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

Lilly

Status and phase: Active, not recruiting; Phase 1

Conditions: Breast Cancer; Non Small Cell Lung Cancer

Treatments: Drug: Abemaciclib; Drug: Pembrolizumab; Drug: Anastrozole

Study type: Interventional

Funder types: Industry

Identifiers

NCT02779751

16177

2015-005156-94 (EudraCT Number)

KEYNOTE 287 (Other Identifier)

I3Y-MC-JPCE (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 100 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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100 participants in 4 patient groups

NSCLC KRAS mt, PD-L1+

Experimental group

Description:

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.

Treatment:

Drug: Pembrolizumab

Drug: Abemaciclib

NSCLC Squamous

Experimental group

Description:

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.

Treatment:

Drug: Pembrolizumab

Drug: Abemaciclib

HR+, HER2- Metastatic Breast Cancer

Experimental group

Description:

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.

Treatment:

Drug: Pembrolizumab

Drug: Abemaciclib

HR+, HER2- Locally Advanced or Metastatic Breast Cancer

Experimental group

Description:

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.

Treatment:

Drug: Anastrozole

Drug: Pembrolizumab

Drug: Abemaciclib