Gastric Cancer, Gastroesophageal Junction Cancer, Biliary Tract Cancer, Pancreatic Ductal Adenocarcinoma
Conditions
Keywords
Gastric cancer, Gastroesophageal junction cancer, Pancreatic Ductal adenocarcinoma, Biliary Tract Cancer, Phase II, Claudin 18.2, AZD0901
Brief summary
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.
Detailed description
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.
Interventions
DRUGAZD0901
Antibody-drug conjugate/Biologic
DRUG5-Fluorouracil
Chemotherapy agents
DRUGLeucovorin
Chemotherapy agents
DRUGl-leucovorin
Chemotherapy agents
DRUGIrinotecan
Chemotherapy agents
Chemotherapy agents
DRUGGemcitabine
Chemotherapy agents
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This study is an open-label, multi-centre study of AZD0901 administered via IV, either as monotherapy or in combination with other anti-cancer agents in participants with advanced solid malignancies expressing CLDN18.2. The substudy design allows for a targeted approach to the different tumour types as monotherapy or in combination with other anti-cancer agents. These substudies include: Substudy 1: AZD0901 monotherapy in gastric and gastric esophageal junction cancer patients Substudy 2: AZD0901 in combination with anti-cancer agents in pancreatic cancer patients. Substudy 3: AZD0901 monotherapy in biliary Tract Cancer.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
The list below is a summarised eligibility criteria for the study - refer to the study protocol for full criteria. Master Inclusion Criteria applicable to all sub studies: * Participant must be ≥ 18 years or the legal age of consent at the time of signing the ICF. * Participants who are CLDN18.2 positive. * Must have at least one measurable lesion according to RECIST v1.1. * ECOG performance status of 0 to 1 with no deterioration over the previous 2 weeks prior first day of dosing. * Predicted life expectancy of ≥ 12 weeks. * Adequate organ and bone marrow function as defined by protocol. * Body weight \> 35 kg. * Participants are willing to comply with contraception requirements. Sub study 1 Specific Inclusion criteria: * Histologically confirmed adenocarcinoma of the stomach or gastroesophageal junction. * Advanced or metastatic GC/GEJC. * Maximum 2 prior lines of systemic treatment for unresectable or metastatic disease. Sub study 2 Specific Inclusion criteria: * Participants diagnosed with histologically confirmed metastatic or advanced PDAC. * Availability of an archival sample or a fresh tumour biopsy taken at screening. * No prior treatments for unresectable or metastatic disease. Prior neoadjuvant/adjuvant chemotherapy is permitted as long as participants progressed ≥ 6 months (183 days) from the last dose. Sub study 3 Specific Inclusion criteria * Histologically confirmed, unresectable advanced, or metastatic adenocarcinoma of biliary tract, including cholangiocarcinoma (intrahepatic or extrahepatic) and gallbladder carcinoma (NOTE: Ampullary cancers are not eligible). * Documented radiographic or clinical disease progression on or after at least one prior regimen and maximum 2 prior lines of systemic treatment for unresectable or metastatic disease. Master
Exclusion criteria
applicable to all sub studies: * Unstable or active peptic ulcer disease or digestive tract bleeding including but not limited to clinically significant bleeding in the setting of prior CLDN18.2 directed therapy. * Participants with clinically significant ascites that require drainage. * A history of drug-induced non-infectious ILD/pneumonitis. * Central nervous system metastases or CNS pathology. * Peripheral neuropathy, sensory, or motor ≥ Grade 2 at screening. * History of another primary malignancy. * Prior exposure to any MMAE-based ADC. * Prior exposure to any CLDN18.2 targeted agents except anti-CLDN18.2 monoclonal antibody. Sub study 1 Specific
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. | 30 days post treatment completion. AE Follow Up for 90 days post AZD0901 discontinuation. | 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. |
| Objective Response Rate (ORR). | From date of first dose of AZD0901 up until progression, or the last evaluable assessment in the absence of progression (approximately 2 years). | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | From date of first dose/randomisation until the date of death due to any cause (approximately 2 years). | 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. |
| Progression Free Survival (PFS) | From date of first dose/randomisation until disease progression or death in the absence of progression (approximately 2 years). | 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. |
| Duration of Response (DoR) | From the date of first documented confirmed response until date of documented progression (approximately 2 years). | 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. |
| Disease control rate (DCR) | Up to 11 weeks post date of first dose/randomisation | 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. |
| Percentage change in tumor size | From start through to study completion. | 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. |
| Serum concentration of AZD0901 (total ADC), total antibody (conjugated and unconjugated) and total unconjugated MMAE | From date of first dose of AZD0901 up until 90 days post AZD0901 discontinuation. | 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. |
| 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. | From date of first dose of AZD0901 up until 90 days post AZD0901 discontinuation. | 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. |
| 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. | From date of first dose of AZD0901 up to 7 weeks. | To investigate baseline and/or on-treatment tissue-based RNA, DNA, and/or proteins, and association with clinical activity of AZD0901 (substudy 1). |
| ADA status will be determined along with prevalence and incidence of anti-drug antibodies to AZD0901, and titer established. | From date of first dose of AZD0901 up until 90 days post AZD0901 discontinuation. | 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. |
Countries
Australia, Canada, China, Georgia, Japan, Malaysia, Moldova, Poland, Singapore, South Korea, Spain, Taiwan, United Kingdom, United States
Contacts
CONTACTAstraZeneca Clinical Study Information Center
Outcome results
None listed