A Study of ASP2138 Given by Itself or Given With Other Cancer Treatments in Adults With Stomach Cancer, Gastroesophageal Junction Cancer, or Pancreatic Cancer
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
4 other identifiers
interventional
398
8 countries
46
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Jun 2022
Longer than P75 for phase_1
46 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 5, 2022
CompletedFirst Posted
Study publicly available on registry
May 9, 2022
CompletedStudy Start
First participant enrolled
June 7, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 31, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
May 31, 2028
May 5, 2026
April 1, 2026
6 years
May 5, 2022
May 4, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (8)
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.
Up to 28 days
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.
Up to 27 months
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.
Up to 27 months
Number of participants with laboratory value abnormalities
Number of participants with potentially clinically significant laboratory values.
Up to 25 months
Number of participants with vital sign abnormalities
Number of participants with potentially clinically significant vital sign values.
Up to 27 months
Number of participants with electrocardiogram (ECG) abnormalities
Number of participants with potentially clinically significant ECG values.
Up to 24 months
Number of participants with physical exam abnormalities
Number of participants with potentially clinically significant physical exam values.
Up to 25 months
Number of participants at each grade of the Eastern Cooperative Oncology Group (ECOG) performance status
The ECOG scale will be used to assess performance status. Grades range from 0 (fully active) to 5 (dead). Negative change scores indicate an improvement. Positive scores indicate a decline in performance.
Up to 25 months
Secondary Outcomes (9)
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)
Up to 12 months
PK of ASP2138 in serum: maximum concentration (Cmax)
Up to 12 months
PK of ASP2138 in serum: concentration immediately prior to dosing at multiple dosing (Ctrough)
Up to 12 motnhs
PK of ASP2138 in serum: time of the maximum concentration (Tmax)
Up to 12 months
Overall response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (Phase 1b dose expansion)
Up to 21 months
- +4 more secondary outcomes
Study Arms (10)
Monotherapy Dose Escalation (Phase 1)
EXPERIMENTALA dose escalation design will be used to determine the Maximum Tolerated Dose (MTD) and/ or the Recommended Phase 2 Dose (RP2D) regimens to be further evaluated in the Monotherapy Dose Expansion arms. Monotherapy Dose escalation part consists of six parts (Part A, B, C, D, E, and F), and approximately 86 patients would be enrolled in total. Participants will be assigned to sequentially escalating dose cohorts of ASP2138 in each part. The study will open with the Part A dosing schedule, while subsequent cohorts will be opened sequentially or in parallel based upon sponsor review of emerging data.
Monotherapy Dose Expansion (Phase 1b) Gastric/GEJ cancer
EXPERIMENTALParticipants will receive ASP2138 at the candidate RP2D regimens determined in Monotherapy Dose Escalation arm.
Monotherapy Dose Expansion (Phase 1b) Pancreatic cancer
EXPERIMENTALParticipants will receive ASP2138 at the candidate RP2D regimens determined in Monotherapy Dose Escalation arm.
Combination Therapy Dose Escalation (Phase 1) Part G - First-line Gastric/GEJ Cancer
EXPERIMENTALA dose escalation design will be used to determine the MTD and/ or the RP2D regimens to be further evaluated in the Combination Dose Expansion arms. In combination dose escalation part G approximately 24 patients would be enrolled in total. Participants will be assigned to sequentially escalating dose cohorts of ASP2138 in combination with pembrolizumab and mFOLFOX6 as first line therapy.
Combination Therapy Dose Escalation (Phase 1) Part H - Second-line Gastric/GEJ Cancer
EXPERIMENTALA dose escalation design will be used to determine the MTD and/ or the RP2D regimens to be further evaluated in the Combination Dose Expansion arms. Participants will be assigned to sequentially escalating dose cohorts of ASP2138 in combination with ramucirumab and paclitaxel as second line therapy.
Combination Therapy Dose Escalation (Phase 1) Part I - First line Pancreatic Cancer
EXPERIMENTALA dose escalation design will be used to determine the MTD and/ or the RP2D regimens to be further evaluated in the Combination Dose Expansion arms. Participants will be assigned to sequentially escalating dose cohorts of ASP2138 in combination with mFOLFIRINOX as first line therapy.
ASP2138 + Pembrolizumab & mFOLFOX6 Combination Therapy Dose Expansion (Phase 1b) Gastric/GEJ Cancer
EXPERIMENTALParticipants will receive candidate RP2D regimens of ASP2138 in combination with pembrolizumab \& mFOLFOX6 as first line therapy determined in Combination Therapy Dose Escalation arm.
ASP2138 + Ramucirumab & Paclitaxel Combination Therapy Dose Expansion (Phase 1b) Gastric/GEJ Cancer
EXPERIMENTALParticipants will receive candidate RP2D regimens of ASP2138 in combination with ramucirumab and paclitaxel as second line therapy determined in Combination Therapy Dose Escalation arm.
ASP2138 + mFOLFIRINOX Combination Therapy Dose Expansion (Phase 1b) Pancreatic Cancer
EXPERIMENTALParticipants will receive candidate RP2D regimens of ASP2138 in combination with mFOLFIRINOX as first line therapy in pancreatic cancer determined in Combination Therapy Dose Escalation arm in combination with mFOLFIRINOX as first line therapy in pancreatic cancer.
ASP2138 + Pembrolizumab & CAPOX CTDE Exploratory Cohort (Phase1b) Gastric/GEJ Cancer - Japan & Korea
EXPERIMENTALParticipants will receive candidate RP2D regimens of ASP2138 in combination with pembrolizumab \& CAPOX as first line therapy determined in Combination Therapy Dose Escalation arm. CTDE: Combination Therapy Dose Expansion
Interventions
Intravenously
Intravenously
Intravenously or Subcutaneously
Intravenously
Intravenously
Intravenously
Intravenously
Intravenously
Oral Administration
Eligibility Criteria
You may qualify if:
- 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.
- +41 more criteria
You may not qualify if:
- 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.
- +42 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (46)
University of California Irvine Medical Center
Orange, California, 92868, United States
UCLA Dept of Medicine - Hematology/Oncology, Santa Monica
Santa Monica, California, 90404, United States
Northwestern University
Chicago, Illinois, 60611, United States
University of Kansas Cancer Center
Westwood, Kansas, 66205, United States
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08901, United States
NYU Langone Medical Center - NYU Medical Oncology Associates
New York, New York, 10016, United States
Columbia University
New York, New York, 10032, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
Duke Children's Hospital and Health Center
Durham, North Carolina, 27710, United States
Wake Forest University Baptist Health
Winston-Salem, North Carolina, 27103, United States
UT Southwestern Medical Center
Dallas, Texas, 75390, United States
Virginia Mason Medical Center
Seattle, Washington, 98101, United States
Froedtert Hospital and the Medical College of Wisconsin
Milwaukee, Wisconsin, 53226, United States
Sun Yat-sen University Cancer Center
Guangzhou, Guangdong, China
Henan Cancer Hospital
Zhengzhou, Henan, China
Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology
Wuhan, Hubei, China
Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Shanghai, Shanghai Municipality, China
The First Affiliated Hospital, College of Medicine, Zhejiang University
Hangzhou, Zhejiang, China
Site FR33005
Vaillant, Villejuif, France
Site FR33003
Lyon, France
Site FR33004
Marseille, France
Site FR33006
Poitiers, France
Site FR33001
Saint-Herblain, France
Site FR33002
Toulouse, France
Site IT39004
Milan, Italy
Site IT39001
Milan, Italy
Site IT39005
Rozzano, Italy
Site IT39003
Verona, Italy
Aichi Cancer Center
Nagoya, Aichi-ken, Japan
National Cancer Center Hospital East
Kashiwa, Chiba, Japan
Kanagawa Cancer Center
Yokohama, Kanagawa, Japan
Kindai University Hospital
Sakai, Osaka, Japan
The University of Osaka Hospital
Suita, Osaka, Japan
National Cancer Center Hospital
Chuo-ku, Tokyo, Japan
The Cancer Institute Hospital of Japanese Foundation for Cancer Research
Koto-ku, Tokyo, Japan
PanOncology Trials
San Juan, Puerto Rico
Site KR82004
Seongnam-si, Gyeonggi-do, South Korea
Site KR82001
Guro-gu, Seoul, South Korea
Site KR82002
Jongno-gu, Seoul, South Korea
Site KR82003
Seocho-gu, Seoul, South Korea
Site KR82005
Seodaemun-gu, Seoul, South Korea
Site ES34001
Barcelona, Spain
Site ES34002
Barcelona, Spain
Site ES34006
Barcelona, Spain
Site ES34007
El Palmar, Spain
Site ES34004
Zaragoza, Spain
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Senior Director
Astellas Pharma Global Development, Inc.
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 5, 2022
First Posted
May 9, 2022
Study Start
June 7, 2022
Primary Completion (Estimated)
May 31, 2028
Study Completion (Estimated)
May 31, 2028
Last Updated
May 5, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, CSR
- Time Frame
- Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
- Access Criteria
- Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.
Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as products terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/