Testing a new treatment for lung cancers after chemotherapy

A Phase 1a/b, Open-label, Dose-escalation Study of the Safety, Pharmacokinetics, and Initial Efficacy of 225Ac-ABD147 in Patients With Small Cell Lung Cancer and Large Cell Neuroendocrine Carcinoma of the Lung Following Platinum-based Chemotherapy

This study is testing a new treatment for small-cell lung cancer and large cell neuroendocrine carcinoma in patients who have already had chemotherapy to see if it’s safe and effective.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 65 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Abdera Therapeutics Inc. (Industry-sponsored)
• Drugs / interventions: chemotherapy, immunotherapy, radiation
• Locations: 3 sites (Newport Beach, California and 2 other locations)
• Trial ID: NCT06736418 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and effectiveness of 225Ac-ABD147 in patients with small-cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC) who have previously undergone platinum-based chemotherapy. The study is divided into two phases: Phase 1a focuses on determining the optimal dose and safety profile, while Phase 1b aims to gather additional efficacy data based on the findings from Phase 1a. A subset of patients will also receive an imaging agent to track the distribution of the treatment within the body. The goal is to establish a recommended dose for future studies.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with confirmed locally advanced or metastatic SCLC or LCNEC who have completed platinum-based chemotherapy.

Not a fit: Patients with early-stage lung cancer or those who have not received prior platinum-based chemotherapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced lung cancers who have limited treatment choices after chemotherapy.

How similar studies have performed: While this approach is novel, similar studies targeting advanced lung cancers have shown promise in the past.

Eligibility criteria

Key Inclusion Criteria:

* Has confirmed, locally advanced or metastatic SCLC or LCNEC of the lung.
* Has completed platinum-based chemotherapy.
* Mentally competent and able to understand and sign an Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved Informed Consent Form (ICF)prior to any study specific evaluation.
* Age ≥18 years old at the time the ICF is signed.
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 2.
* Expected life expectancy of \>12 weeks per the Investigator.
* Has disease that is measurable by RECIST v 1.1.
* Patients with known brain metastases are eligible provided they are considered by the Investigator to be neurologically stable and meet the following criteria: a. Radiotherapy or surgery for brain metastases was completed at least 2 weeks prior to Cycle 1 Day 1 (C1D1); b. Symptoms are stable and steroid/antiepileptic doses remain unchanged for a minimum of 2 weeks prior to C1D1.
* At least 4 weeks from prior major surgery (other than for brain metastases), or at least 7 days from prior non-study-related minor surgery prior to C1D1. In all cases, patient must be sufficiently recovered and stable before study treatment administration.
* Willing to provide archival tumor tissue for central analysis; if unavailable, a pre-study treatment biopsy may be collected and provided.
* Female and male patients of childbearing potential agree to use at least 2 highly effective forms of contraception (1 at least must be barrier method) or agree to completely remain abstinent for duration of study and for 6 months after the last administration of study drug for both female patients and male patients.
* Patients agree to not make semen/egg donations during treatment, within 2 weeks following the last dose of 111In-ABD147, and for 6 months following the last dose of 225Ac-ABD147.

Key Exclusion Criteria:

* Was previously treated with 225Ac-ABD147.
* Has a history of steroid dependent hepatitis caused by treatment with a checkpoint inhibitor.
* Is actively enrolled in another clinical study unless it is an observational (noninterventional) clinical study or the follow-up component of an interventional study.
* Use of an anticancer therapy, radiotherapy (external beam radiotherapy \[EBRT\], brachytherapy, inoperative radiation therapy, radiopharmaceuticals), or immunotherapy within 3 weeks prior to C1D1. Prior treatment with DLL3-targeting agent is acceptable with appropriate washout.
* Has a medical history of myocardial infarction or unstable angina within 6 months before C1D1.
* Has clinically significant cardiac disease not controlled on medical therapy (eg, congestive cardiac failure, arrhythmia, coronary heart disease).
* Has evidence of active infection requiring intravenous (IV) antibiotics during Screening requiring therapy within 7 days prior to C1D1.
* Has active uncontrolled bleeding or a bleeding diathesis within 28 days prior to C1D1.
* Has serious or non-healing wound, fistula, skin ulcer, or non-healing bone fracture within 7 days prior to C1D1.
* Has received any thoracic radiotherapy within 8 weeks prior to C1D1.
* Has a history of idiopathic pulmonary fibrosis, organizing pneumonia (eg, bronchiolitis obliterans), drug-induced pneumonitis (requiring steroids or immunosuppressive agents), or idiopathic pneumonitis, or evidence of active pneumonitis on the Screening chest computed tomography (CT) scan. Note: History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
* Has known hypersensitivity to Ac-225; for patients participating in the 111In-ABD147 dosimetry substudy, also has known hypersensitivity to In-111.
* Has known hypersensitivity to Chinese hamster ovary cell products.
* Has a history of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins.
* Has human immunodeficiency virus infection; patients who are taking an effective antiviral therapy with undetectable viral load prior to C1D1 are eligible.
* Has chronic hepatitis B virus (HBV) infection. Patients who are taking an effective suppressive therapy and have an undetectable HBV viral load are eligible.
* Has a history of hepatitis C virus (HCV) infection, unless treated and cured; patients with HCV infection who are currently on treatment and have an undetectable HCV viral load are eligible.
* Has carcinomatous meningitis.
* Has active symptomatic cord compression.
* Has active symptomatic superior vena cava syndrome.
* Has another primary malignancy that has not been treated with curative intent (discuss with Medical Monitor), except for non-metastatic cutaneous basal cell or squamous cell carcinoma, or non-muscle invasive bladder cancer.
* Is unwilling or unable to follow protocol requirements.
* Has any condition that, in the opinion of the Investigator, would interfere with evaluation of the investigational product or interpretation of the patient's safety or study results.

Where this trial is running

Newport Beach, California and 2 other locations

• Hoag Memorial Hospital Presbyterian — Newport Beach, California, United States (Recruiting)
• United Theranostics — Glen Burnie, Maryland, United States (Recruiting)
• Memorial Sloan Kettering Cancer Center — New York, New York, United States (Recruiting)

Study contacts

• Study coordinator: Abdera Therapeutics

Conditions Small-Cell Lung Cancer; Large Cell Neuroendocrine Carcinoma of the Lung; Actinium; Ac-225; 225Ac-ABD147; Indium; In-111; 111In-ABD147