ADCT-701 for Rare Cancers

Recruiting in Palo Alto (17 mi)

Overseen by Jaydira Del Rivero, M.D.

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: National Cancer Institute (NCI)

Must not be taking: Herbal supplements

Disqualifiers: Active infection, Autoimmune disease, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

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....

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but you cannot have had major surgery, chemotherapy, hormonal therapy, immunotherapy, or radiation therapy within 4 weeks before starting the trial. Also, you should not take any herbal supplements within 14 days before starting the trial.

What safety information is available for ADCT-701 and similar treatments?

Antibody-drug conjugates (ADCs) like ADCT-701 are generally considered safe, but they can cause side effects such as low blood cell counts, liver issues, nerve damage, and eye problems. These side effects are often related to the drug's active components and can vary depending on the specific ADC and cancer type.

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Eligibility Criteria

Adults over 18 with neuroendocrine tumors or adrenocortical carcinoma, who've tried standard treatments without success. They must have measurable disease, be able to perform daily activities to a certain extent, and agree to use contraception. Excluded are those with recent other cancer treatments, uncontrolled illnesses, certain heart conditions, active infections or allergies related to the study drug.

Inclusion Criteria

You must have a disease that can be measured according to specific guidelines.

I can take care of myself but might not be able to do heavy physical work.

I am breastfeeding but willing to stop for the trial.

Exclusion Criteria

I haven't had major surgery or cancer treatment in the last 4 weeks.

I have not taken any herbal supplements in the last 14 days.

I am currently on antibiotics for an infection.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive ADCT-701 through IV infusion on the first day of 21-day treatment cycles. They will visit the clinic 10 times during the first two cycles and 2 times during each subsequent cycle.

up to 2 years

10 visits (in-person) during first two cycles, 2 visits per cycle thereafter

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up visits every 9 weeks including imaging scans.

up to 5 years

4 visits in 4 months, then every 9 weeks

Participant Groups

The trial is testing ADCT-701 in patients with rare cancers of various glands. It involves receiving the drug through an IV on day one of each 21-day cycle for up to two years. Participants will undergo regular clinic visits that include physical exams and various tests like imaging scans and blood draws.

Group I: 1/Arm1 Experimental Treatment 1 Intervention

ADCT-701 given as an IV infusion

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

National Institutes of Health Clinical Center Bethesda, MD

Who Is Running the Clinical Trial?

National Cancer Institute (NCI) Lead Sponsor

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Prognostic and Predictive Value of LIV1 Expression in Early Breast Cancer and by Molecular Subtype. [2023] Label="BACKGROUND" NlmCategory="BACKGROUND">LIV1 is a transmembrane protein that may become a new therapeutic target through the development of antibody-drug conjugates (ADCs). Few studies are available regarding the assessment of LIV1 expression in clinical breast cancer (BC) samples.

2. China pubmed.ncbi.nlm.nih.gov

[Chinese expert consensus of antibody-drug conjugate toxicity management for breast cancer]. [2022] As a newly emerged class of anticancer bioagents in the most precise and selectively targeted way, antibody-drug conjugate (ADC) combines the cancer-targeting abilities of monoclonal antibodies with the cytotoxicity potency of payload, delivering highly cytotoxic drug into tumors via 'targeted chemotherapy'. ADC has revolutionized the treatment landscape of human epidermal growth factor receptor 2 positive and triple negative subtypes in breast cancer. Three ADCs have been approved by U. S. Food and Drug Administration with breast cancer indications, including trastuzumab emtansine (T-DM1; also approved in China), trastuzumab deruxtecan (T-DXd, DS-8201) and sacituzumab govitecan (IMMU-132; also approved in China). Antibodies, cytotoxic drug, linker, and conjugation process are implicated in ADC profile, resulting in unique adverse drug reactions and toxicity heterogeneity within ADC class. For example, more attention should be paid to the management of thrombocytopenia, hepatotoxicity, and reductions in left ventricular ejection fraction (LVEF) in patients treated with trastuzumab emtansine; clinical physicians should pay attention to the risk of neutropenia, interstitial lung disease/pneumonitis, and reductions in LVEF when treated with trastuzumab deruxtecan; sacituzumab govitecan most frequently caused neutropenia, anemia and diarrhea requiring close monitor. ADC has generally favorable safety profiles, and dose modifications and/or symptomatic supporting treatment are effective in terms of toxicity management. This consensus aims at providing guidance for clinical oncologists of early detection, regular assessment, timely management and follow-up monitor of ADC-associated adverse reactions/events.

3. United States pubmed.ncbi.nlm.nih.gov

Brentuximab vedotin in combination with chemotherapy for pediatric patients with ALK+ ALCL: results of COG trial ANHL12P1. [2022] Approximately 30% of pediatric patients with anaplastic large cell lymphoma (ALCL) relapse. Although brentuximab vedotin has demonstrated excellent activity in ALCL, it has not been used for newly diagnosed patients. Children's Oncology Group (COG) trial ANHL12P1 determined the toxicity and efficacy of brentuximab vedotin with chemotherapy in children with newly diagnosed nonlocalized anaplastic large cell lymphoma kinase (ALK)+/CD30+ ALCL. From 2013 to 2017, 68 children with ALK+ ALCL were enrolled and received brentuximab vedotin. All patients received 5-day prophase, followed by 6 cycles of chemotherapy. Brentuximab vedotin was given on day 1 of each of the 6 cycles. Of the 67 patients eligible for toxicity evaluation, 66 completed all 6 cycles of chemotherapy, resulting in 399 evaluable cycles. There were no toxic deaths, no case of progressive multifocal leukoencephalopathy syndrome, and no case of grade 3 or 4 neuropathy. The 2-year event-free survival (EFS) was 79.1% (95% confidence interval [CI], 67.2-87.1). The 2-year overall survival (OS) was 97.0% (95% CI, 88.1-99.2). Fourteen patients relapsed. Eleven of 14 (79%) relapses occurred within 10 months of diagnosis; only 1 patient (1.5%) relapsed during therapy. Quantitative reverse transcription polymerase chain reaction for NPM-ALK at baseline (minimal disseminated disease) demonstrated prognostic value for EFS (P = .0004). Overall, the addition of brentuximab vedotin to standard chemotherapy does not add significant toxicity or alter the desired interval between cycles. The addition of brentuximab vedotin prevented relapses during therapy, and the OS and EFS estimates compare favorably with results obtained using conventional chemotherapy. This trial was registered at www.clinicaltrials.gov as #NCT01979536.

4. England pubmed.ncbi.nlm.nih.gov

Brentuximab vedotin: treatment role for relapsed refractory systemic anaplastic large-cell lymphoma. [2019] The identification of CD30 has been known since 1985. Trials exploring the targeted therapy focusing on this antigen have led to the successful development and approval of brentuximab vedotin (Adcetris®) for treatment of relapsed refractory systemic anaplastic large-cell lymphoma. Brentuximab vedotin has a high-level of response with generally durable remission. Common side effects of brentuximab vedotin include peripheral neuropathy, fatigue, nausea, arthralgia, and pyrexia. Grade 3-4 neutropenia, thrombocytopenia, and hyperglycemia have also been reported. Development of progressive multifocal leukoencephalopathy from John Cunningham virus is a very rare occurrence, but its seriousness has prompted the US FDA to mandate a black box warning. Brentuximab vedotin is currently being evaluated to be used in conjunction with other chemotherapy regimens, including in frontline therapies to induce potentially higher complete remission rate than chemotherapy alone and thus achieve potentially higher progression-free survival rates that might translate ultimately to improve overall survival.

5. United States pubmed.ncbi.nlm.nih.gov

Clinical toxicity of antibody drug conjugates: a meta-analysis of payloads. [2018] Background Antibody drug conjugates (ADCs) utilize a monoclonal antibody to deliver a cytotoxic payload specifically to tumor cells, limiting exposure to healthy tissues. Major clinical toxicities of ADCs include hematologic, hepatic, neurologic, and ophthalmic events, which are often dose-limiting. These events may be off-target effects caused by premature release of payload in circulation. A meta-analysis was performed to summarize key clinical safety data for ADCs by payload, and data permitting, establish a dose-response model for toxicity incidence as a function of payload, dose/regimen, and cancer type. Methods A literature search was performed to identify and extract data from clinical ADC studies. Toxicity incidence and severity were collected by treatment arm for anemia, neutropenia, thrombocytopenia, leukopenia, hepatic toxicity, peripheral neuropathy, and ocular toxicity. Exploratory plots, descriptive summaries, and logistic regression modelling were used to explore Grade ≥ 3 (G3/4) toxicities and assess the impact of covariates, including cancer type and dose/regimen. Results The dataset contained 70 publications; quantitative analysis included 43 studies with G3/4 toxicity information reported for the endpoints above. G3/4 anemia, neutropenia and peripheral neuropathy were consistently reported for MMAE ADCs, thrombocytopenia and hepatic toxicity for DM1, and ocular toxicity for MMAF. Safety profiles of MMAE, DM1, and DM4 ADCs differed between solid and hematologic cancers. Conclusions Published ADC clinical data is limited by non-uniform reporting for toxicity and lack of dosing information, limiting the ability to develop quantitative models relating toxicity to exposure. However, the current analysis suggests that key G3/4 toxicities of ADCs in the clinic are likely off-target and related to payload.