Clinical Trial for Safety and Effectiveness Evaluation of Tarlatamab (AMG757) With Etoposide, Carboplatin and Atezolizumab in Transformed Small Cell Lung Cancer Patients From Adenocarcinoma After EGFR TKI Treatment

Inclusion criteria

• Histologically confirmed SCLC and no prior systemic treatment for SCLC
• Patient initially diagnosed with activating EGFR mutation (L858R, Del 19) and treated with any kind of EGFR TKI.
• Confirmed SCLC transformation right after EGFR TKI treatment failure.
• Age ≥19 years
• ECOG performance status of 0 to 1
• Had at least one measurable lesion.
• Adequate organ function

• Absolute neutrophil count ≥ 1.5 x 109/L
• Platelet count ≥ 100 x 109/L
• Hemoglobin ≥ 9 g/dL
• Estimated glomerular filtration rate based on Modification of Diet in Renal Disease calculation > 30 mL/min/1.73 m2
• Aspartate aminotransferase and alanine aminotransferase ≤ 3 x upper limit of normal (ULN) (or ≤ 5 x ULN for subjects with liver involvement)
• Total bilirubin ≤ 1.5 x ULN (or ≤ 2 x ULN for subjects with liver metastases)
• Prothrombin time (PT)/international normalized ratio and partial thromboplastin time or activated partial thromboplastin time ≤ 1.5 x institutional ULN Note: Subjects on stable anticoagulation therapy are allowed.
• Pulmonary function: No clinically significant pleural effusion at the timepoint of screening. Pleural effusion with no significant symptom is allowed for enrollment.
• Cardiac function: Cardiac ejection fraction ≥ 50%
• Female subjects must either be of non-reproductive potential
• Female subject with reproductive potential can be enrolled with agreement to following guidance.

• subject uses contraception during treatment and through 60 days after receiving last dose of tarlatamab or for 6 months after last dose of carboplatin and/or etoposide and 5 months after last dose of atezolizumab.
• Subject is willing and able to comply with the protocol
• Signed written informed consent

Exclusion criteria

• Treated with additional chemotherapy after confirmed with transformed SCLC.
• Previously exposed to the immune checkpoint inhibitor treatment.
• Untreated symptomatic brain metastases or leptomeningeal disease.

• Asymptomatic brain metastases can be enrolled per investigator decision
• Uncontrolled systemic illness including uncontrolled hypertension, active bleeding, or active infection.
• Past medical history of interstitial lung disease, drug induced interstitial lung disease, radiation pneumonitis which required steroid treatment, active non- infectious pneumonitis
• Active or prior documented autoimmune or inflammatory disorders
• Myocardial infarction and/or symptomatic congestive heart failure (New York Heart Association > class II) within 6 months prior to first dose of study treatment
• History of solid organ transplant.
• Major surgical procedures within 28 days prior to first dose of study treatment.
• History of allergic reactions or acute hypersensitivity reactions to antibody therapies, platinum chemotherapy, or etoposide.
• Disagree to the guidance of contraception during the study.