Antibody Drug Conjugate ADCT-701 in Neuroendocrine Tumors and Carcinomas

Neuroendocrine Tumors Clinical Trial

Official title: A First-in-Human Phase I Trial With Antibody Drug Conjugate ADCT-701 in Neuroendocrine Tumors and Carcinomas

Status Recruiting

Clinical Trial Summary

Background:

Neuroendocrine neoplasms (NENs) are rare cancers in the gastrointestinal tract, pancreas, lungs, adrenal glands, and other areas of the body. Many of these cancers have a high risk of relapse and a low chance of survival. Better treatments are needed.

Objective:

To test a new drug, ADCT-701, in people with NENs.

Eligibility:

Adults aged 18 and older with NENs.

Design:

Participants will be screened. They will have a physical exam with blood and urine tests. They will have imaging scans and tests of heart functioning. Their ability to perform normal daily activities will be tested. A biopsy may be needed: A sample of tissue will be removed from the tumor.

ADCT-701 is given through a tube attached to a needle inserted into a vein in the arm. Participants will receive the drug treatment on the first day of 21-day treatment cycles. They will visit the clinic a total of 10 times during the first two cycles. After that, they will visit the clinic 2 times during each cycle. Imaging scans, blood draws, heart function tests, and other tests will be repeated during study visits. Each visit will last up to 8 hours.

Participants may continue receiving treatment with the study drug for up to 2 years.

After treatment ends, participants will have follow-up clinic visits 4 times in 4 months. They will have a physical exam, with heart and blood tests, at each visit. After that, they will have follow-up clinic visits every 9 weeks; these visits will include imaging scans.

Follow-up visits will continue for up to 5 years after treatment began....

Clinical Trial Description

Background:

-Neuroendocrine neoplasms (NENs) are divided into neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs). These are rare malignancies occurring in areas such as the gastrointestinal tract, islets of the pancreas, lung, adrenal gland, and other areas of

the body.

• Poorly differentiated neuroendocrine carcinomas are all high-grade carcinomas that resemble small-cell lung cancer (SCLC). Poorly differentiated NECs are also treated with platinum-based regimens in accordance with small cell carcinoma guidelines and have a high risk of relapse as well as a poor response to further systemic therapies.

• Adrenocortical carcinoma (ACC) is a rare malignancy with an average survival from the time of diagnosis of 14.5 months. In advanced diseases, chemotherapy options have limited benefits. To date, no "targeted therapy" has been shown to have significant efficacy in this disease.

• Pre-clinical studies have shown that Delta-like non-canonical notch ligand 1 (DLK1) is expressed in multiple neuroendocrine neoplasms such as ACC, SCLC, neuroblastoma, pheochromocytoma, and paraganglioma.

• ADCT-701 a humanized antibody directed against DLK1 effectively suppresses tumor growth and improves survival in multiple cancer models which express DLK1.

Objective:

-To determine the maximum tolerated dose (MTD) of ADCT-701 in participants with neuroendocrine neoplasms or malignant adrenocortical carcinoma

Eligibility:

• Histologically or cytologically confirmed neuroendocrine neoplasms or malignant ACC.

• Age >= 18 years.

• Evaluable disease, per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.

• Adequate organ and bone marrow function.

• Eastern Cooperative Oncology Group (ECOG) <= 2.

Design:

• This is a First in Human phase I dose escalation study of ADCT-701-single agent in participants with NENs.

• Participants will be enrolled in a dose-finding trial. A 3+3 design with up to ten dose levels of ADCT-701 will be evaluated in this trial. The study drug dose will be escalated unless the occurrence of dose-limiting toxicities limits further escalation or until the maximum tolerated dose level is reached or an optimal dose is determined.

• Up to 70 evaluable patients will be enrolled over a maximum of 10 dose levels. ;

Related Conditions & MeSH terms

• Adrenocortical Carcinoma
• Carcinoma
• Carcinoma, Adrenal Cortical
• Carcinoma, Neuroendocrine
• Neuroendocrine Carcinomas
• Neuroendocrine Tumors

• NCT number: NCT06041516
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Contact: Kimberley J Cooper
• Phone: (240) 858-7989
• Email: kimberley.cooper@nih.gov
• Status: Recruiting
• Phase: Phase 1
• Start date: June 17, 2024
• Completion date: October 30, 2029