A single-arm phase II-study to confirm efficacy and feasibility of tarlatamab treatment in patients with extensive stage small-cell lung cancer with poor performance status (SPACE-T)

Prior treatment

• Prior DLL3-directed treatment
• Prior systemic therapy (chemotherapy, CPI) within 14 days prior to first dose of study treatment
• Previous treatment in the present study (does not include screening failure)
• Concurrent malignancy other than SCLC requiring active treatment
• Clinically significant pleural effusion (Clinically significant pleural effusions must be managed by drainage. Re-check within 3 days prior to initiation of treatment)

Other illness

• Respiratory compromise leading to an unjustifiable risk in case of higher-grade CRS, in the judgment of the investigator (possible criteria leading to such judgment: oxygen support at rest >2l/min, active pneumonia or pneumonitis)
• History of immune-mediated encephalitis
• HIV infection not on stable antiviral treatment

Lab values

• Bone marrow insufficiency: a. neutrophil count < 1.5/nl or b. hemoglobin <8 mg/dl or c. platelets <100/nl
• Advanced liver disease: a. Subjects with pre-existing chronic liver disease: i. Total bilirubin > 1.5xULN or ii. ALT or AST > 3xULN b. Subjects with no relevant prior chronic liver disease and elevated liver parameters due to liver metastases: i. Total bilirubin > 3xULN or ii. ALT or AST > 10xULN c. International normalized ratio (INR) > 2.0 and partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT) ≥ 1.5 x ULN, except for subjects undergoing new class anticoagulant therapy (eg, Apixaban, Rivaroxaban, Edoxaban) with stable dose for 2 weeks prior to enrollment
• Advanced kidney disease: CKD-EPI GFR <20 ml/min/1.73m²
• Heart failure with reduced ejection fraction (EF < 40%)

Other

• ECOG performance status 0, 1, 3 or 4
• Women of childbearing potential or men with partners of childbearing potential who are not adhering to contraceptive measures
• Female subjects of childbearing potential a. unwilling to use appropriate method(s) of contraception. WOCBP should use an adequate method to avoid pregnancy for 60 days after the last dose of tarlatamab b. who are breastfeeding or who plan to breastfeed while on study through 60 days after the last dose of tarlatamab c. planning to become pregnant or donate eggs while on study through 60 days after the last dose of tarlatamab d. with a positive pregnancy test at screening
• Male subjects a. 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 b. 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 c. unwilling to abstain from donating sperm during treatment and for an additional 60 days after the last dose of tarlatamab
• Life expectancy less than one month
• Patient who has been incarcerated or involuntarily institutionalized by court order or by the authorities [§ 40 Abs. 1 S. 3 Nr. 4 AMG]
• Patients who are unable to consent because they do not understand the nature, significance and implications of the clinical trial and therefore cannot form a rational intention in the light of the facts [§ 40 Abs. 1 S. 3 Nr. 3a AMG]
• Active brain metastases with unstable symptoms (new or progressive neurological symptoms within the last 3 weeks)
• Hemodynamically significant pericardial effusion

• Written informed consent obtained from the subject prior to performing any protocol-related procedures.
• Age ≥ 18 years
• ECOG performance status 2
• Histologically confirmed small-cell lung cancer (initial mixed histology / combined SCLC permitted if re-biopsy of current progression shows SCLC)
• Recurrent or metastatic disease. In case of local-only recurrence, availability of local treatment options must have been excluded
• Has received at least one prior line of treatment in the recurrent or metastatic setting
• Has received a prior treatment line with platinum, etoposide, and a PD-L1 antibody. Treatment with chemotherapy only is acceptable if the patient had a contraindication for CPI treatment
• Measurable disease according to RECIST v1.1