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Neuroendocrine CarcinomasPhase 1NCT06041516

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

A Phase 1 study testing ADCT-701 in people with Neuroendocrine Carcinomas and Neuroendocrine Tumors, run by National Cancer Institute (NCI) at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

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. Read more about this study

Who is it for?
Ages 18 to 120 years
What is being tested?
ADCT-701
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
70 participants
Where
1 siteUnited States
Study dates
17 Jun 2024to 30 Oct 2029
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 120 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <= 2.5 x ULN, (unless liver metastases are present, then values must be <= 5 x ULN).
  • Participants serologically positive for hepatitis C virus (HCV) must have an undetectable HCV viral load.
  • Participants serologically positive for Hepatitis B (HBV) core antibody or surface antigen must be on adequate anti-viral therapy and Hepatitis B Viral deoxyribonucleic acid (DNA) load must be <2000 IU/mL.
  • Participants serologically positive for human immunodeficiency virus (HIV) must be on stable antiretroviral therapy for at least 4 weeks before treatment initiation, have no reported opportunistic infections or Castleman s disease within 12 months prior to treatment initiation, have a viral load that is undetectable by quantitative polymerase chain reaction (PCR) and CD4 count >= 200 cells per cubic millimeter.
  • Participants with brain metastasis are eligible if at least 4 weeks status post radiotherapy or surgery before treatment initiation with no evidence of progression or associated symptoms.
  • Individuals of child-bearing potential (IOCBP) must agree to use a highly effective method of contraception (hormonal, intrauterine device (IUD), surgical sterilization) for the duration of the study treatment and up to 9.5 months after the last dose of the ADCT-701 (restriction period).
  • Individuals who can father children must agree to use an effective method of contraception (barrier, surgical sterilization) at study entry and up to 6.5 months after the last dose of the ADCT-701.
  • Nursing participants must be willing to discontinue nursing from study treatment initiation through 6.5 months after study treatment discontinuation.
  • Participants or legally authorized representative (LAR) must be able to understand and be willing to sign a written informed consent document.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

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

United States1 site, 1 recruiting

  • National Institutes of Health Clinical Center

    Bethesda, Maryland, 20892

    National Cancer Institute Medical Oncology, 888-624-1937, NCIMO_Referrals@mail.nih.gov

    Jaydira Del Rivero, M.D., (240) 858-3851, delriveroj@mail.nih.gov

    Recruiting

Other trials in United States

About this study

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.

Read more

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....

Read the detailed 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.
  • Malignant peripheral nerve sheath tumors (MPNST) are the most common Neurofibromatosis Type 1 (NF1) associated malignancy and leading cause of death in patients with NF1 with no effective medical therapies available.
  • 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, paraganglioma, and MPNST.
  • 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, malignant adrenocortical carcinoma or malignant peripheral nerve sheath tumor (MPNST)

Eligibility:

  • Histologically or cytologically confirmed neuroendocrine neoplasms, malignant ACC, or refractory or metastatic MPNST.
  • 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 or MPNST.
  • 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 (MTD) level is reached or an optimal dose is determined.
  • Up to 70 evaluable patients will be enrolled over a maximum of 10 dose levels.
Being tested
ADCT-701
Keywords
Pheochromocytoma, Neuroblastoma, Neuroendocrine Tumor, Neuroendocrine carcinoma, Neuroendocrine neoplasms, Paraganglioma, Adrenocortical Carcinoma
Medical subject headings
Carcinoma, Neuroendocrine, Neuroendocrine Tumors, Adrenocortical Carcinoma, Pheochromocytoma, Neuroblastoma, Paraganglioma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ADCT-701Drug

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

Study groups in NCT06041516
Study groupRoleWhat they receive
1/Arm1ExperimentalADCT-701 given as an IV infusion
Receives: Drug: ADCT-701

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: cycle 1, days 1-21

Secondary outcomes (4)

  1. Safety of ADCT-701

    Adverse Events (AE) by type and grade of toxicity

    Measured: through 30 days after the last ADCT-701 infusion

  2. Preliminary anti-tumor activity of ADCT-701

    To capture response rate and durations to assess: overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS)

    Measured: up to 5 years

  3. PK profile of ADCT-701

    Assessment of PBD-conjugated antibody, total antibody, and unconjugated warhead SG3199 in blood.

    Measured: up to 2 years

  4. Immunogenicity of ADCT-701

    Assessment of ADAs using a screening assay for the identification of antibody-positive samples, a confirmation assay, and a titer assessment in blood.

    Measured: up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Sep 2023
  2. Study start17 Jun 2024
  3. Primary completion30 Oct 2027 (estimated)
  4. Study completion30 Oct 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
70 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06041516
Sponsor's protocol ID
10001547
Other IDs
001547-C
Status last verified
28 Oct 2026
First submitted
15 Sep 2023
Last updated
2 Nov 2026
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: All IPD recorded in the medical record will be shared with intramural investigators upon request.

Publications

  • 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.

    PubMed 40595495

  • 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.

    PubMed 39416174

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing ADCT-701 in people with Neuroendocrine Carcinomas and Neuroendocrine Tumors, run by National Cancer Institute (NCI) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 24 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 2 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Anna Liza F Rivero ((240) 858-7946, anna.rivero@nih.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Determine the maximum tolerated dose (MTD) of ADCT-701 (time frame: cycle 1, days 1-21). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06041516, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Nov 2026.

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