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.

This is an open-label, Phase 1a/b, first-in-human study to assess the safety profile, tolerability, biodistribution, pharmacokinetics (PK), and preliminary antitumor activity of 225Ac-ABD147 in patients with confirmed locally advanced or metastatic small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC) of the lung. All patients must have previously received platinum-based chemotherapy.

Phase 1a will determine the safety, tolerability, dosimetry, PK, and the dose of 225Ac-ABD147 for expansion in the Phase 1b portion.

In addition to receiving treatment, a subset of patients in Phase 1a will undergo either 111In-ABD147-based or 225Ac-ABD147 dosimetry assessments to confirm tumor specificity, identify biodistribution, and to provide insight into dose absorption into tumor and normal tissues.

Phase 1b will evaluate the safety and preliminary efficacy of 225Ac-ABD147 as based on the Phase 1a dose level for expansion by the Safety Review Committee to determine the recommended Phase 2 dose (RP2D).

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.