RECRUITING

Tarlatamab in Advanced Delta-like 3 (DLL3)-Expressing Tumors Including Neuroendocrine Neoplasms

Conditions

DLL3-expressing Tumors Advanced Tumors tumor

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This study is being done to learn more about the drug tarlatamab in people with your condition. The purpose of this study is to see the efficacy (how well something works) of study treatment (tarlatamab) and whether it causes any side effects. Tarlatamab is being developed as an anti-cancer drug for tumors and is FDA-approved for extensive-stage small cell lung cancer. Tarlatamab is investigational for the purpose of this study.

Official Title

Tarlatamab in Advanced DLL3-Expressing Tumors Including Neuroendocrine Neoplasms

Quick Facts

Study Start:2025-03-21

Study Completion:2029-04-24

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06788938

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Participant has provided informed consent prior to initiation of any study specific activities/procedures. 2. Male or female ≥ 18 years of age and willing and able to provide informed consent. 3. Histologically or cytologically confirmed malignancy other than de novo (i.e., non-transformed) SCLC or NEPC. Must be stage IV (metastatic); participants with stage III disease are eligible provided that they are not candidates for surgery and/or radiotherapy with curative intent. Acceptable tumor types include the following: * Low and intermediate grade neuroendocrine carcinoma (including carcinoid and atypical carcinoid) * Gastroenteropancreatic NEN * Large cell neuroendocrine carcinoma * SCLC transformed from previously-treated NSCLC * Extrapulmonary small cell carcinoma, with the exception of NEPC * Any other tumor type that meets staging and DLL3 positivity criteria 4. Positive DLL3 expression by immunohistochemistry on tumor biopsy. 5. Participants must have progressed on or following at least one line of therapy, if a standard of care therapy exists for the tumor type. 6. Measurable disease, as per RECIST 1.1 7. ECOG performance status of 0-1. 8. Adequate organ function as defined in Table 3 below. System Laboratory Value Hematological Absolute neutrophil count (ANC) ≥ 1.0 x 109/L Platelets ≥ 100 x 109/L Hemoglobin ≥ 9 g/dL Renal Estimated glomerular filtration rate (eGFR) based on Modification of Diet in Renal Disease (MDRD) ≥ 30 mL/min/1.73 m2 Hepatic Serum total bilirubin ≤ 1.5 x ULN, with the exception of participants with Gilbert's disease AST (SGOT) and ALT (SGPT) ≤ 3 x ULN≤ 5 x ULN for patients with liver metastasis or primary liver cancer Coagulation International Normalized Ratio (INR) or Prothrombin Time (PT), and Activated Partial Thromboplastin Time (aPTT) ≤ 1.5 x ULN unless participant is receiving anticoagulant therapy, and then only as long as PT or PTT is within therapeutic range of intended use of anticoagulants	1. Diagnosis of SCLC (with the exception of SCLC transformed from previously-treated NSCLC) or NEPC. 2. Tumor specimen is not evaluable for DLL3 expression or tumor has DLL3 surface expression \< 1% by immunohistochemistry. 3. Progressive or symptomatic brain metastases. Brain metastases that have been radiated, are asymptomatic, and on a stable or decreasing dose of steroids are allowed. Leptomeningeal disease is excluded. 4. Evidence of interstitial lung disease or active, non-infectious pneumonitis. Exception: pneumonitis related to prior radiation therapy that is grade 1 and stable or improving without treatment. 5. Concurrent enrollment in another clinical study, unless enrolled only in the follow-up period or an observational study. Use of any investigational anticancer therapy must not have been received within 28 days prior to the first dose of study drugs. 6. Any chemotherapy, antibody drug conjugate or immunotherapy for cancer treatment in the prior 21 days, or small molecular inhibitor in the prior 7 days. 7. Prior therapy with any selective inhibitor of the DLL3 pathway. 8. Prior history of severe or life-threatening events from any immune-mediated therapy. 9. Receiving systemic corticosteroid therapy or any other form of immunosuppressive therapy within 7 days prior to enrollment. Low-dose corticosteroids (prednisone ≤ 10 mg per day or equivalent is permitted) 10. Major surgical procedures within 28 days prior to first dose of study treatment. 11. Treatment with live virus, including live-attenuated vaccination, within 14 days prior to the first dose of study treatment. Inactive vaccines (e.g., non-live or non-replicating agent) and live viral non-replicating vaccines within 3 days prior to first dose of study treatment. 12. History of other malignancy within the past 2 years, with the following exceptions: * Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease. * Adequately treated cervical carcinoma in situ without evidence of disease. * Adequately treated breast ductal carcinoma in situ without evidence of disease. * Prostatic intraepithelial neoplasia without evidence of prostate cancer. * Adequately treated urothelial papillary noninvasive carcinoma or carcinoma in situ. 13. History of myocardial infarction and/or symptomatic congestive heart failure (New York Heart Association, class II) within 6 months prior to first dose of study treatment. 14. History of arterial thrombosis (e.g., stroke or transient ischemic attack) within 6 months prior to first dose of study treatment. 15. Human immunodeficiency virus (HIV) infection. 16. Active hepatitis C infection. 17. Active hepatitis B infection. • Defined as presence of hepatitis B surface antigen \[HBsAg-positive\] and hepatitis B virus \[HBV\] DNA viral load above the limit of quantification \[HBV DNA positive\] • Participants with resolved HBV infection defined as absence of HBV surface antigen (HBsAg-negative) and presence of HBV core antibody (anti-HBc positive) followed by an HBV DNA viral load below the limit of quantification (HBV DNA negative) are allowed, with a requirement for regular monitoring for reactivation for the duration of treatment on the study and assessing the need for HBV prophylaxis therapy per local or institutional guidelines. 18. Participants 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 study treatment. * Upon completion of antibiotics and resolution of symptoms, the participant may be considered eligible for the study from an infection standpoint. * Simple urinary tract infection (UTI) and uncomplicated bacterial pharyngitis are permitted if responding to active treatment. Participants requiring oral antibiotics who have been afebrile \> 24 hours, have no leukocytosis, nor clinical signs of infection are eligible. Screening for chronic infectious conditions is not required unless otherwise noted as exclusion criteria. 19. Female participants of childbearing potential unwilling to use protocol specified method of contraception (see Section 5.7.2) during treatment and for an additional 60 days after the last dose of study treatment. 20. Female participants who are breastfeeding or who plan to breastfeed while on study through 60 days after the last dose of study treatment. 21. Female participants planning to become pregnant or donate eggs while on study through 60 days after the last dose of study treatment. 22. Female participants of childbearing potential with a positive pregnancy test assessed at screening by a highly sensitive serum pregnancy test. 23. Male participants with a female partner of childbearing potential who are unwilling to practice sexual abstinence (refrain from heterosexual intercourse) or use contraception during treatment and for an additional 60 days after the last dose. 24. Male participants with a pregnant partner who are unwilling to practice abstinence or use a condom during treatment and for an additional 60 days after the last dose of study treatment. 25. Male participants unwilling to abstain from donating sperm during treatment and for an additional 60 days after the last dose of study treatment. 26. Participant has known sensitivity to any of the products or components to be administered during dosing. 27. Participant likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures (e.g., Clinical Outcome Assessments) to the best of the participant's and investigator's knowledge. 28. History or evidence of any other clinically significant disorder, condition, or disease (with the exception of those outlined above) that, in the opinion of the investigator, if consulted, would pose a risk to participant safety or interfere with the study evaluation, procedures or completion.

Inclusion Criteria

Exclusion Criteria

1. Participant has provided informed consent prior to initiation of any study specific activities/procedures.
2. Male or female ≥ 18 years of age and willing and able to provide informed consent.
3. Histologically or cytologically confirmed malignancy other than de novo (i.e., non-transformed) SCLC or NEPC. Must be stage IV (metastatic); participants with stage III disease are eligible provided that they are not candidates for surgery and/or radiotherapy with curative intent. Acceptable tumor types include the following:
* Low and intermediate grade neuroendocrine carcinoma (including carcinoid and atypical carcinoid)
* Gastroenteropancreatic NEN
* Large cell neuroendocrine carcinoma
* SCLC transformed from previously-treated NSCLC
* Extrapulmonary small cell carcinoma, with the exception of NEPC
* Any other tumor type that meets staging and DLL3 positivity criteria
4. Positive DLL3 expression by immunohistochemistry on tumor biopsy.
5. Participants must have progressed on or following at least one line of therapy, if a standard of care therapy exists for the tumor type.
6. Measurable disease, as per RECIST 1.1
7. ECOG performance status of 0-1.
8. Adequate organ function as defined in Table 3 below. System Laboratory Value Hematological Absolute neutrophil count (ANC) ≥ 1.0 x 109/L Platelets ≥ 100 x 109/L Hemoglobin ≥ 9 g/dL Renal Estimated glomerular filtration rate (eGFR) based on Modification of Diet in Renal Disease (MDRD) ≥ 30 mL/min/1.73 m2 Hepatic Serum total bilirubin ≤ 1.5 x ULN, with the exception of participants with Gilbert's disease AST (SGOT) and ALT (SGPT) ≤ 3 x ULN≤ 5 x ULN for patients with liver metastasis or primary liver cancer Coagulation International Normalized Ratio (INR) or Prothrombin Time (PT), and Activated Partial Thromboplastin Time (aPTT) ≤ 1.5 x ULN unless participant is receiving anticoagulant therapy, and then only as long as PT or PTT is within therapeutic range of intended use of anticoagulants

1. Diagnosis of SCLC (with the exception of SCLC transformed from previously-treated NSCLC) or NEPC.
2. Tumor specimen is not evaluable for DLL3 expression or tumor has DLL3 surface expression \< 1% by immunohistochemistry.
3. Progressive or symptomatic brain metastases. Brain metastases that have been radiated, are asymptomatic, and on a stable or decreasing dose of steroids are allowed. Leptomeningeal disease is excluded.
4. Evidence of interstitial lung disease or active, non-infectious pneumonitis. Exception: pneumonitis related to prior radiation therapy that is grade 1 and stable or improving without treatment.
5. Concurrent enrollment in another clinical study, unless enrolled only in the follow-up period or an observational study. Use of any investigational anticancer therapy must not have been received within 28 days prior to the first dose of study drugs.
6. Any chemotherapy, antibody drug conjugate or immunotherapy for cancer treatment in the prior 21 days, or small molecular inhibitor in the prior 7 days.
7. Prior therapy with any selective inhibitor of the DLL3 pathway.
8. Prior history of severe or life-threatening events from any immune-mediated therapy.
9. Receiving systemic corticosteroid therapy or any other form of immunosuppressive therapy within 7 days prior to enrollment. Low-dose corticosteroids (prednisone ≤ 10 mg per day or equivalent is permitted)
10. Major surgical procedures within 28 days prior to first dose of study treatment.
11. Treatment with live virus, including live-attenuated vaccination, within 14 days prior to the first dose of study treatment. Inactive vaccines (e.g., non-live or non-replicating agent) and live viral non-replicating vaccines within 3 days prior to first dose of study treatment.
12. History of other malignancy within the past 2 years, with the following exceptions:
* Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
* Adequately treated cervical carcinoma in situ without evidence of disease.
* Adequately treated breast ductal carcinoma in situ without evidence of disease.
* Prostatic intraepithelial neoplasia without evidence of prostate cancer.
* Adequately treated urothelial papillary noninvasive carcinoma or carcinoma in situ.
13. History of myocardial infarction and/or symptomatic congestive heart failure (New York Heart Association, class II) within 6 months prior to first dose of study treatment.
14. History of arterial thrombosis (e.g., stroke or transient ischemic attack) within 6 months prior to first dose of study treatment.
15. Human immunodeficiency virus (HIV) infection.
16. Active hepatitis C infection.
17. Active hepatitis B infection. • Defined as presence of hepatitis B surface antigen \[HBsAg-positive\] and hepatitis B virus \[HBV\] DNA viral load above the limit of quantification \[HBV DNA positive\] • Participants with resolved HBV infection defined as absence of HBV surface antigen (HBsAg-negative) and presence of HBV core antibody (anti-HBc positive) followed by an HBV DNA viral load below the limit of quantification (HBV DNA negative) are allowed, with a requirement for regular monitoring for reactivation for the duration of treatment on the study and assessing the need for HBV prophylaxis therapy per local or institutional guidelines.
18. Participants 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 study treatment.
* Upon completion of antibiotics and resolution of symptoms, the participant may be considered eligible for the study from an infection standpoint.
* Simple urinary tract infection (UTI) and uncomplicated bacterial pharyngitis are permitted if responding to active treatment. Participants requiring oral antibiotics who have been afebrile \> 24 hours, have no leukocytosis, nor clinical signs of infection are eligible. Screening for chronic infectious conditions is not required unless otherwise noted as exclusion criteria.
19. Female participants of childbearing potential unwilling to use protocol specified method of contraception (see Section 5.7.2) during treatment and for an additional 60 days after the last dose of study treatment.
20. Female participants who are breastfeeding or who plan to breastfeed while on study through 60 days after the last dose of study treatment.
21. Female participants planning to become pregnant or donate eggs while on study through 60 days after the last dose of study treatment.
22. Female participants of childbearing potential with a positive pregnancy test assessed at screening by a highly sensitive serum pregnancy test.
23. Male participants with a female partner of childbearing potential who are unwilling to practice sexual abstinence (refrain from heterosexual intercourse) or use contraception during treatment and for an additional 60 days after the last dose.
24. Male participants with a pregnant partner who are unwilling to practice abstinence or use a condom during treatment and for an additional 60 days after the last dose of study treatment.
25. Male participants unwilling to abstain from donating sperm during treatment and for an additional 60 days after the last dose of study treatment.
26. Participant has known sensitivity to any of the products or components to be administered during dosing.
27. Participant likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures (e.g., Clinical Outcome Assessments) to the best of the participant's and investigator's knowledge.
28. History or evidence of any other clinically significant disorder, condition, or disease (with the exception of those outlined above) that, in the opinion of the investigator, if consulted, would pose a risk to participant safety or interfere with the study evaluation, procedures or completion.

Contacts and Locations

Study Contact

CRU Hotline

CONTACT

888-798-0719

istteam@mednet.ucla.edu

CRU Direct line

CONTACT

310-206-2632

Principal Investigator

Jonathan Goldman, MD

PRINCIPAL_INVESTIGATOR

UCLA / Jonsson Comprehensive Cancer Center

Study Locations (Sites)

UC Davis Comprehensive Cancer Center

Davis, California, 95817

United States

UCI Health Chao Family Comprehensive Cancer Center

Irvine, California, 92612

United States

University of California at Los Angeles

Los Angeles, California, 90095

United States

UC San Diego Moores Cancer Center

San Diego, California, 92093

United States

Collaborators and Investigators

Sponsor: Jonsson Comprehensive Cancer Center

Jonathan Goldman, MD, PRINCIPAL_INVESTIGATOR, UCLA / Jonsson Comprehensive Cancer Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-03-21

Study Completion Date2029-04-24

Study Record Updates

Study Start Date2025-03-21

Study Completion Date2029-04-24

Terms related to this study

Keywords Provided by Researchers

tumor

Additional Relevant MeSH Terms

DLL3-expressing Tumors
Advanced Tumors