Trilaciclib and Lurbinectedin for the Treatment of Patients with Extensive Stage Small Cell Lung Cancer

Inclusion Criteria

• Written informed consent obtained to participate in the study and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information
• Age >= 18 years at the time of consent
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1
• Histological or cytological evidence/confirmation of ES-CLC
• Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 within 28 days prior to start of treatment
• Previous treatment with a platinum agent, PD1 or PDL1 agent
• Chemotherapy free interval (CTFI) < 90 days
• A subject with prior brain metastasis may be considered eligible if they have completed their treatment for brain metastasis at least 4 weeks prior to start of treatment, have been off of corticosteroids for >= 2 weeks, are asymptomatic and have no imaging demonstrated growth. Note that an MRI is not required, however if standard of care (SOC) requires a magnetic resonance imaging (MRI) and identifies growth, it will be considered an active metastasis and preclude enrollment
• Prior cancer treatment must be completed at least 14 days prior to start of treatment and the subject must have recovered from all reversible acute toxic effects of the regimen (other than alopecia) to =< Grade 1. Toxicities that are not expected to reverse and that are not expected to impact safety and efficacy of the study therapy may be allowed (example: Grade 2 hypothyroidism induce by atezolizumab and effectively treated by levothyroxine)
• Subjects with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
• Hemoglobin (Hgb) >= 9 g/dL (at least two weeks since last transfusion) (obtained within 4 days prior to initiating study treatment) * Note: Hematology and other lab parameters that are =< grade 2 BUT still meet criteria for study entry are allowed. Furthermore, changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy
• White blood cell (WBC) >= 2 x 10^9/L (obtained within 4 days prior to initiating study treatment) * Note: Hematology and other lab parameters that are =< grade 2 BUT still meet criteria for study entry are allowed. Furthermore, changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy
• Absolute neutrophil count (ANC) >= 1.5 x 10^9/L (obtained within 4 days prior to initiating study treatment) * Note: Hematology and other lab parameters that are =< grade 2 BUT still meet criteria for study entry are allowed. Furthermore, changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy
• Platelets >= 75 x 10^9/L (obtained within 4 days prior to initiating study treatment) * Note: Hematology and other lab parameters that are =< grade 2 BUT still meet criteria for study entry are allowed. Furthermore, changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy
• Calculated creatinine clearance >= 40 mL/min using the Cockcroft-Gault formula (obtained within 4 days prior to initiating study treatment) * Note: Hematology and other lab parameters that are =< grade 2 BUT still meet criteria for study entry are allowed. Furthermore, changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy
• Bilirubin =< 1.5 x upper limit of normal (ULN) (obtained within 4 days prior to initiating study treatment). Subjects with Gilbert's syndrome may be enrolled despite a total bilirubin level of < 3 x ULN) * Note: Hematology and other lab parameters that are =< grade 2 BUT still meet criteria for study entry are allowed. Furthermore, changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy
• Aspartate aminotransferase (AST) =< 2.5 x ULN unless liver metastases are present, in which case it must be =< 5 x ULN (obtained within 4 days prior to initiating study treatment) * Note: Hematology and other lab parameters that are =< grade 2 BUT still meet criteria for study entry are allowed. Furthermore, changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy
• Alanine aminotransferase (ALT) =< 2.5 x ULN unless liver metastases are present, in which case it must be =< 5 x ULN (obtained within 4 days prior to initiating study treatment) * Note: Hematology and other lab parameters that are =< grade 2 BUT still meet criteria for study entry are allowed. Furthermore, changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy
• International normalized ratio (INR) or prothrombin time (PT) activated partial thromboplastin time (aPTT) =< 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT and PTT is within therapeutic range of intended use of anticoagulants (obtained within 4 days prior to initiating study treatment) * Note: Hematology and other lab parameters that are =< grade 2 BUT still meet criteria for study entry are allowed. Furthermore, changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy
• Females of childbearing potential must have a negative serum pregnancy test within 72 hours prior to study treatment NOTE: Females are considered of childbearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months. Documentation of postmenopausal status must be provided
• Females of childbearing potential must be willing to abstain from heterosexual activity or to use 2 forms of effective methods of contraception from the time of informed consent until 6 months after the last dose of lurbinectedin. The two contraception methods can be comprised of two barrier methods, or a barrier method plus a hormonal method or an intrauterine device that meets < 1% failure rate for protection from pregnancy in the product label
• Male subjects with female partners must have had a prior vasectomy or agree to use an adequate method of contraception (i.e., double barrier method: condom plus spermicidal agent) starting with the first dose of study therapy through 6 months after the last dose of lurbinectedin
• Subjects is willing and able to comply with study procedures based on the judgement of the investigator or protocol designee

Exclusion Criteria

• Active infection requiring systemic therapy
• Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study)
• Active central nervous system (CNS) metastases . For the purposes of this study, lesions without growth across two subsequent studies are considered not “active.” For the purposes of this study, lesions treated at least four weeks before start of treatment and without known growth, symptoms, or need for corticosteroids within two weeks of registration are considered not “active.” For the purposes of this study, asymptomatic lesions =< 5mm which are not, in the opinion of the treating investigator, a threat to the well-being of the subject in the next 6 months are not exclusionary
• Treatment with any investigational drug within 4 weeks prior to start of treatment
• A known allergy or sensitivity to either study drug or its excipients
• Subject is receiving prohibited medications or treatments that cannot be discontinued/replaced by an alternative therapy within 14 days prior to the start of study treatment