Clinical trial NCT06346392: AZD0901 Compared With Investigator's Choice of Therapy in Participants With Second- or Later-line Advanced or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma Expressing Claudin18.2
Official title: A Phase III Multi-center, Open-label, Sponsor-blinded, Randomized Study of AZD0901 Monotherapy Compared With Investigator's Choice of Therapy in Second- or Later-Line Adult Participants With Advanced/Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma Expressing Claudin18.2 (CLARITY Gastric 01)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Gastric Cancer
Gastroesophageal Junction Cancer
Keywords: Gastric cancer
Gastroesophageal junction cancer
Phase III
Claudin 18.2
AZD0901
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2024-04-04
Enrollment: 572
Sex: ALL
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants were randomized in a 1:1:1 ratio to one of the following intervention arms until the dose selection decision was made. Randomization will continue in a 1:1 ratio to the 2 remaining arms:

Arm 1: AZD0901 arm 1 IV, Q3W Arm 2: AZD0901 arm 2 IV, Q3W (Enrolment was closed) Arm 3: Participants in the Investigator's choice arm, including regionally accepted chemotherapies or targeted therapies 2L: Ramucirumab 8 mg/kg IV on Days 1 and 15 and paclitaxel 80 mg/m2 IV on Days 1, 8, and 15, Q4W 2L: Paclitaxel 80 mg/m2 IV on Days 1, 8, and 15, Q4W (for participants with contraindication to ramucirumab only) 2L: Docetaxel 75-100 mg/m2 IV on Day 1, Q3W (for participants with contraindication to ramucirumab only) 3L+: Irinotecan 150-180 mg/m2 IV on Days 1 and 15, Q4W 3L+: TAS-102 35 mg/m2 up to a maximum of 80 mg orally twice a day on Days 1 to 5 and Days 8 to 12, Q4W (except China) 3L+: Apatinib 500-850 mg, orally once daily, Q4W (China only)
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to measure the efficacy and safety of AZD0901 compared to Investigator's choice of therapy as 2L+ treatment for participants with advanced or metastatic gastric or GEJ adenocarcinoma expressing CLDN18.2.

Detailed description: This is a Phase III, multi-center, open-label, sponsor-blinded, randomized, global study to assess the efficacy and safety of AZD0901 compared to Investigator's choice of therapy as the 2L+ treatment for participants with advanced or metastatic gastric or GEJ adenocarcinoma expressing CLDN18.2, and the clinical performance of the investigational IVD. As part of this combined approach, the efficacy analyses from this study will also provide the basis to evaluate the clinical performance of Ventana CLDN18.2 assay as an IVD device for the identification of patients with advanced or metastatic gastric or GEJ adenocarcinoma expressing CLDN18.2 who may benefit from AZD0901.

Eligibility criteria: Inclusion Criteria:

1. Capable of giving signed informed consent prior to any study procedure.
2. Participant must be at least 18 years or the legal age of consent in the jurisdiction in which the study is taking place at the time of signing the ICF.
3. Histologically confirmed unresectable, locally advanced or metastatic adenocarcinoma of gastric, GEJ, or distal esophagus (distal third of the esophagus) and the following requirement:

   (a) Participants with positive CLDN18.2 expression from archival tumor collected within past 24 months or from a fresh biopsy.
4. Disease progression on or after at least one prior line of treatment (LoT) for advanced or metastatic disease, which included a fluoropyrimidine and a platinum, for advanced or metastatic disease.
5. Must have at least one measurable or evaluable lesion assessed by the Investigator based on RECIST 1.1.
6. ECOG performance status of 0 or 1 with no deterioration over the previous 2 weeks prior to baseline or day of first dosing.
7. Predicted life expectancy of ≥ 12 weeks.
8. Adequate organ and bone marrow function
9. Body weight of ≥ 35 kg.
10. Sex and Contraceptive Requirements

Exclusion Criteria:

1. Participants with known HER2 positive status as defined as IHC 3+ or IHC 2+/ISH + (Cases with HER2: CEP17 ratio ≥ 2 or an average HER2 copy number ≥ 6.0 signals/cell are considered positive by ISH). Participants must undergo local (or have had) HER2 testing by IHC/ISH, and the most recent result of HER2 status will be used to determine the eligibility.
2. Participant has significant or unstable gastric bleeding and/or untreated gastric ulcers.
3. CNS metastases or CNS pathology including: epilepsy, seizures or aphasia within 3 months prior to consent, severe brain injury, dementia, Parkinson's disease, neurodegenerative diseases, cerebellar disease, severe uncontrolled mental illness, psychosis, CNS involvement of autoimmune diseases.
4. Participant has known clinically significant corneal disease (eg, active keratitis or corneal ulcerations).
5. Persistent toxicities (CTCAE Grade ≥ 2) caused by previous anticancer therapy, excluding alopecia. Participants with irreversible toxicity that is not reasonably expected to be exacerbated by study intervention may be included (eg, hearing loss).
6. Prior exposure to any ADC with MMAE payload or any CLDN18.2 targeting treatment other than naked monoclonal antibody (eg, CLDN18.2 targeting CAR-T cell therapy, multi-specific antibody including targeting CLDN18.2, etc).
7. History of thromboembolic events:

   1. Participants with venous thromboembolism within the past 6 months prior to randomization: participants with venous port or catheter thrombosis or superficial venous thrombus that do not require treatment or are stable on treatment with anticoagulants are excepted
   2. History of arterial thromboembolism within the past 12 months prior to randomization
8. As judged by the Investigator, any evidence of diseases which in the Investigator's opinion, makes it undesirable for the participant to participate in the study or that would jeopardize compliance with the protocol.

Primary outcomes:
measure: Progression Free Survival (PFS) in all randomized participants
timeFrame: From date of first dose/randomisation until disease progression or death in the absence of progression (approximately 3 years).
measure: Overall Survival (OS) for 3L+ participants
timeFrame: From date of first dose/randomisation until the date of death due to any cause (approximately 3 years).
Secondary outcomes:
measure: OS in all randomized participants
timeFrame: From date of first dose/randomisation until the date of death due to any cause (approximately 3 years).
measure: PFS for 3L+ participants
timeFrame: From date of first dose/randomisation until disease progression or death in the absence of progression (approximately 3 years).
measure: Objective Response Rate (ORR) in all randomized participants
timeFrame: From date of first dose of AZD0901 up until progression, or the last evaluable assessment in the absence of progression (approximately 3 years).
measure: ORR for 3L+ participants
timeFrame: From date of first dose of AZD0901 up until progression, or the last evaluable assessment in the absence of progression (approximately 3 years).
measure: Duration of Response (DoR) in all randomized participants
timeFrame: From the date of first documented confirmed response until date of documented progression (approximately 3 years).
measure: Serum concentrations of AZD0901, total antibody and MMAE
timeFrame: From date of first dose of AZD0901 up until 30 days post AZD0901 discontinuation.
measure: Status of ADA to AZD0901
timeFrame: From date of first dose of AZD0901 up until 30 days post AZD0901 discontinuation.
measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]. Changes from baseline in vital signs, clinical laboratory results, and ECGs
timeFrame: From start through 30 days post treatment completion and follow up for 90 days.
measure: PK parameters (such as peak concentration, as data allow) of AZD0901, total antibody and MMAE
timeFrame: From date of first dose of AZD0901 up until 30 days post AZD0901 discontinuation.
measure: PK parameters (such as trough concentration, as data allow) of AZD0901, total antibody and MMAE
timeFrame: From date of first dose of AZD0901 up until 30 days post AZD0901 discontinuation.
measure: Prevalence and incidence of ADA to AZD0901
timeFrame: From date of first dose of AZD0901 up until 30 days post AZD0901 discontinuation.
measure: Titer of ADA to AZD0901
timeFrame: From date of first dose of AZD0901 up until 30 days post AZD0901 discontinuation.
Other outcomes:
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city: New York
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city: New York
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city: North York
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city: Montreal
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city: Hangzhou
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city: Harbin
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facility: Research Site
city: Hefei
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facility: Research Site
city: Hefei
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facility: Research Site
city: Hefei
country: China
facility: Research Site
city: Jinan
country: China
facility: Research Site
city: Jining
country: China
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city: Lanzhou
country: China
facility: Research Site
city: Lishui
country: China
facility: Research Site
city: Luoyang
country: China
facility: Research Site
city: Nanjing
country: China
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city: Nanjing
country: China
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city: Qingdao
country: China
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city: Shanghai
country: China
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city: Shanghai
country: China
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city: Shanghai
country: China
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city: Shenyang
country: China
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city: Shijiazhuang
country: China
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city: Suzhou
country: China
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city: Tianjin
country: China
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city: Urumqi
country: China
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city: Wuhan
country: China
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city: Wuhan
country: China
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city: Xi'an
country: China
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city: Yinchuan
country: China
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city: Zhengzhou
country: China
facility: Research Site
city: Besançon Cedex
country: France
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city: Brest
country: France
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city: Lille
country: France
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city: Lyon
country: France
facility: Research Site
city: Nantes
country: France
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city: PARIS Cedex 12
country: France
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city: Poitiers
country: France
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city: Berlin
country: Germany
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city: Berlin
country: Germany
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city: Dresden
country: Germany
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city: Dresden
country: Germany
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city: Essen
country: Germany
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city: Frankfurt
country: Germany
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city: Göttingen
country: Germany
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city: Hamburg
country: Germany
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city: Heidelberg
country: Germany
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city: Heilbronn
country: Germany
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city: Leipzig
country: Germany
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city: Mainz
country: Germany
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city: Marburg
country: Germany
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city: Moers
country: Germany
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city: München
country: Germany
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city: Hong Kong
country: Hong Kong
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city: Hong Kong
country: Hong Kong
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city: Hong Kong
country: Hong Kong
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city: Ahmedabad
country: India
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country: India
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country: India
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country: India
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country: Italy
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city: Milano
country: Italy
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city: Milan
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city: Modena
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city: Napoli
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city: Vicenza
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city: Fukuoka-shi
country: Japan
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city: Kashiwa
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city: Koto-ku
country: Japan
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city: Nagoya-shi
country: Japan
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country: Japan
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country: Japan
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country: Japan
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country: Japan
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country: Japan
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city: Seoul
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city: Seoul
country: Korea, Republic of
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city: Seoul
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city: Seoul
country: Korea, Republic of
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city: Bielsko-Biała
country: Poland
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city: Gdańsk
country: Poland
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city: Katowice
country: Poland
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city: Kraków
country: Poland
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city: Lublin
country: Poland
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city: Szczecin
country: Poland
facility: Research Site
city: Słupsk
country: Poland
facility: Research Site
city: Tomaszów Mazowiecki
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Barcelona
country: Spain
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: Orense
country: Spain
facility: Research Site
city: Santander
country: Spain
facility: Research Site
city: Sevilla
country: Spain
facility: Research Site
city: Bern
country: Switzerland
facility: Research Site
city: Genève 14
country: Switzerland
facility: Research Site
city: Lausanne
country: Switzerland
facility: Research Site
city: Zürich
country: Switzerland
facility: Research Site
city: Kaohsiung
country: Taiwan
facility: Research Site
city: Kaohsiung
country: Taiwan
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Tainan
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taoyuan
country: Taiwan
facility: Research Site
city: Bangkok
country: Thailand
facility: Research Site
city: Dusit
country: Thailand
facility: Research Site
city: Hat Yai
country: Thailand
facility: Research Site
city: Khon-Kaen
country: Thailand
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Diyarbakir
country: Turkey
facility: Research Site
city: Erzurum
country: Turkey
facility: Research Site
city: Istanbul
country: Turkey
facility: Research Site
city: Cambridge
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Manchester
country: United Kingdom
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city: Oxford
country: United Kingdom
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city: Taunton
country: United Kingdom
facility: Research Site
city: Hanoi
country: Vietnam
facility: Research Site
city: Ho Chi Minh city
country: Vietnam
facility: Research Site
city: Ho Chi Minh
country: Vietnam
facility: Research Site
city: Vinh
country: Vietnam
facility: Research Site
Study officials:
References: