Clinical trial NCT06219941: AZD0901 in Participants With Advanced Solid Tumours Expressing Claudin18.2
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 (CLARITY-PanTumour01)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Gastric Cancer
Gastroesophageal Junction Cancer
Biliary Tract Cancer
Pancreatic Ductal Adenocarcinoma
Keywords: Gastric cancer
Gastroesophageal junction cancer
Pancreatic Ductal adenocarcinoma
Biliary Tract Cancer
Phase II
Claudin 18.2
AZD0901
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2024-01-23
Enrollment: 190
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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.

Eligibility 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 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.

Primary outcomes:
measure: 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.
timeFrame: 30 days post treatment completion. AE Follow Up for 90 days post AZD0901 discontinuation.
measure: Objective Response Rate (ORR).
timeFrame: From date of first dose of AZD0901 up until progression, or the last evaluable assessment in the absence of progression (approximately 2 years).
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: From date of first dose/randomisation until the date of death due to any cause (approximately 2 years).
measure: Progression Free Survival (PFS)
timeFrame: From date of first dose/randomisation until disease progression or death in the absence of progression (approximately 2 years).
measure: Duration of Response (DoR)
timeFrame: From the date of first documented confirmed response until date of documented progression (approximately 2 years).
measure: Disease control rate (DCR)
timeFrame: Up to 11 weeks post date of first dose/randomisation
measure: Percentage change in tumor size
timeFrame: From start through to study completion.
measure: Serum concentration of AZD0901 (total ADC), total antibody (conjugated and unconjugated) and total unconjugated MMAE
timeFrame: From date of first dose of AZD0901 up until 90 days post AZD0901 discontinuation.
measure: 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.
timeFrame: From date of first dose of AZD0901 up until 90 days post AZD0901 discontinuation.
measure: 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.
timeFrame: From date of first dose of AZD0901 up to 7 weeks.
measure: ADA status will be determined along with prevalence and incidence of anti-drug antibodies to AZD0901, and titer established.
timeFrame: From date of first dose of AZD0901 up until 90 days post AZD0901 discontinuation.
Other outcomes:
Locations:
city: Orange
country: United States
facility: Research Site
state: California
city: Palo Alto
country: United States
facility: Research Site
state: California
city: Santa Rosa
country: United States
facility: Research Site
state: California
city: Louisville
country: United States
facility: Research Site
state: Kentucky
city: Commack
country: United States
facility: Research Site
state: New York
city: Providence
country: United States
facility: Research Site
state: Rhode Island
city: Houston
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facility: Research Site
state: Texas
city: Melbourne
country: Australia
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city: Murdoch
country: Australia
facility: Research Site
city: Randwick
country: Australia
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city: Kingston
country: Canada
facility: Research Site
state: Ontario
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Sherbrooke
country: Canada
facility: Research Site
state: Quebec
city: Tbilisi
country: Georgia
facility: Research Site
city: Chuo-ku
country: Japan
facility: Research Site
city: Kashiwa
country: Japan
facility: Research Site
city: Kitaadachi-gun
country: Japan
facility: Research Site
city: Koto-ku
country: Japan
facility: Research Site
city: Nagoya-shi
country: Japan
facility: Research Site
city: Osakasayama-shi
country: Japan
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: George Town
country: Malaysia
facility: Research Site
city: Johor Bahru
country: Malaysia
facility: Research Site
city: Kuala Lumpur
country: Malaysia
facility: Research Site
city: Kuching
country: Malaysia
facility: Research Site
city: Selangor
country: Malaysia
facility: Research Site
city: Chisinau
country: Moldova, Republic of
facility: Research Site
city: Kraków
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Bukit Merah
country: Singapore
facility: Research Site
city: Singapore
country: Singapore
facility: Research Site
city: Singapore
country: Singapore
facility: Research Site
city: Singapore
country: Singapore
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Kaohsiung
country: Taiwan
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Tainan City
country: Taiwan
facility: Research Site
city: Taipei City
country: Taiwan
facility: Research Site
city: Taoyuan
country: Taiwan
facility: Research Site
city: Glasgow
country: United Kingdom
facility: Research Site
city: Leeds
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Oxford
country: United Kingdom
facility: Research Site
Study officials:
References: