HPN328 in Advanced Cancers Associated with DLL3

What is the Purpose of this Study?

The purpose of this study is to test the safety and effects of an experimental drug called HPN328 alone and in combination with another drug, atezolizumab, in patients who have small cell lung cancer or other cancers including neuroendocrine carcinoma that make a protein marker called DLL3 and whose cancer has relapsed (returned) or is refractory (not responsive to treatment). HPN328 and atezolizumab are intended to stimulate the immune system to attack the body’s cancer cells. All patients enrolled in this study will receive HPN328. Since researchers are looking for the highest dose of the drug that can be given safely to participants without unmanageable side effects, various doses of HPN328 will be given. The drug dose will depend on which group the participant is assigned to. The combined use of atezolizumab and HPN328 in this study is investigational.

Eligibility

* Has a histologically or cytologically confirmed malignancy associated with expression of Delta-like Canonical Notch Ligand 3 (DLL3)
* Has small cell lung cancer (SCLC) which is relapsed/refractory following at least 1 prior line of systemic therapy that included platinum-based chemotherapy

Inclusion Criteria:

* Has a histologically or cytologically confirmed malignancy associated with expression of Delta-like Canonical Notch Ligand 3 (DLL3)
* Has small cell lung cancer (SCLC) which is relapsed/refractory following at least 1 prior line of systemic therapy that included platinum-based chemotherapy
* Has Neuroendocrine Prostate Cancer (NEPC; de novo or treatment-emergent) which is relapsed/refractory to standard systemic therapy
* Has high-grade neuroendocrine tumor types other than SCLC and NEPC, with at least one of the following:
* Disease that is relapsed/refractory to standard systemic therapy
* Disease for which standard therapy does not exist
* Disease for which standard therapy is not considered appropriate by the Investigator
* Must be able to provide archival tissue sample or fresh biopsy tissue sample

Exclusion Criteria:

* Has untreated central nervous system (CNS) metastases
* Has a glioma or other primary CNS malignancy
* Has spinal cord compression or symptomatic/uncontrolled epidural disease
* Has a history of intracranial hemorrhage or spinal cord hemorrhage
* Has active neurologic paraneoplastic syndrome
* Has uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (e.g., biweekly or more frequently)
* Has active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, psoriatic arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, or multiple sclerosis
* Is ongoing treatment with immunosuppressive medications (including, but not limited to, systemic corticosteroids \[prednisone dose \>10mg per day or equivalent\], cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor \[TNF\] alpha agents) within 2 weeks prior to initiation of treatment, or anticipation of need for systemic immunosuppressive medication during study treatment (except protocol-required pre-medications)
* Has a history of clinically significant cardiovascular disease such as myocardial infarction, symptomatic congestive heart failure (New York Heart Association \> class II), and/or uncontrolled cardiac arrhythmia within 6 months of the first dose of study drug
* Has a history of arterial thrombosis (e.g., stroke or transient ischemic attack) within 6 months
* Has active viral hepatitis, defined as hepatitis A (hepatitis A virus immunoglobulin M \[IgM\] positive), hepatitis B (hepatitis B virus surface antigen \[HbsAg\] positive), or hepatitis C (hepatitis C virus \[HCV\] antibody positive, confirmed by HCV ribonucleic acid). HCV with undetectable virus after treatment are eligible. Hepatitis B virus (HBV) with undetectable viral load by quantitative polymerase chain reaction (PCR) are eligible.
* Has uncontrolled infection with Human Immunodeficiency Virus (HIV)-1 or HIV-2. Well-controlled HIV are eligible.
* Has a history of allogeneic stem cell transplant or solid-organ transplant
* Has had treatment with systemic immunostimulatory agents (including, but not limited to, interferon and IL-2) within 4 weeks or 5 drug-elimination half-lives (whichever is longer) prior to initiation of study treatment
* Has a history of severe anaphylactic reactions to chimeric or humanized antibodies or fusion proteins
* Has a history of interstitial lung disease, idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT). History of radiation pneumonitis in the radiation field is permitted
* Has had treatment with other investigational drug within 3 weeks of scheduled dosing (or 5 half-lives of drug, whichever is shorter)

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Where can I participate?

CS Cancer at Cedars-Sinai Medical Center

More about this Clinical Trial

What is the full name of this clinical trial?

HPN328-4001: A Phase 1/2 Open-label, Multicenter, Dose Escalation and Dose Expansion Study of the Safety, Tolerability, and Pharmacokinetics of HPN328 in Patients with Advanced Cancers Associated with Expression of Delta-Like Canonical Notch Ligand 3 Who Have Failed Standard Available Therapy

Study Details

Disease Type/Condition

Lung

Principal Investigator

Sankar, Kamya

Co-Investigators

Alain Mita, Andrew Hendifar, Karen Reckamp, Ronald Natale

Age Group

Adult

Phase

I/II

IRB Number

STUDY00002098

ClinicalTrials.gov ID

NCT04471727

Key Eligibility

ClinicalTrials.gov

How do I learn more about this study?

clinicaltrials@cshs.org