CTRI/2025/02/080588 [Registered on: 14/02/2025] Trial Registered Prospectively
Last Modified On:
05/03/2025
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Randomized, Parallel Group, Active Controlled Trial
Public Title of Study
Global Phase III Randomized Clinical trial in which we are comparing sponsor test drug with Standard care of Chemotherapy SOC when given to Second or Later Line Adult Participants with Advanced Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma.
Scientific Title of Study
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
Trial Acronym
CLARITY Gastric 01 Study
Secondary IDs if Any
Secondary ID
Identifier
D9802C00001 Version Number: 1.0 Version Date: 13 Oct 2023
Protocol Number
NCT06346392
ClinicalTrials.gov
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Mr Sandeep AV
Designation
Senior Director, Oncology Country Head, Oncology Site Management & Monitoring India
Affiliation
AstraZeneca Pharma India Ltd
Address
Block N1, 12th Floor, Manyata Embassy Business Park
Rachenahalli, Outer Ring Road, Bangalore – 560045, India
Bangalore KARNATAKA 560045 India
Phone
9845079472
Fax
080-67748857
Email
sandeep.av@astrazeneca.com
Details of Contact Person Scientific Query
Name
Mr Sandeep AV
Designation
Senior Director, Oncology Country Head, Oncology Site Management & Monitoring India
Affiliation
AstraZeneca Pharma India Ltd
Address
Block N1, 12th Floor, Manyata Embassy Business Park
Rachenahalli, Outer Ring Road, Bangalore – 560045, India
KARNATAKA 560045 India
Phone
9845079472
Fax
080-67748857
Email
sandeep.av@astrazeneca.com
Details of Contact Person Public Query
Name
Mr Sandeep AV
Designation
Senior Director, Oncology Country Head, Oncology Site Management & Monitoring India
Affiliation
AstraZeneca Pharma India Ltd
Address
Block N1, 12th Floor, Manyata Embassy Business Park
Rachenahalli, Outer Ring Road, Bangalore – 560045, India
KARNATAKA 560045 India
Phone
9845079472
Fax
080-67748857
Email
sandeep.av@astrazeneca.com
Source of Monetary or Material Support
AstraZeneca AB (Study Sponsor company)
151 85 Sodertalje, Sweden
Primary Sponsor
Name
AstraZeneca AB
Address
151 85 Sodertalje, Sweden
Type of Sponsor
Pharmaceutical industry-Global
Details of Secondary Sponsor
Name
Address
AstraZeneca Pharma India Ltd
Block N1, 12th Floor, Manyata Embassy Business Park
Rachenahalli, Outer Ring Road, Bangalore – 560045, India
Countries of Recruitment
Austria Belgium Brazil Canada China Denmark France Germany Hungary India Italy Japan Malaysia Poland Republic of Korea Spain Taiwan Thailand Turkey United Kingdom United States of America Viet Nam
Sites of Study
No of Sites = 5
Name of Principal
Investigator
Name of Site
Site Address
Phone/Fax/Email
Dr Vamshi Krishna M
AIG Hospitals (A Unit of Asian Institute of Gastroenterology)
Director & HOD Department of Medical Oncology
Survey 136, Plot 2/3/4/5 AIG Hospitals
Minspace Road Gochibowli Hyderabad 500032 Telangana India Hyderabad TELANGANA
9959778112
drmvkrishnaonco@gmail.com
Dr Satheesh CT
Healthcare Global Enterprises (HCG) Limited
Senior Consultant, Department of Medical Oncology, #8 P Kalinga Rao Road HCG Towers Sampangi Rama Nagar Bangalore- 560027 Karnataka India Bangalore KARNATAKA
9242698750
drsatheeshct@gmail.com
Dr Vineet Talwar
Rajiv Gandhi Cancer Institute and Research Centre
Department of Medical Oncology Rajiv Gandhi Cancer Institute and Research Centre
Rohini Institutional Area, Sector 5, Rohini, Delhi 110085 INDIA New Delhi DELHI
011-47022222
drvineettalwar@yahoo.com
Dr Viraj Lavingia
Shalby Hospital
Senior Consultant, Department of Medical Oncology Shalby Hospital, Opposite Karnavati Club, S. G. Highway, Ahmedabad-380015, Gujarat India Ahmadabad GUJARAT
9908711057
drvirajlavingia@gmail.com
Dr Vikas Sureshchand Ostwal
Tata Memorial Hospital
Department of Medical Oncology
Homi Baba Block 11th floor Dr. E. Borges Road, Parel, Mumbai 400012 Maharashtra India Mumbai MAHARASHTRA
Institutional Ethics Committee, Tata Memorial Hospital
Approved
Institutional Review Board, Rajiv Gandhi Cancer Institute and Research Centre
Approved
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
(1) ICD-10 Condition: C768||Malignant neoplasm of other specified ill-defined sites,
Intervention / Comparator Agent
Type
Name
Details
Intervention
Drug Code- AZD0901
Route- Injectable (IV)
Frequency- Once Daily (OD) every 3 weeks
Dose - 1.8 mg/kg or 2.22 mg/kg
Duration- Till Disease progression or death which ever earlier
Comparator Agent
Drug Code- AZD0901
Ramucirumab IV on Day 1 and 15, paclitaxel IV on Day 1, 8 and 15, repeat those treatment every 28 days (4 weeks)
Paclitaxel IV on Days 1, 8, and 15, repeat those treatment every 28 days (4 weeks)
Docetaxel IV on Day 1, repeat this treatment every 21 days (3 weeks)
Irinotecan IV on Days 1 and 15, repeat those treatment every 28 days (4 weeks)
Inclusion Criteria
Age From
18.00 Year(s)
Age To
99.00 Year(s)
Gender
Both
Details
Inclusion criteria
1. Capable of giving signed informed consent prior to any mandatory study-specific
procedures, sampling, and analyses as described in Appendix A which includes
compliance with the requirements and restrictions listed in the ICF
2. Provision of signed and dated written Optional Genomics Initiative Research Information and Consent Form prior to collection of samples for optional genomics initiative research that supports the Genomic Initiative (see Appendix D 2).Participants not giving consent
for optional genomics initiative research will still be eligible for the main study.
3. 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.
Type of Participant and Disease Characteristics
4. 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 defined as tumour cell expression 25 with IHC at any intensity, as determined prospectively by central IHC testing using the investigational Ventana CLDN18.2 (SP455) IHC assay (prototype assay and or validated assay or an alternative central test as required) from archival tumor collected within past 24 months or from a fresh biopsy. For participants who have received prior CLDN18.2 targeting therapies a new biopsy upon progression must be provided for testing to determine CLDN18.2 expression. Participants with unknown CLDN18.2 status or CLDN18.2 tumour cell expression 25 with IHC at any
intensity based on the central test result are ineligible for the study.
b) Participants must undergo local (or have had) HER2 testing by IHC/ISH
5. Disease progression on or after at least one prior regimen for advanced or metastatic disease, which included a fluoropyrimidine and a platinum, for advanced or metastatic disease. NOTE:
a) Progression within 6 months of prior adjuvant or neoadjuvant chemotherapy is considered as equivalent to progression on one regimen for advanced or metastatic disease.
b) If one of the components of prior combination therapy discontinued due to AE and the other continued, this is considered to be ‘one prior regimen
a) If the prior therapy is discontinued due to poor tolerability or AE with no documented progression, this is not considered to be ‘one prior regimen.
b) Change in dose or route of administration (eg, IV or oral fluoropyrimidine) of prior regimen without progression is considered to be ‘one prior regimen’.
c) Participants who received prior immune checkpoint inhibitor or prior naked CLDN18.2 targeting monoclonal antibody are eligible.
1. Must have at least one measurable or evaluable lesion assessed by the Investigator based on RECIST 1.1.
(a) A previously irradiated lesion can be considered a target lesion if the lesion had progressed after the latest radiotherapy and well defined.
(b) For participants who undergo biopsies at screening and/or treatment, it is preferred, though not required, that the biopsied lesion be distinct from any target lesion used in the RECIST 1.1 evaluation
2. ECOG performance status of 0 or 1 with no deterioration over the previous 2 weeks prior to baseline or day of first dosing.
3. Predicted life expectancy of 12 weeks.
4. Adequate organ and bone marrow function as
1. Body weight of 35 kg.
2. FOCBP:
(a) Must have negative pregnancy test at screening and prior to the infusion of each cycle.
(b) If sexually active with a non-sterilized male partner, must use at least one highly effective method of birth control from screening and must agree to continue using such precautions for 7 months (210 days) after the last dose of AZD0901 or as required by prescribing information for the Investigator’s choice of therapy received. The longest washout period must be followed
(c) Non-sterilized male partners of FOCBP must use a male condom plus spermicide throughout the period specified above for female participant (Note: Male condoms are not reliable as a sole contraception method).
3. Female participants must not breastfeed and must not donate, or retrieve for their own use, ova throughout the period specified above for female participant
13. Non-sterilized male participants who are sexually active with a FOCBP must use a condom with spermicide (condom alone in countries where spermicides are not approved) from screening and must agree to continue using such precautions for 7 months (210 days) after the last dose of AZD0901 or as required by prescribing information for the Investigator’s choice of therapy received. The longest washout period must be followed. (Note: Male condoms are not reliable as a sole contraception method)
A) Female partners of a male participant must also use at least one highly effective method of contraception throughout the period specified above for male participant. In addition, male participants must refrain from fathering a child or donating sperm throughout this period
ExclusionCriteria
Details
Exclusion Criteria
Medical Conditions
1. Participants with known HER2 positive status as defined as IHC 3 plus or IHC 2plues ISH Plus (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. Active or prior documented autoimmune or inflammatory disorders that required systemic treatment or assessed by Investigator as not appropriate to participate due to undue risk.
The following are exceptions to this criterion:
(a) Vitiligo or alopecia.
(b) Hypothyroidism (eg, following Hashimoto’s disease) stable on hormone replacement.
(c) Psoriasis or eczema not requiring systemic treatment
4. CNS metastases or CNS pathology including: epilepsy, seizures, aphasia, or stroke 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. The following are exceptions to this criterion:
(a) Participants with history of seizures are permitted if no active seizures in last 5 years.
(b) Participants with brain metastases treated, asymptomatic, stable, and not requiring steroids for at least 4 weeks prior to randomization. A minimum of 2 weeks must have elapsed between the end of brain radiotherapy and study enrolment.
5. Participant has known clinically significant corneal disease (eg, active keratitis or corneal ulcerations).
6. 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).
7. Peripheral neuropathy, sensory or motor, CTCAE Grade 2 at screening
8. History of thromboembolic events within the past 3 months prior to randomization.
(a) Participants with venous thromboembolism without history of pulmonary embolism, who either do not require treatment or who have already been on stable treatment with anticoagulants for 14 days or longer prior to start of study intervention may be enrolled randomized and should be closely monitored.
9. The participant has any of the following cardiac abnormalities:
(a) Mean resting corrected QT interval (QTcF) 470 milliseconds, obtained from triplicate ECGs performed at screening.
(b) LVEF 50 percentage by ECHO.
(c) NYHA classification for cardiac function Class II.
(d) Other cardiovascular and cerebrovascular diseases that, as assessed by the Investigator, are not suitable for participation in this study.
10. History of another primary malignancy except for malignancy treated with curative intent with no known active disease ( 2 years) before randomization and of low potential risk for recurrence. Exceptions include basal cell carcinoma of the skin and squamous cell carcinoma of the skin that has undergone potentially curative therapy.
11. Infectious disease exclusions:
(a) Known uncontrolled hepatitis B and or chronic or active hepatitis B with HBV DNA 100 IU or mL,
1 Participants with HBsAg positive are eligible if HBV DNA 100 IU mL and
agrees to start or maintain antiviral treatment.
2 Participants with HBsAg negative and HBV viral load ‘detectable’ are eligible if HBV DNA 100 IU or mL and agrees to start or maintain antiviral treatment.
3 Participants with HBsAg negative, anti HBc positive, and HBV DNA
‘undetectable’ are eligible.
4 Participants with HBsAg negative, anti HBc negative, and anti-HBs positive are eligible.
5 Participants with HBsAg positive or HBV DNA detectable should receive
antiviral prophylactic therapy for the duration of anticancer therapy, as well as for at least 12 months after the last dose of anticancer therapy. Participants should have at least 2 weeks of antiviral prophylaxis before starting study drug.
b) Known chronic, active, or uncontrolled hepatitis C, defined as anti HCV IgM or IgG positive and HCV RNA detectable by polymerase chain reaction. Participants with a history of HCV infection are eligible if they have been treated and cured with an undetectable HCV viral load at least 12 weeks post antiviral treatment of HCV.
(c) Active HIV infection (verified by positive HIV1 or HIV2 antibodies).
(d) Uncontrolled active systemic fungal, bacterial, or other infection (defined as exhibiting ongoing signs/symptoms related to the infection and without
improvement, despite appropriate antibiotics or other treatment).
(e) Active tuberculosis infection (clinical evaluation that may include clinical history, physical examination, and radiographic findings, or tuberculosis testing in line with local practice)
12. Uncontrolled diabetes or diabetic neuropathy within 3 months prior to randomization
13. As judged by the Investigator, any evidence of diseases (such as severe or uncontrolled systemic diseases, including uncontrolled hypertension, renal transplant and active bleeding diseases, serious chronic gastrointestinal conditions associated with nausea, vomiting, and diarrhea), 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.
Prior/Concomitant Therapy
1. 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).
15. Receipt of the last dose of anticancer therapy within 28 days (for chemotherapy, antibody-based therapy, or immunotherapy) or 5 half-lives (for targeted therapy) prior to randomization. Herbal or natural products intended as treatment or prophylaxis for any type of cancer that may interfere with the activity of the study intervention are excluded.
16. Receiving any concurrent anticancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (eg, HRT) is allowed.
17. Palliative radiotherapy with a limited field of radiation within 2 weeks or with wide field of radiation or to more than 30% of the bone marrow within 4 weeks before randomization. Participants who have not recovered from radiotherapy-related toxicity to Grade 1 or baseline will not be eligible.
18. Major surgical procedure (excluding placement of vascular access) or significant traumatic injury within 4 weeks of randomization or an anticipated need for major surgery during the study.
19. Any investigational agents or study interventions from a previous clinical study: 28 days or 5 half-lives (whichever is shorter).
Other Exclusions
20. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
21. Judgment by the Investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions, and requirements.
22. Previous enrollment or randomization in the present study.
23. Currently pregnant (confirmed with positive pregnancy test) or breast-feeding females, or females who are planning to become pregnant.
24. Participants who are not suitable to receive at least one of the approved chemotherapeutic/anticancer agents based on the prescribing information and line of therapy, or have known hypersensitivity to any component of AZD0901 will not be eligible to enroll/randomize in this study. Contraindication to ramucirumab should be documented in the eCRF for participants with only one prior line of therapy.
Method of Generating Random Sequence
Stratified block randomization
Method of Concealment
Centralized
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
To demonstrate the superiority of AZD0901 relative to Investigator’s choice of therapy
by assessment of PFS in all randomized
participants
To demonstrate the superiority of AZD0901 relative to Investigator’s choice of therapy by assessment of OS for 3L+ participants
To demonstrate the superiority of AZD0901 relative to Investigator’s choice of therapy
by assessment of PFS in all randomized
participants
OS is defined as time from randomization until the date
of death due to any cause.
The analysis will include all randomized participants
who had at least 2 prior lines of systemic therapy. All deaths will be included, regardless of whether the
participant withdraws from therapy or receives another anticancer therapy.
The measure of interest is the HR of OS
Secondary Outcome
Outcome
TimePoints
To demonstrate the superiority of AZD0901 relative to Investigator’s choice of therapy by assessment of OS in all randomized participants
OS is defined as time from randomization until the date of death due to any cause.
The analysis will include all randomized participants. All deaths will be included, regardless of whether the participant withdraws from therapy or receives another anticancer therapy.
The measure of interest is the HR of OS.
To demonstrate the effectiveness of
AZD0901 relative to Investigator’s choice of therapy by assessment of PFS for 3L+ participants
PFS is defined as time from randomization until progression per RECIST 1.1 as assessed by BICR or death due to any cause.
The analysis will include all randomized participants who had at least 2 prior lines of systemic therapy. All events will be included, regardless of whether the participant withdraws from therapy or
receives another anticancer therapy.
However, if the participant progresses or dies immediately after 2 or more consecutive missed visits, the participant will be censored at the time of the latest
evaluable assessment prior to the 2 missed visits.
The measure of interest is the HR of PFS
To demonstrate the effectiveness of
AZD0901 relative to Investigator’s choice of therapy by assessment of ORR in all randomized participants
ORR is defined as the proportion of participants with at least one visit response of confirmed CR or confirmed PR, as determined by BICR per RECIST 1.1.
The analysis will include all randomized participants with measurable disease at baseline.
Data obtained from randomization up until progression, or the last evaluable assessment in the absence of progression, will be included in the assessment of ORR, regardless of whether the participant withdraws from therapy. Participants who discontinue treatment without a response or progression, receive a subsequent therapy, and then respond will not be included as responders in the ORR.
The measure of interest is the odds ratio of the ORR.
To demonstrate the effectiveness of
AZD0901 relative to Investigator’s choice of therapy by assessment of ORR for 3L+ participants
The analysis will include all randomized participants who had at least 2 prior lines of systemic therapy, with measurable disease at baseline.
Others are same as above objective.
To demonstrate the effectiveness of
AZD0901 relative to Investigator’s choice of therapy by assessment of DoR in all randomized participants
DoR is defined as the time from the date of first documented confirmed response until date of documented progression per RECIST 1.1 as assessed by BICR or death due to any cause.
The analysis will include all randomized participants with measurable disease at baseline who have a confirmed response. All events after achieving confirmed response will be included, regardless of whether the participant withdraws from therapy, receives another anticancer therapy or clinically progresses prior to RECIST 1.1.
To demonstrate the effectiveness of
AZD0901 relative to Investigator’s choice of therapy by assessment of DoR for 3L+ participants
The analysis will include all randomized participants who had at least 2 prior lines of systemic therapy, with measurable disease at baseline and who have a confirmed response.
Others are same as above objective
To assess the PK of AZD0901
Serum concentrations of AZD0901, total antibody and MMAE, and PK parameters (such as peak concentration and trough, as data allow)
To assess the immunogenicity of AZD0901
Presence of ADAs against AZD0901 in serum
To assess the safety and tolerability of AZD0901 as compared with Investigator’s choice of therapy in all randomized participants who have received at least one dose of study intervention
Incidence of AEs and SAEs
Changes from baseline in vital signs, clinical laboratory results, and ECGs
To assess the efficacy of AZD0901
according to RECIST 1.1 using Investigator assessments
Analyses of PFS, ORR, and DoR will be repeated using Investigator assessment based on RECIST 1.1 on all randomized participants as well as participants who had
at least 2 prior lines of systemic therapy.
To assess participant reported physical
function in participants treated with
AZD0901 as compared to Investigator’s choice of therapy in all randomized participants
The measure of interest will be the proportion of participants with maintained or improved physical functioning while on treatment, as measured by the EORTC QLQ-C30 physical functioning subscale and select IL items, at each time point for each treatment arm.
The analysis will include all randomized participants. Participants will be analyzed according to the treatment they actually received.
To describe participant reported tolerability, including symptomatic AEs and overall side-effect bother, of AZD0901compared to Investigator’s choice of therapy in all randomized participants who have received
at least one dose of study intervention
Describe symptomatic AEs while on treatment:
• Descriptive summary based on the proportion of all treated participants, as treated, reporting different levels of symptomatic AEs while on treatment using items from the EORTC IL.
Describe overall side-effect bother while on treatment:
• Descriptive summary based on the proportion of all treated participants, as treated, reporting each level of overall side-effect bother on the PGI-TT, while on treatment.
Describe the reversibility of symptomatic toxicity following treatment discontinuation:
• Descriptive summary of change in symptomatic AEs following treatment discontinuation based on items from the EORTC IL.
• Descriptive summary of change in overall side-effect bother following treatment discontinuation based on the PGI-TT.
All analyses will include participants in the safety analysis set. Participants will be analyzed according to the treatment they actually received.
Target Sample Size
Total Sample Size="625" Sample Size from India="20" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Phase of Trial
Phase 3
Date of First Enrollment (India)
24/02/2025
Date of Study Completion (India)
Applicable only for Completed/Terminated trials
Date of First Enrollment (Global)
04/03/2024
Date of Study Completion (Global)
Applicable only for Completed/Terminated trials
Estimated Duration of Trial
Years="1" Months="6" Days="0"
Recruitment Status of Trial (Global)
Open to Recruitment
Recruitment Status of Trial (India)
Open to Recruitment
Publication Details
N/A
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This is a Phase III, 3-arm, randomized, open-label, multi-center, global clinical studyin which we are comparingsponsor test drug (AZD0901) with Standard care of Chemotherapy when given to Second- or Later-Line Adult Participants with Advanced/Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma with CLAUDIN 18.2 Positivity.
Approximately625participantswill be randomized globally out of which 20 patients will be taken from India . The patient will be randomized 1.1.1 ratio.
Recruitment of participants who have progressed on or after only one line of prior treatment
will be capped at approximately 33% of the total randomized participants.
AZD0901/Investigator’s choice of therapy until PD, or any other discontinuation criteria is met. AZD0901 may continue beyond PD if participant continues to show clinical benefit and provides informed consent. During study treatment crossover is not allowed
Randomization will be stratified by geographical region (Japan and South Korea vs Other Asia
vs RoW), prior gastrectomy (yes vs no), and line of therapy (2L vs 3L+).