AZD0901 in Participants With Advanced Solid Tumours Expressing Claudin18.2

A Phase II, Open-label, Multi-centre Study to Evaluate Safety, Tolerability, Efficacy, PK, and Immunogenicity of AZD0901 as Monotherapy and in Combination With Anti-cancer Agents in Participants With Advanced Solid Tumours Expressing Claudin 18.2 (CLARITY-PanTumour01)

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.

Study Overview

• Status: Recruiting
• Conditions: Gastric Cancer; Pancreatic Ductal Adenocarcinoma; Gastroesophageal Junction Cancer; Biliary Tract Cancer
• Intervention / Treatment: Drug: AZD0901; Drug: 5-Fluorouracil; Drug: Leucovorin; Drug: l-leucovorin; Drug: Irinotecan; Drug: Nanoliposomal Irinotecan; Drug: Gemcitabine

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.

• Study Type: Interventional
• Enrollment (Estimated): 224
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: AstraZeneca Clinical Study Information Center; Phone Number: 1-877-240-9479; Email: information.center@astrazeneca.com

Study Locations

• Australia
  • Melbourne, Australia, 3000
    • Recruiting
    • Research Site
  • Murdoch, Australia, WA6150
    • Recruiting
    • Research Site
  • Randwick, Australia, 2031
    • Recruiting
    • Research Site
• Canada
  • Ontario
    • Kingston, Ontario, Canada, K7L 2V7
      • Withdrawn
      • Research Site
    • Toronto, Ontario, Canada, M5G 2M9
      • Recruiting
      • Research Site
  • Quebec
    • Montreal, Quebec, Canada, H3G 1A4
      • Recruiting
      • Research Site
    • Sherbrooke, Quebec, Canada, J1G 2E8
      • Recruiting
      • Research Site
• China
  • Changsha, China, 410013
    • Not yet recruiting
    • Research Site
  • Chengdu, China, 610041
    • Not yet recruiting
    • Research Site
• Georgia
  • Tbilisi, Georgia, 0112
    • Recruiting
    • Research Site
• Japan
  • Chūōku, Japan, 104-0045
    • Recruiting
    • Research Site
  • Kashiwa, Japan, 227-8577
    • Recruiting
    • Research Site
  • Kitaadachi-gun, Japan, 362-0806
    • Recruiting
    • Research Site
  • Kōtoku, Japan, 135-8550
    • Recruiting
    • Research Site
  • Nagoya, Japan, 464-8681
    • Recruiting
    • Research Site
  • Osakasayama-shi, Japan, 589-8511
    • Recruiting
    • Research Site
• Malaysia
  • George Town, Malaysia, 10450
    • Recruiting
    • Research Site
  • Johor Bahru, Malaysia, 81100
    • Completed
    • Research Site
  • Kuala Lumpur, Malaysia, 59100
    • Recruiting
    • Research Site
  • Kuala Selangor, Malaysia, 62250
    • Recruiting
    • Research Site
  • Kuching, Malaysia, 93586
    • Recruiting
    • Research Site
• Moldova
  • Chisinau, Moldova, MD-2025
    • Recruiting
    • Research Site
• Poland
  • Krakow, Poland, 31-501
    • Recruiting
    • Research Site
  • Warsaw, Poland, 02-034
    • Recruiting
    • Research Site
• Singapore
  • Bukit Merah, Singapore, 169610
    • Recruiting
    • Research Site
  • Singapore, Singapore, 308433
    • Recruiting
    • Research Site
  • Singapore, Singapore, 119074
    • Recruiting
    • Research Site
  • Singapore, Singapore, 329563
    • Recruiting
    • Research Site
• South Korea
  • Gyeonggi-do, South Korea, 13620
    • Recruiting
    • Research Site
  • Seoul, South Korea, 03080
    • Recruiting
    • Research Site
  • Seoul, South Korea, 06351
    • Recruiting
    • Research Site
  • Seoul, South Korea, 05505
    • Recruiting
    • Research Site
  • Seoul, South Korea, 03722
    • Recruiting
    • Research Site
• Spain
  • Barcelona, Spain, 08035
    • Recruiting
    • Research Site
  • Madrid, Spain, 28007
    • Recruiting
    • Research Site
  • Madrid, Spain, 28040
    • Recruiting
    • Research Site
• Taiwan
  • Kaohsiung City, Taiwan, 80756
    • Recruiting
    • Research Site
  • Taichung, Taiwan, 404
    • Recruiting
    • Research Site
  • Tainan, Taiwan, 70403
    • Recruiting
    • Research Site
  • Taipei, Taiwan, 11217
    • Recruiting
    • Research Site
  • Taoyuan District, Taiwan, 00333
    • Recruiting
    • Research Site
• United Kingdom
  • Glasgow, United Kingdom, G12 0YN
    • Withdrawn
    • Research Site
  • Leeds, United Kingdom, LS9 7TF
    • Withdrawn
    • Research Site
  • London, United Kingdom, NW3 2QG
    • Withdrawn
    • Research Site
  • Oxford, United Kingdom, OX3 7LE
    • Withdrawn
    • Research Site
• United States
  • California
    • Orange, California, United States, 92868
      • Recruiting
      • Research Site
    • Palo Alto, California, United States, 94304
      • Recruiting
      • Research Site
    • Santa Rosa, California, United States, 95403
      • Recruiting
      • Research Site
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Recruiting
      • Research Site
  • New York
    • Commack, New York, United States, 11725
      • Recruiting
      • Research Site
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Recruiting
      • Research Site
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Exclusion criteria:

• Participants with HER2-positive (3+ by IHC, or 2+ by IHC, and positive by ISH) or indeterminate GC/GEJC unless they have failed/not tolerated/or are not eligible for standard anti-HER2 therapy, where available.
• Any factors that increase the risk of QTc prolongation or risk of arrhythmic events.
• The use of concomitant medications known to prolong the QT/QTc interval.

Sub study 2 Specific Exclusion criteria:

• Known DPD enzyme deficiency based on local testing where testing is SoC.
• Use of strong inhibitor or inducer of UGT1A1.
• Use of strong inhibitors or inducers of CYP3A4.
• Known homozygous for the UGT1A1*28 allele based on local testing where testing is SoC.

Sub study 3 Specific Exclusion criteria

• Clinically significant biliary obstruction that has not resolved before enrollment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sub Study 1 - AZD0901 MONOTHERAPY; Sub Study 1 will investigate AZD0901 monotherapy in order to evaluate the safety, tolerability, and efficacy of AZD0901.	Drug: AZD0901; Antibody-drug conjugate/Biologic; Other Names: CMG901
Experimental: Sub Study 2 - AZD0901 IN COMBINATION WITH ANTI-CANCER AGENTS IN PANCREATIC DUCTAL ADENOCARCINOMA; Substudy 2 will investigate the safety and efficacy of AZD0901 as first line systemic treatment used in combination with different chemotherapy agents	Drug: AZD0901; Antibody-drug conjugate/Biologic; Other Names: CMG901; Drug: 5-Fluorouracil; Chemotherapy agents; Other Names: 5-FU; Drug: Leucovorin; Chemotherapy agents; Other Names: LV; Drug: l-leucovorin; Chemotherapy agents; Other Names: I-LV; Drug: Irinotecan; Chemotherapy agents; Other Names: Camptosar; Drug: Nanoliposomal Irinotecan; Chemotherapy agents; Other Names: ONIVYDE; Drug: Gemcitabine; Chemotherapy agents; Other Names: Gemzar
Experimental: Sub Study 3: AZD0901 MONOTHERAPY IN BILIARY TRACT CANCER; Substudy 3 Further evaluate the preliminary anti-tumour activity of AZD0901 monotherapy by assessment of DRR.	Drug: AZD0901; Antibody-drug conjugate/Biologic; Other Names: CMG901

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	From date of first dose of AZD0901 up until progression, or the last evaluable assessment in the absence of progression (approximately 2 years).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	From date of first dose/randomisation until disease progression or death in the absence of progression (approximately 2 years).
Duration of Response (DoR)	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.	From the date of first documented confirmed response until date of documented progression (approximately 2 years).
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.	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.	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.	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).	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.	From date of first dose of AZD0901 up until 90 days post AZD0901 discontinuation.
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.	Up to 11 weeks post date of first dose/randomisation

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): December 13, 2023
• Primary Completion (Estimated): August 11, 2026
• Study Completion (Estimated): September 30, 2027

Study Registration Dates

• First Submitted: November 21, 2023
• First Submitted That Met QC Criteria: January 12, 2024
• First Posted (Actual): January 23, 2024

Study Record Updates

• Last Update Posted (Actual): February 12, 2026
• Last Update Submitted That Met QC Criteria: February 11, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Gastric cancer; Phase II; Gastroesophageal junction cancer; Biliary Tract Cancer; Claudin 18.2; AZD0901; Pancreatic Ductal adenocarcinoma
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Biliary Tract Diseases; Stomach Neoplasms; Biliary Tract Neoplasms; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Camptothecin; Alkaloids; Enzymes and Coenzymes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Uracil; Pyrimidinones; Coenzymes; Irinotecan; Gemcitabine; Fluorouracil; Leucovorin; irinotecan sucrosofate
• Other Study ID Numbers: D9800C00001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

"Yes", indicates that AZ are accepting requests for IPD, but this does not mean all requests will be approved.

• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA/PhRMA Data-Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No