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

Plain English Summary

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 is a Phase 2 clinical trial sponsored by National Cancer Institute (NCI) studying Extensive-Stage Small Cell Lung Cancer, Extrapulmonary Neuroendocrine Carcinoma, Small Cell Carcinoma. This trial tests a combination of two drugs, tarlatamab and sacituzumab govitecan, for patients with specific types of advanced lung cancer (small cell lung cancer) or neuroendocrine cancer that has returned or not responded to prior treatment. It is for adults aged 18 and older with extensive-stage small cell lung cancer or extrapulmonary neuroendocrine carcinoma that has progressed after at least one prior chemotherapy regimen. Participation involves regular intravenous infusions of the study drugs, physical exams, blood tests, heart function tests, and imaging scans to monitor safety and effectiveness. Alternative treatments may include other chemotherapy regimens, targeted therapies, or immunotherapy, depending on the specific cancer type and prior treatments. The trial aims to enroll 120 participants.

Official 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.

Who Can Participate

Here is what you need to know about eligibility for this trial. Patients with small cell lung cancer or extrapulmonary neuroendocrine carcinoma that has progressed or returned after previous treatment. Must be 18 years or older and have a performance status of 2 or less (meaning they can perform light self-care activities). Must have adequate blood counts, liver, and kidney function, and measurable disease. Cannot have active autoimmune conditions, be pregnant or breastfeeding, or be receiving other investigational treatments. This trial is studying Extensive-Stage Small Cell Lung Cancer, Extrapulmonary Neuroendocrine Carcinoma, Small Cell Carcinoma, so participants generally need a confirmed diagnosis.

What They're Measuring

The primary outcome measures how well the combination therapy shrinks tumors (Objective Response Rate) and how long patients live without their cancer getting worse (Progression-Free Survival), indica The specific primary outcome measures are: Phase I: Maximum Tolerated Dose (MTD) (Dose Limiting Toxicity (DLT) period (C1D1 through C1D28)); Phase II: Objective Response Rate (ORR) (Until disease progression). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial addresses a critical need for better treatments for aggressive small cell lung cancer and extrapulmonary neuroendocrine cancer, which have limited options after initial therapies fail. Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Extensive-Stage Small Cell Lung Cancer, Extrapulmonary Neuroendocrine Carcinoma, Small Cell Carcinoma, where improved treatment options are needed.

Investor Insight

This trial targets a significant unmet need in aggressive cancers, with potential for a novel combination therapy to improve outcomes, signaling a promising area for investment in oncology drug develo Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor about the potential benefits and risks of tarlatamab and sacituzumab govitecan, and how this combination might fit with your specific situation. Be prepared for regular clinic visits for infusions, monitoring tests, and potential side effects. Understand that treatment cycles are 4 weeks long and can continue for up to 2 years, or until the cancer progresses or side effects become too severe. The trial is being conducted at 1 site. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NA
• Model: SEQUENTIAL
• Masking: NONE
• Enrollment: 120 participants

Interventions

• DRUG: Tarlatamab — 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
• DRUG: Sacituzumab Govitecan — 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

Primary Outcomes

• Phase I: Maximum Tolerated Dose (MTD) (Dose Limiting Toxicity (DLT) period (C1D1 through C1D28))
• Phase II: Objective Response Rate (ORR) (Until disease progression)

Secondary Outcomes

• Safety (Study duration)
• Overall survival (OS) (Until death or study is stopped)
• Duration of response (DOR) and Progression free survival (PFS) (Until disease progression)

Full Eligibility Criteria

* INCLUSION CRITERIA:
* 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
* 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.

1. Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks.
2. 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.

EXCLUSION CRITERIA:

* 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

Trial Locations

• National Institutes of Health Clinical Center, Bethesda, Maryland, United States

Frequently Asked Questions

Related Conditions

• Small Cell Lung Cancer
• Extrapulmonary Neuroendocrine Carcinoma
• Neuroendocrine Tumors
• Lung Cancer
• Oncology
• Cancer Immunotherapy
• Targeted Therapy
• Chemotherapy
• Advanced Cancer
• Metastatic Cancer

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