About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Participant has locally-advanced (unresectable or metastatic solid tumor) confirmed by available pathology records or current biopsy.
TNBC defined as unequivocal TNBC histology (ER 1 negative/progesterone receptor-negative/HER2-negative). This is defined by < 1% expression of ER and progesterone receptor by IHC and that are, for HER2, either 0 to 1+ by IHC, or IHC 2+ and FISH negative (not amplified) as per current ASCO/CAP guidelines [Hammond et al, 2010].
Monotherapy expansion mCRC/mAPMR-PCa cohort: Participants with MSS/MSI-L mCRC/mAPMR-PCa, are eligible.
Monotherapy expansion select CLDN4-expressing tumors cohort: Participants with metastatic solid tumors known to highly express CLDN4 are eligible.
Disqualifiers
Participant weighs < 40 kg.
Ongoing toxicity that has not resolved to ≤ grade 1 per CTCAE version 5.0 and is considered clinically significant and in the opinion of the investigator, attributable to prior antineoplastic therapy.
Symptomatic CNS metastases or evidence of uncontrolled CNS disease even if asymptomatic (e.g. progression on scans). Participants with previously treated CNS metastases are eligible, if they are clinically stable/have no evidence of CNS progression by imaging for at least 4 weeks prior to start of study intervention and are not requiring immunosuppressive doses of systemic steroids (equivalent to > 10 mg per day of prednisone) for longer than 2 weeks.
Active autoimmune disease, a history of inflammatory bowel disease (IBD)or other immune-related GI disorders (e.g., ulcerative colitis, Crohn's disease). Participant with type 1 diabetes mellitus, endocrinopathies stably maintained on appropriate replacement therapy, or skin disorders (e.g., vitiligo, psoriasis or alopecia) not requiring systemic treatment are allowed.
Trial design
Sequential
Treatments tested in this trial
ASP1002
DrugIntravenous (IV) infusion. Dose interruptions, reductions, and treatment discontinuations will be implemented according to protocol-defined toxicity management criteria.
Bevacizumab
DrugIV infusion
Oxaliplatin
DrugIV infusion
Leucovorin
DrugIV infusion
Fluorouracil
DrugIV infusion
Irinotecan
DrugIV infusion
Trifluridine-Tipiracil
DrugFilm-coated tablet
Pembrolizumab
DrugIV infusion
Pemetrexed
DrugIV infusion
Carboplatin
DrugIV infusion
Ramucirumab
DrugIV infusion
Docetaxel
DrugIV infusion
Treatment groups
18
Treatment groupsSee each treatment group below.
Trial outcomes
Primary outcomes
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.
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.
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.
Number of participants with laboratory value abnormalities and/or adverse events (AEs)
Number of participants with potentially clinically significant laboratory values.
Secondary outcomes
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.
Pharmacokinetics (PK) of ASP1002 in serum: Cmax
Maximum concentration (Cmax) will be recorded from the PK serum samples collected.
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.
Pharmacokinetics (PK) of ASP1002 in serum: tmax
Time of maximum concentration (tmax) will be recorded from the PK serum samples collected.
Sponsors and contacts
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