AMG 757 and AMG 404 in Subjects With Small Cell Lung Cancer (SCLC)

A DLT was any of the following during the DLT window, assessed by Common Terminology Criteria for Adverse Events v4.0:

• Grade 3 adverse event (AE) except for fatigue lasting < 7 days, Grade 3 nonfebrile neutropenia that improved to ≤ Grade 1 within 3 weeks, endocrinopathies if managed with replacement therapy, Grade 3 nausea/vomiting or diarrhea for < 72 hours, Grade 3 amylase or lipase values not associated with pancreatitis, Grade 3 hematologic laboratory abnormalities not clinically relevant, or Grade 3 electrolyte abnormality up to 72 hours.
• Grade 4 AE except for Grade 4 nonfebrile neutropenia lasting ≤ 7 days, Grade 4 electrolyte abnormality lasting up to 72 hours, Grade 4 amylase or lipase values not associated with pancreatitis, or Grade 4 hematologic laboratory abnormalities no clinically relevant.
• Grade 5 AE
• Recurrent Grade ≥ 2 pneumonitis
• Any other toxicity requiring permanent discontinuation of AMG 404.

An AE was defined as any untoward medical occurrence in a clinical trial participant. A TEAE was an AE that started on or after the first dose of investigational product (IP; tarlatamab) up to 65 days after the last dose of tarlatamab or AMG 404 or the end of study (EOS), whichever was earlier. A TEAE for the EP was an AE that occurred after the 65th day after the last dose of tarlatamab or AMG 404 up to 145 days after the last dose of tarlatamab or AMG 404 or end of study, whichever was later. A treatment-related AE was any TEAE where there was a reasonable possibility that the TEAE could have been caused by tarlatamab or AMG 404. Any clinically significant changes in vital signs, physical examinations, electrocardiograms, and clinical laboratory tests were included as TEAEs.

The objective response rate was defined as the percentage of participants with a confirmed best overall response of complete response (CR) or partial response (PR) based on the modified RECIST v1.1.

CR: complete disappearance of all lesions and pathologic lymph nodes reduced in short axis to < 10 mm. PR: decrease in tumor burden of ≥ 30% relative to baseline, or complete disappearance of all index lesions with the presence of non-index lesions. Confirmation scans were required within 4 weeks of the first documented response of CR or PR. Exact 95% confidence intervals (CIs) were calculated using the Clopper-Pearson method.

The duration of response was defined as the time from first evidence of CR or PR to progressive disease (PD) or death due to any cause, whichever occurred first, estimated via Kaplan-Meier methods.

CR: complete disappearance of all lesions and pathologic lymph nodes reduced in short axis to < 10 mm. PR: decrease in tumor burden of ≥ 30% relative to baseline, or complete disappearance of all index lesions with the presence of non-index lesions. Confirmation scans were required within 4 weeks of the first documented response of CR or PR. PD: radiologic detection of ≥ 20% increase in tumor burden relative to nadir and ≥ 5 mm absolute increase, or unequivocal progression of non-index lesions, or presence of new lesions. 95% CIs were calculated using the Brookmeyer and Crowley method.

The disease control rate was defined as the percentage of participants with a best overall response of a confirmed response (CR/PR) or stable disease (SD) while on the study as defined by modified RECIST v1.1.

CR: complete disappearance of all lesions and pathologic lymph nodes reduced in short axis to < 10 mm. PR: decrease in tumor burden of ≥ 30% relative to baseline, or complete disappearance of all index lesions with the presence of non-index lesions. Confirmation scans were required within 4 weeks of the first documented response of CR or PR SD: Index lesions not meeting the criteria for CR, PR, or PD or the persistence of one or more non-index lesions. Exact 95% CIs were calculated using the Clopper-Pearson method.

Progression-free survival was defined as the interval from the earlier date of the first dose of IP to the earlier of PD per modified RECIST v1.1 or death due to any cause, estimated via Kaplan-Meier methods.

PD: radiologic detection of ≥ 20% increase in tumor burden to nadir and ≥ 5 mm absolute increase, or unequivocal progression of non-index lesions, or the presence of new lesions.

Confirmation scans were required within 4 weeks of the first documented response of CR or PR, and 4-6 weeks for PD. 95% CIs were calculated using the Brookmeyer and Crowley method.

Overall survival was defined as the interval from the earlier date of the first dose of IP to the event of death due to any cause, estimated via Kaplan-Meier methods. Participants who were still alive were censored at the date last known to be alive. If the date last known to be alive was after the data cutoff date, the participant was censored at the analysis trigger date. 95% CIs were calculated using the Brookmeyer and Crowley method.

Cmax was obtained using noncompartmental analysis, which was performed for tarlatamab PK parameter estimation. PK analysis is presented per dose received as pre-specified.

Ctrough was obtained at the end of a dosing interval or just before the administration of the next planned dose using noncompartmental analysis, which was performed for tarlatamab PK parameter estimation. PK analysis is presented per dose received as pre-specified.

AUC0-336 was defined as the actual body exposure to the drug over time following administration of a dose, calculated from time zero to 336 hours post-dose using noncompartmental analysis, which was performed for tarlatamab PK parameter estimation. PK analysis is presented per dose received as pre-specified.