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....
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
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.
Single group
ADCT-701
DrugADCT-701 in 2microgram/kg-255microgram/kg (weight based dosing), IV over 30 minutes (+15 minutes)
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.
Safety of ADCT-701
Adverse Events (AE) by type and grade of toxicity
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)
PK profile of ADCT-701
Assessment of PBD-conjugated antibody, total antibody, and unconjugated warhead SG3199 in blood.
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.
Click on the lead sponsor to view all of their trials.
