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    Summary
    EudraCT Number:2021-004327-32
    Sponsor's Protocol Code Number:D9075C00001
    National Competent Authority:Greece - EOF
    Clinical Trial Type:EEA CTA
    Trial Status:Trial now transitioned
    Date on which this record was first entered in the EudraCT database:2022-03-02
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedGreece - EOF
    A.2EudraCT number2021-004327-32
    A.3Full title of the trial
    A Phase III, Randomized, Doubleblind, Placebo-controlled, Multicentre, International Study of Durvalumab plus Domvanalimab (AB154) in Participants with Locally Advanced (Stage III), Unresectable Nonsmall Cell Lung Cancer Whose Disease has not Progressed Following Definitive Platinumbased Concurrent Chemoradiation Therapy (PACIFIC-8)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Global Study to Assess the Effects of Durvalumab + Domvanalimab Following Concurrent Chemoradiation in Patients With Stage III Unresectable Non-Small Cell Lung Cancer (PACIFIC 8)
    A.3.2Name or abbreviated title of the trial where available
    PACIFIC-8
    A.4.1Sponsor's protocol code numberD9075C00001
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT05211895
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorAstraZeneca AB
    B.1.3.4CountrySweden
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportAstrazeneca AB
    B.4.2CountrySweden
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAstraZeneca AB
    B.5.2Functional name of contact pointClinical Study Information Center
    B.5.3 Address:
    B.5.3.1Street Address1800 Concorde Pike
    B.5.3.2Town/ cityWilmington
    B.5.3.3Post code19803
    B.5.3.4CountryUnited States
    B.5.4Telephone number18772409479
    B.5.6E-mailInformation.Center@astrazeneca.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameDurvalumab
    D.3.2Product code MEDI4736
    D.3.4Pharmaceutical form Concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNDurvalumab
    D.3.9.1CAS number 1428935-60-7
    D.3.9.2Current sponsor codeMEDI4736
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number50
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameDomvanalimab
    D.3.2Product code AB154
    D.3.4Pharmaceutical form Concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNDomvanalimab
    D.3.9.1CAS number 2368219-35-4
    D.3.9.2Current sponsor codeAB154
    D.3.9.3Other descriptive nameDomvanalimab
    D.3.9.4EV Substance CodeSUB207237
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number60
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboSolution for injection
    D.8.4Route of administration of the placeboIntravenous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    The target population of interest in this study is participants with locally advanced (Stage III), unresectable NSCLC, whose tumours express PD L1 TC ≥ 1% as assessed by a central reference laboratory using the VENTANA PD-L1 (SP263) IHC assay, and who did not progress after definitive platinum based cCRT.
    E.1.1.1Medical condition in easily understood language
    Unresectable, locally advanced (Stage III) lung cancer (non-small cell lung cancer) with PD-L1 biomarker expression
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level PT
    E.1.2Classification code 10061873
    E.1.2Term Non-small cell lung cancer
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    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 PD-L1 TC ≥ 50%, progression free survival (PFS) assessed by blind independent committee review (BICR).
    E.2.2Secondary objectives of the trial
    To demonstrate superiority of durvalumab plus domvanalimab relative to durvalumab plus placebo in participants with TC ≥ 1%, progression free survival (PFS) assessed by Blinded Independent Central Review (BICR).

    To demonstrate superiority of durvalumab plus domvanalimab relative to durvalumab plus placebo in participants with TC ≥ 1% or TC ≥ 50% in the following outcomes:
    • Overall response rate (ORR)
    • Duration of response (DoR)
    • Time to second progression (PFS2)
    • Time to death or distant metastatis (TTDM)
    • Time to First Subsequent Therapy (TFST)
    • PFS at 6, 12, 18 and 24 months
    • Overall Survival at 24 months (OS 24)
    • Overall Survival (OS)
    • PFS as assessed by investigator
    • Time to deterioration in pulmonary symptoms
    Test the above objectives using an alternative PD-L1 IHC assay, PD-L1 IHC 22C3 pharmDx

    PK and immunogenicity of durvalumab and domvanalimab
    To assess the safety and tolerability of durvalumab plus domvanalimab as compared to durvalumab plus placebo.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Participant must be ≥ 18 years at the time of screening.
    2. Histologically- or cytologically-documented NSCLC and have been treated with concurrent CRT for locally advanced, unresectable (Stage III) disease
    3. Provision of a tumour tissue sample obtained prior to CRT
    4. Documented tumour PD-L1 status ≥ 1% by central lab
    5. Documented EGFR and ALK wild-type status (local or central).
    6. Patients must not have progressed following definitive, platinum-based, concurrent chemoradiotherapy
    7. Participants must have received at least 2 cycles of platinum-based chemotherapy concurrent with radiation therapy
    8. Participants must have received a total dose of radiation of 60 Gy ±10% (54 Gy to 66 Gy) as part of the chemoradiation therapy, to be randomised. Radiation therapy should be administered by intensity modulated RT (preferred) or 3D-conforming technique.
    9. WHO performance status of 0 or 1 at randomization
    10. Adequate organ and marrow function
    E.4Principal exclusion criteria
    Participants are excluded from the study if any of the following criteria apply:
    1. History 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. Exceptions include adequately resected non-melanoma skin, cancer and curatively treated in situ disease, or adequately treated carcinoma in situ or Ta tumours treated with curative intent and without evidence of disease.
    2. Mixed small cell and non-small cell lung cancer histology.
    3. Participants who receive sequential (not inclusive of induction) chemoradiation therapy for locally advanced (Stage III) unresectable NSCLC.
    4. Participants with locally advanced (Stage III) unresectable NSCLC who have progressed during platinum-based cCRT.
    5. Any unresolved toxicity CTCAE >Grade 2 from the prior chemoradiation therapy (excluding alopecia).
    6. Participants with ≥grade 2 pneumonitis from prior chemoradiation therapy.
    7. History of idiopathic pulmonary fibrosis, drug-induced pneumonitis, or idiopathic pneumonitis regardless of time of onset prior to randomisation. Evidence of active non-CRT induced pneumonitis, (≥ Grade 2), active pneumonia, active ILD, active or recently treated pleural effusion, or current pulmonary fibrosis.
    8. Active or prior documented autoimmune or inflammatory disorders (with exceptions)
    9. Active EBV infection, or known or suspected chronic active EBV infection at screening
    10. Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab.
    E.5 End points
    E.5.1Primary end point(s)
    Progression Free Survival (PFS) using Blinded Independent Central Review (BICR) assessment according to RECIST 1.1 with participants with PD-L1 TC>=50%.
    E.5.1.1Timepoint(s) of evaluation of this end point
    PFS will be evaluated every 8 weeks (±7 days) from randomisation through 48 weeks, and q12w (± 7 days) thereafter until RECIST 1.1 defined radiological progression, plus 1 or more follow-up scans.
    E.5.2Secondary end point(s)
    PFS measured by hazard ratio (HR), in participants with PD-L1 TC ≥ 1%. % as assessed by BICR.

    Comparison of durvalumab plus domvanalimab relative to durvalumab plus placebo in participants with TC ≥ 1% or TC ≥ 50% in the following outcomes

    1. Overall Survival (OS)
    2. PFS assessment by investigator according to RECIST 1.1
    3. PFS6, PFS12, PFS18, PFS24
    4. Overall Survival at 24 months (OS 24)
    5. Objective response rate (ORR) using BICR assessment according to RECIST 1.1.
    6. Duration of response (DoR) using BICR assessment according to RECIST 1.1
    7. Time from randomization to second progression (PFS2)
    8. Time from randomization until the first date of distant metastasis or death in the absence o distant metastasis (TTDM).
    9. Time to first subsequent therapy (TFST)
    10. The pharmacokinetics (PK) of durvalumab and domvanalimab as determined by concentration.
    11. The immunogenicity of Durvalumab and domvanalimab as assessed by presence of anti-drug antibodies (ADAs)
    12. Time to First Confirmed Deterioration (TTFCD)in pulmonary symptoms measured by the NSCLC-SAQ.
    13. Test the above objectives using an alternative PD-L1 IHC assay, PD- L1 IHC 22C3 pharmDx
    E.5.2.1Timepoint(s) of evaluation of this end point
    PFS will be evaluated every 8 weeks (±7 days) from randomisation through 48 weeks, and q12w (± 7 days) thereafter until RECIST 1.1 defined radiological progression, plus 1 or more follow-up scans.

    ORR, DoR, PFS by investigator, PFS2, PFS6, PFS12, PFS18, PFS24, TTDM, TFST, TTFCD, up to approximately 8 years after first patient randomized

    OS and OS24, up to approximately 8 years after first patient randomized.

    ADA and PK: from date of randomization to approximately 12 weeks after last IP dose.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic Yes
    E.6.11Pharmacogenomic Yes
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    Tolerability
    Symptoms and Health-related quality of life
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned8
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA61
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Chile
    Malaysia
    Philippines
    Switzerland
    Taiwan
    Belgium
    Brazil
    China
    France
    Germany
    Greece
    Hungary
    India
    Japan
    Korea, Republic of
    Mexico
    Norway
    Poland
    Romania
    South Africa
    Spain
    Turkey
    United Kingdom
    United States
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    The end of study is defined as the date of the last visit for the last participant in the study globally.
    A participant is considered to have completed the study if he/she has completed all phases of the study including the last expected visit. Participants may be withdrawn from the study if the study itself is stopped. The study may be stopped if, in the judgement of AstraZeneca, participants are placed at undue risk because of clinically significant findings.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years7
    E.8.9.1In the Member State concerned months2
    E.8.9.1In the Member State concerned days20
    E.8.9.2In all countries concerned by the trial years7
    E.8.9.2In all countries concerned by the trial months8
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 942
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 628
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    If yes a legal representative may provide consent on behalf of a subject incapable of giving consent personally, where permitted by local regulations.
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state50
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 682
    F.4.2.2In the whole clinical trial 1570
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    Treatment plan after the end of participation in the trial is not different from the expected normal treatment of Unresectable Non small Cell Lung Cancer .
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2022-05-10
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2022-05-20
    P. End of Trial
    P.End of Trial StatusTrial now transitioned
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