Active, not recruiting
Phase 1/2
A Study in Participants With Advanced Cancers Associated With Expression of DLL3 (MK-6070-001/HPN328-4001)
Condition(s) studied
Small-Cell Lung CancerNeuroendocrine Carcinoma
Investigational drug(s) / intervention(s)
GocatamigAtezolizumabIfinatamab Deruxtecan (I-DXd)
Gocatamig: IV infusion
Atezolizumab: IV infusion
Ifinatamab Deruxtecan (I-DXd): IV infusion
Study 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
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 outcome measure(s)
- Percentage of participants who experience an adverse event — Up to ~4 years
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.
- Percentage of participants who discontinue due to an adverse event — Up to ~4 years
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.
- Number of participants with dose limiting toxicity (DLT) following treatment with HPN328 as monotherapy or in combination with atezolizumab or I-DXd — Up to ~4 years
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.
- Maximum concentration (Cmax) of Gocatamig — At designated time points up to ~4 years
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.
- Cmax of Atezolizumab — At designated time points up to ~4 years
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.
- Cmax of I-DXd — At designated time points up to ~4 years
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.
- Time to maximum concentration (Tmax) of Gocatamig — At designated time points up to ~4 years
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.
- Tmax of atezolizumab — At designated time points up to ~4 years
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.
- Tmax of I-DXd — At designated time points up to ~4 years
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.
- Area under the concentration-time curve over the dosing interval t (AUCt) of Gocatamig — At designated time points up to ~4 years
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.
- AUCt of atezolizumab — At designated time points up to ~4 years
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.
- AUCt of I-DXd — At designated time points up to ~4 years
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.
- Area under the concentration-time curve extrapolated to infinity (AUCinf) of Gocatamig — At designated time points up to ~4 years
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.
- AUCinf of atezolizumab — At designated time points up to ~4 years
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.
- AUCinf of I-DXd — At designated time points up to ~4 years
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.
- Terminal half-life (t1/2) of Gocatamig — At designated time points up to ~4 years
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.
- t1/2 of atezolizumab — At designated time points up to ~4 years
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.
- t1/2 of I-DXd — At designated time points up to ~4 years
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.
- Single dose clearance (CL) of Gocatamig — At designated time points up to ~4 years
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.
- CL of atezolizumab — At designated time points up to ~4 years
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.
- CL of I-DXd — At designated time points up to ~4 years
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.
- Steady state maximum concentration (Cmax,ss) of Gocatamig — At designated time points up to ~4 years
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.
- Cmax,ss of atezolizumab — At designated time points up to ~4 years
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.
- Cmax,ss of I-DXd — At designated time points up to ~4 years
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.
- Steady state Ctrough (Ctrough,ss) of Gocatamig — At designated time points up to ~4 years
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.
- Ctrough,ss of atezolizumab — At designated time points up to ~4 years
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.
- Ctrough,ss of I-DXd — At designated time points up to ~4 years
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.
- Steady state time to maximum concentration (Tmax,ss) of Gocatamig — At designated time points up to ~4 years
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.
- Tmax,ss of atezolizumab — At designated time points up to ~4 years
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.
- Tmax,ss of I-DXd — At designated time points up to ~4 years
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.
- Area under the steady state concentration-time curve over dosing interval t (AUCt,ss) of Gocatamig — At designated time points up to ~4 years
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.
- AUCt,ss of atezolizumab — At designated time points up to ~4 years
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.
- AUCt,ss of I-DXd — At designated time points up to ~4 years
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.
- Steady state t1/2 (t1/2,ss) of Gocatamig — At designated time points up to ~4 years
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.
- t1/2,ss of Gocatamig with atezolizumab — At designated time points up to ~4 years
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.
- t1/2,ss of IDXd — At designated time points up to ~4 years
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.
- Steady state CL (CL,ss) of Gocatamig — At designated time points up to ~4 years
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.
- CL,ss of Gocatamig with atezolizumab — At designated time points up to ~4 years
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.
- CL,ss of I-DXd — At designated time points up to ~4 years
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.
- Steady state volume of distribution (V,ss) of Gocatamig — At designated time points up to ~4 years
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.
- V,ss of atezolizumab — At designated time points up to ~4 years
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.
- V,ss of I-DXd — At designated time points up to ~4 years
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.
- Steady state accumulation ratio (AC) of Gocatamig — At designated time points up to ~4 years
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.
- AC of atezolizumab — At designated time points up to ~4 years
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.
- AC of I-DXd — At designated time points up to ~4 years
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.
Trial sites (11)
| Facility | City | Region | Status |
|---|
| Cedar-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute |
Los Angeles |
California |
|
| University of California San Francisco |
San Francisco |
California |
|
| University of Colorado |
Aurora |
Colorado |
|
| Dana Farber Cancer Institute |
Boston |
Massachusetts |
|
| Karmanos Cancer Center |
Detroit |
Michigan |
|
| Roswell Park Comprehensive Cancer Center |
Buffalo |
New York |
|
| Memorial Sloan Kettering Cancer Center |
New York |
New York |
|
| University Hospitals Cleveland Medical Center |
Cleveland |
Ohio |
|
| Providence |
Portland |
Oregon |
|
| Tennessee Oncology |
Nashville |
Tennessee |
|
| Medical College of Wisconsin |
Milwaukee |
Wisconsin |
|
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