CTRI/2025/02/080588尚未招募3 期
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
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 625
- 试验地点
- 5
- 主要终点
- To demonstrate the superiority of AZD0901 relative to Investigator’s choice of therapy
研究概览
简要总结
| This is a Phase III, 3-arm, randomized, open-label, multi-center, global clinical study in which we are comparing sponsor 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. |
Approximately 625 participants will 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+).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- None
入排标准
- 年龄范围
- 18.00 Year(s) 至 99.00 Year(s)（—）
- 性别
- All
入选标准
- •Inclusion criteria
- •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
- •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.
- •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
- •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
- •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.
- •Must have at least one measurable or evaluable lesion assessed by the Investigator based on RECIST 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
- •ECOG performance status of 0 or 1 with no deterioration over the previous 2 weeks prior to baseline or day of first dosing.
- •Predicted life expectancy of 12 weeks.
- •Adequate organ and bone marrow function as
- •Body weight of 35 kg.
- •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).
- •Female participants must not breastfeed and must not donate, or retrieve for their own use, ova throughout the period specified above for female participant
- •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.
排除标准
- •Exclusion Criteria Medical Conditions
- •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.
- •Participant has significant or unstable gastric bleeding and/or untreated gastric ulcers.
- •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
- •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.
- •Participant has known clinically significant corneal disease (eg, active keratitis or corneal ulcerations).
- •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).
- •Peripheral neuropathy, sensory or motor, CTCAE Grade 2 at screening
- •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.
- •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.
- •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.
- •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.
- •(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).
- •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
- •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).
- •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.
- •Receiving any concurrent anticancer treatment.
- •Concurrent use of hormonal therapy for non-cancer-related conditions (eg, HRT) is allowed.
- •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.
- •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.
- •Any investigational agents or study interventions from a previous clinical study: 28 days or 5 half-lives (whichever is shorter).
- •Other Exclusions
- •Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
- •Previous enrollment or randomization in the present study.
- •Currently pregnant (confirmed with positive pregnancy test) or breast-feeding females, or females who are planning to become pregnant.
- •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.
结局指标
主要结局
To demonstrate the superiority of AZD0901 relative to Investigator’s choice of therapy
时间窗: 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
by assessment of PFS in all randomized
时间窗: 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
participants
时间窗: 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
To demonstrate the superiority of AZD0901 relative to Investigator’s choice of therapy by assessment of OS for 3L+ participants
时间窗: 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
次要结局
- 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.)
- To demonstrate the effectiveness of(AZD0901 relative to Investigator’s choice of therapy by assessment of PFS for 3L+ participants)
- To demonstrate the effectiveness of(AZD0901 relative to Investigator’s choice of therapy by assessment of ORR in all randomized participants)
- To demonstrate the effectiveness of(AZD0901 relative to Investigator’s choice of therapy by assessment of ORR for 3L+ participants)
- To demonstrate the effectiveness of(AZD0901 relative to Investigator’s choice of therapy by assessment of DoR in all randomized participants)
- To demonstrate the effectiveness of(AZD0901 relative to Investigator’s choice of therapy by assessment of DoR for 3L+ participants)
- 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)
- To assess the efficacy of AZD0901(according to RECIST 1.1 using Investigator assessments)
- To assess participant reported physical(function in participants treated with)
- 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)
研究者
Mr Sandeep AV
AstraZeneca Pharma India Ltd
研究点 (5)
Loading locations...
相似试验
招募中
3 期
Compare Radiotherapy Plus Nimotuzumab Versus Radiotherapy Alone in Platinum-ineligible Patients With Locoregionally Advanced Head and Neck Squamous Cell CarcinomaNCT07333274Shandong Cancer Hospital and Institute335
招募中
3 期
A Phase III Study Comparing HRS-4357 With Novel Androgen Receptor Pathway Inhibitors in Patients With Progressive, PSMA-Positive Metastatic Castration-Resistant Prostate CancerNCT07311694Jiangsu HengRui Medicine Co., Ltd.370
尚未招募
3 期
Famitinib Combined With SHR-A1811, Versus SHR-A1811 for CDK4/6 Inhibitors-resistent Advanced HR+/HER2- Breast Cancer With SNF4 SubtypeBreast CancerNCT07382687Fudan University248
尚未招募
3 期
A Phase III Study of KN026 in Combination With HB1801 as Adjuvant Therapy for Resectable HER2-Positive Breast CancerNCT07441460Shanghai JMT-Bio Inc.1,800
进行中（未招募）
3 期
A Trial Evaluating Brelovitug vs Delayed Treatment for the Treatment of Chronic Hepatitis Delta Infection (AZURE-4)NCT07298330Mirum Pharmaceuticals, Inc.80