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

NCT04471727 | Active Not Recruiting Phase 1 FDA Drug

• 2 other identifiers: HPN328-4001MK-6070-001
• Study Type: interventional
• Target: 232
• Locations: 1 country
• Sites: 11

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).

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

Outcome Measures

Primary Outcomes (45)

• Percentage of participants who experience an adverse event

  An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. AEs will be graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTACAE) version 5.0 (American Society for Transplant and Cellular Therapy (ASTCT) grading criteria for cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS)). The percentage of participants who experience an AE in the study will be presented.

  Up to ~4 years

• Percentage of participants who discontinue due to an adverse event

  An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. AEs will be graded according to NCI CTACAE version 5.0 (ASTCT grading criteria for CRS and ICANS). The percentage of participants who discontinue due to an AE in the study will be presented.

  Up to ~4 years

• Number of participants with dose limiting toxicity (DLT) following treatment with HPN328 as monotherapy or in combination with atezolizumab or I-DXd

  A DLT is defined as an AE that represents a clinically significant shift from baseline and must be considered related or suspected to be related to study drug (gocatamig and/or atezolizumab or I-DXd) by the Investigator or Sponsor. AEs will be graded according to NCI CTACAE version 5.0 (ASTCT grading criteria for CRS and ICANS). The number of participants with a DLT will be presented.

  Up to ~4 years

• Maximum concentration (Cmax) of Gocatamig

  Cmax is the maximum concentration of the drug observed in serum. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine Cmax of gocatamig.

  At designated time points up to ~4 years

• Cmax of Atezolizumab

  Cmax is the maximum concentration of the drug observed in serum. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine Cmax of Atezolizumab.

  At designated time points up to ~4 years

• Cmax of I-DXd

  Cmax is the maximum concentration of the drug observed in plasma. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine Cmax of I-DXd.

  At designated time points up to ~4 years

• Time to maximum concentration (Tmax) of Gocatamig

  Tmax is the amount of time that a drug is present at the maximum concentration observed in serum. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine the Tmax of gocatamig.

  At designated time points up to ~4 years

• Tmax of atezolizumab

  Tmax is the amount of time that a drug is present at the maximum concentration observed in serum. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine the Tmax of atezolizumab.

  At designated time points up to ~4 years

• Tmax of I-DXd

  Tmax is the amount of time that a drug is present at the maximum concentration observed in plasma. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine the Tmax of I-DXd.

  At designated time points up to ~4 years

• Area under the concentration-time curve over the dosing interval t (AUCt) of Gocatamig

  AUC is a measure of serum drug concentration and time and is estimated as the area under the plot of serum concentration against time after drug administration. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine t (AUCt) of gocatamig.

  At designated time points up to ~4 years

• AUCt of atezolizumab

  AUC is a measure of serum drug concentration and time and is estimated as the area under the plot of serum concentration against time after drug administration. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine t (AUCt) of atezolizumab.

  At designated time points up to ~4 years

• AUCt of I-DXd

  AUC is a measure of plasma drug concentration and time and is estimated as the area under the plot of plasma concentration against time after drug administration. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine t (AUCt) of I-DXd.

  At designated time points up to ~4 years

• Area under the concentration-time curve extrapolated to infinity (AUCinf) of Gocatamig

  AUCinf is a measure of serum drug concentration and time to infinity and is estimated as the area under the plot of serum concentration against time to infinity after drug administration. Blood samples collected at multiple timepoints post-dose will be used to determine the AUCinf of gocatamig.

  At designated time points up to ~4 years

• AUCinf of atezolizumab

  AUCinf is a measure of serum drug concentration and time to infinity and is estimated as the area under the plot of serum concentration against time to infinity after drug administration. Blood samples collected at multiple timepoints post-dose will be used to determine the AUCinf of atezolizumab.

  At designated time points up to ~4 years

• AUCinf of I-DXd

  AUCinf is a measure of plasma drug concentration and time to infinity and is estimated as the area under the plot of plasma concentration against time to infinity after drug administration. Blood samples collected at multiple timepoints post-dose will be used to determine the AUCinf of I-DXd.

  At designated time points up to ~4 years

• Terminal half-life (t1/2) of Gocatamig

  t1/2 is a measure of how long it takes to clear 50% of the drug from serum after reaching Cmax. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine the t1/2 of gocatamig.

  At designated time points up to ~4 years

• t1/2 of atezolizumab

  t1/2 is a measure of how long it takes to clear 50% of the drug from serum after reaching Cmax. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine the t1/2 of atezolizumab.

  At designated time points up to ~4 years

• t1/2 of I-DXd

  t1/2 is a measure of how long it takes to clear 50% of the drug from plasma after reaching Cmax. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine the t1/2 of I-DXd.

  At designated time points up to ~4 years

• Single dose clearance (CL) of Gocatamig

  CL is the apparent total clearance of the drug from serum after oral administration. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine CL of gocatamig.

  At designated time points up to ~4 years

• CL of atezolizumab

  CL is the apparent total clearance of the drug from serum after oral administration. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine CL of atezolizumab.

  At designated time points up to ~4 years

• CL of I-DXd

  CL is the apparent total clearance of the drug from plasma after oral administration. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine CL of I-DXd.

  At designated time points up to ~4 years

• Steady state maximum concentration (Cmax,ss) of Gocatamig

  Cmax,ss is the maximum concentration of the drug in serum observed in serum under steady state conditions. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine Cmax,ss of gocatamig.

  At designated time points up to ~4 years

• Cmax,ss of atezolizumab

  Cmax,ss is the maximum concentration of the drug observed in serum under steady state conditions. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine Css,max of atezolizumab.

  At designated time points up to ~4 years

• Cmax,ss of I-DXd

  Cmax,ss is the maximum concentration of the drug observed in plasma under steady state conditions. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine Cmax,ss of I-DXd.

  At designated time points up to ~4 years

• Steady state Ctrough (Ctrough,ss) of Gocatamig

  Ctrough,ss is the lowest concentration reached by a drug in serum under steady state conditions before the next dose is administered. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine Ctrough,ss of gocatamig.

  At designated time points up to ~4 years

• Ctrough,ss of atezolizumab

  Ctrough,ss is the lowest concentration reached by a drug in serum under steady state conditions before the next dose is administered. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine Ctrough,ss of atezolizumab.

  At designated time points up to ~4 years

• Ctrough,ss of I-DXd

  Ctrough,ss is the lowest concentration reached by a drug in plasma under steady state conditions before the next dose is administered. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine Ctrough,ss of I-DXd.

  At designated time points up to ~4 years

• Steady state time to maximum concentration (Tmax,ss) of Gocatamig

  Tmax,ss is the amount of time that a drug is present at the maximum concentration observed in serum under steady state conditions. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine the Tmax,ss of gocatamig.

  At designated time points up to ~4 years

• Tmax,ss of atezolizumab

  Tmax,ss is the amount of time that a drug is present at the maximum concentration observed in serum under steady state conditions. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine the Tmax,ss of atezolizumab.

  At designated time points up to ~4 years

• Tmax,ss of I-DXd

  Tmax,ss is the amount of time that a drug is present at the maximum concentration observed in plasma under steady state conditions. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine the Tmax,ss of I-DXd.

  At designated time points up to ~4 years

• Area under the steady state concentration-time curve over dosing interval t (AUCt,ss) of Gocatamig

  AUCt,ss is a measure of serum drug concentration and time and is estimated as the area under the plot of serum concentration against time after drug administration under steady state conditions. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine AUCt,ss of gocatamig.

  At designated time points up to ~4 years

• AUCt,ss of atezolizumab

  AUCt,ss is a measure of serum drug concentration and time and is estimated as the area under the plot of serum concentration against time after drug administration under steady state conditions. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine AUCt,ss of atezolizumab.

  At designated time points up to ~4 years

• AUCt,ss of I-DXd

  AUCt,ss is a measure of plasma drug concentration and time and is estimated as the area under the plot of plasma concentration against time after drug administration under steady state conditions. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine AUCt,ss of I-DXd.

  At designated time points up to ~4 years

• Steady state t1/2 (t1/2,ss) of Gocatamig

  t1/2,ss is a measure of how long it takes to clear 50% of the drug in serum after reaching Cmax under steady state conditions. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine the t1/2,ss of gocatamig.

  At designated time points up to ~4 years

• t1/2,ss of Gocatamig with atezolizumab

  t1/2,ss is a measure of how long it takes to clear 50% of the drug after reaching Cmax under steady state conditions. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine the t1/2,ss of atezolizumab.

  At designated time points up to ~4 years

• t1/2,ss of IDXd

  t1/2,ss is a measure of how long it takes to clear 50% of the drug in plasma after reaching Cmax under steady state conditions. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine the t1/2,ss of I-DXd.

  At designated time points up to ~4 years

• Steady state CL (CL,ss) of Gocatamig

  CL,ss is the apparent total clearance of the drug from serum after administration under steady state conditions. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine CL,ss of gocatamig.

  At designated time points up to ~4 years

• CL,ss of Gocatamig with atezolizumab

  CL,ss is the apparent total clearance of the drug from serum after administration under steady state conditions. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine CL,ss of atezolizumab.

  At designated time points up to ~4 years

• CL,ss of I-DXd

  CL,ss is the apparent total clearance of the drug from plasma after administration under steady state conditions. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine CL,ss of I-DXd.

  At designated time points up to ~4 years

• Steady state volume of distribution (V,ss) of Gocatamig

  V,ss is defined as the volume of distribution in serum under steady state conditions. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine the V,ss of gocatamig.

  At designated time points up to ~4 years

• V,ss of atezolizumab

  V,ss is defined as the volume of distribution in serum under steady state conditions. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine the V,ss of atezolizumab.

  At designated time points up to ~4 years

• V,ss of I-DXd

  V,ss is defined as the volume of distribution in plasma under steady state conditions. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine the V,ss of I-DXd.

  At designated time points up to ~4 years

• Steady state accumulation ratio (AC) of Gocatamig

  AC is the ratio of accumulation of a drug in serum under steady state conditions after repeated administration as compared to a single dose. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine AC of gocatamig.

  At designated time points up to ~4 years

• AC of atezolizumab

  AC is the ratio of accumulation of a drug in serum under steady state conditions after repeated administration as compared to a single dose. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine AC of atezolizumab.

  At designated time points up to ~4 years

• AC of I-DXd

  AC is the ratio of accumulation of a drug in plasma under steady state conditions after repeated administration as compared to a single dose. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine AC of I-DXd.

  At designated time points up to ~4 years

Secondary Outcomes (11)

• 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))

  Up to ~4 years

• Extra-cranial objective response rate (EC-ORR) based on modified RECIST v1.1

  Up to ~4 years

• Best Overall Response (BOR)

  Up to ~4 years

• Progression-free survival (PFS)

  Up to ~4 years

• Extra-cranial progression free survival (EC-PFS)

  Up to ~4 years

Study Arms (5)

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: Gocatamig

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: Gocatamig

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: Gocatamig

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: Gocatamig; Biological: Atezolizumab

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

Interventions

Atezolizumab BIOLOGICAL

IV infusion

Gocatamig dose escalation with atezolizumab

Ifinatamab Deruxtecan (I-DXd) BIOLOGICAL

IV infusion

Also known as: DS-7300a, MK-2400

Gocatamig dose escalation in combination with I-DXd

Gocatamig BIOLOGICAL

IV infusion

Also known as: HPN328, MK-6070

Gocatamig dose escalation in combination with I-DXd; Gocatamig dose escalation with atezolizumab; Gocatamig monotherapy dose escalation with 1 week dosing interval; Gocatamig monotherapy dose escalation with 2 week dosing interval; Gocatamig monotherapy dose escalation with 3 week dosing interval

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Daiichi Sankyo: collaborator
• Harpoon Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA): lead

Study Sites (11)

Cedar-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute

Los Angeles, California, 90048, United States

Location

University of California San Francisco

San Francisco, California, 94143, United States

Location

University of Colorado

Aurora, Colorado, 80045, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02467, United States

Location

Karmanos Cancer Center

Detroit, Michigan, 48201, United States

Location

Roswell Park Comprehensive Cancer Center

Buffalo, New York, 14263, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10021, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

Providence

Portland, Oregon, 97213, United States

Location

Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Links

• Merck Clinical Trials Information

MeSH Terms

Conditions

Small Cell Lung Carcinoma; Carcinoma, Neuroendocrine; Lung Neoplasms; Prostatic Neoplasms; Neuroendocrine Tumors

Interventions

atezolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Genital Neoplasms, Male; Urogenital Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 6, 2020
• First Posted: July 15, 2020
• Study Start: December 14, 2020
• Primary Completion (Estimated): January 28, 2028
• Study Completion (Estimated): January 28, 2028
• Last Updated: February 24, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share

Locations

US (11)