AZD0901 in Participants With Advanced Solid Tumours Expressing Claudin18.2

June 12, 2024 updated by: AstraZeneca

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.

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

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

123

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Australia
      • Melbourne, Australia, 3000
        • Not yet recruiting
        • Research Site
      • Murdoch, Australia, WA6150
        • Not yet recruiting
        • Research Site
      • Randwick, Australia, 2031
        • Not yet 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        • Withdrawn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
        • Not yet recruiting
        • Research Site
      • Sherbrooke, Quebec, Canada, J1G 2E8
        • Not yet recruiting
        • Research Site
  • Georgia
      • Tbilisi, Georgia, 0112
        • Recruiting
        • Research Site
  • Japan
      • Chuo-ku, Japan, 104-0045
        • Recruiting
        • Research Site
      • Kashiwa, Japan, 227-8577
        • Recruiting
        • Research Site
      • Kitaadachi-gun, Japan, 362-0806
        • Recruiting
        • Research Site
      • Koto-ku, Japan, 135-8550
        • Recruiting
        • Research Site
      • Nagoya-shi, Japan, 464-8681
        • Recruiting
        • Research Site
      • Osakasayama-shi, Japan, 589-8511
        • Recruiting
        • Research Site
  • Korea, Republic of
      • Seoul, Korea, Republic of, 03722
        • Recruiting
        • Research Site
      • Seoul, Korea, Republic of, 05505
        • Recruiting
        • Research Site
      • Seoul, Korea, Republic of, 06351
        • Recruiting
        • Research Site
      • Seoul, Korea, Republic of, 03080
        • Not yet recruiting
        • Research Site
  • Malaysia
      • George Town, Malaysia, 10450
        • Not yet recruiting
        • Research Site
      • Johor Bahru, Malaysia, 81100
        • Not yet recruiting
        • Research Site
      • Kuala Lumpur, Malaysia, 59100
        • Recruiting
        • Research Site
      • Kuching, Malaysia, 93586
        • Not yet recruiting
        • Research Site
      • Selangor, Malaysia, 62250
        • Not yet recruiting
        • Research Site
  • Moldova, Republic of
      • Chisinau, Moldova, Republic of, MD-2025
        • Recruiting
        • Research Site
  • Poland
      • Kraków, Poland, 31-501
        • Not yet recruiting
        • Research Site
      • Warszawa, Poland, 02-034
        • Not yet recruiting
        • Research Site
  • Singapore
      • Bukit Merah, Singapore, 169610
        • Not yet recruiting
        • Research Site
      • Singapore, Singapore, 119074
        • Not yet recruiting
        • Research Site
      • Singapore, Singapore, 308433
        • Not yet recruiting
        • Research Site
      • Singapore, Singapore, 329563
        • Not yet recruiting
        • Research Site
  • Spain
      • Barcelona, Spain, 08035
        • Not yet recruiting
        • Research Site
      • Madrid, Spain, 28040
        • Not yet recruiting
        • Research Site
      • Madrid, Spain, 28007
        • Not yet recruiting
        • Research Site
  • Taiwan
      • Kaohsiung, Taiwan, 80756
        • Recruiting
        • Research Site
      • Taichung, Taiwan, 404
        • Recruiting
        • Research Site
      • Tainan City, Taiwan, 70403
        • Recruiting
        • Research Site
      • Taipei City, Taiwan, 11217
        • Recruiting
        • Research Site
      • Taoyuan, Taiwan, 00333
        • Recruiting
        • Research Site
  • United Kingdom
      • Glasgow, United Kingdom, G12 0YN
        • Not yet recruiting
        • Research Site
      • Leeds, United Kingdom, LS9 7TF
        • Not yet recruiting
        • Research Site
      • London, United Kingdom, NW3 2QG
        • Not yet recruiting
        • Research Site
      • Oxford, United Kingdom, OX3 7LE
        • Not yet recruiting
        • Research Site
  • United States
    • California
      • Orange, California, United States, 92868
        • Not yet recruiting
        • Research Site
      • Palo Alto, California, United States, 94304
        • Not yet recruiting
        • Research Site
      • Santa Rosa, California, United States, 95403
        • Recruiting
        • Research Site
    • Kentucky
      • Louisville, Kentucky, United States, 40202
        • Not yet 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
        • Not yet recruiting
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Master Inclusion Criteria applicable to both 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.

Master Exclusion Criteria applicable to both 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 ≥ 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.
  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

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
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

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.
Time Frame: 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.
30 days post treatment completion. AE Follow Up for 90 days post AZD0901 discontinuation.
Objective Response Rate (ORR).
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).
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)
Time Frame: 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.
From date of first dose/randomisation until the date of death due to any cause (approximately 2 years).
Progression Free Survival (PFS)
Time Frame: 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.
From date of first dose/randomisation until disease progression or death in the absence of progression (approximately 2 years).
Duration of Response (DoR)
Time Frame: 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.
From the date of first documented confirmed response until date of documented progression (approximately 2 years).
Disease control rate (DCR)
Time Frame: From start until 12 weeks.
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 for at least 11 weeks after date of first dose/randomisation.
From start until 12 weeks.
Percentage change in tumor size
Time Frame: 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.
From start through to study completion.
Serum concentration of AZD0901 (total ADC), total antibody (conjugated and unconjugated) and total unconjugated MMAE
Time Frame: 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.
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.
Time Frame: 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.
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.
Time Frame: 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).
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.
Time Frame: 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.
From date of first dose of AZD0901 up until 90 days post AZD0901 discontinuation.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

AstraZeneca

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 13, 2023

Primary Completion (Estimated)

May 2, 2025

Study Completion (Estimated)

January 19, 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)

June 13, 2024

Last Update Submitted That Met QC Criteria

June 12, 2024

Last Verified

June 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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