The primary objective of this study is to describe the antitumor activity of tarlatamab in participants with small cell lung cancer (SCLC).

Inclusion Criteria:

• Participant has provided informed consent prior to initiation of any study specific activities/procedures.
• Age ≥ 18 years (or legal adult age within country, whichever is older) at the time of signing the informed consent.
• Histologically or cytologically confirmed SCLC with demonstrated progression or relapse.
• 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) including epidermal growth factor receptor activating mutation positive NSCLC that has transformed to SCLC.
  • Symptomatic central nervous system (CNS) metastases with exceptions defined in the protocol.

• Other Medical Conditions

  • History of other malignancy within the past 2 years, with exceptions defined in the 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 (except replacement therapy) within the past 2 years or any other diseases requiring immunosuppressive therapy while on study.
  • History of solid organ transplantation.
  • 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 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 uncontrolled active systemic infection requiring antibiotics within 7 days prior to the first 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 study treatment.

• Prior/Concomitant Therapy

  • Prior anticancer therapy within 30 days of enrollment (14 days for conventional chemotherapy).
  • Prior enrollment on a tarlatamab clinical trial OR prior therapy with any selective inhibitor of the DLL3 pathway.
  • Current anti-cancer therapy such as chemotherapy, immunotherapy, or targeted therapy with exceptions.
  • Receiving systemic corticosteroid therapy or any other immunosuppressive therapy within 7 days prior to first dose as described per protocol.
  • Live and live-attenuated vaccines within 14 days prior to the start of study treatment. Inactive vaccines and live viral non-replicating vaccines within 3 days 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 another investigational device or drug study(ies). Other investigational procedures while participating in this study are excluded.

• Other Exclusions

  • Female participants of childbearing potential unwilling to use protocol specified method of contraception during treatment and for an additional 60 days after the last dose of tarlatamab.
  • Female participants who are breastfeeding or who plan to breastfeed while on study through 60 days after the last dose of tarlatamab.
  • Female participants planning to become pregnant or donate eggs while on study through 60 days after the last dose of tarlatamab.
  • Female participants of childbearing potential with a positive pregnancy test assessed at screening and/or day 1 by a highly sensitive urine or serum pregnancy test.
  • Male participants with a female partner of childbearing potential who are unwilling to practice sexual abstinence (refrain from heterosexual intercourse) or use contraception during treatment and for an additional 60 days after the last dose of tarlatamab.
  • Male participants with a pregnant partner who are unwilling to practice abstinence or use a condom during treatment and for an additional 60 days after the last dose of tarlatamab.
  • Male participants unwilling to abstain from donating sperm during treatment and for an additional 60 days after the last dose of tarlatamab.
  • Participant has known sensitivity or is contraindicated to any of the products or components to be administered during dosing.
  • Participant likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures.
  • History or evidence of any other clinically significant disorder, condition or disease determined by the investigator or Amgen physician, if consulted, would pose a risk to the subject safety or interfere with the study evaluation procedure or completion.