Efficacy and Safety Evaluation of Tarlatamab in Advanced Extrapulmonary Neuroendocrine Carcinoma Patients

NCT06893783 | Recruiting Phase 2

• 1 other identifier: DeLLight
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 4

Brief Summary

This is a phase 2 single-arm, open-label clinical trial designed to evaluate the efficacy and safety of tarlatamab in patients with relapsed extrapulmonary neuroendocrine carcinoma (EPNEC) who have previously received platinum-based first-line chemotherapy. Participants will receive tarlatamab on Cycle 1 Day 1 (C1D1), Day 8 (C1D8), and Day 15 (C1D15), followed by administration every two weeks thereafter. No placebo control is included in this study.

Conditions

Neuroendocrine Carcinomas (NEC); Neuroendocrine Carcinoma of Pancreas; Neuroendocrine Carcinoma of Prostate

Keywords

extrapulmonary neuroendocrine carcinoma; Tarlatamab; bispecific t-cell engager; DLL3

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR)

  defined as the percentage of participants who have a partial response or complete response based on investigator assessment per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

  From the date of first dose until the date of the first confirmed objective response (PR or CR) per RECIST v1.1, assessed up to 36 months

Secondary Outcomes (3)

• Progression free survival (PFS)

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months

• Overall Survival(OS)

  From the date of the safety follow-up visit for up to 36 months after the last subject is enrolled or 1 year after the last subject's final dose of study treatment, whichever is later

• Duration of response (DOR)

  From the date of the first recorded objective response (partial response [PR] or complete response [CR]) for up to 36 months, until the first documented date of disease progression or death from any cause, whichever occurs first.

Study Arms (1)

All patient

EXPERIMENTAL

The study will be divided into a gastrointestinal and pancreatic-biliary cohort and a genitourinary cohort; however, the dosage, frequency, duration, and administration route of the investigational drug will remain the same as outlined below. Tarlatamab 1 mg step dose on cycle 1 day 1 10 mg target dose starting cycle 1 day 8, cycle 1 day 15, and every 2weeks thereafter

Drug: Tarlatamab

Interventions

Tarlatamab DRUG

1 mg step dose on cycle 1 day 1 10 mg target dose starting cycle 1 day 8, cycle 1 day 15, and every 2weeks thereafter

Also known as: Delta-like ligand 3 (DLL3) Bispecific T-Cell Engager

All patient

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- Subject has provided informed consent prior to initiation of any study specific activities/procedures.
• Age ≥19 years at the time of signing the informed consent.
• Histologically confirmed relapsed/refractory extra-pulmonary neuroendocrine carcinoma. Neuroendocrine carcinoma includes small cell carcinoma, large cell carcinoma, and mixed histology of neuroendocrine and other histology (e.g., adenoneuroendocrine carcinoma, urothelial carcinoma with neuroendocrine component). In patients with prostate cancer, treatment-emergent neuroendocrine carcinoma (initially adenocarcinoma, but transdifferentiate into neuroendocrine carcinoma after androgen deprivation therapy) will be permitted.
• Cohort 1 (gastrointestinal and pancreaticobiliary cohort): cancers originated from stomach, esophagus, small intestine, colorectal, pancreas, or bile ducts.
• Cohort 2 (genitourinary cohort): cancers originated from prostate, bladder, ureter, urethra, or kidney.
• Subject has progressed or recurred following 1 platinum-based regimen:
• documented first disease progression must be during or following first-line platinum-based systemic chemotherapy. For patients with prostate cancer, especially in cases with treatment-emergent neuroendocrine carcinoma, platinum-based chemotherapy will not need to be the first line therapy.
• patients who received treatment for localized disease who recur are eligible
• patients who received adjuvant Platinum-Etoposide (EP) after resection of their primary tumor who recur are eligible
• Measurable disease as defined per RECIST 1.1 within the 21-day screening period.
• Screening scans performed as SOC(Standard of Care) and prior to informed consent, may be used to confirm subject eligibility if completed within the 21-day screening period, provided that informed consent for the use of these scans is obtained prior to any transfer of data.
• In patients with prostate cancer, patients without RECIST-defined measurable lesion can be included, if disease can be evaluated with Prostate Cancer Working Group(PCWG)-3 criteria.
• Eastern Cooperative Oncology Group (ECOG) PS(Performance Status) of 0 - 2.
• Minimum life expectancy of 12 weeks.
• Adequate organ function, defined as follows:

You may not qualify if:

• Symptomatic central nervous system (CNS) metastases:
• Subjects with treated brain metastases are eligible provided the following criteria are met:
• Subject is asymptomatic from brain metastases
• Whole brain radiation or surgery was completed at least 2 weeks prior to first dose of study treatment (stereotactic radiosurgery completed at least 7 days prior to first dose of study treatment)
• Any CNS disease is clinically stable, subject is off steroids for CNS disease for at least 5 days (unless steroids are indicated for a reason unrelated to CNS disease), and subject is off or on stable doses of anti-epileptic drugs at least 14 days prior to first dose of study treatment • Subjects with untreated brain metastases that are asymptomatic and do not require corticosteroids, nor local therapy per investigators standard of practice are allowed Diagnosis or evidence of leptomeningeal disease.
• Prior history of immune checkpoint inhibitors resulting in:
• Any severe or life-threatening immune-mediated adverse event, History of immune-mediated encephalitis or other immune-mediated CNS event (any grade)
• Grade ≥ 2 immune-mediated recurrent pneumonitis, Infusion-related reactions leading to permanent discontinuation of immunotherapy agent Exception: Subjects with a history of immune checkpoint inhibitor-induced endocrinopathy which is clinically stable on replacement therapy.
• Active autoimmune disease that has required systemic treatment (except replacement therapy) within the past 2 years or any other diseases requiring immunosuppressive therapy while on study.
• History of solid organ transplantation.
• History of other malignancy within the past 2 years, with the following exceptions:
• low-risk malignancy treated with curative intent and with no known active disease present for ≥ 1 year before enrollment and believed to be at low risk for recurrence per investigator discretion.
• adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease, cervical carcinoma in situ without evidence of disease, breast ductal carcinoma in situ without evidence of disease.
• prostatic intraepithelial neoplasia without evidence of prostate cancer. (For non-prostate cancer patient)
• adequately treated urothelial papillary noninvasive carcinoma or carcinoma in situ.

Sponsors & Collaborators

• Inkeun Park: lead
• Seoul National University Hospital: collaborator
• Severance Hospital: collaborator
• Samsung Medical Center: collaborator

Study Sites (4)

Asan Medical Center

Seoul, 05505, South Korea

RECRUITING

Samsung Medical Center

Seoul, South Korea

NOT YET RECRUITING

Seoul National University Hospital

Seoul, South Korea

RECRUITING

Yonsei Severance Hospital

Seoul, South Korea

NOT YET RECRUITING

MeSH Terms

Conditions

Carcinoma, Neuroendocrine

Interventions

DLL3 protein, human

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Inkeun Park, M.D, Ph D

  Asan Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Inkeun Park, M.D, Ph D

CONTACT

+82-2-3010-3266; ikpark@amc.seoul.kr

Hung-Don Kim, M.D, Ph D

CONTACT

+82-2-3010-0236; kimhdmd@amc.seoul.kr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Associate professor

Model Details: The study will be divided into a gastrointestinal and pancreatic-biliary cohort and a genitourinary cohort; however, the dosage, frequency, duration, and administration route of the investigational drug will remain the same as outlined below. Tarlatamab 1 mg step dose on cycle 1 day 1 10 mg target dose starting cycle 1 day 8, cycle 1 day 15, and every 2weeks thereafter

Study Record Dates

• First Submitted: February 21, 2025
• First Posted: March 25, 2025
• Study Start: September 2, 2025
• Primary Completion (Estimated): April 30, 2029
• Study Completion (Estimated): April 30, 2029
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

KR (4)