Clinical trial NCT04471727: A Study in Participants With Advanced Cancers Associated With Expression of DLL3 (MK-6070-001/HPN328-4001)
Official title: A Phase 1/2 Open-label, Multicenter, Dose Escalation and Dose Expansion Study of the Safety, Tolerability, and Pharmacokinetics of HPN328 Monotherapy and HPN328 With Atezolizumab or Ifinatamab Deruxtecan (I-DXd) in Patients With Advanced Cancers Associated With Expression of Delta-like Canonical Notch Ligand 3 (DLL3).
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Small-Cell Lung Cancer
Neuroendocrine Carcinoma
Keywords: Lung Cancer
Small-Cell Lung Cancer
DLL3
Harpoon
TriTAC
Prostate Cancer
Neuroendocrine Tumors
High Grade Neuroendrocrine Features
Delta Like Canonical Notch Ligand 3
T-cell Engager
Lead sponsor: Harpoon Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
Sponsor class: INDUSTRY
Collaborators: name: Daiichi Sankyo
First posted: 2020-07-15
Enrollment: 232
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: 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)

Primary outcomes:
measure: Percentage of participants who experience an adverse event
timeFrame: Up to ~4 years
measure: Percentage of participants who discontinue due to an adverse event
timeFrame: Up to ~4 years
measure: Number of participants with dose limiting toxicity (DLT) following treatment with HPN328 as monotherapy or in combination with atezolizumab or I-DXd
timeFrame: Up to ~4 years
measure: Maximum concentration (Cmax) of Gocatamig
timeFrame: At designated time points up to ~4 years
measure: Cmax of Atezolizumab
timeFrame: At designated time points up to ~4 years
measure: Cmax of I-DXd
timeFrame: At designated time points up to ~4 years
measure: Time to maximum concentration (Tmax) of Gocatamig
timeFrame: At designated time points up to ~4 years
measure: Tmax of atezolizumab
timeFrame: At designated time points up to ~4 years
measure: Tmax of I-DXd
timeFrame: At designated time points up to ~4 years
measure: Area under the concentration-time curve over the dosing interval t (AUCt) of Gocatamig
timeFrame: At designated time points up to ~4 years
measure: AUCt of atezolizumab
timeFrame: At designated time points up to ~4 years
measure: AUCt of I-DXd
timeFrame: At designated time points up to ~4 years
measure: Area under the concentration-time curve extrapolated to infinity (AUCinf) of Gocatamig
timeFrame: At designated time points up to ~4 years
measure: AUCinf of atezolizumab
timeFrame: At designated time points up to ~4 years
measure: AUCinf of I-DXd
timeFrame: At designated time points up to ~4 years
measure: Terminal half-life (t1/2) of Gocatamig
timeFrame: At designated time points up to ~4 years
measure: t1/2 of atezolizumab
timeFrame: At designated time points up to ~4 years
measure: t1/2 of I-DXd
timeFrame: At designated time points up to ~4 years
measure: Single dose clearance (CL) of Gocatamig
timeFrame: At designated time points up to ~4 years
measure: CL of atezolizumab
timeFrame: At designated time points up to ~4 years
measure: CL of I-DXd
timeFrame: At designated time points up to ~4 years
measure: Steady state maximum concentration (Cmax,ss) of Gocatamig
timeFrame: At designated time points up to ~4 years
measure: Cmax,ss of atezolizumab
timeFrame: At designated time points up to ~4 years
measure: Cmax,ss of I-DXd
timeFrame: At designated time points up to ~4 years
measure: Steady state Ctrough (Ctrough,ss) of Gocatamig
timeFrame: At designated time points up to ~4 years
measure: Ctrough,ss of atezolizumab
timeFrame: At designated time points up to ~4 years
measure: Ctrough,ss of I-DXd
timeFrame: At designated time points up to ~4 years
measure: Steady state time to maximum concentration (Tmax,ss) of Gocatamig
timeFrame: At designated time points up to ~4 years
measure: Tmax,ss of atezolizumab
timeFrame: At designated time points up to ~4 years
measure: Tmax,ss of I-DXd
timeFrame: At designated time points up to ~4 years
measure: Area under the steady state concentration-time curve over dosing interval t (AUCt,ss) of Gocatamig
timeFrame: At designated time points up to ~4 years
measure: AUCt,ss of atezolizumab
timeFrame: At designated time points up to ~4 years
measure: AUCt,ss of I-DXd
timeFrame: At designated time points up to ~4 years
measure: Steady state t1/2 (t1/2,ss) of Gocatamig
timeFrame: At designated time points up to ~4 years
measure: t1/2,ss of Gocatamig with atezolizumab
timeFrame: At designated time points up to ~4 years
measure: t1/2,ss of IDXd
timeFrame: At designated time points up to ~4 years
measure: Steady state CL (CL,ss) of Gocatamig
timeFrame: At designated time points up to ~4 years
measure: CL,ss of Gocatamig with atezolizumab
timeFrame: At designated time points up to ~4 years
measure: CL,ss of I-DXd
timeFrame: At designated time points up to ~4 years
measure: Steady state volume of distribution (V,ss) of Gocatamig
timeFrame: At designated time points up to ~4 years
measure: V,ss of atezolizumab
timeFrame: At designated time points up to ~4 years
measure: V,ss of I-DXd
timeFrame: At designated time points up to ~4 years
measure: Steady state accumulation ratio (AC) of Gocatamig
timeFrame: At designated time points up to ~4 years
measure: AC of atezolizumab
timeFrame: At designated time points up to ~4 years
measure: AC of I-DXd
timeFrame: At designated time points up to ~4 years
Secondary outcomes:
measure: Objective response rate (ORR) based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) (Prostate cancer clinical trials working group 3 (PCWG3) for participants with neuroendocrine prostate cancer (NEPC))
timeFrame: Up to ~4 years
measure: Extra-cranial objective response rate (EC-ORR) based on modified RECIST v1.1
timeFrame: Up to ~4 years
measure: Best Overall Response (BOR)
timeFrame: Up to ~4 years
measure: Progression-free survival (PFS)
timeFrame: Up to ~4 years
measure: Extra-cranial progression free survival (EC-PFS)
timeFrame: Up to ~4 years
measure: Overall survival (OS)
timeFrame: Up to ~4 years
measure: Duration of response (DOR)
timeFrame: Up to ~4 years
measure: Duration of extra-cranial response (EC-DOR)
timeFrame: Up to ~4 years
measure: Incidence of anti-drug antibodies (ADAs) against Gocatamig
timeFrame: At designated time points up to ~4 years
measure: Incidence of ADAs against atezolizumab (for combination-treatment patients)
timeFrame: At designated time points up to ~4 years
measure: Incidence of ADAs against I-DXd (for combination-treatment patients)
timeFrame: At designated time points up to ~4 years
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Cedar-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Center
state: Michigan
city: Buffalo
country: United States
facility: Roswell Park Comprehensive Cancer Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Portland
country: United States
facility: Providence
state: Oregon
city: Nashville
country: United States
facility: Tennessee Oncology
state: Tennessee
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: