Active, not recruiting
Phase 1
Study of 225Ac-ABD147 to Establish Optimal Dose in Patients With SCLC and LCNEC of the Lung That Previously Received Platinum-based Chemotherapy
Condition(s) studied
Small-Cell Lung Cancer (SCLC)Large Cell Neuroendocrine Carcinoma of the Lung
Investigational drug(s) / intervention(s)
225Ac-ABD147
225Ac-ABD147: A delta-like ligand 3 (DLL3)-targeting antibody fragment conjugated with a linker-chelator that effectively coordinates Ac-225
Study 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.
Primary outcome measure(s)
- Ph 1a: Safety of 225Ac-ABD147 - Number and Grade of Adverse Events — 12 months
Incidence of adverse events and serious adverse events graded according to NCI-CTCAE v5.0; Clinically significant changes from baseline for laboratory values, ECGs, and vital signs will be evaluated as adverse events.
- Ph 1a: Tolerability of 225Ac-ABD147 - Number of Dose Limiting Toxicities — 12 months
Incidence and nature of dose limiting toxicities.
- Ph 1b: Safety of 225Ac-ABD147 to Determine the RP2D for Further Development - Number and Grade of Adverse Events — 12 months
Incidence of adverse events and serious adverse events graded according to NCI-CTCAE v5.0; Clinically significant changes from baseline for laboratory values, ECGs, and vital signs will be evaluated as adverse events.
- Ph 1b: Preliminary Efficacy of 225Ac-ABD147 - Overall Response Rate (ORR) — 12 months
ORR of confirmed complete response (CR) and partial response (PR) per investigator assessment using RECIST v1.1.
- Ph 1b: Preliminary Efficacy of 225Ac-ABD147 - Disease Control Rate (DCR) — 12 months
DCR per investigator assessment using RECIST v1.1.
- Ph 1b: Preliminary Efficacy of 225Ac-ABD147 - Duration of Response (DOR) — 12 months
DOR of confirmed CR and PR per investigator assessment using RECIST v1.1.
- Ph 1b: Preliminary Efficacy of 225Ac-ABD147 - Duration of Progression Free Survival (PFS) — 12 months
PFS per investigator assessment using RECIST v1.1.
- Ph 1b: Preliminary Efficacy of 225Ac-ABD147 - Overall Survival (OS) — 12 months
OS.
- Ph 1b: Preliminary Efficacy of 225Ac-ABD147 - PFS Rate — 12 months
6 monthly PFS rate per investigator assessment using RECIST v1.1.
- Ph 1b: Preliminary Efficacy of 225Ac-ABD147 - OS Rate — 12 months
6 monthly OS rate.
- Ph 1b: Biodistribution and Absorbed Dose - Measurement of Activity — 6 months
Whole blood radioactivity with whole blood gamma counting.
- Ph 1b: Immunogenicity of 225Ac-ABD147 - Measurement of Anti-drug Antibodies — 6 months
Anti-drug antibody to ABD147.
Trial sites (12)
| Facility | City | Region | Status |
| Hoag Memorial Hospital Presbyterian |
Newport Beach |
California |
|
| University of California, San Francisco |
San Francisco |
California |
|
| University of California, Los Angeles |
Santa Monica |
California |
|
| Mayo Clinic - Jacksonville |
Jacksonville |
Florida |
|
| Sylvester Comprehensive Cancer Center, Univ of Miami |
Miami |
Florida |
|
| Florida Cancer Specialists - Sarasota |
Sarasota |
Florida |
|
| United Theranostics |
Glen Burnie |
Maryland |
|
| Dana-Farber Cancer Institute |
Boston |
Massachusetts |
|
| Mayo Clinic - Rochester |
Rochester |
Minnesota |
|
| Memorial Sloan Kettering Cancer Center |
New York |
New York |
|
| MD Anderson |
Houston |
Texas |
|
| Huntsman Cancer Institute |
Salt Lake City |
Utah |
|
Other trials for the same condition