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

NCT07328490 | Withdrawn Phase 1 FDA Drug

• 2 other identifiers: 10001942001942-C
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief 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. Better treatments are needed for these cancers. 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.

Conditions

Extensive-Stage Small Cell Lung Cancer; Small Cell Carcinoma; Extrapulmonary Neuroendocrine Carcinoma

Keywords

Tarlatamab; Sacituzumab Govitecan; Bispecific T-cell Engager; Immunotherapy; Antibody Drug Conjugate; Targeted Therapy

Outcome Measures

Primary Outcomes (2)

• Phase I: Maximum Tolerated Dose (MTD)

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

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

• 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.

  Until disease progression

Secondary Outcomes (3)

• Safety

  Study duration

• Overall survival (OS)

  Until death or study is stopped

• Duration of response (DOR) and Progression free survival (PFS)

  Until disease progression

Study Arms (2)

1/ Phase I

EXPERIMENTAL

Dose escalated Tarlatamab and Sacituzumab Govitecan

Drug: Tarlatamab; Drug: Sacituzumab Govitecan

2/ Phase II

EXPERIMENTAL

Maximum tolerated dose (MTD) Tarlatamab and Sacituzumab Govitecan

Drug: Tarlatamab; Drug: Sacituzumab Govitecan

Interventions

Sacituzumab Govitecan DRUG

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.

1/ Phase I; 2/ Phase II

Tarlatamab DRUG

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.

1/ Phase I; 2/ Phase II

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Small Cell Lung Carcinoma; Carcinoma, Small Cell

Interventions

sacituzumab govitecan

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Study Officials

• Anish Thomas, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 8, 2026
• First Posted: January 9, 2026
• Study Start: April 25, 2026
• Primary Completion: April 25, 2026
• Study Completion: April 25, 2026
• Last Updated: April 28, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Data will be made available as soon as possible or at the time of associated publication, whichever comes first.
• Access Criteria: Data from this study may be requested by contacting the PI.

Locations

US (1)