The purpose of this study is to assess the safety, tolerability, efficacy, pharmacokinetics (PK), and immunogenicity of AZD0901 as monotherapy and in combination with anti-cancer agents in participants with locally advanced unresectable or metastatic solid tumours expressing CLDN18.2.
This open-label, multi-centre study consists of individual sub studies, each evaluating the safety and tolerability of AZD0901. Sub study 1 will investigate the safety, tolerability, and anti-tumour activity of AZD0901 monotherapy in participants with advanced or metastatic gastric esophageal cancer expressing CLDN18.2. Participants will receive AZD0901 monotherapy via intravenous (IV) infusion and will be randomised in to one of 2 arms. Sub study 2 will consist of two parts, a safety run-in and a dose expansion part to investigate the safety and efficacy of AZD0901 in combination with different chemotherapy agents in participants with pancreatic cancer. Substudy 3 will investigate the safety, tolerability, and anti-tumour activity of AZD0901 monotherapy in participants with advanced or metastatic Biliary tract cancer.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
226
Antibody-drug conjugate/Biologic
Chemotherapy agents
Chemotherapy agents
Incidence of adverse events (AEs), serious AEs (SAEs). Changes from baseline in clinical laboratory parameters, vital signs, ECGs and physical examination. Rate of AEs leading to discontinuation of AZD0901, Occurrence of DLTs.
To investigate the safety and tolerability, of AZD0901 monotherapy or in combination with anti-cancer agents in particpants with advanced or metastatic solid tumours expressing CLDN18.2.
Time frame: 30 days post treatment completion. AE Follow Up for 90 days post AZD0901 discontinuation.
Objective Response Rate (ORR).
Proportion of participants with a confirmed Complete Response (CR) or Partial Response (PR) as determined by the Investigator at local site as per RECIST v1.1.
Time frame: From date of first dose of AZD0901 up until progression, or the last evaluable assessment in the absence of progression (approximately 2 years).
Overall Survival (OS)
The analysis will include all dosed/randomised participants as assigned/randomised. All deaths will be included, regardless of whether the participant withdraws from therapy or receives another anticancer therapy.
Time frame: From date of first dose/randomisation until the date of death due to any cause (approximately 2 years).
Progression Free Survival (PFS)
Progression-free survival is defined as the time date of randomisation or enrollment until progression per RECIST v1.1 as assessed by the Investigator at local site, or death due to any cause, regardless of whether the participant withdraws from randomized therapy, receives another anti-cancer therapy or clinically progresses prior to RECIST v1.1 progression.
Time frame: From date of first dose/randomisation until disease progression or death in the absence of progression (approximately 2 years).
Duration of Response (DoR)
AstraZeneca Clinical Study Information Center
CONTACT
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Chemotherapy agents
Chemotherapy agents
Chemotherapy agents
Chemotherapy agents
Research Site
Orange, California, United States
RECRUITINGResearch Site
Palo Alto, California, United States
RECRUITINGResearch Site
Santa Rosa, California, United States
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Louisville, Kentucky, United States
RECRUITINGResearch Site
Commack, New York, United States
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Providence, Rhode Island, United States
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Houston, Texas, United States
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Melbourne, Australia
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Murdoch, Australia
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Randwick, Australia
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The time from the date of first documented confirmed response until date of first documented progression per RECIST v1.1 or death due to any cause.
Time frame: From the date of first documented confirmed response until date of documented progression (approximately 2 years).
Disease control rate (DCR)
The percentage of participants who have a confirmed CR or PR or who have SD per RECIST v1.1 as assessed by the Investigator at local site and derived from the raw tumour data up to 11 weeks after date of first dose/randomisation.
Time frame: Up to 11 weeks post date of first dose/randomisation
Percentage change in tumor size
The best percentage change from baseline in tumor size is the largest decrease (or smallest increase) from baseline for a participant, using RECIST v1.1 assessments.
Time frame: From start through to study completion.
Serum concentration of AZD0901 (total ADC), total antibody (conjugated and unconjugated) and total unconjugated MMAE
To characterise the PK of AZD0901 monotherapy or in combination with anti cancer agents in participants with advanced or metastatic solid tumours expressing CLDN18.2.
Time frame: From date of first dose of AZD0901 up until 90 days post AZD0901 discontinuation.
Serum PK parameters of AZD0901, total antibody (conjugated and unconjugated) and MMAE including but not limited to AUC, Cmax, tmax, clearance and half-life, as data allow.
To characterise the PK of AZD0901 monotherapy or in combination with anti cancer agents in participants with advanced or metastatic solid tumours expressing CLDN18.2.
Time frame: From date of first dose of AZD0901 up until 90 days post AZD0901 discontinuation.
Clinical activity by baseline and/or on-treatment tissue-based biomarkers including, but not limited to, gene expression, mutation profiles, DNA damage, protein expression, immune response and/or mechanisms of resistance.
To investigate baseline and/or on-treatment tissue-based RNA, DNA, and/or proteins, and association with clinical activity of AZD0901 (substudy 1).
Time frame: From date of first dose of AZD0901 up to 7 weeks.
ADA status will be determined along with prevalence and incidence of anti-drug antibodies to AZD0901, and titer established.
To determine the immunogenicity of AZD0901 monotherapy or in combination with anti-cancer agents in participants with advanced or metastatic solid tumours expressing CLDN18.2.
Time frame: From date of first dose of AZD0901 up until 90 days post AZD0901 discontinuation.