leuven		Belgium	3000
8	Centre Hospitalier Universitaire Sart Tilman	Liege		Belgium	4000
9	Centre Oscar Lambret	Lille Cedex		France	59020
10	CHU de Montpellier-Hopital Arnaud de Villeneuve	Montpellier Cedex 5		France	34295
11	Hopital Larrey	Toulouse		France	31059
12	Istituto Scientifico Romagnolo - Studio e la Cura dei Tumori	Meldola	Forli	Italy	47014
13	IRCCS Ospedale San Raffaele	Milano		Italy	20132
14	Nuestra Senora de Sonsoles	Avila		Spain	05004
15	Hospital San Pedro de Alcantara	Caceres		Spain	10003
16	Hospital Universitario 12 de Octubre	Madrid		Spain	28041
17	Hospital Madrid Norte Sanchinarro	Madrid		Spain	28050
18	Tri-Service General Hospital	Neihu Taipei		Taiwan	11490
19	Taipei Medical University- Shuang Ho Hospital	New Taipei City		Taiwan	235
20	Chi-Mei Meical Center, Liouying	Tainan		Taiwan	73657
21	National Taiwan University Hospital	Taipei		Taiwan	10048
22	Istanbul University Cerrahpasa Medical Faculty	Istanbul		Turkey	34098
23	Ege University Faculty of Medicine	Izmir		Turkey	35100

Sponsors and Collaborators

Eli Lilly and Company
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