Extensive Stage Small Cell Lung Cancer
Conditions
Keywords
Extensive Stage Small Cell Lung Cancer, Advanced Small Cell Lung Cancer, SCLC, AMG 757, Tarlatamab, IMDELLTRA, Tumor, Programmed Cell Death Protein 1, Programmed Cell Death Ligand 1, PD-1 Protein, PD-L1 Protein, Pharmacokinetics, Malignancy, Cancer, Chinese Participants, China, Platinum, Platinum-based, Neuroendocrine tumor, Bi-specific T-cell engager, BiTE molecule
Brief summary
The primary aim of this study is to evaluate the efficacy of tarlatamab as assessed by objective response rate (ORR) based on blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).
Interventions
DRUGTarlatamab
IV infusion
Sponsors
Amgen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participant has provided informed consent prior to initiation of any study specific activities/procedures. * Participant must be a resident in China, and of Chinese ancestry ≥ 18 years of age (or legal adult age within country) at the time of signing the informed consent. * Histologically or cytologically confirmed small cell lung cancer. * Extensive-stage SCLC participants who progressed on or recurred following 1 platinum-based regimen as 1L therapy (including a PD-1/PD-\[L\]1) and at least 1 other prior line of therapy. * Measurable lesions as defined per RECIST 1.1 within 21 days prior to the first dose of study drug. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. * Minimum life expectancy of 12 weeks. * Adequate organ function.
Exclusion criteria
Disease Related * Any previous diagnosis of transformed non-small cell lung cancer (NSCLC), epidermal growth factor receptor (EGFR) activating mutation positive NSCLC that has transformed to SCLC. * Symptomatic central nervous system (CNS) metastases. * Diagnosis or evidence of leptomeningeal disease. * Prior history of severe or life-threatening events from any immune-mediated therapy. Other Medical Conditions * 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. * Evidence of interstitial lung disease or active, non-infectious pneumonitis. * History of other malignancy within the past 2 years, with certain exceptions * Myocardial infarction and/or symptomatic congestive heart failure (New York Heart Association \> class II) within 12 months of first dose of study drug. * History of arterial thrombosis (eg, stroke or transient ischemic attack) within 12 months of first dose of study drug. * Participants with symptoms and/or clinical signs and/or radiographic signs that indicate an acute and/or uncontrolled active systemic infection within 7 days prior to the first dose of study drug. * HIV, Hepatitis B, and Hepatitis C, with certain exceptions. * Major surgery within 28 days of first dose study drug. Prior/Concomitant Therapy * Currently or previously enrolled in a tarlatamab study. * Prior therapy with any selective inhibitor of the DLL3 pathway. * Prior anti-cancer therapy within 21 days prior to first dose of study treatment, with certain exceptions. * Receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug, with certain exceptions. * Treatment with live virus, including live-attenuated vaccination, within 14 days prior to the first dose of study drug. Inactive vaccines (eg, non-live or non-replicating agent) and live viral non-replicating vaccines (eg, Jynneos for mpox infection) within 3 days prior to first dose of study drug. Prior/Concurrent Clinical Study Experience • Currently receiving treatment in another investigational device or drug study, or less than 30 days 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 period of time after the last dose of study drug as specified in the study protocol. * Female participants who are breastfeeding or who plan to breastfeed while on study and for an additional period of time after the last dose of study drug as specified in the study protocol. * Female participants planning to become pregnant or donate eggs while on study and for an additional period of time after the last dose of study drug as specified in the study protocol. * Female participants of childbearing potential with a positive pregnancy test assessed at screening by a highly sensitive 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 period of time after the last dose of study drug as specified in the study protocol. * Male participants with a pregnant partner who are unwilling to practice abstinence or use a condom during treatment and for an additional period of time after the last dose of study drug as specified in the study protocol. * Male participants unwilling to abstain from donating sperm during treatment and for an additional period of time after the last dose of study drug as specified in the study protocol. * Participants has known sensitivity to any of the products or components to be administered during dosing. * Participants 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 that, in the opinion of the investigator or medical monitor if consulted, would pose a risk to participant safety or interfere with the study evaluation, procedures, or completion.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) Based on Blinded Independent Central Review (BICR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) | From first dose of trial drug up to a minimum of last dose + 65 days or data cutoff date; median (min, max) time on trial was 3.4 (2.2, 6.5) months at data cut off | ORR based on BICR was defined as the percentage of participants with best overall response (BOR) of complete response (CR) plus partial response (PR). CR: Disappearance of all target non-nodal lesions. Any target lymph node must have had a reduction in short axis to \<10 mm, NOT total disappearance. PR: At least a 30% decrease in the sum of the diameters of target lesions, taken as reference the baseline sum of diameters. The percentage of participants who experience a CR or PR as assessed by BICR based on RECIST 1.1 is presented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response (DOR) Based on BICR Per RECIST 1.1 | Approximately 24 months | DOR was defined as time from the first documentation of OR until the first documentation of disease progression (PD) or death due to any cause, whichever occured first. Only participants who had achieved OR were evaluated for DOR. CR: Disappearance of all target non-nodal lesions. Any target lymph node must have reduction in short axis to \<10 mm, NOT total disappearance. PD: At least 20% increase in the sum of the diameters of target lesions, taken as reference smallest sum on trial (this included the baseline sum if that is the smallest on trial). In addition to the relative increase of 20%, the sum must have also demonstrated an absolute increase of at least 5 mm. If a participant was missing lesion data at a disease assessment and yet progressive disease criteria was met despite the missing data, the participant would be classified as having PD. |
| Disease Control (DC) Based on BICR Per RECIST 1.1 | Approximately 24 months | DC was defined as CR + PR + stable disease (SD). CR: Disappearance of all target non-nodal lesions. Any target lymph node must have had a reduction in short axis to \<10 mm, NOT total disappearance. PR: At least a 30% decrease in the sum of the diameters of target lesions, taken as reference the baseline sum of diameters. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. PD: At least 20% increase in the sum of the diameters of target lesions, taken as reference smallest sum on trial (this included the baseline sum if that is the smallest on trial). In addition to the relative increase of 20%, the sum must have also demonstrate an absolute increase of at least 5 mm. If a participant was missing lesion data at a disease assessment and yet progressive disease criteria was met despite the missing data, the participant would be classified as having PD. |
| Duration of DC Based on BICR Per RECIST 1.1 | Approximately 24 months | Duration of DC was defined as time from first documentation of CR,PR, or SD until first documentation of disease progression or death due to any cause, whichever occurred first. Only participants who had achieved CR,PR, or SD would be evaluated for Duration of DC. CR:Disappearance of all target non-nodal lesions.Any target lymph node must have reduction in short axis to \<10 mm,NOT total disappearance.PR:At least a 30% decrease in sum of diameters of target lesions, taken as reference baseline sum of diameters. SD:Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. PD:At least 20% increase in sum of diameters of target lesions, taken as reference smallest sum on trial.In addition to relative increase of 20%, sum must have also demonstrated an absolute increase of at least 5 mm.If participant was missing lesion data at disease assessment and yet progressive disease criteria was met despite missing data, participant would be classified as having PD. |
| Progression-free Survival (PFS) Based on BICR Per RECIST 1.1 | Approximately 24 months | PFS was defined as the time from first dose of tarlatamab until PD or death from any cause, whichever occurred first. At least a 20% increase in the sum of the diameters of target lesions, taken as reference the smallest sum on trial (this included the baseline sum if that was the smallest on trial). In addition to the relative increase of 20%, the sum must have also demonstrated an absolute increase of at least 5 mm. If a participant was missing lesion data at a disease assessment and yet progressive disease criteria was met despite the missing data, the participant would be classified as having PD. |
| ORR Based on Investigator Assessment Per RECIST 1.1 | Approximately 24 months | ORR based on investigator assessment was defined as the percentage of participants with BOR of CR plus PR. CR: Disappearance of all target non-nodal lesions. Any target lymph node must have had a reduction in short axis to \<10 mm, NOT total disappearance. PR: At least a 30% decrease in the sum of the diameters of target lesions, taken as reference the baseline sum of diameters. |
| DOR Based on Investigator Assessment Per RECIST 1.1 | Approximately 24 months | DOR was defined as time from the first documentation of OR until the first documentation of PD or death due to any cause, whichever occurred first. Only participants who had achieved OR would be evaluated for DOR. PD: At least 20% increase in the sum of the diameters of target lesions, taken as reference smallest sum on trial (this included the baseline sum if that was the smallest on trial). In addition to the relative increase of 20%, the sum must have also demonstrated an absolute increase of at least 5 mm. If a participant was missing lesion data at a disease assessment and yet progressive disease criteria was met despite the missing data, the participant would be classified as having PD. |
| DC Based on Investigator Assessment Per RECIST 1.1 | Approximately 24 months | DC was defined as CR + PR + SD. CR: Disappearance of all target non-nodal lesions. Any target lymph node must have had a reduction in short axis to \<10 mm, NOT total disappearance. PR: At least a 30% decrease in the sum of the diameters of target lesions, taken as reference the baseline sum of diameters. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. PD: At least 20% increase in the sum of the diameters of target lesions, taken as reference smallest sum on trial (this included the baseline sum if that was the smallest on trial). In addition to the relative increase of 20%, the sum must have also demonstrated an absolute increase of at least 5 mm. If a participant was missing lesion data at a disease assessment and yet progressive disease criteria was met despite the missing data, the participant would be classified as having PD. |
| Duration of DC Based on Investigator Assessment Per RECIST 1.1 | Approximately24 months | Duration of DC was defined as time from first documentation of CR,PR, or SD until first documentation of disease progression or death due to any cause, whichever occurred first. Only participants who had achieved CR,PR, or SD would be evaluated for Duration of DC. CR:Disappearance of all target non-nodal lesions.Any target lymph node must have reduction in short axis to \<10 mm,NOT total disappearance.PR:At least a 30% decrease in sum of diameters of target lesions, taken as reference baseline sum of diameters. SD:Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. PD:At least 20% increase in sum of diameters of target lesions, taken as reference smallest sum on trial.In addition to relative increase of 20%, sum must have also demonstrated an absolute increase of at least 5 mm.If participant was missing lesion data at disease assessment and yet progressive disease criteria was met despite missing data, participant would be classified as having PD. |
| PFS Based on Investigator Assessment Per RECIST 1.1 | Approximately 24 months | PFS was defined as time from enrollment until PD or death from any cause, whichever occurred first. At least a 20% increase in the sum of the diameters of target lesions, taken as reference the smallest sum on trial (this included the baseline sum if that was the smallest on trial). In addition to the relative increase of 20%, the sum must have also demonstrated an absolute increase of at least 5 mm. If a participant was missing lesion data at a disease assessment and yet progressive disease criteria was met despite the missing data, the participant would be classified as having PD. |
| Overall Survival (OS) | Approximately 24 months | OS was defined as time from the first dose of tarlatamab until death from any cause. |
| Number of Participants Who Experience Treatment-emergent Adverse Events (TEAEs) | Approximately 24 months | An AE was any untoward medical occurrence in a clinical trial participant irrespective of a causal relationship with the trial treatment. TEAEs were defined as AEs starting on or after the first dose of tarlatamab up to the safety follow-up (SFU) visit or 60 days after the last dose of tarlatamab, whichever was later. |
| Trough Concentration (Ctrough) of Tarlatamab | Approximately 24 months | Ctrough of tarlatamab was calculated using standard noncompartmental methods. |
| Number of Participants With Anti-tarlatamab Antibodies Formation | Approximately 24 months | Number of participants with anti-tarlatamab (binding and neutralizing) antibodies was presented. |
Countries
China
Contacts
STUDY_DIRECTORMD
Amgen
Participant flow
Recruitment details
Participants were enrolled at 12 trial centers in China from 27 August 2024. The trial is ongoing, he primary analysis data is presented based on the database snapshot date of 30 April 2025.
Pre-assignment details
Chinese participants with advanced small cell lung cancer (SCLC) who had progressed on or recurred following 1 platinum-based regimen as 1L therapy (including a programmed cell death 1 \[PD-1\]/programmed death ligand 1 \[PD-L1\]) and at least 1 other prior line of therapy received tarlatamab.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 58.0 years STANDARD_DEVIATION 6.2 |
| Race/Ethnicity, Customized Asian | 31 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 31 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 3 / 32 |
| other Total, other adverse events | 31 / 31 |
| serious Total, serious adverse events | 7 / 31 |
Outcome results
None listed