Clinical trial NCT02779751: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Non Small Cell Lung Cancer
Breast Cancer
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2016-05-20
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Number of Participants with One or More Serious Adverse Event(s) (SAEs)
timeFrame: Baseline through Study Treatment Completion (Approximately 6 Months)
measure: Number of Participants with Non-Serious Adverse Event(s)
timeFrame: Baseline through Study Treatment Completion (Approximately 6 Months)
Secondary outcomes:
measure: Objective Response Rate (ORR) per RECIST v1.1: Percentage of Participants With a Complete or Partial Response
timeFrame: Baseline to Measured Progressive Disease or Start of New Anti-Cancer Therapy (Approximately 6 Months)
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
timeFrame: Baseline to Measured Progressive Disease or Start of New Anti-Cancer Therapy (Approximately 6 Months)
measure: Duration of Response (DoR) per RECIST v1.1
timeFrame: Date of Complete Response or Partial Response to Date of Objective Disease Progression or Death Due to Any Cause (Approximately 12 Months)
measure: Progression Free Survival (PFS) per RECIST v1.1
timeFrame: Baseline to Measured Progressive Disease or Death (Approximately 10 Months)
measure: Overall Survival (OS)
timeFrame: Baseline to Date of Death Due to Any Cause (Approximately 18 Months)
measure: Pharmacokinetics (PK): Mean Steady State Exposure of Abemaciclib in Combination with Pembrolizumab with or without Anastrozole
timeFrame: Predose Cycle One Day One through Predose Cycle Eight Day One (21 Day Cycles)
Other outcomes:
Locations:
city: Springdale
country: United States
facility: Highlands Oncology Group - Duplicate 2
state: Arkansas
city: San Francisco
country: United States
facility: Univ of California San Francisco
state: California
city: Aurora
country: United States
facility: University of Colorado School of Medicine
state: Colorado
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Farmington Hills
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Leuven
country: Belgium
facility: Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg
city: Liege
country: Belgium
facility: Centre Hospitalier Universitaire Sart Tilman
city: Montpellier
country: France
facility: Hôpital Arnaud de Villeneuve - CHU Montpellier
state: Hérault
city: Lille
country: France
facility: Centre Oscar Lambret
state: Nord-Pas-de-Calais
city: Toulouse
country: France
facility: Hopital Larrey
city: Meldola
country: Italy
facility: Istituto Scientifico Romagnolo - Studio e la Cura dei Tumori
state: Forli
city: Milano
country: Italy
facility: IRCCS Ospedale San Raffaele
city: Avila
country: Spain
facility: Hospital Nuestra Senora de Sonsoles
city: Caceres
country: Spain
facility: Hospital San Pedro de Alcantara
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Madrid Norte Sanchinarro
city: Neihu Taipei
country: Taiwan
facility: Tri-Service General Hospital
city: New Taipei City
country: Taiwan
facility: Taipei Medical University- Shuang Ho Hospital
city: Tainan
country: Taiwan
facility: Chi Mei Hospital - Liouying Branch
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Istanbul
country: Turkey
facility: Istanbul Universitesi-Cerrahpasa Cerrahpasa Tip Fakultesi Yerleskesi
city: Izmir
country: Turkey
facility: Ege Universitesi Hastanesi
Study officials:
affiliation: Eli Lilly and Company
name: 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)
role: STUDY_DIRECTOR
References:
citation: 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.