Trial Outcomes & Findings for Study Comparing Tarlatamab With Standard of Care Chemotherapy in Relapsed Small Cell Lung Cancer (NCT NCT05740566)

Last Updated: 2026-01-05

Results Overview

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.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE3

Target enrollment

509 participants

Primary outcome timeframe

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

Results posted on

2026-01-05

Participant Flow

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.

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).

Participant milestones

Participant milestones
Measure	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.	Tarlatamab 1 mg to 10 mg Q2W Participants were randomized to receive tarlatamab as an intravenous (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 every 2 weeks (Q2W) thereafter.
Overall Study STARTED	255	254
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	255	254

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	Tarlatamab 1 mg to 10 mg Q2W Participants were randomized to receive tarlatamab as an intravenous (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 every 2 weeks (Q2W) thereafter.
Overall Study Death	151	111
Overall Study Withdrawal by Subject	2	0
Overall Study Ongoing in study	102	143

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Standard of Care (SOC) n=255 Participants Participants were randomized to receive treatment according to the local SOC chemotherapy (lurbinectedin, topotecan, or amrubicin \[Japan only\]) in 21-day cycles.	Tarlatamab 1 mg to 10 mg Q2W n=254 Participants 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.	Total n=509 Participants Total of all reporting groups
Age, Continuous	64.2 years STANDARD_DEVIATION 9.2 • n=9667 Participants	63.6 years STANDARD_DEVIATION 9.4 • n=6597 Participants	63.9 years STANDARD_DEVIATION 9.3 • n=16264 Participants
Sex: Female, Male Female	86 Participants n=9667 Participants	72 Participants n=6597 Participants	158 Participants n=16264 Participants
Sex: Female, Male Male	169 Participants n=9667 Participants	182 Participants n=6597 Participants	351 Participants n=16264 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	11 Participants n=9667 Participants	12 Participants n=6597 Participants	23 Participants n=16264 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	128 Participants n=9667 Participants	140 Participants n=6597 Participants	268 Participants n=16264 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	116 Participants n=9667 Participants	102 Participants n=6597 Participants	218 Participants n=16264 Participants
Race/Ethnicity, Customized Asian	107 Participants n=9667 Participants	97 Participants n=6597 Participants	204 Participants n=16264 Participants
Race/Ethnicity, Customized Black or African American	3 Participants n=9667 Participants	2 Participants n=6597 Participants	5 Participants n=16264 Participants
Race/Ethnicity, Customized White	139 Participants n=9667 Participants	152 Participants n=6597 Participants	291 Participants n=16264 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	1 Participants n=9667 Participants	1 Participants n=6597 Participants	2 Participants n=16264 Participants
Race/Ethnicity, Customized Other	3 Participants n=9667 Participants	1 Participants n=6597 Participants	4 Participants n=16264 Participants
Race/Ethnicity, Customized Unknown or Not Reported	2 Participants n=9667 Participants	1 Participants n=6597 Participants	3 Participants n=16264 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Standard of Care (SOC) n=255 Participants Participants were randomized to receive treatment according to the local SOC chemotherapy (lurbinectedin, topotecan, or amrubicin \[Japan only\]) in 21-day cycles.	Tarlatamab 1 mg to 10 mg Q2W n=254 Participants 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.
Overall Survival (OS)	8.3 months Interval 7.0 to 10.2	13.6 months Interval 11.1 to Upper CI was not calculable due to insufficient event data occurring above the median.

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 1 year

Blood samples were collected for measurement of serum concentrations of tarlatamab.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 1 year

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to approximately 4 years

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

Adverse Events

Standard of Care (SOC)

Serious events: 125 serious events

Other events: 234 other events

Deaths: 152 deaths

Tarlatamab 1 mg to 10 mg Q2W

Serious events: 129 serious events

Other events: 244 other events

Deaths: 111 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Amgen Inc.

Phone: 866-572-6436

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
Publication restrictions are in place

Restriction type: OTHER