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NCT06219941PHASE2Recruiting

AZD0901 in Participants With Advanced Solid Tumours Expressing Claudin18.2

AstraZeneca

Start Date

12/13/2023

Completion Date

6/28/2027

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.

Eligibility Criteria

Age Range: 18 years to No maximum

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.

Interventions

DRUG

AZD0901

DRUG

5-Fluorouracil

DRUG

Leucovorin

DRUG

l-leucovorin

DRUG

Irinotecan

DRUG

Nanoliposomal Irinotecan

DRUG

Gemcitabine

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Conditions

Gastric CancerGastroesophageal Junction CancerBiliary Tract CancerPancreatic Ductal Adenocarcinoma

Locations

Research Site

Orange, California 92868

United States

Research Site

Palo Alto, California 94304

United States

Research Site

Santa Rosa, California 95403

United States

Research Site

Louisville, Kentucky 40202

United States

Research Site

Commack, New York 11725

United States

Research Site

Providence, Rhode Island 02903

United States

Research Site

Houston, Texas 77030

United States

Research Site

Melbourne, 3000

Australia

Research Site

Murdoch, WA6150

Australia

Research Site

Randwick, 2031

Australia

Research Site

Kingston, Ontario K7L 2V7

Canada

Research Site

Toronto, Ontario M5G 2M9

Canada

Research Site

Montreal, Quebec H3G 1A4

Canada

Research Site

Sherbrooke, Quebec J1G 2E8

Canada

Research Site

Changsha, 410013

China

Research Site

Chengdu, 610041

China

Research Site

Tbilisi, 0112

Georgia

Research Site

Chūōku, 104-0045

Japan

Research Site

Kashiwa, 227-8577

Japan

Research Site

Kitaadachi-gun, 362-0806

Japan

Research Site

Kōtoku, 135-8550

Japan

Research Site

Nagoya, 464-8681

Japan

Research Site

Osakasayama-shi, 589-8511

Japan

Research Site

George Town, 10450

Malaysia

Research Site

Johor Bahru, 81100

Malaysia

Research Site

Kuala Lumpur, 59100

Malaysia

Research Site

Kuala Selangor, 62250

Malaysia

Research Site

Kuching, 93586

Malaysia

Research Site

Chisinau, MD-2025

Moldova

Research Site

Krakow, 31-501

Poland

Research Site

Warsaw, 02-034

Poland

Research Site

Bukit Merah, 169610

Singapore

Research Site

Singapore, 119074

Singapore

Research Site

Singapore, 308433

Singapore

Research Site

Singapore, 329563

Singapore

Research Site

Gyeonggi-do, 13620

South Korea

Research Site

Seoul, 03080

South Korea

Research Site

Seoul, 03722

South Korea

Research Site

Seoul, 05505

South Korea

Research Site

Seoul, 06351

South Korea

Research Site

Barcelona, 08035

Spain

Research Site

Madrid, 28007

Spain

Research Site

Madrid, 28040

Spain

Research Site

Kaohsiung City, 80756

Taiwan

Research Site

Taichung, 404

Taiwan

Research Site

Tainan, 70403

Taiwan

Research Site

Taipei, 11217

Taiwan

Research Site

Taoyuan, 00333

Taiwan

Research Site

Glasgow, G12 0YN

United Kingdom

Research Site

Leeds, LS9 7TF

United Kingdom

Research Site

London, NW3 2QG

United Kingdom

Research Site

Oxford, OX3 7LE

United Kingdom