ASP1002 is being studied in people with tumors that have spread to nearby tissue (locally advanced) that cannot be removed by surgery (unresectable) or tumors that have spread to other parts of the body (metastatic). Claudin 4 protein, or CLDN4, is a protein found on tumors in different parts of the body. ASP1002 is thought to work by attaching to the CLDN4 protein in the tumor. This switches on the body's immune system to attack the tumor. Before ASP1002 can be used, researchers need to collect information about the safety of ASP1002 and how people with tumors tolerate it. In this study, ASP1002 will be given to humans for the first time. It will either be given by itself or together with other cancer treatments. These include standard chemotherapies (mFOLFOX6, FOLFIRI, TAS-102, pemetrexed, carboplatin, and docetaxel) and immunotherapies (bevacizumab, pembrolizumab, and ramucirumab). Immunotherapy is a treatment that works with the body's immune system to treat tumors. This is an early development study. These studies are mostly about safety, but also to find the most suitable dose. Other aims are to learn if ASP1002 shows signs of slowing down tumor growth, to learn how the body processes ASP1002, and to check if there are changes in the CLDN4 protein or the immune system after treatment. The main aims of the study are to check the safety of ASP1002 by itself and given with standard chemotherapies and immunotherapies in people with solid tumors and how well they tolerate the study treatments, and to find a suitable dose of ASP1002 by itself and in combination with standard chemotherapies and immunotherapies. People in this study will be adults with tumors that have spread to nearby tissue (locally advanced) that cannot be removed by surgery (unresectable) or tumors that have spread to other parts of the body (metastatic). They will have been previously treated with available standard therapies, or they will have refused to receive those treatments. The key reasons people cannot take part are if they have symptoms of cancer in the brain or nervous system, have recently had other cancers that required treatment, or have diseases that affect the immune system or the heart. This study will be in 2 parts. In Part 1, different small groups of people will receive lower to higher doses of ASP1002 by itself and given with chemotherapies and immunotherapies. Any medical problems will be recorded at each dose. This is done to find suitable doses of ASP1002 to use in Part 2 of the study. In Part 2, other different small groups of people will receive doses of ASP1002, the chemotherapies and immunotherapies that worked the best in Part 1. In both parts of the study, ASP1002 will be given by itself and with standard chemotherapies and immunotherapies to people slowly through a tube into a vein. This is called an infusion. This will happen every 2 to 4 weeks, in treatment cycles. Treatment cycles may be 21 or 28 days long. People will continue to receive study treatment for up to 2 years or until their cancer gets worse, they can't tolerate the study treatment, they start other cancer treatments, or the doctor decides the person should stop receiving study treatment, or sadly, they pass away. They can also choose to stop taking the study treatment at any time without giving a reason. During the study, people will visit the clinic several times for a health check. This includes standard safety checks and reporting any medical problems. Every 2 months, the study doctors will check if each person's cancer has stayed the same, shrunk or disappeared over time. This will be done by scans (CT or MRI scans). Tumor samples will be taken during the study, and people will have the option of giving a tumor sample after study treatment has finished. People will have follow-up health checks for up to 1 year after their last dose of study treatment or until they start a different study treatment on a new study, whichever happens first.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
798
Intravenous (IV) infusion. Dose interruptions, reductions, and treatment discontinuations will be implemented according to protocol-defined toxicity management criteria.
IV infusion
IV infusion
IV infusion
IV infusion
IV infusion
Film-coated tablet
IV infusion
IV infusion
IV infusion
IV infusion
IV infusion
Yale University Cancer Center
New Haven, Connecticut, United States
RECRUITINGHartford HealthCare Cancer Institute at The Hospital of Central Connecticut
Plainville, Connecticut, United States
RECRUITINGUniversity of Florida
Gainesville, Florida, United States
RECRUITINGUniversity of Iowa Hospitals
Iowa City, Iowa, United States
RECRUITINGNorton Cancer Institute
Louisville, Kentucky, United States
RECRUITINGHenry Ford Hospital
Detroit, Michigan, United States
RECRUITINGHealthPartners Cancer Research Center
Saint Paul, Minnesota, United States
RECRUITINGIcahn School of Medicine at Mount Sinai
New York, New York, United States
RECRUITINGUniversity Hospitals of Cleveland
Cleveland, Ohio, United States
RECRUITINGPrisma Health-Upstate Cancer Institute
Greenville, South Carolina, United States
COMPLETED...and 5 more locations
Incidence of Dose Limiting Toxicities (DLTs) for ASP1002
A DLT is defined as any of the following AEs that the investigator (or sponsor) cannot clearly attribute to a cause other than study intervention.
Time frame: Up to 24 months
Number of participants with Adverse Events (AEs)
Adverse events (AEs) will be coded using MedDRA. An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
Time frame: Up to 25 months
Number of participants with Serious Adverse Events (SAEs)
A Serious Adverse event (SAE) is defined as any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or other medically important event.
Time frame: Up to 27 months
Number of participants with laboratory value abnormalities and/or adverse events (AEs)
Number of participants with potentially clinically significant laboratory values.
Time frame: Up to 27 months
Number of participants with vital sign abnormalities and/or adverse events (AEs)
Number of participants with potentially clinically significant vital sign values.
Time frame: Up to 27 months
Number of participants with electrocardiogram (ECG) abnormalities and/or Adverse Events (AEs)
Number of participants with potentially clinically significant ECG values.
Time frame: Up to 27 months
Number of participants with physical exam abnormalities and/or Adverse Events (AEs)
Number of participants with potentially clinically significant physical exam values.
Time frame: Up to 24 months
Number of participants at each grade of Eastern Cooperative Oncology Group (ECOG) performance status scores
The ECOG scale will be used to assess performance status. Grades range from 0 (fully active) to 4 (completely disabled). Negative change scores indicate an improvement. Positive scores indicate a decline in performance.
Time frame: Up to 27 months
Pharmacokinetics (PK) of ASP1002 in serum: Area under the concentration-time curve from time zero to time of the last measurable concentration (AUC0-tlast)
AUC0-tlast will be recorded from the PK serum samples collected.
Time frame: Up to 12 months
Pharmacokinetics (PK) of ASP1002 in serum: Cmax
Maximum concentration (Cmax) will be recorded from the PK serum samples collected.
Time frame: Up to 12 months
Pharmacokinetics (PK) of ASP1002 in serum: Ctrough
Concentration immediately prior to dosing at multiple dosing (Ctrough) will be recorded from the PK serum samples collected.
Time frame: Up to 12 months
Pharmacokinetics (PK) of ASP1002 in serum: tmax
Time of maximum concentration (tmax) will be recorded from the PK serum samples collected.
Time frame: Up to 12 months
Objective Response Rate (ORR) per Immune Response Evaluation Criteria in Solid Tumors (iRECIST)
ORR is defined as the proportion of participants whose best overall response is a Complete Response (CR) or Partial Response (PR).
Time frame: Up to 28 months
Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
ORR is defined as the proportion of participants whose best overall response is a Complete Response (CR) or Partial Response (PR).
Time frame: Up to 28 months
Duration of Response (DOR) per iRECIST
DOR is defined as the time from the date of first documented response (CR or PR) to the date of first documented disease progression (PD) or death due to any cause, whichever occurs first.
Time frame: Up to 28 months
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Duration of Response (DOR) per RECIST v1.1
DOR is defined as the time from the date of first documented response (CR or PR) to the date of first documented disease progression (PD) or death due to any cause, whichever occurs first.
Time frame: Up to 28 months
Disease Control Rate (DCR) per iRECIST
DCR is defined as the proportion of participants whose best overall response is CR, PR or stable disease (SD).
Time frame: Up to 28 months
Disease Control Rate (DCR) per RECIST v1.1
DCR is defined as the proportion of participants whose best overall response is CR, PR or stable disease (SD).
Time frame: Up to 28 months
Incidence rate of Claudin-4 (CLDN4) by immunohistochemistry (IHC)
Characterization of CLDN4 expression in tumor biopsies at baseline and up to six weeks will be performed.
Time frame: Baseline and up to 6 weeks
Changes in expression levels of Claudin-4 (CLDN4) by immunohistochemistry (IHC)
Comparison of CLDN4 expression at baseline versus on-treatment tumor biopsies will be performed.
Time frame: Baseline and up to 6 weeks
Radiographic disease progression
Radiographic disease progression will be assessed by CT/MRI per RECIST v1.1 and iRECIST, and by bone scan according to PCWG4 criteria (applicable for evaluation of bone lesions in participants with mAPMR-PCa).
Time frame: Baseline and up to 28 months
Prostate-Specific Antigen (PSA) Response Rate (PSA50)
PSA response will be assessed per Prostate Cancer Working Group 3 (PCWG3) criteria for metastatic androgen pathway modulation resistant (mAMPR) prostate cancer participants. Percentage of participants with a ≥50% decrease from baseline in PSA levels, confirmed by a subsequent assessment at least 3 weeks later.
Time frame: Baseline and up to 28 months
Time to PSA Progression
PSA testing will be performed for mAMPR prostate cancer participants. Time from baseline (or PSA nadir) to first documented increase in PSA, confirmed by a second rising value at least 3 weeks later. A minimum rise of 0.2 ng/mL is required. The date of progression is defined as the date of the first increase.
Time frame: Baseline and up to 28 months