Informations générales (source: ClinicalTrials.gov)
A Phase 1/1b Study of ASP2138 as Monotherapy and in Combination With Pembrolizumab and mFOLFOX6 or Ramucirumab and Paclitaxel in Participants With Metastatic or Locally Advanced Unresectable Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma and in Combination With mFOLFIRINOX in Participants With Metastatic or Locally Advanced Unresectable Pancreatic Adenocarcinoma Whose Tumors Have Claudin (CLDN) 18.2 Expression
Interventional
Phase 1
Astellas Pharma Global Development, Inc. (Voir sur ClinicalTrials)
juin 2022
mai 2027
02 mars 2026
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.
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT GUSTAVE ROUSSY | Antoine HOLLEBECQUE | 30/04/2026 10:15:07 | Contacter | ||
Critères
Tous
- Participant is considered an adult according to local regulation at the time of
signing the informed consent form (ICF).
- Female participant is not pregnant, confirmed by serum pregnancy test &vmedical
evaluation by interview & at least 1 of the following conditions apply:
- 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.
- Female participant must not donate ova starting at screening & throughout the study
period & for 6 months after the final study intervention administration.
- Male participant with female partner(s) of childbearing potential (including
breastfeeding partner) must agree to use contraception throughout the treatment
period & for 6 months after the final study intervention administration.
- Male participant must not donate sperm during the treatment period & for 6 months
after the final study intervention administration.
- Male participant with pregnant or breastfeeding partner(s) must agree to remain
abstinent or use a condom for the duration of the pregnancy or time partner is
breastfeeding throughout the study period & for 6 months after the final study
intervention administration.
- Participant's tumor sample is positive for claudin (CLDN)18.2 expression by central
immunohistochemistry (IHC) testing.
- Participant has radiographically-confirmed, locally advanced, unresectable or
metastatic disease within 28 days prior to the first dose of study intervention.
- Participant has at least 1 measurable disease according to Response Evaluation
Criteria in Solid Tumors (RECIST) 1.1 within 28 days prior to the first dose of
study intervention. Lesions situated in a previously irradiated area are considered
measurable if progression has been demonstrated in such lesions.
- Participant has QT interval by Fredericia (QTcF) =< 470 msec.
- Participant agrees not to participate in another interventional study while
receiving study Intervention in the present study.
- Participant has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
1.
- Participant has predicted life expectancy >= 12 weeks.
- Participant must meet all of criteria based on laboratory tests within 7 days prior
to the first dose of study Intervention. In case of multiple laboratory data within
this period, the most recent data should be used. If a participant has received a
recent blood transfusion, the laboratory tests must be obtained >= 1 week after any
blood transfusion.
Monotherapy Disease specific Criteria: Gastric/GEJ Cancer
- Participant has histologically confirmed metastatic, locally advanced unresectable
gastric/gastroesophageal junction (GEJ) adenocarcinoma.
- Escalation: Participant with gastric/GEJ adenocarcinoma who has progressed, is
intolerant, has refused, or for whom there is no standard approved therapies that
impart significant clinical benefit (no limit to the number of prior treatment
regimens).
- Unique to South Korea: Participant with gastric/GEJ adenocarcinoma who has
refused standard approved therapies is not allowed.
- Expansion: Participant with gastric/GEJ adenocarcinoma must have received no more
than 3 prior lines of systemic chemotherapy treatment.
- Unique to EU: Expansion: Participant with gastric/GEJ adenocarcinoma must have
received at least first-line standard therapies in the metastatic setting, must
have received ramucirumab treatment if eligible & where ramucirumab is
available, & no more than 3 prior lines of systemic chemotherapy treatment.
Monotherapy Disease specific Criteria: Pancreatic Cancer
- Participant has histologically or cytologically confirmed metastatic pancreatic
adenocarcinoma.
- Escalation: Participant with pancreatic adenocarcinoma who has progressed, is
intolerant, has refused, or for whom there is no standard approved therapies that
impart significant clinical benefit (no limit to the number of prior treatment
regimens).
- Unique to South Korea: Participant with pancreatic adenocarcinoma who has
refused standard approved therapies is not allowed.
- Expansion: Participants with pancreatic adenocarcinoma must have received no more
than 2 prior lines of systemic chemotherapy treatment.
Note: Participants with locally advanced unresectable pancreatic adenocarcinoma will not
be admitted in monotherapy arms.
- Unique to EU: Participant with pancreatic adenocarcinoma must have received at least
first-line standard therapies in the metastatic setting & no more than 2 prior lines
of systemic chemotherapy treatment.
For all participants in combination therapy (CT) administration:
- If a participant has received a recent blood transfusion, the laboratory tests must
be obtained ≥ 1 week after any blood transfusion.
Combination Therapy Disease-specific (CTDS) Inclusion Criteria: ASP2138 in Combination
with Pembrolizumab & mFOLFOX6 as First-line Therapy in Gastric/GEJ Cancer
- Participant has histologically confirmed diagnosis of gastric/GEJ adenocarcinoma.
- Participant has metastatic or locally advanced unresectable gastric/GEJ
adenocarcinoma.
- Participant with gastric/GEJ adenocarcinoma has progressed & must not have been
previously treated for metastatic disease with either chemotherapy or prior
checkpoint inhibitor therapy.
- Participant has a human epidermal growth factor receptor 2 (HER2)-negative tumor per
local testing.
- For CT with oxaliplatin, follow contraception guidelines from time of informed
consent through at least 9 months after final study intervention.
(Unique to South Korea: For CT with oxaliplatin, follow contraception guidelines from
time of informed consent through at least 15 months after final study intervention for
women & 12 months after final study intervention for men).
Unique to EU:
- Participant must have a PD-L1 CPS ≥ 1.
CTDS Inclusion Criteria: ASP2138 in Combination with Ramucirumab & Paclitaxel as
Second-line Therapy in Gastric/GEJ Cancer
- Participant has histologically confirmed diagnosis of gastric/GEJ adenocarcinoma.
- Participant has metastatic or locally advanced unresectable gastric/GEJ
adenocarcinoma.
- Participant with gastric/GEJ adenocarcinoma must have previously received 1 line of
systemic chemotherapy treatment (i.e., documented objective radiological or clinical
disease progression after first line platinum & fluoropyrimidine treatment in the
metastatic setting or disease progression during or within 4 months of the last dose
of perioperative treatment.
CTDS Inclusion Criteria: ASP2138 in Combination with mFOLFIRINOX as First-line Therapy in
Pancreatic Cancer
- Participant has histologically or cytologically confirmed diagnosis of pancreatic
adenocarcinoma.
- Participant has confirmed metastatic or locally advanced unresectable pancreatic
adenocarcinoma.
- Participant has pancreatic adenocarcinoma, has progressed & must not have received
prior systemic anticancer therapy for their advanced disease.
- For CT with oxaliplatin, follow contraception guidelines from time of informed
consent through at least 9 months after final study intervention.
(Unique to South Korea: For CT with oxaliplatin, follow contraception guidelines from
time of informed consent through at least 15 months after final study intervention for
women & 12 months after final study intervention for men).
Japan & Korea Specific:
For All Participants in ASP2138 in Combination with Pembrolizumab & CAPOX:
- If a participant has received a recent blood transfusion, the laboratory tests must be
obtained ≥ 1 week after any blood transfusion.
CTDS Inclusion Criteria: ASP2138 in Combination with Pembrolizumab & CAPOX as First-line
Therapy in Gastric/GEJ Cancer
- Participant has histologically confirmed diagnosis of gastric/GEJ adenocarcinoma.
- Participant has metastatic or locally advanced unresectable gastric/GEJ
adenocarcinoma.
- Participant with gastric/GEJ adenocarcinoma must not have been previously treated
for metastatic disease with either chemotherapy or prior checkpoint inhibitor
therapy.
- Participants have a HER2-negative tumor per local testing.
- For CT with oxaliplatin, follow contraception guidelines from time of informed
consent through at least 9 months after final study intervention.
Exclusion Criteria:
- 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.
- Participant weighs < 40 kg.
- Participant has received systemic immunosuppressive therapy, including systemic
corticosteroids 14 days prior to first dose of study intervention. Participant using
a physiologic replacement dose of hydrocortisone or its equivalent (defined as up to
10 mg per day of prednisone or equivalent), receiving a single daily dose of
systemic corticosteroids or receiving systemic corticosteroids as pre-medication for
radiologic imaging contrast use are allowed.
- Participant has a complete gastric outlet syndrome or a partial gastric outlet
syndrome with persistent/recurrent vomiting.
- Participant has significant gastric bleeding &/or untreated gastric ulcers that
exclude the participant from participation.
- Participant has symptomatic CNS metastases or participant has evidence of unstable
CNS metastases 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 & are not requiring immunosuppressive doses of systemic steroids
(> 10 mg per day of prednisone or equivalent) for longer than 2 weeks.
- Participant is known to have HIV infection. However, participants with cluster of
differentiation (CD4) + T cell counts >= 350 cells/µL & no history of acquired
immunodeficiency syndrome (AIDS)-defining opportunistic infections within the past 6
months are eligible. NOTE: Screening for human immunodeficiency virus (HIV)
infection should be conducted per local requirements.
- Participant is known to have active hepatitis B (positive hepatitis B surface
antigen [HBsAg]) or hepatitis C infection. Testing is required for known history of
these infections or as mandated by local requirements. NOTE: Screening for these
infections should be conducted per local requirements.
- For participant who is negative for HBsAg, but hepatitis B core antibody (HBc
Ab) positive, a hepatitis B virus (HBV) deoxyribonucleic acid (DNA) test will
be performed & if positive the participant will be excluded.
- Participant with positive hepatitis C virus (HCV) serology, but negative HCV
ribonucleic acid (RNA) test results are eligible.
- Participant treated for HCV with undetectable viral load results are eligible
- Participant has had within 6 months prior to first dose of study intervention any of
the following: unstable angina, myocardial infarction, ventricular arrhythmia
requiring intervention or hospitalization for heart failure.
- Participant has active infection requiring systemic therapy that has not completely
resolved within 7 days prior to the start of study intervention.
- Participant has active autoimmune disease that has required systemic
immunosuppressive treatment within the past 1 month prior to the start of study
intervention.
- Participant has a clinically significant disease or co-morbidity that may adversely
affect the safe delivery of treatment within this study or make the participant
unsuitable for study participation.
- Participant has psychiatric illness or social situations that would preclude study
compliance.
- Participant has had a major surgical procedure 28 days before start of study
intervention & has not fully recovered.
- Participant has received radiotherapy metastatic or for locally advanced
unresectable gastric/GEJ or metastatic pancreatic adenocarcinoma 14 days prior to
start of study intervention & has NOT recovered from any related toxicity.
- Participant has another malignancy for which treatment is required.
- Participant who has received CLDN18.2-targeted therapy (e.g., zolbetuximab or
chimeric antigen receptor CLDN18.2-specific T cells) prior to first dose of study
intervention administration is not eligible for dose escalation cohorts. However, a
participant who has received CLDN18.2-targeted therapy greater than 28 days or 5
half-lives (whichever is longer) prior to first dose study intervention
administration is eligible for dose expansion cohorts only, with the exception of
participants who have experienced Grade >= 3 gastrointestinal toxicity after
receiving an CLDN18.2-targeted therapy.
- Participant has a history or complication of interstitial lung disease.
China Specific:
Participant who has received treatment with herbal medications that have known antitumor
activity within 28 days prior to first dose of study treatment.
For all participants in CT administration:
- Participant has prior severe allergic reaction; suspected, known immediate or
delayed hypersensitivity; or intolerance or contraindication to any study
intervention (i.e., pembrolizumab & mFOLFOX6 [all components], ramucirumab &
paclitaxel or mFOLFIRINOX [all components]).
- For 5 FU (fluorouracil): Participant has known dihydropyrimidine dehydrogenase (DPD)
deficiency. (NOTE: Screening for DPD deficiency should be conducted per local
requirements).
- Participants who have received systemic immunosuppressive therapy, including
systemic corticosteroids 14 days prior to the first dose of study intervention are
generally excluded; however, participants using a physiologic replacement dose of
hydrocortisone or its equivalent (defined as up to 10 mg per day of prednisone or
equivalent), receiving a single daily dose of systemic corticosteroids or receiving
systemic corticosteroids as pre-medication for radiologic imaging contrast or for
chemotherapy (as part of CT administration) are allowed.
- Participant is known to have HIV infection.
- NOTE: Differing from monotherapy administration, participants with CD4+ T cell
counts ≥ 350 cells/µL & no history of AIDS-defining opportunistic infections within
the past 6 months remain ineligible.
- NOTE: Screening for HIV infection should be conducted per local requirements.
- Participant has had uncontrolled high blood pressure within 6 months prior to the
first dose of study intervention (Unique to EU: high blood pressure Stage 2 is
defined as ≥ 140/90 mmHg).
- Participant has a history of ascites requiring drainage more than twice in the past
7 days.
CTDS Exclusion Criteria: ASP2138 in Combination with Pembrolizumab & mFOLFOX6 as
First-line Therapy in Gastric/GEJ Cancer:
- Participant has history of (non-infectious) pneumonitis that required steroids,
current pneumonitis, or has a history of interstitial lung disease.
- Participant received live-virus vaccination within 30 days prior to the first dose
of study intervention.
- Participant has a diagnosis of immunodeficiency or is receiving systemic steroid
therapy or any other form of immunosuppressive therapy within 7 days prior to the
first dose of study intervention or has been diagnosed with an autoimmune disease
that has required systemic treatment in past 2 years (i.e., with use of disease
modifying agents, corticosteroids or immunosuppressive drugs). Patients that require
replacement therapy (e.g., thyroxine [T4], insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency, etc.) may be enrolled.
CTDS Exclusion Criteria: ASP2138 in Combination with Ramucirumab & Paclitaxel as
Second-line Therapy in Gastric/GEJ Cancer:
- History of cerebrovascular accident or transient ischemic attack within 6 months
prior to study intervention.
- Participant has significant vascular disease (e.g., aortic aneurysm requiring
surgical repair or recent peripheral arterial thrombosis) within 6 months prior to
study intervention.
- Participant has evidence of a bleeding diathesis or significant coagulopathy.
- Participant has initiated new treatment with medications that affect the coagulation
cascade with an INR ≥ 2 such as vitamin K antagonists, heparins & direct thrombin
inhibitors or the use of factor Xa inhibitors within 28 days prior to the start of
study intervention.
Note: If the participant started receiving such medications more than 28 days prior to
the start of study intervention & needs to continue, this is allowed. However, new
anticoagulation medications may not be initiated within 28 days prior to the start of
study intervention.
Japan & Korea Specific:
For All Participants in ASP2138 in Combination with Pembrolizumab & CAPOX:
- Participant has prior severe allergic reaction; suspected, known immediate or
delayed hypersensitivity; or intolerance or contraindication to any study
intervention (i.e., pembrolizumab & CAPOX [all components]).
- Participants who have received systemic immunosuppressive therapy, including
systemic corticosteroids 14 days prior to the first dose of study intervention are
generally excluded, however, participants using a physiologic replacement dose of
hydrocortisone or its equivalent (defined as up to 10 mg per day of prednisone or
equivalent), receiving a single dose of systemic corticosteroids or receiving
systemic corticosteroids as pre-medication for radiologic imaging contrast or for
chemotherapy (as part of CT administration) are allowed.
- Participant is known to have HIV infection.
- NOTE: Differing from monotherapy administration, participants with CD4+ T cell
counts ≥ 350 cells/μL & no history of AIDS-defining opportunistic infections within
the past 6 months remain ineligible.
- NOTE: Screening for HIV infection should be conducted per local requirements.
- Participant has had uncontrolled high blood pressure within 6 months prior to the
first dose of study intervention.
- Participant has a history of ascites requiring drainage more than twice in the past
7 days.
- Participant has known DPD deficiency. (NOTE: Screening for DPD deficiency should be
conducted per local requirements).
CTDS Exclusion Criteria:
ASP2138 in Combination with Pembrolizumab & CAPOX as First-line Therapy in Gastric/GEJ
Cancer:
- Participant has history of (noninfectious) pneumonitis that required steroids,
current pneumonitis, or has a history of interstitial lung disease.
- Participant received live-virus vaccination within 30 days prior to the first dose
of study intervention.
- Participant has a diagnosis of immunodeficiency or is receiving systemic steroid
therapy or any other form of immunosuppressive therapy within 7 days prior to the
first dose of study intervention or has been diagnosed with an autoimmune disease
that has required systemic treatment in past 2 years (i.e., with use of disease
modifying agents, corticosteroids or immunosuppressive drugs). Participants who
require replacement therapy (e.g., thyroxine [T4], insulin, or physiologic
corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) may
be enrolled.