A Study in Participants With Advanced Cancers Associated With Expression of DLL3 (MK-6070-001/HPN328-4001)

Harpoon Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Neuroendocrine Carcinoma; Small-Cell Lung Cancer

Treatments: Biological: Atezolizumab; Biological: Gocatamig; Biological: Ifinatamab Deruxtecan (I-DXd)

Study type: Interventional

Funder types: Industry

Identifiers

NCT04471727

MK-6070-001 (Other Identifier)

HPN328-4001

Details and patient eligibility

About

This study will investigate the maximum tolerated dose, the recommended dose for expansion (RDE), safety, efficacy, and pharmacokinetics of gocatamig alone, gocatamig with Atezolizumab and gocatamig with I-DXd in participants with advanced cancers associated with expression of Delta-like Canonical Notch Ligand 3 (DLL3).

Enrollment: 232 estimated patients

Sex: All

Ages: 18 to 100 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

The main inclusion criteria include but are not limited to the following:

• 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

The main exclusion criteria include but are not limited to the following:

• 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)

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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232 participants in 5 patient groups

Gocatamig monotherapy dose escalation with 1 week dosing interval

Experimental group

Description:

Participants will receive gocatamig once weekly (Q1W) via intravenous (IV) infusion during each 21-day cycle. Dose escalation may continue until one or more RDEs are identified, participant discontinuation or the Sponsor decides to stop enrollment.

Treatment:

Biological: Gocatamig

Gocatamig monotherapy dose escalation with 2 week dosing interval

Experimental group

Description:

Participants will receive gocatamig via IV infusion once every 2 weeks (Q2W) of a 28-day cycle. Dose escalation may continue until one or more RDEs are identified, participant discontinuation, or the Sponsor decides to stop enrollment.

Treatment:

Biological: Gocatamig

Gocatamig monotherapy dose escalation with 3 week dosing interval

Experimental group

Description:

Participants will receive gocatamig via IV infusion once every 3 weeks (Q3W) of a 21-day cycle. Dose escalation may continue until one or more RDEs are identified, participant discontinuation, or the Sponsor decides to stop enrollment.

Treatment:

Biological: Gocatamig

Gocatamig dose escalation with atezolizumab

Experimental group

Description:

Small cell lung cancer (SCLC) participants will receive gocatamig via IV infusion Q2W during each 28-day cycle and Atezolizumab via IV infusion every 4 weeks (Q4W) on Day 1 of each 28-day cycle. Dose escalation may continue until one or more RDEs are identified, participant discontinuation, or the Sponsor decides to stop enrollment.

Treatment:

Biological: Gocatamig

Biological: Atezolizumab

Gocatamig dose escalation in combination with I-DXd

Experimental group

Description:

SCLC participants will receive gocatamig via IV infusion Q2W during each 42-day cycle and I-DXd via IV infusion Q3W on Day 1 and Day 22 of each 42-day cycle. Dose escalation may continue until one or more RDEs are identified, participant discontinuation, or the Sponsor decides to stop enrollment.

Treatment:

Biological: Ifinatamab Deruxtecan (I-DXd)

Biological: Gocatamig