Trilaciclib

Extensive-stage small cell lung cancer, Chemotherapy-Induced Myelosuppression

Intravenous Extensive-stage small cell lung cancer Adult: To decrease the incidence of chemotherapy-induced myelosuppression when administered before a platinum/etoposide-containing regimen or topotecan-containing regimen: 240 mg/m2 via infusion over 30 minutes to be completed within 4 hours before starting chemotherapy on each day chemotherapy is given. The dosing interval on sequential days should not be >28 hours. Hepatic impairment Mild (Child-Pugh class A): No dosage adjustment necessary Moderate or severe (Child-Pugh class B or C): Reduce dose to 170 mg/m2

Renal impairment Mild-to-moderate (eGFR 30-89 mL/min/1.73 m2): No dosage adjustment necessary Severe (eGFR <30 mL/min/1.73 m2), end-stage renal disease, or dialysis: Not studied

IV Preparation Reconstitution Calculate dose, total drug volume, and number of vials needed Reconstitute each 300-mg vial with 19.5 mL of 0.9% NaCl or D5W, obtaining a concentration of 15 mg/mL Gently swirl vial for up to 3 min until sterile lyophilized cake completely dissolves; do not shake Visually inspect for discoloration and particulate matter; reconstituted solution should be a clear, yellow solution; discard if discolored, cloudy, or contains visible particulates Dilution Withdraw required dosage volume from reconstituted vial(s); dilute into 0.9% NaCl or D5W IV infusion bag to obtain final concentration of 0.5-3 mg/mL Gently invert diluted solution to mix; do not shake Visually inspect for particulate matter and discoloration; diluted solution is a clear, yellow solution IV Administration Infuse over 30 min Complete infusion within 4 hr before starting chemotherapy Administer with an infusion set, including an in-line 0.2- or 0.22-micron filter; compatible in-line filters include polyethylene sulfone, polyvinylidene fluoride, and cellulose acetate Flush infusion line/cannula with sterile 0.9% NaCl or D5W once infusion completes

Hypersensitivity. Pregnancy and lactation.

Severe, life-threatening, or fatal interstitial lung disease (ILD) and/or pneumonitis reported with cyclin-dependent kinases (CDK)4/6 inhibitors, including trilaciclib; monitor for symptoms (eg, cough, dyspnea, hypoxia) May cause fetal harm This drug is mainly metabolized in the liver; drug exposure is increased with moderate and severe hepatic impairment (Child-Pugh classes B and C) Injection-site reactions Injection-site reactions (eg, phlebitis, thrombophlebitis) may occur Acute drug hypersensitivity reactions May cause acute drug hypersensitivity reactions, including facial edema and urticaria

Not Classi Pregnancy Based on mechanism of action, fetal harm may occur when administer to pregnant females No human or animal data are available Advise pregnant females of potential risks to fetus Pregnancy test recommended in females of reproductive potential Contraception Females of reproductive potential: Use effective contraception during treatment and for at least 3 weeks after final dose Infertility No studies performed Based on animal studies, fertility may be impaired in females of reproductive potential Lactation No data are available Advise to not breastfeed during treatment and for at least 3 weeks after last dose

May increase the concentration or net accumulation of certain organic cation transporter (OCT) 2, multidrug and toxin extrusion (MATE) transporter 1, and MATE-2K substrates in the kidney (e.g. dofetilide, dalfampridine, cisplatin).

>10% All grades Fatigue (34%) Hypocalcemia (24%) Hypokalemia (22%) Hypophosphatemia (21%) AST increased (17%) Headache (13%) Grade ≥3 Neutropenia (32%); placebo (69%) Thrombocytopenia (18%); placebo (33%) Anemia (16%); placebo (34%) 1-10% All grades Pneumonia (10%) Rash (9%) Infusion-related reaction (8%) Peripheral edema (7%) Upper abdominal pain (7%) Thrombosis (7%) Hyperglycemia (6%) Grade >3 H4 Hypophosphatemia (7%) Pneumonia (7%) Hypokalemia (6%) Leukopenia (4%); placebo (17%) Fatigue (3%) Thrombosis (3%) Febrile neutropenia (3%); placebo (9%) Hemorrhage (>3%) Respiratory failure (≥2%) Hyperglycemia (2%) Asthenia (2%) <1% Grade >3 Cerebrovascular accident Ischemic stroke Hemoptysis Myositis Lymphopenia Acute respiratory failure (fatal)

Trilaciclib is a selective, highly potent, and reversible inhibitor of cyclin-dependent kinase 4 and 6 (CDK4/6). It transiently induces haematopoietic stem and progenitor cell (HSPC) G1 cell cycle arrest, thereby preventing cell proliferation and resulting in myelopreservation.