A First-in-Human Phase I Trial With Antibody Drug Conjugate ADCT-701 in Neuroendocrine Tumors, Carcinomas and Malignant Peripheral Nerve Sheath Tumors

NCT06041516 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: 10001547001547-C
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief 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....

Conditions

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

Keywords

Pheochromocytoma; Neuroblastoma; Neuroendocrine Tumor; Neuroendocrine carcinoma; Neuroendocrine neoplasms; Paraganglioma; Adrenocortical Carcinoma

Outcome Measures

Primary Outcomes (1)

• Determine the maximum tolerated dose (MTD) of ADCT-701

  Number of dose-limiting toxicities (DLTs) by assessing adverse events (AE) by type and grade of toxicity.

  cycle 1, days 1-21

Secondary Outcomes (4)

• Safety of ADCT-701

  through 30 days after the last ADCT-701 infusion

• Preliminary anti-tumor activity of ADCT-701

  up to 5 years

• PK profile of ADCT-701

  up to 2 years

• Immunogenicity of ADCT-701

  up to 2 years

Study Arms (1)

1/Arm1

EXPERIMENTAL

ADCT-701 given as an IV infusion

Drug: ADCT-701

Interventions

ADCT-701 DRUG

ADCT-701 in 2microgram/kg-255microgram/kg (weight based dosing), IV over 30 minutes (+15 minutes)

1/Arm1

Eligibility Criteria

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

You may qualify if:

• Participants must have histologically or cytologically confirmed neuroendocrine neoplasms or malignant adrenocortical carcinoma (ACC) or malignant peripheral nerve sheath tumors (MPNST).
• Locally advanced, unresectable or metastatic disease (as confirmed by a radiological evaluation)
• Participants must have measurable disease per RECIST 1.1.
• Participants must have received prior standard of care treatment and be refractory to or intolerant to standard of care therapy(s). Note: Patients with MPNST who have refused cytotoxic chemotherapy or for whom treatment on this protocol prior to receiving cytotoxic
• chemotherapy is felt to be in the best interest for the patient by the local investigator and treating investigator will also be eligible.
• Age \>= 18 years.
• ECOG performance status \<= 2.
• Adequate hematologic function as follows:
• Leukocytes \>= 3,000/microliter
• Absolute neutrophil count (ANC) \>= 1,200/microliter (off-growth factors for 72 hours prior to treatment initiation)
• Hemoglobin (Hgb) \>= 9 g/dL with no blood transfusion within 2 weeks prior to treatment initiation
• Platelets \>= 100,000/microliter with no platelet transfusion within 1 week.
• Adequate renal and hepatic function as follows:
• Creatinine clearance (CrCl) \>= 50 mL/min/1.73 m\^2 (calculated CrCl (Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) or calculated eGFR provided by a laboratory))
• Total bilirubin \<= 1.5 x ULN OR in participants with known or suspected Gilbert's syndrome, total bilirubin \<= 3.0 x ULN

You may not qualify if:

• Major surgery, prior treatment with chemotherapy, hormonal therapy, immunotherapy, treatment with an investigational agent, and/or radiation therapy within 4 weeks or 5 half-lives, whichever is shorter, prior to treatment initiation.
• Participants taking any herbal supplements within 14 days prior to treatment initiation.
• Participants who have wound dehiscence from prior surgeries.
• Clinically significant third space fluid accumulation (i.e., ascites requiring drainage or any serosal effusion that is either requires drainage or is associated with shortness of breath) at screening.
• Active infection requiring systemic antibiotic therapy at screening.
• Active bleeding diathesis or therapeutic anticoagulation with an oral vitamin K antagonist with target international normalized ratio (INR) \> 2 at screening.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to the study drug.
• An active autoimmune disease. Note: Participants with type 1 diabetes, eczema, vitiligo, alopecia, psoriasis, hypo- or hyperthyroid disease, adrenal insufficiency on systemic oral corticosteroid therapy (\<= the equivalent of prednisone 10 mg/day), or other mild autoimmune disorders (Type 1 diabetes, eczema, vitiligo, alopecia, rheumatoid arthritis, psoriasis, systemic lupus erythematosus, adrenal insufficiency due to Addison's disease, hypothyroidisms due to Hashimoto's thyroiditis, hyperthyroidisms due to Graves disease, Sjogren s syndrome, celiac disease, pernicious anemia) not requiring immunosuppressive treatment are eligible.
• Congenital long QT syndrome, or a corrected QTcF interval of \>=480 ms, at screening (unless secondary to the pacemaker or bundle branch block).
• Active second primary malignancy other than non-melanoma skin cancers, nonmetastatic prostate cancer, in situ cervical cancer, ductal or lobular carcinoma in situ of the breast, or other malignancy that does not require current anticancer treatment per standard of care.
• Live vaccine administration within 30 days prior to treatment initiation.
• Pregnant individuals (confirmed by Beta-Human Chorionic Gonadotropin \[Beta-HCG\] serum or urine pregnancy test) performed at screening.
• Uncontrolled intercurrent illness that would limit compliance with study requirements.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Publications (2)

• Sun NY, Kumar S, Kim YS, Varghese D, Mendoza A, Nguyen R, Okada R, Reilly K, Widemann B, Pommier Y, Elloumi F, Dhall A, Taniyama D, Patel M, Aber E, Contreras CF, Kaplan RN, Kiseljak-Vassiliades K, Wierman ME, Martinez D, Pogoriler J, Hamilton AK, Diskin SJ, Maris JM, Robey RW, Gottesman MM, Del Rivero J, Roper N. Identification of the Notch ligand DLK1 as an immunotherapeutic target and regulator of tumor cell plasticity and chemoresistance in adrenocortical carcinoma. Nat Commun. 2025 Jul 1;16(1):5511. doi: 10.1038/s41467-025-60649-w.

  PMID: 40595495 DERIVED

• Sun NY, Kumar S, Kim YS, Varghese D, Mendoza A, Nguyen R, Okada R, Reilly K, Widemann B, Pommier Y, Elloumi F, Dhall A, Patel M, Aber E, Contreras-Burrola C, Kaplan R, Martinez D, Pogoriler J, Hamilton AK, Diskin SJ, Maris JM, Robey RW, Gottesman MM, Rivero JD, Roper N. Identification of DLK1, a Notch ligand, as an immunotherapeutic target and regulator of tumor cell plasticity and chemoresistance in adrenocortical carcinoma. bioRxiv [Preprint]. 2024 Oct 11:2024.10.09.617077. doi: 10.1101/2024.10.09.617077.

  PMID: 39416174 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Carcinoma, Neuroendocrine; Neuroendocrine Tumors; Adrenocortical Carcinoma; Pheochromocytoma; Neuroblastoma; Paraganglioma

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Adrenal Cortex Neoplasms; Adrenal Gland Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Adrenal Cortex Diseases; Adrenal Gland Diseases; Endocrine System Diseases; Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial

Study Officials

• Jaydira Del Rivero, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Anna Liza F Rivero

CONTACT

(240) 858-7946; anna.rivero@nih.gov

Jaydira Del Rivero, M.D.

CONTACT

(240) 858-3851; delriveroj@mail.nih.gov

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 15, 2023
• First Posted: September 18, 2023
• Study Start: June 17, 2024
• Primary Completion (Estimated): October 30, 2027
• Study Completion (Estimated): October 30, 2029
• Last Updated: March 27, 2026

Record last verified: 2026-03-19

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data will be available during the study and indefinitely.
• Access Criteria: Clinical data will be made available via subscription to BTRIS and with the permission of the study PI

Locations

US (1)