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Extensive-Stage Small Cell Lung CancerPhase 1/2NCT07328490

Bispecific T-Cell Engager Tarlatamab and TROP2 Targeted Antibody Drug Conjugate Sacituzumab Govitecan in Previously Treated Extensive-Stage Small Cell Lung Cancer and Extrapulmonary Neuroendocrine Cancer

A Phase 1/2 study testing Tarlatamab and Sacituzumab Govitecan in people with Extensive-Stage Small Cell Lung Cancer and Extrapulmonary Neuroendocrine Carcinoma, run by National Cancer Institute (NCI) at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
Search all trials

Trial summary

Background: Small-cell lung cancer (SCLC) is the most deadly form of lung cancer. It kills at least 250,000 worldwide each year. Extra-pulmonary neuroendocrine cancer (EP-NEC) is a similar type of cancer that develops anywhere other than the lungs. EP-NEC is also very aggressive. Read more about this study

Who is it for?
Ages 18 to 120 years
What is being tested?
Tarlatamab and Sacituzumab Govitecan
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteUnited States
Study dates
25 Apr 2026to 25 Apr 2026
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 120 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Must have histologically or cytologically confirmed SCLC or EP-NEC meeting the criteria below:
  • SCLC that has progressed or recurred after a combination of platinum-based regimen and immunotherapy. Participants may be eligible after treatment with chemo or immunotherapy alone if they were intolerant to one of the components. Participants with previously locally advanced SCLC who have completed definitive chemoradiation therapy, with or without surgical resection, and subsequently experienced disease progression or recurrence, are also eligible. OR
  • EP-NEC that has progressed or recurred after at least one prior chemotherapy.
  • Must have measurable disease, per RECIST 1.1
  • Age >=18 years.
  • Eastern Cooperative Oncology Group (ECOG) performance status <=2.
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  • Must have adequate organ and marrow function as defined below:
  • System/Laboratory Value
  • Hematological
  • Hemoglobin/>=9 g/dL(a)
  • Absolute neutrophil count/>= 1,500/mcL
  • Platelets/>= 100,000/mcL
  • System/Laboratory Value
  • Hepatic
  • Total bilirubin/within normal institutional limits
  • AST (SGOT) and ALT (SGPT) <= 2.5 X institutional ULN (<=5 X ULN for participants with liver metastases)
  • Renal
  • -Creatinine/ within normal institutional limits
  • OR
  • -Calculated (b) creatinine clearance (GFR can also be used in place of creatinine or CrCl)/>=60 mL/min for participant with creatinine levels above institutional normal
  • OR
  • Coagulation
  • Prothrombin time (PT) <=1.5 x ULN unless participant is receiving anticoagulant therapy if PT or PTT is within therapeutic range of intended use of anticoagulants
  • Partial thromboplastin time (PTT) <=1.5 x ULN unless participant is receiving anticoagulant therapy if PT or PTT is within therapeutic range of intended use of anticoagulants
  • ALT (SGPT)=alanine aminotransferase (serum glutamic pyruvic transaminase);
  • AST (SGOT)=aspartate aminotransferase (serum glutamic oxaloacetic transaminase);
  • GFR=glomerular filtration rate; ULN=upper limit of normal.
  • Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks.
  • Creatinine clearance (CrCl) should be calculated per institutional standard.
  • Individuals with neurologically stable brain metastases defined as asymptomatic metastasis, or treated metastasis having no evidence of progression or hemorrhage for at least 1 week after treatment (including brain radiotherapy) may be included. Individuals must be off any systemic corticosteroids for the treatment of brain metastases for at least 7 days prior to study drug initiation.
  • Individuals with human immunodeficiency virus (HIV) must be on effective antiretroviral therapy with undetectable viral load at screening.
  • Individuals with evidence of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load at screening.
  • Individuals with a history of hepatitis C virus (HCV) infection must have been treated and cured. Individuals with active HCV infection who are currently on treatment are eligible if they have an undetectable HCV viral load at screening.
  • Must agree to use an effective method of contraception (barrier, hormonal, intrauterine device [IUD], surgical sterilization, abstinence) during study treatment and for 3 months thereafter for males or 6 months for women of childbearing potential (WOCBP).
  • Willingness to discontinue nursing during study treatment and for 2 months after the last dose of study treatment.
  • Ability to understand and the willingness to sign a written informed consent document.

Who cannot join

  • Receiving any other investigational agents or concurrent systemic anti-cancer therapies. Any previous non-investigational treatment must be completed at least 2 weeks prior to study drug initiation.
  • Prior exposure to tarlatamab or other DLL3-targeting agents/T-cell engagers (TCE).
  • Requiring radiation therapy during study treatment. Radiation therapy may be allowed if needed for palliative/symptom control (e.g., bone metastasis) but must be completed at least 7 days before study drug initiation.
  • Severe and unresolved active autoimmune inflammatory conditions.
  • Pregnant women, breastfeeding women, and women planning to become pregnant or donate eggs should not take part in this study.
  • Requiring immunosuppressive agents with the exception of those required by protocol, treatment for adverse events, Central Nervous System (CNS) metastases corticosteroid replacement therapy.
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  • Require live and live-attenuated vaccines during study treatment with tarlatamab or within 4 weeks of first dose of tarlatamab. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, yellow fever, rabies, Bacillus Calmette-Guerin (BCG), and typhoid (oral) vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed. However, intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines and are not allowed.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to study drugs or other agents used in study.
  • Requiring treatment with inhibitors or inducers of UGT1A1 during the planned period of study treatment.
  • QTc >= 470 msec or any conditions or factors that may increase the risk of QTc prolongation.
  • Uncontrolled intercurrent illness, evaluated by medical history and physical exam which would potentially increase risk to the participant.

Trial locations and contacts

1 site in 1 country.

United States1 site
  • National Institutes of Health Clinical Center

    Bethesda, Maryland, 20892

Other trials in United States

About this study

Official title: A Phase I/II Study to Assess the Safety and Antitumor Activity of Bispecific T-cell Engager Tarlatamab and TROP2 Targeted Antibody Drug Conjugate Sacituzumab Govitecan in Previously Treated Extensive-Stage Small Cell Lung Cancer and Extrapulmonary Neuroendocrine Cancer

Background:

Small-cell lung cancer (SCLC) is the most deadly form of lung cancer. It kills at least 250,000 worldwide each year. Extra-pulmonary neuroendocrine cancer (EP-NEC) is a similar type of cancer that develops anywhere other than the lungs. EP-NEC is also very aggressive. Better treatments are needed for these cancers.

Read more

Objective:

To test 2 drugs (tarlatamab combined with sacituzumab govitecan [SG]) in people with SCLC or EP-NEC.

Eligibility:

People aged 18 years and older with SCLC or EP-NEC that either did not respond to or returned after treatment.

Design:

Participants will be screened with a physical exam, blood tests, heart function testing, and imaging scans.

Both study drugs are given intravenously (through a needle in the arm). Participants will receive a small starter dose of tarlatamab (1 mg) 2 weeks before beginning regular treatment, followed by the full dose (10 mg) one week later. Treatment then follows a repeating 4-week cycle: tarlatamab (10 mg) on days 1 and 15, and sacituzumab govitecan (7.5 or 10 mg/kg) on days 1 and 8. Treatment continues for up to 2 years, unless the cancer worsens, the participant passes away, or side effects become too severe.

Participants will have regular check-ups including physical exams, blood tests, and imaging scans to monitor safety and treatment response. Blood and tumor samples will be collected for research purposes.

After stopping treatment, participants will return for a safety check at 30 days, then be contacted every 3 months to check on their health and survival. Those who stop treatment for reasons other than cancer progression will continue CT scans every 8 weeks until their disease progresses.

Read the detailed description

Background:

  • Small-cell lung cancer (SCLC) is the most fatal and metastatic form of lung cancer which kills at least 250,000 people globally each year including more than 30,000 in the United States. SCLC constitutes approximately 14% of all lung cancers.
  • SCLC consists of tumor cells with neuroendocrine (NE) and non-neuroendocrine (non-NE) features. SCLC subtypes exhibit distinct therapeutic vulnerabilities. Immunogenic plasticity and Notch signaling of non-NE SCLC underlie their responses to immune checkpoint blockade. NE SCLC is characterized by replication stress, rendering them susceptible to deoxyribonucleic acid (DNA) repair-targeted agents.
  • The inhibitory Notch delta-like ligand 3 (DLL3) is aberrantly expressed on the surface of up to 85% of SCLC, mostly NE cells and minimally expressed in normal tissues, making it a compelling therapeutic target for NE SCLC. Trophoblast cell-surface antigen 2 (TROP2) is a transmembrane glycoprotein aberrantly expressed in SCLC during its progression from NE to the non-NE cell state, making it a compelling therapeutic target of non-NE SCLC.
  • Tarlatamab is a bispecific T cell engager (BiTE) molecule which binds DLL3 on cancer cells and cluster of differentiation 3 (CD3) on T cells leading to T cell-mediated tumor lysis. Sacituzumab govitecan (SG) is an antibody drug conjugate (ADC) carrying a topoisomerase 1 (TOP1) inhibitor SN-38 payload to cancer cells expressing TROP2.
  • Extrapulmonary neuroendocrine cancers (EP-NEC) are rare and aggressive orphan cancers that share morphological and transcriptomic similarities and potentially therapeutic vulnerabilities with SCLC, with no standard treatments at relapse.
  • In the current study, combination therapies targeting DLL3 and TROP2, using a combination of tarlatamab and sacituzumab govitecan will be evaluated as potential drivers of durable response in SCLC and EP-NEC.

Objectives:

Phase I:

-To determine the maximum tolerated dose (MTD) of bispecific T-cell engager tarlatamab and TROP2 targeted antibody drug conjugate sacituzumab govitecan in participants with previously treated relapsed SCLC or EP-NEC.

Phase II:

-To determine the clinical benefit in terms of objective response rates (ORR) in participants with previously treated relapsed SCLC or EP-NEC.

Eligibility:

->=18 years.

  • Histologically or cytologically confirmed SCLC or EP-NEC that has progressed or recurred after at least one previous platinum-based regimen and immunotherapy.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less.

Design:

  • This is a Phase I/II, open label clinical trial aimed at identifying the MTD of Sacituzumab govitecan in combination with tarlatamab and assessing the efficacy with respect to objective response rate in recurrent SCLC and EP-NEC.
  • Participants will receive a step dose of 1mg tarlatamab 14 days prior to the first cycle followed by a full dose (10mg) starting a week later. Thereafter, tarlatamab will be administered on days 1 and 15 and sacituzumab govitecan (7.5 or 10 mg/Kg) will be administered on days 1 and 8 of every 4-week cycle. Treatment will be administered for up to 2 years or until disease progression/death or development of intolerable side effects (whichever occurs first).
  • During treatment, participants will have clinical assessments, laboratory evaluations, and imaging studies for safety and response assessment. Blood and tumor samples will be collected for correlative studies at various timepoints.
  • Participants will be followed for survival every 3 months following objective disease progression.
Being tested
Tarlatamab, Sacituzumab Govitecan
Keywords
Tarlatamab, Sacituzumab Govitecan, Bispecific T-cell Engager, Immunotherapy, Antibody Drug Conjugate, Targeted Therapy
Medical subject headings
Small Cell Lung Carcinoma, Carcinoma, Small Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TarlatamabDrug

    For both Phase I and Phase II, participants will receive a step dose of 1 mg of Tarlatamab (IV) followed by a full dose of 10 mg starting 7 days later (i.e., step dosing phase). Cycle 1 will begin following the Tarlatamab step-dosing (i.e., 14 days after the first dose and 7 days after the second dose of Tarlatamab alone) with participants receiving a combination of Tarlatamab (full dose) and Sacituzumab Govitecan (IV 7.5 or 10 mg/Kg) on day 1, SG alone on day 8 and Tarlatamab alone on day 15 of every cycle (4-week cycles) for up to 2 years or until disease progression/death, development of intolerable side effects.

  • Sacituzumab GovitecanDrug

    For both Phase I and Phase II, participants will receive a step dose of 1 mg of Tarlatamab (IV) followed by a full dose of 10 mg starting 7 days later (i.e., step dosing phase). Cycle 1 will begin following the Tarlatamab step-dosing (i.e., 14 days after the first dose and 7 days after the second dose of Tarlatamab alone) with participants receiving a combination of Tarlatamab (full dose) and Sacituzumab Govitecan (IV 7.5 or 10 mg/Kg) on day 1, SG alone on day 8 and Tarlatamab alone on day 15 of every cycle (4-week cycles) for up to 2 years or until disease progression/death, development of intolerable side effects.

Study groups in NCT07328490
Study groupRoleWhat they receive
1/ Phase IExperimentalDose escalated Tarlatamab and Sacituzumab Govitecan
Receives: Drug: Tarlatamab; Drug: Sacituzumab Govitecan
2/ Phase IIExperimentalMaximum tolerated dose (MTD) Tarlatamab and Sacituzumab Govitecan
Receives: Drug: Tarlatamab; Drug: Sacituzumab Govitecan

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Phase I: Maximum Tolerated Dose (MTD)

    The toxicities identified at each dose level will be reported, by dose level, type, and grade.

    Measured: Dose Limiting Toxicity (DLT) period (C1D1 through C1D28)

  2. Phase II: Objective Response Rate (ORR)

    In each of the two main cohorts, the fraction of participants who experience a partial response (PR) or complete response (CR) will be reported along with a 95% confidence interval.

    Measured: Until disease progression

Secondary outcomes (3)
  1. Safety

    Toxicities identified at each dose level will be reported, by dose level, type, and grade.

    Measured: Study duration

  2. Overall survival (OS)

    OS will be calculated from the on-study date until date of death, or 6 months after the last study participant goes off-treatment, whichever comes earlier.

    Measured: Until death or study is stopped

  3. Duration of response (DOR) and Progression free survival (PFS)

    Duration of response will be calculated by the Kaplan-Meier method, starting at date response was identified until progression or the response is declared to have ended, if the participants have a PR or CR.PFS will be calculated from on-study date until date of progression or death without progression, using the Kaplan-Meier method.

    Measured: Until disease progression

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Jan 2026
  2. Study start25 Apr 2026
  3. Primary completion25 Apr 2026
  4. Study completion25 Apr 2026

Why it stopped: Study drug supplier withdrew support; no participants were enrolled.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Sequential
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07328490
Sponsor's protocol ID
10001942
Other IDs
001942-C
Status last verified
Apr 2026
First submitted
8 Jan 2026
Last updated
28 Apr 2026
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: All IPD recorded in the medical record will be shared with intramural investigators upon request. This study will comply with the NIH Data Management and Sharing (DMS) Policy, which applies to all new and ongoing NIH-funded research in the IRP, as of January 25, 2023, that is associated with a ZIA, with a clinical protocol that undergoes scientific review.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Tarlatamab and Sacituzumab Govitecan in people with Extensive-Stage Small Cell Lung Cancer and Extrapulmonary Neuroendocrine Carcinoma, run by National Cancer Institute (NCI) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 36 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 28 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase I: Maximum Tolerated Dose (MTD) (time frame: Dose Limiting Toxicity (DLT) period (C1D1 through C1D28)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Apr 2026.

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