A Phase 2, Open-label, Randomized, Multicenter Study of Tarlatamab Dosing Regimens in Subjects With SCLC

Inclusion Criteria:

• Participant has provided informed consent prior to initiation of any study specificactivities/procedures.

• Age ≥ 18 years (or legal adult age within country, whichever is older) at the timeof signing the informed consent.

• Histologically or cytologically confirmed SCLC with demonstrated progression orrelapse.

• Participants who progressed or recurred following 1 platinum-based regimen.

• Measurable disease as defined per RECIST 1.1 within the 21-day screening period.

• Eastern Cooperative Oncology Group (ECOG) PS of 0 or 1.

• Minimum life expectancy of 12 weeks.

• Adequate organ function as described per protocol.

Exclusion Criteria:

• Disease Related

• Previous diagnosis of transformed non-small cell lung cancer (NSCLC) includingepidermal growth factor receptor activating mutation positive NSCLC that hastransformed to SCLC.

• Symptomatic central nervous system (CNS) metastases with exceptions defined inthe protocol.

• Other Medical Conditions

• History of other malignancy within the past 2 years, with exceptions defined inthe protocol.

• Evidence of interstitial lung disease or active, non-infectious pneumonitis

• Diagnosis or evidence of leptomeningeal disease.

• Active autoimmune disease that has required systemic treatment (exceptreplacement therapy) within the past 2 years or any other diseases requiringimmunosuppressive therapy while on study.

• History of solid organ transplantation.

• Myocardial infarction and/or symptomatic congestive heart failure (New YorkHeart Association > class II) within 6 months prior to first dose of studytreatment.

• History of arterial thrombosis (eg, stroke or transient ischemic attack) within 6 months prior to first dose of study treatment

• Presence or history of viral infection based on criteria per protocol.

• Symptoms and/or radiographic signs that indicate an acute and/or uncontrolledactive systemic infection requiring antibiotics within 7 days prior to thefirst dose study treatment.

• Known or active infection requiring parenteral antibiotic treatment.

• History of severe or life-threatening events from any immune-mediated therapy.

• Major surgical procedures within 21 days of prior to first dose of studytreatment.

• Prior/Concomitant Therapy

• Prior anticancer therapy within 30 days of enrollment (14 days for conventionalchemotherapy).

• Prior enrollment on a tarlatamab clinical trial OR prior therapy with anyselective inhibitor of the DLL3 pathway.

• Current anti-cancer therapy such as chemotherapy, immunotherapy, or targetedtherapy with exceptions.

• Receiving systemic corticosteroid therapy or any other immunosuppressivetherapy within 7 days prior to first dose as described per protocol.

• Live and live-attenuated vaccines within 14 days prior to the start of studytreatment. Inactive vaccines and live viral non-replicating vaccines within 3days prior to the first dose of study treatment.

• Prior/Concurrent Clinical Study Experience

• Currently receiving treatment in another investigational device or drug study,or less than 30 days or 5 half-lives since ending treatment on anotherinvestigational device or drug study(ies). Other investigational procedureswhile participating in this study are excluded.

• Other Exclusions

• Female participants of childbearing potential unwilling to use protocolspecified method of contraception during treatment and for an additional 60days after the last dose of tarlatamab.

• Female participants who are breastfeeding or who plan to breastfeed while onstudy through 60 days after the last dose of tarlatamab.

• Female participants planning to become pregnant or donate eggs while on studythrough 60 days after the last dose of tarlatamab.

• Female participants of childbearing potential with a positive pregnancy testassessed at screening and/or day 1 by a highly sensitive urine or serumpregnancy test.

• Male participants with a female partner of childbearing potential who areunwilling to practice sexual abstinence (refrain from heterosexual intercourse)or use contraception during treatment and for an additional 60 days after thelast dose of tarlatamab.

• Male participants with a pregnant partner who are unwilling to practiceabstinence or use a condom during treatment and for an additional 60 days afterthe last dose of tarlatamab.

• Male participants unwilling to abstain from donating sperm during treatment andfor an additional 60 days after the last dose of tarlatamab.

• Participant has known sensitivity or is contraindicated to any of the productsor components to be administered during dosing.

• Participant likely to not be available to complete all protocol-required studyvisits or procedures, and/or to comply with all required study procedures.

• History or evidence of any other clinically significant disorder, condition ordisease determined by the investigator or Amgen physician, if consulted, wouldpose a risk to the subject safety or interfere with the study evaluationprocedure or completion.