Study of Trilaciclib and Lurbinectidin

The proportion of subjects that experience grade 4 neutropenia as graded by the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v5.0 will be determined.

CTCAE is descriptive terminology that can be used for Adverse Event (AE) grading and reporting. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local, or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE.

The median duration of subjects that experience grade 4 neutropenia as graded by the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v5.0 will be reported.

The mean duration of grade 4 neutropenia in cycle 1 will be defined as the start of grade 4 neutropenia to the time of decreased grade as measured in days or censored at the time of death if a subject dies with Grade 4 neutropenia in Cycle 1.

Toxicity will be evaluated, as the number of grade 3/4 anemia, grade 3/4 thrombocytopenia, and febrile neutropenia based on the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v5.0 criteria, in any cycle (including cycle 1).

To characterize use of secondary/reactive supportive measures any supportive measures such as Granulocyte colony-stimulating factor ( G-CSF) and erythropoietin stimulating agents (ESA) administration, red blood cell and platelet transfusion will be recorded.

The dose Intensity of Chemotherapy/ Number of chemotherapy dose reductions will be defined as the ratio of the subjects who required chemotherapy dose reductions to all subjects who received study treatment.

The dose Intensity of Chemotherapy/ Number of chemotherapy cycles will be defined as the median number of chemotherapy cycles among the subject who received study treatment.

The dose Intensity of Chemotherapy/ Number of chemotherapy delays will be defined as the median number of chemotherapy cycle delays dates among the subject who received study treatment.

The dose Intensity of Chemotherapy/ the total chemotherapy dose will be defined as the median chemotherapy dose among the subject who received study treatment.

To estimate the ORR, the proportion of subjects that respond (CR + PR) will be measured according to RESIST 1.1 will be calculated.

RECIST: Radiographic response will be measured by RECIST, Response Evaluation Criteria In Solid Tumors Criteria, indicating if the subject experienced a Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), no response or less response than Partial or Progressive; or Progressive Disease (PD), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

PFS will be measured from the initiation of study therapy until progression per RECIST 1.1 or death of any cause or at last date of disease assessment if no progression is observed during the study period.

OS will be measured from the initiation of therapy until death of any cause or censored at the last time known to be alive.

The kinetics of response will be reported as tumor size over time for all patients, including the pace of progression from prior therapy.

Scores from QOL assessments FACT-L version 4, from prior to study therapy through cycle 12 will be obtained, as described in the protocol.

The FACT-L is a lung cancer specific subscale given at baseline, after each cycle and at end of treatment. Items are rated by patients on a Likert scale from 0 to 4. Higher scores represent better QOL.

Scores from QOL assessments FACT-An version 4, from prior to study therapy through cycle 12 will be obtained, as described in the protocol.

The FACT-An is an anemia specific subscale given at baseline, after each cycle and at end of treatment. Items are rated by patients on a Likert scale from 0 to 4. Higher scores represent better QOL.