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

Protocol # :
Non Small Cell Lung Cancer
Breast Cancer
Disease Sites
Principal Investigator
Tolaney, Sara, M
Site Research Nurses
Bowers, Jordan
Campbell, Margaret
Caradonna, Lisa
Carrier, Amy
Dishman, Rachel, C.
Drevers, Dawn
Ficociello, Samantha
Germon, Victoria
Huff, Kimberly
Jeon, Maryangel, H.
Kasparian, Elizabeth
Kelley, Elaine
LaPointe, Janet
Lehnus, Jaclyn
Loeser, Wendy
Lucca, Joan
Marchetti, Kelly
Morse, Linda, K.
Morse, Linda, K.
O'Driscoll, Mary
O'Neil, Kelly
Orechia, Meghan
Roche, Kathleen, A.
Rutter, Morgan
Selland, Britt
Sullivan, Molly, O'Brien
Wong, Christine

Trial Description

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 Requirements

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)

- 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.