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临床试验/CTRI/2022/06/043460
CTRI/2022/06/043460招募中3 期

A Phase III, Randomised, Double blind, Placebo controlled, Multicentre, International Study of Durvalumab plus Domvanalimab (AB154) in Participants with Locally Advanced (Stage III), Unresectable Non-small Cell Lung Cancer Whose Disease has not Progressed Following Definitive Platinum based Concurrent Chemoradiation Therapy (PACIFIC-8)

ASTRAZENECA AB16 个研究点 分布在 1 个国家目标入组 860 人开始时间: 2022年6月27日最近更新:
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试验速览

阶段
3 期
状态
招募中
入组人数
860
试验地点
16
主要终点
To demonstrate superiority of durvalumab plus domvanalimab relative to durvalumab plus placebo in participants with locally advanced, unresectable NSCLC who have not progressed on prior platinum based cCRT, with:
研究概览研究设计入排标准结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

This is a Phase III,randomised, double blind, placebo controlled, multicentre, international studyassessing the efficacy and safety of durvalumab and domvanalimab compared withdurvalumab plus placebo in adults with locally advanced (Stage III),unresectable NSCLC whose disease has not progressed following definitiveplatinum based cCRT. It is estimated that approximately 860 participants withPD-L1 TC ≥ 1% will be randomised at approximately 200 sites in approximately 20countries. Participants will be randomised in a 1:1 ratio to one of thefollowing intervention arms. Participants in the durvalumab plus domvanalimabarm will assigned treatement for up to a maximum of 12 months (maximum 13cycles with the last administration by Week 48), or until clinical progression,confirmed RECIST 1.1 defined radiological progression, unacceptable toxicity,withdrawal of consent, or an intervention discontinuation criterion is met,whichever is earlier. After study intervention discontinuation, allparticipants will be followed up for safety assessments 90 days after theirlast dose of study intervention (ie, the safety follow up visit). Allparticipants randomised in the study should be followed up for survival.

研究设计

研究类型
Interventional
分配方式
Stratified block randomization
盲法
Participant and Investigator Blinded

入排标准

年龄范围
18.00 Year(s) 至 90.00 Year(s)（—）
性别
All

入选标准

  • •Part I Screening 1Participant must be ≥ 18 years at the time of screening.
  • •2Participants must have histologically or cytologically documented NSCLC and have been treated with concurrent CRT for locally advanced (Stage III), unresectable disease .
  • •3Tumour sample requirements as follows: Provision of a tumour tissue sample (obtained ≤ 3 months prior to screening Part 1 is preferred; ≤ 6 months old is acceptable if no sample of ≤ 3 months is available).
  • •An FFPE block sufficient for sectioning 20 slides (5 micron thickness) is preferred.
  • •If FFPE blocks cannot be submitted, then a set of newly-cut, unstained slides to enable the necessary testing may be provided.
  • •4Tumour PD L1 status ≥ 1% as determined using the Ventana SP263 PD L1 IHC assay by a central laboratory.
  • •5Documented EGFR and ALK wild-type status.
  • •7Capable of giving signed informed consent for tumour sample collection that includes compliance with the requirements and restrictions listed in the pre-screening informed consent form (Part I screening ICF), which includes compliance with the requirements and restrictions listed in the ICF and this protocol.
  • •Part II Screening Participants are eligible to be randomised to the study only if all of the following Part II inclusion criteria and none of the exclusion criteria apply: 8Participants must have not progressed following definitive, platinum based, concurrent chemoradiation therapy.
  • •Screening imaging should include brain imaging (MRI is the preferred modality however high-quality CT with IV contrast is acceptable).
  • •9Participants must have received at least 2 cycles of platinum- based chemotherapy concurrent with radiation therapy, which must be completed within 1 to 28 days prior to the first dose of study intervention in the study (1 cycle is defined as 21 or 28 days).
  • •For participants who are recovering from toxicities associated with prior treatment, the first dose of study intervention may be delayed by up to 28 days from the end of chemoradiation therapy.
  • •Sites are strongly encouraged to complete screening within the first 14 days of the 28 day screening period.
  • •10The platinum-based chemotherapy regimen must have contained cisplatin or carboplatin and one of the following agents: etoposide, vinblastine, vinorelbine, a taxane (paclitaxel or docetaxel), or pemetrexed, according to the local standard of care regimens.
  • •Gemcitabine is not permitted.
  • •11The last dose of chemotherapy must be administered prior to, or concurrently with, the final dose of radiation.
  • •Consolidation chemotherapy after radiation is not permitted but administration of 1 2 induction cycles of chemotherapy prior to cCRT is acceptable.
  • •Where possible, chemotherapy regimens should be given according to National Comprehensive Cancer Network (NCCN) Guidelines or European Society for Medical Oncology (ESMO) Guidelines.
  • •12A total dose of radiation of 60 Gy ± 10% (54 Gy to 66 Gy) as part of the chemoradiation therapy is required to be randomised.
  • •Radiation therapy should be administered by intensity modulated RT (preferred) or a 3D conforming technique.
  • •13World Health Organization (WHO) Performance Status of 0 or 1 at randomisation.
  • •14Adequate organ and marrow function 15Minimum life expectancy of 12 weeks at randomisation 16Body weight > 30 kg at enrolment and randomisation 17Male or female.
  • •Reproduction: Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
  • •18Negative pregnancy test (serum) for WOCBP: 19Female participants must be 1 year post menopausal, surgically sterile, or using 1 highly effective form of birth control (a highly effective method of contraception is defined as one that can achieve a failure rate of less than 1% per year when used consistently and correctly).
  • •WOCBP must agree to use one highly effective method of birth control.
  • •They should have been stable on their chosen method of birth control for a minimum of 3 months before entering the study to 115 days after the last dose.
  • •Non sterilised male partners of a WOCBP must use a male condom and spermicide throughout this period.
  • •20Male participants who intend to be sexually active with a WOCBP must be surgically sterile or using an acceptable method of contraception from the time of screening throughout the total duration of the study, and for drugs that are potentially genotoxic the drug washout period (115 days after the last dose of study intervention) to prevent pregnancy in a partner.
  • •Male participants must not donate or bank sperm during this same time period.
  • •Informed Consent 21Capable of giving signed informed consent.
  • •For Optional Genomic initiative participation only: Provision of signed and dated written Optional Genetic Research Information informed consent prior to collection of sample for optional genetic research that supports Genomic Initiative.
  • •If a participant declines to participate in the genetics research, there will be no penalty or loss of benefit to the participant.
  • •A participant who declines genetics research participation will not be excluded from any other aspect of the main study.

排除标准

  • •Participants are excluded from the study if any of the following criteria apply: 1As judged by the investigator, any evidence of diseases (such as severe or uncontrolled systemic diseases, including uncontrolled hypertension, active bleeding diseases, active infection, active ILD/pneumonitis, serious chronic gastrointestinal conditions associated with diarrhoea, psychiatric illness/social situations); or a history of allogeneic organ transplant, 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 2History of another primary malignancy, except for malignancy treated with curative intent with no known active disease ≥ 5 years before the first dose of study intervention and of low potential risk for recurrence, basal cell carcinoma of the skin, squamous cell carcinoma of the skin or lentigo maligna that has undergone potentially curative therapy or adequately treated carcinoma in situ or Ta tumours without evidence of disease 3Prior allogeneic bone marrow transplantation or stem cell/solid organ transplantation 4Active or prior documented autoimmune or inflammatory disorders (with exception) 5Severe infection within 4 weeks prior to initiation of study treatment 6History of idiopathic pulmonary fibrosis, organizing pneumonia, drug induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis, ILD, pleural effusion, or pulmonary fibrosis .
  • •7History of leptomeningeal carcinomatosis 8History of primary immunodeficiency 9Active hepatitis infection, positive HCV antibody, HBV surface antigen (HbsAg) or HBV core antibody (anti HBc) at screening.
  • •Participants with a past or resolved HBV infection (defined as the presence of anti HBc and absence of HbsAg) are eligible.
  • •Participants positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV RNA 10Positive test for HIV (positive HIV 1/2 antibodies) or known to have active tuberculosis infection (clinical evaluation that may include clinical history, physical examination, and radiographic findings, or tuberculosis testing in line with local practice) 11Active EBV infection, or known or suspected chronic active EBV infection at screening 12Mixed small cell and NSCLC cancer histology 13Participants who receive sequential (not inclusive of induction) chemoradiation therapy for locally advanced, unresectable NSCLC 14Participants with locally advanced, unresectable NSCLC who have progressed during definitive platinum- based cCRT 15Participants who have had disease considered for surgical treatment as part of their care plan, such as Pancoast or superior sulcus tumours 16Participants with T4 lesions that invade major vascular structures such as pulmonary artery or cardiac tissues are ineligible.
  • •17Investigator judgement of 1 or more of the following: Mean resting corrected QT interval > 470 ms, obtained from triplicate ECGs performed at screening History of QT prolongation associated with other medications that required discontinuation of that medication, or any current concomitant medication known to prolong the QT interval and cause TdP Congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden cardiac death < 40 years of age in first degree relatives 18History of symptomatic congestive heart failure; unstable angina pectoris; uncontrolled cardiac arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia), which is symptomatic or requires treatment (CTCAE Grade 3); symptomatic or uncontrolled atrial fibrillation despite treatment; or asymptomatic sustained ventricular tachycardia.
  • •Participants with atrial fibrillation controlled by medication or arrhythmias controlled by pacemakers may be permitted upon discussion with the clinical study lead.
  • •19Subjects with a history of myocardial infarction, transient ischemic attack, pulmonary embolism, or stroke diagnosed in the past 6 months, or venous thrombosis diagnosed in the past 3 months 20Known allergy or hypersensitivity to any of the study interventions.
  • •21Receipt of prior or current cancer treatment for NSCLC, including but not limited to, radiation therapy, investigational agents, chemotherapy, and mAbs.
  • •Prior surgical resection of metachronus NSCLC (ie, Stage I or II) is permitted.
  • •22Prior exposure to immune mediated therapy including, but not limited to, anti-TIGIT, anti–CTLA 4, anti-PD 1, anti-PD-L1, anti-PD L2 antibodies, excluding therapeutic anticancer vaccines.
  • •Live attenuated vaccines within 30 days prior to the first dose of the study intervention are not permitted.
  • •23Participants who are expected to require any other form of antineoplastic therapy while participating in the trial are excluded.
  • •Prior surgical resection of metachronous NSCLC (i.e., Stage I or II) is permitted.
  • •26Any unresolved toxicity CTCAE > Grade 2 from the prior chemoradiation therapy (excluding alopecia).
  • •27Participants with CTCAE ≥ Grade 2 pneumonitis from prior chemoradiation therapy 28Any prior Grade ≥ 3 immune related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE > Grade
  • •29Any concurrent anticancer treatment.
  • •Concurrent use of hormonal therapy for noncancer related conditions (eg, hormone replacement therapy) is allowed.
  • •30Previous treatment in the present study 31Concurrent participation in another clinical study, unless it is an observational (non interventional) clinical study, or the follow up period of an interventional study 32Participation in another clinical study with a study intervention during the last 3 months prior to randomisation or concurrent enrolment in another clinical study, unless it is an observational, noninterventional clinical study during the follow up period of an interventional study 33Prior randomisation or treatment in a previous durvalumab or domvanalimab clinical study regardless of treatment arm assignment 34Receipt of any immunotherapy, or investigational drug within 4 weeks prior to the first dose of study drug; and in the case of monoclonal antibodies 6 weeks prior to the first dose of study drug 35Participants with a known sensitivity to durvalumab or domvanalimab, any anti-TIGIT, or any excipients of the products 36Judgement by the investigator that the participant is unsuitable to participate in the study and the participant is unlikely to comply with study procedures, restrictions, and requirements 37Female participants who are pregnant or breastfeeding, or male or female participants of reproductive potential who are not willing to employ effective birth control from screening to 115 days after the last dose of study treatment.

结局指标

主要结局

To demonstrate superiority of durvalumab plus domvanalimab relative to durvalumab plus placebo in participants with locally advanced, unresectable NSCLC who have not progressed on prior platinum based cCRT, with:

时间窗: PFS measured by HR | up to approximately 77 months

1 PD-L1 TC ≥ 50%

时间窗: PFS measured by HR | up to approximately 77 months

2 assessment by PFS as assessed by BICR

时间窗: PFS measured by HR | up to approximately 77 months

次要结局

  • As primary, with:(PD-L1 TC ≥ 50%, or)
  • To test the above objectives using an alternative PD-L1 IHC assay, PD-L1 IHC 22C3 pharmDx, who have not progressed on prior platinum based cCRT, with:(PD-L1 TPS ≥ 50%, or)
  • To assess the PK of durvalumab when given in combination with domvanalimab, in participants with locally advanced, unresectable NSCLC, with PD-L1 TC ≥ 1% as measured by the VENTANA PD-L1 (SP263) IHC assay, who have not progressed on prior platinum based cCRT(Concentration of durvalumab in serum and PK parameters)
  • To assess the PK of domvanalimab when given in combination with durvalumab, in participants with locally advanced, unresectable NSCLC, with PD-L1 TC ≥ 1% as measured by the VENTANA PD-L1 (SP263) IHC assay, who have not progressed on prior platinum based cCRT(Concentration of domvanalimab in serum and PK parameters)
  • To investigate the immunogenicity of durvalumab, in participants with locally advanced, unresectable NSCLC with PD-L1 TC ≥ 1% as measured by the VENTANA PD-L1 (SP263) IHC assay, who have not progressed on prior platinum-based cCRT(Presence of ADAs for durvalumab as measured by rates of occurrence of ADAs and titres)
  • To investigate the immunogenicity of domvanalimab in participants with locally advanced, unresectable NSCLC with PD-L1 TC ≥ 1% as measured by the VENTANA PD-L1 (SP263) IHC assay, who have not progressed on prior platinum-based cCRT(Presence of ADAs for domvanalimab as measured by rates of occurrence of ADAs and titres)
  • To assess time to deterioration in pulmonary symptoms(cough, dyspnoea, chest pain)
  • Safety objective(To assess the safety and tolerability of durvalumab plus domvanalimab as compared to durvalumab plus placebo in participants with locally advanced, unresectable NSCLC who have not progressed on prior platinum based cCRT)

研究者

申办方类型
Pharmaceutical industry-Global

研究点 (16)

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