Small Cell Lung Cancer (SCLC)
Conditions
Keywords
Small Cell Lung Cancer, SCLC, AMG 757, Tarlatamab
Brief summary
The main objective is to compare the efficacy of tarlatamab with standard of care (SOC) on prolonging overall survival (OS).
Interventions
DRUGTarlatamab
Tarlatamab will be administered as an IV infusion.
DRUGLurbinectedin
Lurbinectedin will be administered per local SOC.
DRUGTopotecan
Topotecan will be administered per local SOC.
DRUGAmrubicin
Amrubicin will be administered per local SOC.
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
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. * 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.
Exclusion criteria
* Disease Related * Symptomatic central nervous system (CNS) metastases with exceptions defined in the protocol. * Diagnosis or evidence of leptomeningeal disease. * Prior history of immune checkpoint inhibitors resulting in events defined in the protocol. * 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. * History of solid organ transplantation. * History of other malignancy within the past 2 years, with exceptions defined in the protocol. * Myocardial infarction and/or symptomatic congestive heart failure (New York Heart Association \> class II) within 12 months prior to first dose of study treatment. * History of arterial thrombosis (eg, stroke or transient ischemic attack) within 12 months prior to first dose of study treatment. * Presence or history of viral infection based on criteria per protocol. * Receiving systemic corticosteroid therapy or any other form of immunosuppressive therapy within 7 days prior to first dose of study treatment. * 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. * Evidence of interstitial lung disease or active, non-infectious pneumonitis. * Prior/Concomitant Therapy * Prior therapy with tarlatamab or any of the standard of care chemotherapy included as part of this trial or participation in any tarlatamab or any other DLL3 targeted agent clinical trial. * Prior therapy with any selective inhibitor of the DLL3 pathway. * Participant received more than one prior systemic therapy regimen for SCLC. * Prior anti-cancer therapy within 21 days prior to first dose of study treatment with exceptions defined in protocol. * Current anti-cancer therapy such as chemotherapy, immunotherapy, or targeted therapy with exceptions. * Use of herbal or prescription/non-prescription medications known to inhibit membrane transporters P-glycoprotein (P-gp) and/or breast cancer resistance protein (BCRP) within 7 days prior to the first dose of study treatment. * Use of herbal or prescription/non-prescription medications known to be moderate or strong inhibitors of cytochrome P450 3A (CYP3A) enzymes within 7 days prior to the first dose of study treatment. * Use of herbal or prescription/non-prescription medications known to be moderate or strong inducers of CYP3A enzymes within 28 days prior to first dose of study treatment. * Participants who have reached the limit dose of prior treatment with cardiotoxic drugs. * Major surgical procedures within 28 days prior to first dose of study treatment. * 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. * 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. * Diagnostic Assessments * 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, with exceptions defined in the protocol. * 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 by a 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. * Contraception requirements for male and female participants receiving SOC therapies are based on regional prescribing information. * Breastfeeding restrictions for female participants receiving SOC therapies are based on regional prescribing information. * 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 that would pose a risk to the subject safety or interfere with the study evaluation..
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | From randomization up to minimum of death or primary completion DCO date 29 January 2025; median (min, max) time on the study was 8.6 (0.1, 18.5) months | OS was defined as time from randomization until death from any cause. Median overall survival was estimated using Kaplan-Meier method. 95% confidence intervals (CIs) were calculated using the Brookmeyer and Crowley method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Selected Functional Scales and Disease Symptom Items Included in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Up to approximately 4 years | The EORTC QLQ-C30 was developed to assess quality of life in cancer participants across tumor types. It was a self-reported, 30-item generic instrument that assessed five functional scales (physical, role, emotional, cognitive, social); nine disease symptom items (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, financial difficulties); and a global health status (GHS)/quality of life (QOL) scale. Questionnaire score ranged from 0 to 100. For the functional scales, higher scores indicated high/healthy level of functioning; for the disease symptom scales, higher scores indicated greater symptom burden; and for the GHS/QoL scale, higher scores represented a high QoL. A negative change from baseline indicated reduction in functioning, improvement in symptom burden and reduction in health and quality of life. |
| Change From Baseline in Selected Disease Symptoms Included in the European Organization for Research and Treatment of Lung Cancer Quality of Life Questionnaire (EORTC-QLQ-LC13) | Up to approximately 4 years | The EORTC QLQ-LC13 was a disease-specific supplement to the EORTC QLQ-C30. It included multi-item and single-item measures of lung cancer symptoms (coughing, hemoptysis, dyspnea, pain) and treatment side effects (hair loss, neuropathy, sore mouth, dysphagia). Scores ranged from 0 to 100, with higher scores indicating a greater degree of symptom severity. A negative change from baseline indicated improvement in symptom burden or side effect severity. |
| Objective Response Rate (ORR) | Up to approximately 4 years | ORR was defined as the percentage of participants with a confirmed best overall response of complete response (CR) or partial response (PR) based on the 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. 95% CIs were calculated using the Brookmeyer and Crowley method. |
| Disease Control Rate (DCR) | Up to approximately 4 years | DCR was defined as the percentage of participants documented to have a CR, PR or stable disease (SD) per 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. 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. |
| Duration of Response (DOR) | Up to approximately 4 years | DOR was defined as the time from the first documentation of OR until the first documentation of PD or death due to any cause, whichever occurred first determined by the investigator per RECIST v1.1. Only participants who had achieved OR will be evaluated for DOR. PD: radiologic detection of ≥ 20% increase in in the sum of diameters of target lesions and ≥ 5 mm absolute increase, or unequivocal progression of non-index lesions, or the presence of new lesions. |
| PFS at Year 1 | 1 year | PFS was defined as time from randomization until PD or death from any cause, whichever occurs first for all participants. Progression was based on investigator assessment of disease response per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. PD: radiologic detection of ≥ 20% increase in in the sum of diameters of target lesions and ≥ 5 mm absolute increase, or unequivocal progression of non-index lesions, or the presence of new lesions. 95% CIs were calculated using the Brookmeyer and Crowley method. |
| OS at Year 1, 2 and 3 | 1 year, 2 years and 3 years | OS was defined as time from randomization until death from any cause. Median overall survival was estimated using Kaplan-Meier method. 95% CIs were calculated using the Brookmeyer and Crowley method. |
| Number of Participants With Anti-tarlatamab Antibodies | Up to approximately 4 years | Incidence of treatment emergent adverse events including grade ≥ 3 treatment emergent adverse events, serious treatment emergent adverse events, treatment emergent adverse events leading to treatment discontinuation, fatal treatment emergent adverse events, and treatment-related treatment emergent adverse events. |
| Progression Free Survival (PFS) | Up to approximately 4 years | PFS was defined as time from randomization until disease progression (PD) or death from any cause, whichever occurs first for all participants. Progression was based on investigator assessment of disease response per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. PD: radiologic detection of ≥ 20% increase in the sum of diameters of target lesions and ≥ 5 mm absolute increase, or unequivocal progression of non-index lesions, or the presence of new lesions. 95% CIs were calculated using the Brookmeyer and Crowley method. |
| Number of Participants Who Experienced Anti-tarlatamab Antibodies | Up to 1 year | — |
| Change From Baseline in Pain Severity as Measured by Brief Pain Inventory - Short Form (BPI-SF) | Up to approximately 4 years | The BPI-SF (Pain) was a valid and reliable instrument, which was a commonly used tool to capture severity of pain and its impact on daily functioning. The BPI-SF measured intensity of pain at four time points (worst, least, average, and right now), pain relief, and seven interference items (general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life). Scoring for pain ranged from 0 (no pain) to 10 (worst pain), and for pain interference from 0 (no interference) to 10 (complete interference). A negative change from baseline indicated a reduction in pain severity or interference. |
| Change From Baseline in Symptom Severity as Measured by Patient Global Impression of Severity (PGIS) Questionnaire | Up to approximately 4 years | PGIS was used to measure a patient's perceived severity of symptoms. PGIS scale asked respondents to describe the severity of their symptoms, overall status, etc, over the past week. The 4-level PGIS response options were: 1: none, 2: mild, 3: moderate, and 4: severe. Higher scores indicated severe condition. A negative change from baseline indicated an improvement in severity. |
| Change From Baseline in Symptoms and Overall Status as Measured by Patient Reported Impression of Change (PGIC) Questionnaire | Up to approximately 4 years | PGIC measures were used in the measurement of within-patient meaningful change (response) thresholds for disease symptoms/impacts of interest. The PGIC scale asked respondents to rate the overall change in symptoms, overall status, etc., since initiating treatment with the medication. The 5-level PGIC response options were: 1: much better, 2: a little better, 3: about the same, 4: a little worse, and 5: much worse. Higher scores indicated worsening condition. A negative change from baseline indicated an improvement in symptoms. |
| Summary Scores of Patient-perceived Health at Each Assessment Visit Using the Visual Analogue Scale (VAS) as Measured by the 5-Level EuroQol-5 Dimension (EQ-5D-5L) | Up to approximately 4 years | The EQ5D-5L questionnaire was a standardized instrument used as a measure of health outcome developed by the EuroQol group. It was comprised of a 5-dimension health status measure and a VAS. The 5-dimension health status measure evaluated: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression based on a 5-level scale: 1: no problems, 2: slight problems, 3: moderate problems, 4: severe problems, 5: an extreme problem. Higher scores (closer to 5) indicated worse health status. The VAS recorded the participant's self-rated health on a vertical VAS where the endpoints were labelled 'Worst imaginable health state' and 'Best imaginable health state'. VAS ranged from 0 to 100. Higher scores indicated better perceived health. |
| Change From Baseline in Patient Perceived Health Using VAS Score as Measured by EQ5D-5L | Up to approximately 4 years | The EQ5D-5L questionnaire was a standardized instrument used as a measure of health outcome developed by the EuroQol group. It was comprised of a 5-dimension health status measure and a VAS. The 5-dimension health status measure evaluated: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression based on a 5-level scale: 1: no problems, 2: slight problems, 3: moderate problems, 4: severe problems, 5: an extreme problem. Higher scores (closer to 5) indicated worse health status. The VAS recorded the participant's self-rated health on a vertical VAS where the endpoints were labelled 'Worst imaginable health state' and 'Best imaginable health state'. VAS ranged from 0 to 100. Higher scores indicated better Perceived health. A negative change from baseline indicated a reduction in better perceived health. |
| Responses to Patient-Reported Adverse Events Questionnaire (PRO-CTCAE) | Up to approximately 4 years | PRO-CTCAE was a 78-item library used to measure patient-reported symptomatic adverse events. Users selected items that were most relevant to the disease, treatment profile, and fit for purpose to document patients' experience. Each symptom was rated by up to 3 attributes: presence/frequency, severity, and/or interference of the adverse event. Based on the safety profile of tarlatamab and SOC therapy, the study included the following symptoms: shivering or shaking chills, anxiety, constipation, taste changes, vomiting, headache, concentration, rash, palpitations, arm or leg swelling, nausea, dizziness, bruising, fatigue, and decreased appetite, which were deemed relevant for the site of cancer as well as cancer treatment. Responses were typically scored on a 5-point ordinal scale, with values ranging from 0 to 4. Higher scores indicated greater symptom burden. |
| Change From Baseline in Symptom Bother as Measured by Functional Assessment of Cancer Therapy - General (FACT-G) Questionnaire | Up to approximately 4 years | FACT-G was a 27-item questionnaire designed to measure four domains of health-related quality of life in cancer patients: physical, social, emotional, and functional well-being. The GP5 of the FACT-G was a single item: I am bothered by side effects of treatment, rated on a 5-point Likert scale from 0: not at all to 4: very much. Higher scores indicated greater impact of side effects. A negative change from baseline indicated improvement in impact of side effects. |
| Trough Concentration (Ctrough) of Tarlatamab | Up to 1 year | Blood samples were collected for measurement of serum concentrations of tarlatamab. |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, China, Czechia, Denmark, France, Germany, Greece, Hungary, Ireland, Israel, Italy, Japan, Malaysia, Mexico, Netherlands, Poland, Portugal, Romania, Singapore, South Korea, Spain, Switzerland, Taiwan, Turkey (Türkiye), United Kingdom, United States
Participant flow
Recruitment details
Participants were enrolled at 166 centers in 30 countries worldwide starting from 31 May 2023. The primary analysis data is presented from the date of randomization up to the data cutoff date (DCO), 29 January 2025. The study is still ongoing.
Pre-assignment details
Participants were randomized 1:1 to receive tarlatamab or standard of care (SOC) chemotherapy (lurbinectedin, topotecan , or amrubicin \[Japan only\]). Randomization was stratified by prior anti-programmed cell death 1 (PD-1) or prior anti-PD-Ligand (L)1 (yes/no), chemotherapy-free interval (≥180 days; \<180 to ≥90 days; \<90 days), presence of brain metastases (yes/no), and SOC (topotecan/amrubicin versus lurbinectedin).
Participants by arm
| Arm | Count |
|---|---|
| Standard of Care (SOC) Participants were randomized to receive treatment according to the local SOC chemotherapy (lurbinectedin, topotecan, or amrubicin \[Japan only\]) in 21-day cycles. | 255 |
| Tarlatamab 1 mg to 10 mg Q2W Participants were randomized to receive tarlatamab as an IV infusion: A step dose of 1 mg on Cycle 1 Day 1 followed by the target dose 10 mg on Cycle 1 Day 8, Cycle 1 Day 15, and Q2W thereafter. | 254 |
| Total | 509 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 151 | 111 |
| Overall Study | Ongoing in study | 102 | 143 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Total | Tarlatamab 1 mg to 10 mg Q2W | Standard of Care (SOC) |
|---|---|---|---|
| Age, Continuous | 63.9 years STANDARD_DEVIATION 9.3 | 63.6 years STANDARD_DEVIATION 9.4 | 64.2 years STANDARD_DEVIATION 9.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 23 Participants | 12 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 268 Participants | 140 Participants | 128 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 218 Participants | 102 Participants | 116 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 2 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 204 Participants | 97 Participants | 107 Participants |
| Race/Ethnicity, Customized Black or African American | 5 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized Other | 4 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Unknown or Not Reported | 3 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 291 Participants | 152 Participants | 139 Participants |
| Sex: Female, Male Female | 158 Participants | 72 Participants | 86 Participants |
| Sex: Female, Male Male | 351 Participants | 182 Participants | 169 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 152 / 255 | 111 / 254 |
| other Total, other adverse events | 234 / 244 | 244 / 252 |
| serious Total, serious adverse events | 125 / 244 | 129 / 252 |
Outcome results
Primary
Overall Survival (OS)
OS was defined as time from randomization until death from any cause. Median overall survival was estimated using Kaplan-Meier method. 95% confidence intervals (CIs) were calculated using the Brookmeyer and Crowley method.
Time frame: From randomization up to minimum of death or primary completion DCO date 29 January 2025; median (min, max) time on the study was 8.6 (0.1, 18.5) months
Population: The ITT analysis set included all randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Standard of Care (SOC) | Overall Survival (OS) | 8.3 months |
| Tarlatamab 1 mg to 10 mg Q2W | Overall Survival (OS) | 13.6 months |
p-value: <0.00195% CI: [0.468, 0.768]Stratified log-rank test
Secondary
Change From Baseline in Pain Severity as Measured by Brief Pain Inventory - Short Form (BPI-SF)
The BPI-SF (Pain) was a valid and reliable instrument, which was a commonly used tool to capture severity of pain and its impact on daily functioning. The BPI-SF measured intensity of pain at four time points (worst, least, average, and right now), pain relief, and seven interference items (general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life). Scoring for pain ranged from 0 (no pain) to 10 (worst pain), and for pain interference from 0 (no interference) to 10 (complete interference). A negative change from baseline indicated a reduction in pain severity or interference.
Time frame: Up to approximately 4 years
Secondary
Change From Baseline in Patient Perceived Health Using VAS Score as Measured by EQ5D-5L
The EQ5D-5L questionnaire was a standardized instrument used as a measure of health outcome developed by the EuroQol group. It was comprised of a 5-dimension health status measure and a VAS. The 5-dimension health status measure evaluated: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression based on a 5-level scale: 1: no problems, 2: slight problems, 3: moderate problems, 4: severe problems, 5: an extreme problem. Higher scores (closer to 5) indicated worse health status. The VAS recorded the participant's self-rated health on a vertical VAS where the endpoints were labelled 'Worst imaginable health state' and 'Best imaginable health state'. VAS ranged from 0 to 100. Higher scores indicated better Perceived health. A negative change from baseline indicated a reduction in better perceived health.
Time frame: Up to approximately 4 years
Secondary
Change From Baseline in Selected Disease Symptoms Included in the European Organization for Research and Treatment of Lung Cancer Quality of Life Questionnaire (EORTC-QLQ-LC13)
The EORTC QLQ-LC13 was a disease-specific supplement to the EORTC QLQ-C30. It included multi-item and single-item measures of lung cancer symptoms (coughing, hemoptysis, dyspnea, pain) and treatment side effects (hair loss, neuropathy, sore mouth, dysphagia). Scores ranged from 0 to 100, with higher scores indicating a greater degree of symptom severity. A negative change from baseline indicated improvement in symptom burden or side effect severity.
Time frame: Up to approximately 4 years
Secondary
Change From Baseline in Selected Functional Scales and Disease Symptom Items Included in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)
The EORTC QLQ-C30 was developed to assess quality of life in cancer participants across tumor types. It was a self-reported, 30-item generic instrument that assessed five functional scales (physical, role, emotional, cognitive, social); nine disease symptom items (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, financial difficulties); and a global health status (GHS)/quality of life (QOL) scale. Questionnaire score ranged from 0 to 100. For the functional scales, higher scores indicated high/healthy level of functioning; for the disease symptom scales, higher scores indicated greater symptom burden; and for the GHS/QoL scale, higher scores represented a high QoL. A negative change from baseline indicated reduction in functioning, improvement in symptom burden and reduction in health and quality of life.
Time frame: Up to approximately 4 years
Secondary
Change From Baseline in Symptom Bother as Measured by Functional Assessment of Cancer Therapy - General (FACT-G) Questionnaire
FACT-G was a 27-item questionnaire designed to measure four domains of health-related quality of life in cancer patients: physical, social, emotional, and functional well-being. The GP5 of the FACT-G was a single item: I am bothered by side effects of treatment, rated on a 5-point Likert scale from 0: not at all to 4: very much. Higher scores indicated greater impact of side effects. A negative change from baseline indicated improvement in impact of side effects.
Time frame: Up to approximately 4 years
Secondary
Change From Baseline in Symptoms and Overall Status as Measured by Patient Reported Impression of Change (PGIC) Questionnaire
PGIC measures were used in the measurement of within-patient meaningful change (response) thresholds for disease symptoms/impacts of interest. The PGIC scale asked respondents to rate the overall change in symptoms, overall status, etc., since initiating treatment with the medication. The 5-level PGIC response options were: 1: much better, 2: a little better, 3: about the same, 4: a little worse, and 5: much worse. Higher scores indicated worsening condition. A negative change from baseline indicated an improvement in symptoms.
Time frame: Up to approximately 4 years
Secondary
Change From Baseline in Symptom Severity as Measured by Patient Global Impression of Severity (PGIS) Questionnaire
PGIS was used to measure a patient's perceived severity of symptoms. PGIS scale asked respondents to describe the severity of their symptoms, overall status, etc, over the past week. The 4-level PGIS response options were: 1: none, 2: mild, 3: moderate, and 4: severe. Higher scores indicated severe condition. A negative change from baseline indicated an improvement in severity.
Time frame: Up to approximately 4 years
Secondary
Disease Control Rate (DCR)
DCR was defined as the percentage of participants documented to have a CR, PR or stable disease (SD) per 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. 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.
Time frame: Up to approximately 4 years
Secondary
Duration of Response (DOR)
DOR was defined as the time from the first documentation of OR until the first documentation of PD or death due to any cause, whichever occurred first determined by the investigator per RECIST v1.1. Only participants who had achieved OR will be evaluated for DOR. PD: radiologic detection of ≥ 20% increase in in the sum of diameters of target lesions and ≥ 5 mm absolute increase, or unequivocal progression of non-index lesions, or the presence of new lesions.
Time frame: Up to approximately 4 years
Secondary
Number of Participants Who Experienced Anti-tarlatamab Antibodies
Time frame: Up to 1 year
Secondary
Number of Participants With Anti-tarlatamab Antibodies
Incidence of treatment emergent adverse events including grade ≥ 3 treatment emergent adverse events, serious treatment emergent adverse events, treatment emergent adverse events leading to treatment discontinuation, fatal treatment emergent adverse events, and treatment-related treatment emergent adverse events.
Time frame: Up to approximately 4 years
Secondary
Objective Response Rate (ORR)
ORR was defined as the percentage of participants with a confirmed best overall response of complete response (CR) or partial response (PR) based on the 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. 95% CIs were calculated using the Brookmeyer and Crowley method.
Time frame: Up to approximately 4 years
Secondary
OS at Year 1, 2 and 3
OS was defined as time from randomization until death from any cause. Median overall survival was estimated using Kaplan-Meier method. 95% CIs were calculated using the Brookmeyer and Crowley method.
Time frame: 1 year, 2 years and 3 years
Secondary
PFS at Year 1
PFS was defined as time from randomization until PD or death from any cause, whichever occurs first for all participants. Progression was based on investigator assessment of disease response per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. PD: radiologic detection of ≥ 20% increase in in the sum of diameters of target lesions and ≥ 5 mm absolute increase, or unequivocal progression of non-index lesions, or the presence of new lesions. 95% CIs were calculated using the Brookmeyer and Crowley method.
Time frame: 1 year
Secondary
Progression Free Survival (PFS)
PFS was defined as time from randomization until disease progression (PD) or death from any cause, whichever occurs first for all participants. Progression was based on investigator assessment of disease response per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. PD: radiologic detection of ≥ 20% increase in the sum of diameters of target lesions and ≥ 5 mm absolute increase, or unequivocal progression of non-index lesions, or the presence of new lesions. 95% CIs were calculated using the Brookmeyer and Crowley method.
Time frame: Up to approximately 4 years
Secondary
Responses to Patient-Reported Adverse Events Questionnaire (PRO-CTCAE)
PRO-CTCAE was a 78-item library used to measure patient-reported symptomatic adverse events. Users selected items that were most relevant to the disease, treatment profile, and fit for purpose to document patients' experience. Each symptom was rated by up to 3 attributes: presence/frequency, severity, and/or interference of the adverse event. Based on the safety profile of tarlatamab and SOC therapy, the study included the following symptoms: shivering or shaking chills, anxiety, constipation, taste changes, vomiting, headache, concentration, rash, palpitations, arm or leg swelling, nausea, dizziness, bruising, fatigue, and decreased appetite, which were deemed relevant for the site of cancer as well as cancer treatment. Responses were typically scored on a 5-point ordinal scale, with values ranging from 0 to 4. Higher scores indicated greater symptom burden.
Time frame: Up to approximately 4 years
Secondary
Summary Scores of Patient-perceived Health at Each Assessment Visit Using the Visual Analogue Scale (VAS) as Measured by the 5-Level EuroQol-5 Dimension (EQ-5D-5L)
The EQ5D-5L questionnaire was a standardized instrument used as a measure of health outcome developed by the EuroQol group. It was comprised of a 5-dimension health status measure and a VAS. The 5-dimension health status measure evaluated: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression based on a 5-level scale: 1: no problems, 2: slight problems, 3: moderate problems, 4: severe problems, 5: an extreme problem. Higher scores (closer to 5) indicated worse health status. The VAS recorded the participant's self-rated health on a vertical VAS where the endpoints were labelled 'Worst imaginable health state' and 'Best imaginable health state'. VAS ranged from 0 to 100. Higher scores indicated better perceived health.
Time frame: Up to approximately 4 years
Secondary
Trough Concentration (Ctrough) of Tarlatamab
Blood samples were collected for measurement of serum concentrations of tarlatamab.
Time frame: Up to 1 year