NCT05740566 · CITED IN SOURCE DOCUMENTS

Study Comparing Tarlatamab With Standard of Care Chemotherapy in Relapsed Small Cell Lung Cancer

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: ACTIVE NOT RECRUITING
Registry last update: 2026-01-05

The main objective is to compare the efficacy of tarlatamab with standard of care (SOC) on prolonging overall survival (OS).

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

→

baseline

Baseline characteristics

→

outcome · NOT POSTED

Progression Free Survival (PFS)

→

outcome · NOT POSTED

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)

→

outcome · NOT POSTED

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)

→

outcome · NOT POSTED

Objective Response Rate (ORR)

→

outcome · NOT POSTED

Disease Control Rate (DCR)

→

outcome · NOT POSTED

Duration of Response (DOR)

→

outcome · NOT POSTED

PFS at Year 1

→

outcome · NOT POSTED

OS at Year 1, 2 and 3

→

outcome · NOT POSTED

Number of Participants With Anti-tarlatamab Antibodies

→

outcome · NOT POSTED

Trough Concentration (Ctrough) of Tarlatamab

→

outcome · NOT POSTED

Number of Participants Who Experienced Anti-tarlatamab Antibodies

→

outcome · NOT POSTED

Change From Baseline in Pain Severity as Measured by Brief Pain Inventory - Short Form (BPI-SF)

→

outcome · NOT POSTED

Change From Baseline in Symptom Severity as Measured by Patient Global Impression of Severity (PGIS) Questionnaire

→

outcome · NOT POSTED

Change From Baseline in Symptoms and Overall Status as Measured by Patient Reported Impression of Change (PGIC) Questionnaire

→

outcome · NOT POSTED

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)

→

outcome · NOT POSTED

Change From Baseline in Patient Perceived Health Using VAS Score as Measured by EQ5D-5L

→

outcome · NOT POSTED

Responses to Patient-Reported Adverse Events Questionnaire (PRO-CTCAE)

→

outcome · NOT POSTED

Change From Baseline in Symptom Bother as Measured by Functional Assessment of Cancer Therapy - General (FACT-G) Questionnaire

→

outcome · POSTED

Overall Survival (OS)

→

adverse events

Adverse events

→

more info

Limitations, agreements, and source contact

→

Who could take part

eligibility Criteria: 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..
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Participants will receive tarlatamab as an intravenous (IV) infusion.
intervention Names
Drug: Tarlatamab
label
Tarlatamab
type
EXPERIMENTAL
description
Participants will receive treatment per local standard of care (SOC).
intervention Names
Drug: Lurbinectedin
Drug: Topotecan
Drug: Amrubicin
label
Standard of Care
type
ACTIVE_COMPARATOR

interventions

arm Group Labels
Tarlatamab
description
Tarlatamab will be administered as an IV infusion.
name
Tarlatamab
other Names
AMG 757
type
DRUG
arm Group Labels
Standard of Care
description
Lurbinectedin will be administered per local SOC.
name
Lurbinectedin
type
DRUG
arm Group Labels
Standard of Care
description
Topotecan will be administered per local SOC.
name
Topotecan
type
DRUG
arm Group Labels
Standard of Care
description
Amrubicin will be administered per local SOC.
name
Amrubicin
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 509
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
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.
measure
Overall Survival (OS)
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

secondary Outcomes

description
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.
measure
Progression Free Survival (PFS)
time Frame
Up to approximately 4 years
description
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.
measure
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)
time Frame
Up to approximately 4 years
description
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.
measure
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)
time Frame
Up to approximately 4 years
description
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.
measure
Objective Response Rate (ORR)
time Frame
Up to approximately 4 years
description
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.
measure
Disease Control Rate (DCR)
time Frame
Up to approximately 4 years
description
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.
measure
Duration of Response (DOR)
time Frame
Up to approximately 4 years
description
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.
measure
PFS at Year 1
time Frame
1 year
description
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.
measure
OS at Year 1, 2 and 3
time Frame
1 year, 2 years and 3 years
description
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.
measure
Number of Participants With Anti-tarlatamab Antibodies
time Frame
Up to approximately 4 years
description
Blood samples were collected for measurement of serum concentrations of tarlatamab.
measure
Trough Concentration (Ctrough) of Tarlatamab
time Frame
Up to 1 year
measure
Number of Participants Who Experienced Anti-tarlatamab Antibodies
time Frame
Up to 1 year
description
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.
measure
Change From Baseline in Pain Severity as Measured by Brief Pain Inventory - Short Form (BPI-SF)
time Frame
Up to approximately 4 years

Full study description

brief Summary: The main objective is to compare the efficacy of tarlatamab with standard of care (SOC) on prolonging overall survival (OS).

Source references

references

citation
Mountzios G, Sun L, Cho BC, Demirci U, Baka S, Gumus M, Lugini A, Zhu B, Yu Y, Korantzis I, Han JY, Ciuleanu TE, Ahn MJ, Rocha P, Mazieres J, Lau SCM, Schuler M, Blackhall F, Yoshida T, Owonikoko TK, Paz-Ares L, Jiang T, Hamidi A, Gauto D, Recondo G, Rudin CM; DeLLphi-304 Investigators. Tarlatamab in Small-Cell Lung Cancer after Platinum-Based Chemotherapy. N Engl J Med. 2025 Jul 24;393(4):349-361. doi: 10.1056/NEJMoa2502099. Epub 2025 Jun 2.
pmid
40454646
type
BACKGROUND
citation
Dirnberger F, Patel S, Boyne DJ, Lan Z, Uyei J, Wang J, Cho S, DeCosta L, Bridges IM, Tapan U. Matching-Adjusted Indirect Comparison of Tarlatamab for Patients with Platinum-Refractory or Platinum-Resistant Extensive-Stage Small-Cell Lung Cancer. Adv Ther. 2026 Sep;43(9):4282-4298. doi: 10.1007/s12325-026-03659-4. Epub 2026 Jun 30.
pmid
42377743
type
DERIVED
citation
Ahn MJ, Cho BC, Felip E, Korantzis I, Ohashi K, Majem M, Juan-Vidal O, Handzhiev S, Izumi H, Lee JS, Dziadziuszko R, Wolf J, Blackhall F, Reck M, Alvarez JB, Hummel HD, Dingemans AC, Sands J, Akamatsu H, Owonikoko TK, Ramalingam SS, Borghaei H, Johnson ML, Huang S, Mukherjee S, Minocha M, Jiang T, Martinez P, Anderson ES, Paz-Ares L. Plain language summary: tarlatamab for patients with previously treated small cell lung cancer. Future Oncol. 2024 Dec;20(40):3355-3364. doi: 10.1080/14796694.2024.2402152. Epub 2024 Nov 12.
pmid
39530627
type
DERIVED