A Study Evaluating the Overall Survival of Patients with Extensive Stage Small Cell Lung Cancer Receiving Trilaciclib or Placebo prior to Topotecan Chemotherapy

Prior treatment

• Concurrent participation in any other interventional clinical trial
• Receipt of a live, attenuated vaccine within 30 days prior to the first dose of study drugs or anticipation that such a live, attenuated vaccine will be required during the study treatment period. Inactive vaccines, including but not limited to influenza vaccine, pneumococcal vaccine, shingles vaccine, and regionally approved Covid-19 vaccines are allowed.
• Prior allogeneic or autologous hematopoietic stem cell or bone marrow transplantation.
• Any chemotherapy, immunotherapy, biologic, investigational, or hormonal therapy for cancer treatment (except for adjuvant hormonal therapy for breast cancer or prostate cancer defined as M0 disease or prostate-specific antigen [PSA] persistence/recurrence without metastatic disease) within 3 weeks prior to the first dose of trilaciclib/placebo.
• Any radiotherapy within 2 weeks prior to the first dose of trilaciclib/placebo.
• Presence of brain metastases/leptomeningeal disease requiring immediate treatment with radiation therapy or steroids. Patient must be off steroids administered for brain metastases for at least 2 weeks prior to the first dose of study drugs.
• Clinically significant (i.e., active) cardiovascular disease at the time of signing the informed consent; for example cerebrovascular accidents (≤ 6 months before the first dose of trilaciclib/placebo), myocardial infarction (≤ 6 months before the first dose of trilaciclib/placebo), unstable angina, serious cardiac arrythmia requiring medication, or uncontrolled symptomatic congestive heart failure [Class II or higher as defined by the New York Heart Association [NYHA] functional classification system])

Other illness

• History of topotecan (or other topoisomerase I inhibitor) or trilaciclib treatment for SCLC.
• Other uncontrolled serious chronic disease or psychiatric condition that in the Investigator’s opinion could affect patient safety, compliance, or follow-up in the protocol
• Known hypersensitivity or allergy to study drugs or any component in their formulations
• History of ILD/pneumonitis.
• Known serious active infection including but not limited to, human immunodeficiency virus (HIV) (e.g., viral load indicative of HIV, HIV 1/2 antibodies), Hepatitis B (e.g., Hepatitis B surface antigen reactive or Hepatitis B DNA detected), Hepatitis C (e.g., Hepatitis C ribonucleic acid [quantitative] is detected) or tuberculosis.

Lab values

• Pregnant or lactating women. Women of childbearing potential must have negative serum pregnancy test result within 7 days prior to initiating study treatment
• QT corrected using Fridericia’s formula (QTcF) interval >480 msec at screening (confirmed on repeat). For patients with ventricular pacemakers, QTcF >500 msec

Age

• History of other malignancies, except for curatively treated solid tumors with no evidence of disease for ≥2 years or other non-clinically significant cancers (e.g., basal or squamous cell carcinoma of the skin, in situ carcinoma of the uterine cervix) which may be considered after discussion with the Medical Monitor.

Other

• Patients who are investigational site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the Investigator, or patients who are employees of G1 Therapeutics, Inc. directly involved in the conduct of the study

• Age ≥18 years
• ECOG performance status of 0-2
• Adequate organ function as demonstrated by the laboratory values listed in the protocol
• Resolution of nonhematologic toxicities from prior systemic therapy, radiation therapy, or surgical procedures to National Cancer Institute Common Terminology Criteria (NCI-CTCAE) version 5.0 ≤ Grade 1. Grade 2 toxicities that would not constitute a safety risk for subsequent treatment and are not expected to resolve in a timely manner (e.g., alopecia, neuropathy, electrolyte abnormalities, immuno-oncology complications) based on the investigator’s judgement are acceptable.
• Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
• Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol
• ES-SCLC with confirmed diagnosis of SCLC by histology or cytology, preferably including the presence of neuroendocrine features by immunohistochemistry
• Progression during or after prior first- or second-line chemotherapy
• Measurable or evaluable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
• Known sensitivity status (sensitive or resistant) to first- line therapy at enrollment
• Considered to be eligible to receive topotecan chemotherapy in the Investigator’s judgment