Tarlatamab for the Treatment of Extensive Stage Small-cell Lung Cancer

A Front-Line Window-of-Opportunity Phase 2 Study of Tarlatamab (Bispecific T Cell Engager: DLL3-CD3) in Patients With Extensive-Stage Small-Cell Lung Cancer

This phase II trial tests the effect of tarlatamab in treating patients with small cell lung cancer (SCLC) that has spread from where it first started to other parts of the body (extensive-stage). SCLC is an aggressive cancer which has a low 5-year survival rate. Tarlatamab is a bispecific antibody that can bind to two different antigens at the same time. Tarlatamab binds to DLL3 which is a protein found on the surface of some types of tumor cells, including small-cell lung cancer, and to CD3 which is present on immune system T-cells (a type of white blood cell) and may interfere with the ability of tumor cells to grow and spread. This may increase the length of time to progression (growing, spreading, or getting worse) and help patients with extensive-stage SCLC live longer.

Study Overview

• Status: Recruiting
• Conditions: Extensive Stage Lung Small Cell Carcinoma
• Intervention / Treatment: Other: Questionnaire Administration; Procedure: Magnetic Resonance Imaging; Procedure: Biospecimen Collection; Procedure: Multigated Acquisition Scan; Other: Electronic Health Record Review; Procedure: Echocardiography Test; Procedure: Biopsy Procedure; Procedure: Computed Tomography; Drug: Tarlatamab

Detailed Description

PRIMARY OBJECTIVES:

I. To assess the 6-month progression-free survival (PFS) rate for extensive-stage SCLC (ES-SCLC) patients treated with tarlatamab as first-line therapy.

II. Interim analysis for futility monitoring: To monitor rate of rapid disease progression (PD) at 4 weeks, with a goal of < 40%.

SECONDARY OBJECTIVES:

I. To evaluate the safety and toxicity of tarlatamab as first-line therapy ES-SCLC using National Cancer Institute (NCI) Common Terminology Criteria (CTCAE) version 5.0 for all adverse events (AEs) and the American Society for Transplantation and Cellular Therapy (ASTCT) Consensus Grading Criteria for cytokine release syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS).

II. To assess objective response rate (ORR), duration of response (DOR), and disease control rate (DCR) in ES-SCLC patients treated with tarlatamab in first-line settings as measured by Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1.

III. To evaluate the intracranial (ic) antitumor activity of tarlatamab as first-line therapy in ES-SCLC with baseline brain metastasis as measured by ic best ORR, time to intracranial response, icDOR, and icPFS rate at 6 months.

IV. To assess median PFS, 12-month overall survival (OS), and median OS in ES-SCLC patients treated with tarlatamab in first-line settings.

EXPLORATORY OBJECTIVES:

I. To assess quality of life (QoL) as measured by the Functional Assessment of Cancer Therapy-Lung (FACT-L) QOL.

II. To assess the clinical efficacy of platinum-based chemotherapy (PC) and immune checkpoint inhibitors (ICI) in second-line settings (progression on tarlatamab) as measured by time to second progression (PFS2).

III. To measure the time to initiation of PC and ICI in ES-SCLC (after disease progression on tarlatamab).

OUTLINE:

Patients receive tarlatamab intravenously (IV) over 60 minutes on days 1, 8, and 15 of cycle 1, then on days 1 and 15 of remaining cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients receive saftey response assessment scan after 4 weeks of starting treatment. Pateints with rapid disease progression will immediatly start standard of care platinum based chemotherapy and immune checkpoint inhibitors. Response assessment scans will be done every 8 weeks (2 cycles).

After completion of study treatment, patients are followed at 30 days then every 3 months for up to 2 years.

• Study Type: Interventional
• Enrollment (Estimated): 39
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: The Ohio State University Comprehensive Cancer Center; Phone Number: 800-293-5066; Email: OSUCCCClinicaltrials@osumc.edu

Study Locations

• United States
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Recruiting
      • Ohio State University Comprehensive Cancer Center
      • Contact: Asrar AlAhmadi, MBBS; Phone Number: 614-293-6786; Email: Asrar.Alahmadi@osumc.edu
      • Principal Investigator: Asrar AlAhmadi, MBBS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information

  • NOTE: HIPAA authorization may be included in the informed consent or obtained separately
• Age ≥ 18 years at the time of consent
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 2

• Have a histologically or cytologically documented new diagnosis of the extensive-stage (i.e., metastatic and/or recurrent) SCLC. Patients with multiple lung nodules and/or lymph node involvement that are too extensive or have tumor/nodal volume that is too large to be encompassed in a tolerable radiation plan are allowed

  • Recurrent limited-stage SCLC disease after 6 months of completing standard-of-care systemic platinum-based chemotherapy and radiation can be considered after discussion with the sponsor
• Measurable disease according to RECIST v 1.1

• All patients must have brain MRI. Subjects with brain metastases are eligible provided they meet the following criteria:

  • Patients with treated brain metastases are eligible if they completed definitive therapy at least 1 week prior to the first dose of tarlatamab, are asymptomatic (unless symptoms are deemed irreversible by the investigator), and on stable dose of steroids (=< 10 mg prednisone equivalent) for at least 7 days prior to study treatment
  • Patients with asymptomatic untreated brain metastases with no radiological evidence of vasogenic edema may be considered for inclusion after discussion with the sponsor
• Absolute neutrophil count (ANC) ≥ 1500 cells/uL
• Platelets ≥ 100,000/uL
• Hemoglobin ≥ 9.0 g/dL
• Lymphocyte count ≥ 500/uL
• Estimated glomerular filtration rate (eGFR) based on MDRD (Modification of Diet in Renal Disease) calculation ≥ 30 mL/min/1.73 m^2
• Total bilirubin < 1.5 x upper limit of normal (ULN) (or < 2 x ULN for subjects with liver metastases, or < 3 x ULN for subjects with known Gilbert disease)
• Aspartate aminotransferase (AST) < 3 x ULN (or < 5 x ULN for subjects with liver involvement)
• Alanine aminotransferase (ALT) < 3 x ULN (or < 5 x ULN for subjects with liver involvement)
• Alkaline phosphatase (ALP) < 3 x ULN (or < 5 x ULN for subjects with liver involvement)
• Albumin ≥ 2.5 g/dL
• Patients with indwelling catheters (e.g., PleurX®) are allowed
• Baseline oxygen saturation ≥ 90% on room air
• Chronic obstructive pulmonary disease (COPD) patients on stable supplementary oxygen (O2) for at least 6 months may be considered for inclusion after discussion with the sponsor
• Left ventricular ejection fraction (LVEF) ≥ 50%, no clinically significant pericardial effusion as determined by an ECHO or MUGA, and no clinically significant electrocardiogram (ECG) findings
• As determined by the enrolling physician or protocol designee, the ability of the subject to understand and comply with study procedures for the entire length of the study
• Availability of archival tissue, preferably a formalin-fixed, paraffin-embedded (FFPE) tumor tissue block (or ideally at least 15 newly cut unstained slides). For eligibility, only confirmation of archival tissue is needed. Verification of tumor burden in the biopsy is encouraged. For optimal biomarker results, tumor content should be > 30% of total tissue area
• Be willing to provide peripheral blood samples at specified time-points during the study

Exclusion Criteria:

• Patients currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy within 4 weeks of the first dose of treatment
• Patients with a prior or concurrent malignancy whose natural history or treatment could potentially interfere with the safety or efficacy assessment of the investigational regimen are not eligible for this trial
• Symptomatic brain metastases and/or leptomeningeal disease
• Clinically significant cardiovascular disease per the investigator. Examples include unstable arrhythmia, unstable angina, myocardial infarction, and/or symptomatic congestive heart failure (New York Heart Association class II) within 3 months of the first dose of tarlatamab

• Current history of active and uncontrolled central nervous system (CNS) disease, such as stroke, transient ischemic attack, epilepsy, CNS vasculitis, or neurodegenerative disease

  • Patients with a history of stroke who have not experienced a stroke or transient ischemic attack in the past 6 months and have no residual neurologic deficits as judged by the investigator are permitted to enroll
  • Patients with a history of epilepsy who have had controlled symptoms and no seizures in the past 2 years are allowed

• Subject 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 tarlatamab administration

  • Subject has known active infection requiring parenteral antibiotic treatment. Upon completion of parenteral antibiotics and resolution of symptoms, the subject may be considered eligible for the study from an infection standpoint
  • NOTE: Simple urinary tract infections and uncomplicated bacterial pharyngitis are permitted if responding to active treatment and after consultation with sponsor. Subjects requiring oral antibiotics who have been afebrile for > 72 hours, have no leukocytosis, nor clinical signs of infection are eligible. Screening for chronic infectious conditions is not required unless otherwise noted as an exclusion criterion

• Subjects with active hepatitis or HIV infection, testing is required

  • Patients with a past or resolved hepatitis B virus (HBV) infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of hepatitis B virus surface antigen [HBsAg]) are eligible
  • In patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
  • Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA
  • Subjects with HIV/AIDS with adequate antiviral therapy to control viral load (i.e., undetectable) and lymphocyte count would be allowed if they are stable and have been on treatment for ≥ 4 weeks prior to the first dose of study drug(s)
  • Subjects with viral hepatitis with controlled viral load would be allowed while on suppressive antiviral therapy
• Subject has known sensitivity and immediate hypersensitivity to any components of tarlatamab

• Prior treatment for SCLC. Subjects with limited-stage SCLC (LS-SCLC) who progressed after 6 months from completing chemotherapy and radiation may be considered for inclusion after discussion with the sponsor

  • Palliative radiotherapy is allowed to non-target lesions, and must have been completed at least 7 days prior to the first dose of tarlatamab
  • Subjects with irreversible toxicity (defined as having been present and stable for > 21 days) that, in the opinion of the treating physician, is not reasonably expected to be exacerbated by the investigational product may be included (e.g., neuropathy, alopecia, hearing loss, hormone deficiency requiring replacement therapy)
• Subjects who received major surgery within 30 days. Subjects must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy

• Subjects with known active autoimmune disease or immune deficiency that has required systemic treatment or steroids (except replacement therapy) within the past 2 years or any other diseases requiring immunosuppressive therapy while on study

  • Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
  • Patients with controlled type 1 diabetes mellitus who are on an insulin regimen are eligible for the study.
  • Physiologic doses of steroids are permitted
• Subjects with a known history of solid organ transplantation
• Subjects with evidence of interstitial lung disease or active, non-infectious pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan. Subjects with history of radiation pneumonitis in the radiation field (fibrosis) are permitted
• Subjects with known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
• Live and live attenuated vaccination are prohibited within 28 days prior to the first dose of tarlatamab treatment and for the duration of study. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination should be avoided during screening at least 14 days prior to the first day of tarlatamab treatment

• Subjects of both genders of child-bearing potential who are not willing to practice an acceptable method(s) of effective birth control while on study, and through 60 days (for female subjects) or through 60 days (for male subjects) after receiving last dose of tarlatamab

  • Females who are pregnant or planning to become pregnant or breastfeeding or who plan to breastfeed while on study through 60 days after receiving the last dose of tarlatamab. Subjects who are willing to suspend breastfeeding prior to starting treatment with tarlatamab and do not intend to resume breastfeeding 60 days after receiving the last dose of tarlatamab can be enrolled.
  • Males who are unwilling to abstain from sperm donation while on study and through 60 days after receiving the last dose of tarlatamab

• Symptomatic pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures

  • Patients with indwelling catheters (e.g., PleurX) are allowed
• Subjects with uncontrolled respiratory symptoms or concern about impending respiratory failure due to tumor compression requiring urgent intervention
• Subjects with a history or current evidence of clinically significant disease, condition, therapeutic intervention, or laboratory abnormality that would pose a risk to subject safety and might confound the study evaluation, procedures or completion or may interfere with the subject's participation for the full duration of the trial, in the opinion of the treating investigator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (tarlatamab); Patients receive tarlatamab IV over 60 minutes on days 1, 8, and 15 of cycle 1, then on days 1 and 15 of remaining cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Other: Questionnaire Administration; Ancillary studies; Procedure: Magnetic Resonance Imaging; Undergo MRI; Other Names: MRI; Magnetic Resonance; Magnetic Resonance Imaging Scan; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; MR; MR Imaging; MRI Scan; NMR Imaging; NMRI; Nuclear Magnetic Resonance Imaging; Magnetic Resonance Imaging (MRI); sMRI; Magnetic resonance imaging (procedure); MRIs; Structural MRI; Procedure: Biospecimen Collection; Undergo blood sample collection; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Procedure: Multigated Acquisition Scan; Undergo MUGA; Other Names: Blood Pool Scan; Equilibrium Radionuclide Angiography; Gated Blood Pool Imaging; MUGA; Radionuclide Ventriculography; RNVG; SYMA Scanning; Synchronized Multigated Acquisition Scanning; MUGA Scan; Multi-Gated Acquisition Scan; Radionuclide Ventriculogram Scan; Gated Heart Pool Scan; RNV Scan; Other: Electronic Health Record Review; Ancillary studies; Procedure: Echocardiography Test; Undergo ECHO; Other Names: Echocardiography; EC; Procedure: Biopsy Procedure; Undergo biopsies; Other Names: Bx; BIOPSY_TYPE; Biopsy; Procedure: Computed Tomography; Undergo computed tomography; Other Names: CT; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized Tomography; CT Scan; tomography; Computerized axial tomography (procedure); Computerized Tomography (CT) scan; Diagnostic CAT Scan; Diagnostic CAT Scan Service Type; Drug: Tarlatamab; Given IV; Other Names: AMG 757; Imdelltra; AMG-757; AMG757; Anti-DLL3 x Anti-CD3 BiTE AMG 757; Bispecific T-cell Engager Antibody AMG 757; BiTE Antibody AMG 757; DLL3/CD3-directed Bispecific T-cell Engager Antibody AMG 757; Tarlatamab-dlle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
6-month progression-free survival (PFS)	Will be evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 or death as a result of any cause. Will be calculated as the proportion of patients who are progression-free and alive divided by the total number of evaluable patients. Exact binomial 95% confidence intervals (CIs) for the 6-month PFS true rate will be calculated.	From the initiation of investigational therapy to progression, symptomatic deterioration, or death due to any cause, whichever comes first, assessed up to 6 months
Rapid progressive disease (PD) on tarlatamab rate probability (Interim analysis for futility monitoring)	Will be measured by RECIST v 1.1. Will be measured by the proportion of patients who have clinical and rapid clinical and radiological progression and move on to receive subsequent standard of care platinum-based chemotherapy and immune checkpoint inhibitors divided by the total number of evaluable patients. Exact binomial 95% CIs for the tarlatamab failure true rate will be calculated.	Within 4 weeks of starting tarlatamab

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of all adverse events (AEs)	Will be summarized using National Cancer Institute Common Terminology Criteria for Adverse Events v 5.0. Frequency and severity and tolerability of the regimen will be collected and summarized using descriptive statistics. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns. The incidence of all and severe (grade 3+) AEs or toxicities will be described. Time to onset and duration will be described. The number of patients who required dose delays and/or treatment discontinuation will be assessed. Will capture the proportion of patients who go off treatment due to adverse reactions or even those who refuse further treatment for lesser toxicities that inhibit their willingness to continue participation on the trial.	Up to 30 days after last dose of study treatment
Rate of all cytokine release syndrome	Will be measured using American Society for Transplantation and Cellular Therapy (ASTCT). Frequency and severity and tolerability of the regimen will be collected and summarized using descriptive statistics. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns. The incidence of all and severe (grade 3+) AEs or toxicities will be described. Time to onset and duration will be described. The number of patients who required dose delays and/or treatment discontinuation will be assessed. Will capture the proportion of patients who go off treatment due to adverse reactions or even those who refuse further treatment for lesser toxicities that inhibit their willingness to continue participation on the trial.	Up to 30 days after last dose of study treatment
Rate of all immune effector cell associated neurotoxicity syndrome	Will be measured using ASTCT. Frequency and severity and tolerability of the regimen will be collected and summarized using descriptive statistics. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns. The incidence of all and severe (grade 3+) AEs or toxicities will be described. Time to onset and duration will be described. The number of patients who required dose delays and/or treatment discontinuation will be assessed. Will capture the proportion of patients who go off treatment due to adverse reactions or even those who refuse further treatment for lesser toxicities that inhibit their willingness to continue participation on the trial.	Up to 30 days after last dose of study treatment
Overall objective response rate (ORR)	Will be calculated by the proportion of patients with confirmed complete response (CR) or partial response (PR) using RECIST v 1.1 divided by the total number of evaluable patients. Exact binomial 95% CIs for the true PR + CR response rate will be calculated.	Up to 2 years after last dose of study treatment
Duration of response (DOR)	Will be determined using RECIST v 1.1. The Kaplan-Meier method will be used to estimate DOR. Median with 95% CI will be calculated.	From first occurrence of a documented objective response to the time of disease progression or death from any cause, whichever comes first, assessed up to 2 years after last dose of study treatment
Disease control rate	Will be calculated as the proportion of patients with stable disease (SD), PR or CR according to RECIST v 1.1 divided by the total number of evaluable patients. Exact binomial 95% CIs for the true SD + PR + CR response rate will be calculated.	Up to 2 years after last dose of study treatment
Intracranial PFS rate (icPFS)	Will be defined as the percentage of patients without intracranial disease progression including development of new lesions, development of symptomatic lesions or leptomeningeal disease, or intervention required for disease control (such as radiation or surgery). The Kaplan-Meier method will be used to estimate icPFS. Median with 95% CI will be calculated.	From initiation of investigational therapy to progression, symptomatic deterioration, or death due to any cause, whichever comes first, assessed up to 6 months
Best intracranial ORR	Will be defined as the best overall intracranial response across all efficacy assessments, based on up to 5 measurable intracranial lesions (as per RECIST 1.1 criteria for measurable/target lesions) as well as unmeasurable and new intracranial disease per RECIST 1.1 principles.	From start of investigational therapy to the first documented objective intracranial response, assessed up to 2 years after last dose of study treatment
Median PFS	Progression will be defined by RECIST v 1.1. The Kaplan-Meier method will be used to estimate PFS. Median with 95% CI will be calculated.	From initiation of investigational therapy until criteria for disease progression is met or death as a result of any cause, assessed up to 2 years after last dose of study treatment
Overall survival (OS)	The Kaplan-Meier method will be used to estimate OS. Median with 95% CI will be calculated.	From initiation of investigational therapy to date of death from any cause, assessed up to 12 months
OS in patients treated with tarlatamab in first-line settings	Will be defined as the percentage of patients alive. The Kaplan-Meier method will be used to estimate OS. Median with 95% CI will be calculated.	From initiation of investigational therapy to death as a result of any cause, assessed up to 12 months

Collaborators and Investigators

• Sponsor: Asrar Alahmadi
• Collaborators: Amgen
• Investigators: Principal Investigator: Asrar AlAhmadi, MBBS, Ohio State University Comprehensive Cancer Center

Publications and helpful links

Helpful Links

• The Jamesline

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: February 13, 2026
• First Submitted That Met QC Criteria: February 13, 2026
• First Posted (Actual): February 20, 2026

Study Record Updates

• Last Update Posted (Actual): February 20, 2026
• Last Update Submitted That Met QC Criteria: February 13, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: extensive stage small cell lung cancer; Small cell lung cancer; window of opportunity; tarlatamab
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Small Cell Lung Carcinoma; Investigative Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Surgical Procedures, Operative; Cytological Techniques; Cytodiagnosis; Diagnostic Techniques, Surgical; Chemistry Techniques, Analytical; Spectrum Analysis; AMG 757; Biopsy; Specimen Handling; Magnetic Resonance Spectroscopy
• Other Study ID Numbers: OSU-25028 (Other Identifier: Ohio State University Comprehensive Cancer Center); NCI-2026-00832 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No