A Study in Participants With Advanced Cancers Associated With Expression of DLL3 (MK-6070-001/HPN328-4001)
Conditions
Small-Cell Lung Cancer, Neuroendocrine CarcinomaSummary
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).
Locations
11 locations Found with status Recruiting
Status
- RECRUITING
Contact Person
- Garrett Crook
- 424-314-0745
- [email protected]
Study Director
- Medical Director
Status
- RECRUITING
Contact Person
- Christopher De Leon
- 415-307-9861
- [email protected]
Study Director
- Medical Director
Status
- RECRUITING
Contact Person
- Himisha Beltran, MD
- 617-632-2429
- [email protected]
Study Director
- Medical Director
Status
- RECRUITING
Contact Person
- Janine Miller
- 716-845-2809
- [email protected]
Study Director
- Medical Director
Status
- RECRUITING
Contact Person
- Cancer Information Services
- 800-641-2422
- [email protected]
Study Director
- Medical Director
Status
- RECRUITING
Contact Person
- Tennessee Oncology Sarah Cannon Research Institute
- 615-329-7478
- [email protected]
Study Director
- Medical Director
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)
Study Plan
Gocatamig monotherapy dose escalation with 1 week dosing interval
EXPERIMENTAL
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.
BIOLOGICAL:
GocatamigDescription:
IV infusion
Gocatamig monotherapy dose escalation with 2 week dosing interval
EXPERIMENTAL
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.
BIOLOGICAL:
GocatamigDescription:
IV infusion
Gocatamig monotherapy dose escalation with 3 week dosing interval
EXPERIMENTAL
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.
BIOLOGICAL:
GocatamigDescription:
IV infusion
Gocatamig dose escalation with atezolizumab
EXPERIMENTAL
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.
BIOLOGICAL:
GocatamigDescription:
IV infusionBIOLOGICAL:
AtezolizumabDescription:
IV infusion
Gocatamig dose escalation in combination with I-DXd
EXPERIMENTAL
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.
BIOLOGICAL:
GocatamigDescription:
IV infusionBIOLOGICAL:
Ifinatamab Deruxtecan (I-DXd)Description:
IV infusion
Outcome Measures
Primary Outcome Measures
Percentage of participants who experience an adverse event
Percentage of participants who discontinue due to an adverse event
Number of participants with dose limiting toxicity (DLT) following treatment with HPN328 as monotherapy or in combination with atezolizumab or I-DXd
Maximum concentration (Cmax) of Gocatamig
Cmax of Atezolizumab
Cmax of I-DXd
Time to maximum concentration (Tmax) of Gocatamig
Tmax of atezolizumab
Tmax of I-DXd
Area under the concentration-time curve over the dosing interval t (AUCt) of Gocatamig
AUCt of atezolizumab
AUCt of I-DXd
Area under the concentration-time curve extrapolated to infinity (AUCinf) of Gocatamig
AUCinf of atezolizumab
AUCinf of I-DXd
Terminal half-life (t1/2) of Gocatamig
t1/2 of atezolizumab
t1/2 of I-DXd
Single dose clearance (CL) of Gocatamig
CL of atezolizumab
CL of I-DXd
Steady state maximum concentration (Cmax,ss) of Gocatamig
Cmax,ss of atezolizumab
Cmax,ss of I-DXd
Steady state Ctrough (Ctrough,ss) of Gocatamig
Ctrough,ss of atezolizumab
Ctrough,ss of I-DXd
Steady state time to maximum concentration (Tmax,ss) of Gocatamig
Tmax,ss of atezolizumab
Tmax,ss of I-DXd
Area under the steady state concentration-time curve over dosing interval t (AUCt,ss) of Gocatamig
AUCt,ss of atezolizumab
AUCt,ss of I-DXd
Steady state t1/2 (t1/2,ss) of Gocatamig
t1/2,ss of Gocatamig with atezolizumab
t1/2,ss of IDXd
Steady state CL (CL,ss) of Gocatamig
CL,ss of Gocatamig with atezolizumab
CL,ss of I-DXd
Steady state volume of distribution (V,ss) of Gocatamig
V,ss of atezolizumab
V,ss of I-DXd
Steady state accumulation ratio (AC) of Gocatamig
AC of atezolizumab
AC of I-DXd
Secondary Outcome Measures
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))
Extra-cranial objective response rate (EC-ORR) based on modified RECIST v1.1
Best Overall Response (BOR)
Progression-free survival (PFS)
Extra-cranial progression free survival (EC-PFS)
Overall survival (OS)
Duration of response (DOR)
Duration of extra-cranial response (EC-DOR)
Incidence of anti-drug antibodies (ADAs) against Gocatamig
Incidence of ADAs against atezolizumab (for combination-treatment patients)
Incidence of ADAs against I-DXd (for combination-treatment patients)
Timeline
Last Updated
February 20, 2025Start Date
July 15, 2020Today
May 9, 2025Completion Date ( Estimated )
June 30, 2027
Sponsors of this trial
Lead Sponsor
Harpoon Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)Collaborating Sponsors
Daiichi Sankyo