Claudin 18.2 protein, or CLDN18.2 is a protein found on cells in the digestive system. It is also found on some tumors. Researchers are looking at ways to attack CLDN18.2 to help control tumors. ASP2138 is thought to bind to CLDN18.2 and a protein on a type of immune cell called a T-cell. This "tells" the immune system to attack the tumor. ASP2138 is a potential treatment for people with stomach cancer, gastroesophageal junction cancer (GEJ cancer) or pancreatic cancer. GEJ is where the tube that carries food (esophagus) joins the stomach. Before ASP2138 is available as a treatment, the researchers need to understand how it is processed by and acts upon the body. In this study, ASP2138 will either be given by itself, or given together with standard treatments for gastric, GEJ and pancreatic cancer. Pembrolizumab and mFOLFOX6, and ramucirumab and paclitaxel are standard treatments for gastric and GEJ cancer. mFOLFIRINOX is a standard treatment for pancreatic cancer. This information will help find a suitable dose of ASP2138 given by itself and together with the standard cancer treatments and to check for potential medical problems from the treatments.
The main aims of the study are:
* To check the safety of ASP2138 and how well people can tolerate medical problems during the study. * To find a suitable dose of ASP2138 to be used later in the study. * These are done for ASP2138 given by itself and when given together with the standard cancer treatments.
Adults 18 years or older with stomach cancer, GEJ cancer, or pancreatic cancer can take part. Their cancer is locally advanced unresectable or metastatic. Locally advanced means the cancer has spread to nearby tissue. Unresectable means the cancer cannot be removed by surgery. Metastatic means the cancer has spread to other parts of the body. There should also be the CLDN18.2 marker in a tumor sample. People cannot take part if they need to take medicines to suppress their immune system, have blockages or bleeding in their gut, have specific uncontrollable cancers, have specific infections, have a condition such as hemophagocytic lymphohistiocytosis (HLH) which is when the body over-reacts to a "trigger" such as infection, or have a specific heart condition ("New York Heart Association Class III or IV").
Phase 1: Lower to higher doses of ASP2138
* ASP2138 is either given through a vein (intravenous infusion) or just under the skin (subcutaneous injection). * Different small groups are given lower to higher doses of ASAP2138. * ASP2138 is either given by itself, or given with 1 of 3 standard treatments: * Pembrolizumab and mFOLFOX6 (first treatment for gastric GEJ cancer) * Ramacirumab and paclitaxel (Second treatment for gastric or GEJ cancer) * ASP2138 with mFOLFIRINOX (first treatment for pancreatic cancer)
Phase 1b: doses of ASP2138 worked out from Phase 1
* ASP2138 is either given through a vein or just under the skin. This depends on the findings from Phase 1. * People with gastric cancer, GEJ cancer or pancreatic cancer are given doses of ASP2138, worked out from Phase 1. * This includes doses of ASP2138 given by itself and ASP2138 given with the standard cancer treatments. * The standard cancer treatments given depends on the type of cancer they have.
End of treatment visit: This is 7 days after final dose of study treatment or if the study doctor decides to stop the person's treatment.
People who have locally advanced unresectable pancreatic cancer will not receive ASP2138 by itself.
Participant is considered an adult according to local regulation at the time of signing the informed consent form (ICF).
Not a woman of childbearing potential (WOCBP)
WOCBP who agrees to follow the contraceptive guidance from the time of informed consent through at least 6 months after final study intervention administration.
Female participant must agree not to breastfeed starting at screening & throughout the study period & for 6 months after the final study intervention administration.
Participant has received other investigational agents, or antineoplastic therapy including other immunotherapy or devices concurrently or within 21 days or 5 times the half-life, whichever is shorter, prior to first dose of study intervention administration.
Participant has any condition which makes the participant unsuitable for study participation.
Participant has known immediate or delayed hypersensitivity or contraindication to any component of study intervention.
Participant has had prior severe allergic reaction or intolerance to known ingredients of ASP2138 or other antibodies, including humanized or chimeric antibodies.
Sequential
ASP2138
DrugIntravenously or Subcutaneously
Pembrolizumab
DrugIntravenously
Oxaliplatin
DrugIntravenously
Leucovorin
DrugIntravenously
Fluorouracil
DrugIntravenously
Ramucirumab
DrugIntravenously
Paclitaxel
DrugIntravenously
Irinotecan
DrugIntravenously
Capecitabine
DrugOral Administration
10
Treatment groupsSee each treatment group below.
Incidence of Dose Limiting Toxicities (DLTs) (Phase 1 Dose Escalation)
A DLT is defined as any of the prespecified Adverse Events (AEs) (graded using National Cancer Institute Common Terminology Criteria for Adverse Events \[NCI-CTCAE\] version 5.0, except cytokine release syndrome \[CRS\] and immune effector cell-associated neurotoxicity syndrome \[ICANS\] which are graded using American Society for Transplantation and Cellular Therapy \[ASTCT\] consensus grading) or laboratory findings that the investigator or sponsor cannot clearly attribute to a cause other than study drug occurring during the DLT evaluation period.
Number of participants with Adverse Events (AEs)
An AE is any untoward medical occurrence temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study intervention. This includes events related to the comparator and events related to the (study) procedures.
Number of participants with serious AEs (SAEs)
An 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 events.
Number of participants with laboratory value abnormalities
Number of participants with potentially clinically significant laboratory values.
Pharmacokinetics (PK) of ASP2138 in serum: Area under the concentration-time curve (AUC) from the time of dosing to the start of the next dosing interval at multiple dose conditions (AUCtau)
AUCtau will be recorded from the PK serum samples collected.
PK of ASP2138 in serum: maximum concentration (Cmax)
Cmax will be recorded from the PK serum samples collected.
PK of ASP2138 in serum: concentration immediately prior to dosing at multiple dosing (Ctrough)
Ctrough will be recorded from the PK serum samples collected.
PK of ASP2138 in serum: time of the maximum concentration (Tmax)
Tmax will be recorded from the PK serum samples collected.
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