Cosela Drug Information

is indicated to decrease the incidence of chemotherapy-induced myelosuppression in adult patients when administered prior to a platinum/etoposide-containing regimen or topotecan-containing regimen for extensive-stage small cell lung cancer (ES-SCLC). COSELA is a kinase inhibitor indicated to decrease the incidence of chemotherapy-induced myelosuppression in adult patients when administered prior to a platinum/etoposide-containing regimen or topotecan-containing regimen for extensive-stage small cell lung cancer.

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. The safety of COSELA was evaluated in Studies 1, 2, and 3 . Patients received COSELA 240 mg/m 2 by 30-minute intravenous infusion prior to chemotherapy on each chemotherapy day. The data described in this section reflect exposure to COSELA among 240 patients (122 patients in the trilaciclib group and 118 patients in the placebo group) being treated for extensive stage-small cell lung cancer (ES-SCLC) in 3 randomized, double-blind, placebo-controlled trials: 32 patients with treatment naïve ES-SCLC received carboplatin (AUC 5 Day 1) + etoposide (100 mg/m 2 Days 1-3) every 21 days; 58 received carboplatin (AUC 5 Day 1) + etoposide (100 mg/m 2 Days 1-3) every 21 days + atezolizumab (1200 mg on Day 1) every 21 days; 32 patients with previously treated ES-SCLC received topotecan (1.5 mg/m 2 Days 1-5) every 21 days.

Study 1: COSELA Prior to Etoposide, Carboplatin, and Atezolizumab (E/P/A) Patients with newly diagnosed ES-SCLC not previously treated with chemotherapy Study 1 (G1T28-05; NCT03041311) was an international, randomized (1:1), double-blind, placebo-controlled study of COSELA or placebo administered prior to treatment with etoposide, carboplatin, and atezolizumab (E/P/A) for patients with newly diagnosed ES-SCLC not previously treated with chemotherapy. The data presented below are for the 105 patients who received study treatment. Eighty-five percent of patients receiving COSELA and 91% receiving placebo completed 4 cycles of induction therapy.

Study 2: COSELA Prior to Etoposide and Carboplatin (E/P) Patients with newly diagnosed ES-SCLC not previously treated with chemotherapy Study 2 (G1T28-02; NCT02499770) was an international, randomized (1:1), double-blind, placebo-controlled study of COSELA or placebo administered prior to treatment with etoposide and carboplatin (E/P) for patients with newly diagnosed ES-SCLC not previously treated with chemotherapy. The data presented below are for the 75 patients who received study treatment. Seventy-six percent of patients in the COSELA group and 87% of patients in the placebo group completed at least 4 cycles of therapy.

The median duration of treatment was 6 cycles in each treatment group. Study 3: COSELA Prior to Topotecan Patients with ES-SCLC previously treated with chemotherapy Study 3 (G1T28-03; NCT02514447) was an international, randomized (2:1), double-blind, placebo-controlled study of COSELA or placebo administered prior to treatment with topotecan for patients with ES-SCLC previously treated with chemotherapy. The data presented below are for the 60 patients who received study treatment with the 1.5 mg/m 2 dose of topotecan.

Thirty-eight percent of patients receiving COSELA and 29% of patients receiving placebo completed 5 or more cycles of therapy. The median duration of treatment was 3 cycles in each treatment group. Integrated Safety Analysis The adverse reaction summary presented in Table 3 are pooled safety results from Studies 1, 2, and 3. The patients included in the pooling are those randomized patients that received at least 1 dose of COSELA (122 patients) or placebo (118 patients). Seventy-one percent of patients receiving COSELA and 78% of patients receiving placebo completed at least 4 cycles of therapy.

The median duration of treatment was the same (4 cycles) for patients receiving COSELA and placebo. Serious adverse reactions occurred in 30% of patients receiving COSELA. Serious adverse reactions reported in >3% of patients who received COSELA included respiratory failure, hemorrhage, and thrombosis. Permanent discontinuation due to an adverse reaction occurred in 9% of patients who received COSELA. Adverse reactions leading to permanent discontinuation of any study treatment for patients receiving COSELA included pneumonia (2%), asthenia (2%), injection-site reaction, thrombocytopenia, cerebrovascular accident, ischemic stroke, infusion-related reaction, respiratory failure, and myositis (<1% each). Fatal adverse reactions were observed in 5% of patients receiving COSELA. Fatal adverse reactions for patients receiving COSELA included pneumonia (2%), respiratory failure (2%), acute respiratory failure (<1%), hemoptysis (<1%), and cerebrovascular accident (<1%). Infusion interruptions due to an adverse reaction occurred in 4.1% of patients who received COSELA. The most common adverse reactions (≥10%) were fatigue, hypocalcemia, hypokalemia, hypophosphatemia, aspartate aminotransferase increased, headache, and pneumonia.

The most frequently reported Grade ≥3 adverse reaction (≥5%) in patients receiving COSELA occurring at the same or higher incidence than in patients receiving placebo was hypophosphatemia. The most common adverse reactions reported in at least 5% of patients receiving COSELA with a ≥2% higher incidence compared to patients receiving placebo are shown in Table 3. Table 3: Adverse Reactions in ≥5% Patients with SCLC Receiving COSELA (with ≥2% Higher Incidence in COSELA Compared to Placebo) Adverse Reaction COSELA (N=122) Placebo (N=118) All Grades a (%) Grade ≥3 (%) All Grades a (%) Grade ≥3 (%) a Graded per NCI CTCAE v4.03 b Hypocalcemia=calcium decreased (lab) or treatment-emergent adverse event (TEAE) preferred term 'Hypocalcemia' c Hypokalemia=potassium decreased (lab) or TEAE preferred terms 'Hypokalemia,' 'Blood potassium decreased' d Hypophosphatemia=phosphate decreased (lab) or TEAE preferred terms 'Hypophosphatemia,' 'Blood phosphorus decreased' e Aspartate aminotransferase increased=aspartate aminotransferase increased (lab) or TEAE preferred term 'Blood aspartate aminotransferase increased' Fatigue 34 3 27 2 Hypocalcemia b 24 <1 21 <1 Hypokalemia c 22 6 18 3 Hypophosphatemia d 21 7 16 2 Aspartate aminotransferase increased e 17 <1 14 <1 Headache 13 0 9 0 Pneumonia 10 7 8 7 Rash 9 <1 6 0 Infusion-related reaction 8 0 2 0 Edema peripheral 7 0 4 <1 Abdominal pain upper 7 0 3 0 Thrombosis 7 3 2 2 Hyperglycemia 6 2 3 0 Grade 3/4 hematological adverse reactions occurring in patients treated with COSELA and placebo included neutropenia (32% and 69%), febrile neutropenia (3% and 9%), anemia (16% and 34%), thrombocytopenia (18% and 33%), leukopenia (4% and 17%), and lymphopenia (<1% and <1%), respectively.

Effect of

COSELA on Other Drugs, Certain OCT2, MATE1, and MATE-2K Substrates COSELA is an inhibitor of OCT2, MATE1, and MATE-2K. Co-administration of COSELA may increase the concentration or net accumulation of OCT2, MATE1, and MATE-2K substrates in the kidney (e.g., dofetilide, dalfampridine, and cisplatin). Refer to the prescribing information for these concomitant medications for assessing the benefit and risk of concomitant use of COSELA. Table 4: Potentially Significant Drug Interactions with COSELA Drugs Recommendations Comments Dofetilide The potential benefits of taking COSELA concurrently with dofetilide should be considered against the risk of QT interval prolongation. Increased dofetilide blood levels may occur in patients who are also receiving COSELA. Increased plasma concentrations of dofetilide may cause serious ventricular arrhythmias associated with QT interval prolongation, including torsade de pointes. Dalfampridine The potential benefits of taking COSELA concurrently with dalfampridine should be considered against the risk of seizures in these patients.

Increased dalfampridine blood levels may occur in patients who are also receiving COSELA. Elevated levels of dalfampridine increase the risk of seizure. Cisplatin Closely monitor for nephrotoxicity. Concurrent treatment with COSELA may increase the exposure and alter the net accumulation of cisplatin in the kidney, which may associate with dose-related nephrotoxicity.

Pregnancy Risk Summary Based on the mechanism of action, COSELA can cause fetal harm when administered to a pregnant woman . There are no available human or animal data on COSELA use to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Advise pregnant women of the potential risk to a fetus. The background risk of major birth defects and miscarriage for the indicated population is unknown.

All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. However, the background risk of major birth defects is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies in the United States general population.

Pediatric Use Safety and effectiveness in pediatric patients have not been established.

is contraindicated in patients with a history of serious hypersensitivity reactions to trilaciclib. Reactions have included anaphylaxis . Patients with a history of serious hypersensitivity reactions to COSELA.