Study of 225Ac-ABD147 to Establish Optimal Dose in Patients With SCLC and LCNEC of the Lung That Previously Received Platinum-based Chemotherapy

Summary

The study has 2 parts, Phase 1a and Phase 1b. The goal of Phase 1a is to gather safety, PK and initial efficacy data for 225Ac-ABD147 to better understand best doses for patients with small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC) of the lung following platinum-based chemotherapy. An initial group of patients will also be given an experimental imaging agent called 111In-ABD147 to help understand where ABD147 goes in the body. The goal of Phase 1b is to gather additional safety and efficacy data on 225Ac-ABD147 to determine the best dose and to understand how those doses affect the same types of patients' cancers explored enrolled in Phase 1a.

Eligibility

Key Inclusion Criteria:

* Has confirmed, locally advanced or metastatic SCLC or LCNEC of the lung.
* Has received 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 1.
* Expected life expectancy of \>12 weeks per the Investigator.
* Has disease that is measurable by RECIST v1.1.
* 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, the patient must be sufficiently recovered and stable before the 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 by 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.

Conditions4

Locations12 sites

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