AZD0901 in Participants With Advanced Solid Tumours Expressing Claudin18.2

Gastric Cancer Clinical Trial

Official title:

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.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06219941
• Other study ID #: D9800C00001
• Status: Recruiting
• Phase: Phase 2
• Start date: December 13, 2023
• Est. completion date: January 19, 2027

Study information

• Verified date: June 2024
• Source: AstraZeneca
• Contact: AstraZeneca Clinical Study Information Center
• Phone: 1-877-240-9479
• Email: information.center[@]astrazeneca.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 123
• Est. completion date: January 19, 2027
• Est. primary completion date: May 2, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Adenocarcinoma
• Gastric Cancer
• Gastroesophageal Junction Cancer
• Pancreatic Adenocarcinoma
• Stomach Neoplasms

Intervention

Drug:
• AZD0901
Antibody-drug conjugate/Biologic
• 5-Fluorouracil
Chemotherapy agents
• Leucovorin
Chemotherapy agents
• l-leucovorin
Chemotherapy agents
• Irinotecan
Chemotherapy agents
• Nanoliposomal Irinotecan
Chemotherapy agents
• Gemcitabine
Chemotherapy agents

Locations

Country	Name	City	State
Australia	Research Site	Melbourne
Australia	Research Site	Murdoch
Australia	Research Site	Randwick
Canada	Research Site	Kingston	Ontario
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Sherbrooke	Quebec
Canada	Research Site	Toronto	Ontario
Georgia	Research Site	Tbilisi
Japan	Research Site	Chuo-ku
Japan	Research Site	Kashiwa
Japan	Research Site	Kitaadachi-gun
Japan	Research Site	Koto-ku
Japan	Research Site	Nagoya-shi
Japan	Research Site	Osakasayama-shi
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Malaysia	Research Site	George Town
Malaysia	Research Site	Johor Bahru
Malaysia	Research Site	Kuala Lumpur
Malaysia	Research Site	Kuching
Malaysia	Research Site	Selangor
Moldova, Republic of	Research Site	Chisinau
Poland	Research Site	Kraków
Poland	Research Site	Warszawa
Singapore	Research Site	Bukit Merah
Singapore	Research Site	Singapore
Singapore	Research Site	Singapore
Singapore	Research Site	Singapore
Spain	Research Site	Barcelona
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Taiwan	Research Site	Kaohsiung
Taiwan	Research Site	Taichung
Taiwan	Research Site	Tainan City
Taiwan	Research Site	Taipei City
Taiwan	Research Site	Taoyuan
United Kingdom	Research Site	Glasgow
United Kingdom	Research Site	Leeds
United Kingdom	Research Site	London
United Kingdom	Research Site	Oxford
United States	Research Site	Commack	New York
United States	Research Site	Houston	Texas
United States	Research Site	Louisville	Kentucky
United States	Research Site	Orange	California
United States	Research Site	Palo Alto	California
United States	Research Site	Providence	Rhode Island
United States	Research Site	Santa Rosa	California

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Georgia,  Japan,  Korea, Republic of,  Malaysia,  Moldova, Republic of,  Poland,  Singapore,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Primary	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	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).
Secondary	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).
Secondary	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).
Secondary	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 for at least 11 weeks after date of first dose/randomisation.	From start until 12 weeks.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.