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* Subjects will receive Abemaciclib (200 mg), orally every 12 hours on days 1 to 28 of a 28-day cycle for a total of 56 doses per cycle.
* Subjects will be evaluated after 4 weeks (1st cycle) and then every 8 weeks (2 cycles) with radiographic imaging to assess response to treatment.

Abemaciclib (CDK4/6 inhibitors) is an investigational drug that works by interrupting the rapid and uncontrolled growth of cancer cells. Some cancer cells develop because their cells overrun the molecular brakes that normally permit cell to divide only when they are needed to replace old ones. These brakes are regulated by a group of enzymes known as cyclin-dependent kinases (CDKs). Alterations causing over-activity of two of these enzymes, CDK4 andCDK6, are found in a variety of cancers, including small cell lung cancer with retinoblastoma (Rb) protein.The drugs work by selectively turning off the overactive CDK4 and CDK6. As a result, the cancer cells' division cycle is halted, preventing them from proliferating.

Abemaciclib,

Afshin Dowlati, MD

The purpose of this study is to:

* Test how well the study medicine Abemaciclib, a CDK4/6 inhibitor, works to shrink lung cancer tumors in the body.
* Test the safety of Abemaciclib when given to participants with small cell lung cancer (SCLC), large cell neuroendocrine lung cancer, extrapulmonary small cell cancers and other high grade neuroendocrine cancers of the lung. Specifically, this study is looking at SCLC, large cell neuroendocrine lung cancer, extrapulmonary small cell cancers and other high grade neuroendocrine cancers of the lung that have not responded to treatment (refractory) or come back after treatment with chemotherapy (relapsed) as the study medication has been shown to be effective any time the disease relapses not just in the first few months.

This is a multicenter, non-randomized, phase 2, single arm study to determine the efficacy and safety of Abemaciclib as a single agent in patients with biopsy-proven wild type Rb extensive stage of SCLC, with platinum refractory disease (defined as no response after 1-2 cycles of chemotherapy or relapse defined as initial response but relapse after completing platinum-based chemotherapy). Subjects with other tumor types with biopsy proven wild type Rb such as large cell neuroendocrine lung cancer, extrapulmonary small cell cancers and other high grade neuroendocrine cancers of the lung may also be enrolled.

Abemaciclib (CDK4/6 inhibitors) is an investigational drug that works by interrupting the rapid and uncontrolled growth of cancer cells. Some cancer cells develop because their cells overrun the molecular brakes that normally permit cell to divide only when they are needed to replace old ones. These brakes are regulated by a group of enzymes known as cyclin-dependent kinases (CDKs). Alterations causing over-activity of two of these enzymes, CDK4 and CDK6, are found in a variety of cancers, including small cell lung cancer with retinoblastoma (Rb) protein. The drugs work by selectively turning off the overactive CDK4 and CDK6. As a result, the cancer cells' division cycle is halted, preventing them from proliferating.

The objectives of this study include determining:

* Overall Response Rate (ORR) after the first cycle (4 weeks) and then every 8 weeks.
* Progression Free Survival (PFS)assessed at 6 months and Overall Survival (OS).
* Safety and adverse events
* Duration of response in all responders

Targeted Therapy With CDK4/6 Inhibitors in Chemo-Refractory, Rb Wild-Type Extensive SCLC

Targeted Therapy With CDK4/6 Inhibitors in Chemo- Refractory/Relapsed, Rb Wild-type Extensive Small Cell Lung Cancer (SCLC), Large Cell Neuroendocrine Lung Cancer, Extrapulmonary Small Cell Cancers and Other High Grade Neuroendocrine Cancers of the Lung, an Open Label Phase 2 Trial.

Individual participant data that underlie or influence the results observed from the study.

Overall Response Rate (ORR) defined as the proportion of subjects in the analysis population who have complete response (CR) or partial response (PR) using RECIST 1.1 criteria at any time during the study. Response for the primary analyses will be determined by independent radiology review.

CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm.

PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.

Defined as the time from allocation to the first documented disease progression according to RECIST 1.1 or death due to any cause, whichever occurs first.

Overall Survival (OS) defined as the time from start of study to death due to any cause.

Safety and adverse events (AE's) (CTCAE grade version 5.0) will be assessed by quantifying the toxicities and grades experienced by subjects who have received Abemaciclib (Verzenio®\[LY2835219\]) including serious adverse events (SAEs). All SE's and grade 3 and 4 AE's will be tabulated.

Duration of response in all responders (DoR using RECIST 1.1) assessed from the time that measurement criteria met until progressive disease is objectively documented.

Progressive disease defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Targeted Therapy With CDK4/6 Inhibitors in Chemo-Refractory, Rb Wild-Type Extensive SCLC	NCT04010357	Small-cell Lung... Large Cell Neur... Extrapulmonary ...	Abemaciclib,	19 Years -	Case Comprehensive Cancer Center
Targeted Therapy With CDK4/6 Inhibitors in Chemo-Refractory, Rb Wild-Type Extensive SCLC	NCT04010357	Small-cell Lung... Large Cell Neur... Extrapulmonary ...	Abemaciclib,	19 Years -	Case Comprehensive Cancer Center

Spots Global Cancer Trial Database for high grade neuroendocrine cancers of the lung