A Phase 1/1b Study of ASP2138 in Participants with Metastatic or Locally Advanced Unresectable Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma or Metastatic Pancreatic Adenocarcinoma Whose Tumors Have Claudin (CLDN) 18.2 Expression
Primary:
To evaluate the safety and tolerability of ASP2138
To determine the MTD and/or the RP2D regimen(s) of ASP2138
Secondary:
To evaluate the PK of ASP2138
To evaluate the antitumor activity of ASP2138
To evaluate changes in CLDN18.2 and PD-L1
tumor expression related to treatment with ASP2138
Exploratory:
To evaluate potential genomic and/or other biomarkers that may correlate with treatment outcome of ASP2138
To evaluate the immunogenicity of ASP2138
To evaluate additional PK parameters of ASP2138
To evaluate antitumor activity of ASP2138
- Rutgers Cancer Institute of New Jersey
Inclusion Criteria
- 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 and medical
evaluation by interview and 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 and throughout
the study period and for 6 months after the final study intervention administration.
- Female participant must not donate ova starting at screening and throughout the study
period and 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
and for 6 months after the final study intervention administration.
- Male participant must not donate sperm during the treatment period and 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 and 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 treatment 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 drug. 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 >= 2 weeks after any blood
transfusion.
Disease Specific Criteria: Gastric/GEJ Cancer
- Participant has histologically confirmed gastric or gastroesophageal junction (GEJ)
adenocarcinoma.
- Escalation: Participant with gastric or 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 or GEJ adenocarcinoma who has
refused standard approved therapies is not allowed.
- Expansion: Participant gastric or GEJ adenocarcinoma must have received no more than 3
prior lines of systemic chemotherapy treatment.
Disease Specific Criteria: Pancreatic Cancer
- Participant has histologically or cytologically confirmed 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.
Exclusion Criteria
- Participant has received other investigational agents, or antineoplastic therapy
including 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 treatment.
- 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 30
mg per day of hydrocortisone or up to 10 mg per day of prednisone), 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 and/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 and have
no evidence of CNS progression by imaging for at least 4 weeks prior to start of study
treatment and are not requiring immunosuppressive doses of systemic steroids (> 30 mg
per day of hydrocortisone or > 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 and 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 and 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 and has not fully recovered.
- Participant has received radiotherapy for locally advanced unresectable or metastatic
gastric or GEJ or metastatic pancreatic adenocarcinoma 14 days prior to start of study
intervention and has NOT recovered from any related toxicity.
- Participant has another malignancy for which treatment is required.
- Participant who has received an CLDN18.2-targeted investigational agent (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 an CLDN18.2-targeted investigational agent
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 (GI)
toxicity after receiving an CLDN18.2-targeted investigational agent.
- 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.
Please note that we have obtained the inclusion and exclusion criteria information from the National Institutes of Health’s clinical trials web site ClinicalTrials.gov. The listed criteria may not necessarily reflect recent amendments to the protocol and the current criteria.
For further information about clinical trials, please contact us at 732-235-7356.