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A Global Study to Assess the Effects of Durvalumab + Domvanalimab Following Concurrent Chemoradiation in Participants With Stage III Unresectable NSCLC (PACIFIC-8)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05211895
Recruitment Status : Recruiting
First Posted : January 27, 2022
Last Update Posted : November 23, 2022
Sponsor:
Collaborator:
Arcus Biosciences, Inc.
Information provided by (Responsible Party):
AstraZeneca

Brief Summary:
This is a Phase III, randomised, double-blind, placebo-controlled, multicentre, international study assessing the efficacy and safety of durvalumab (MEDI4736) and domvanalimab (AB154) compared with durvalumab plus placebo in adults with locally advanced (Stage III), unresectable NSCLC whose disease has not progressed following definitive platinum-based cCRT.

Condition or disease Intervention/treatment Phase
Non-Small Cell Lung Cancer Drug: Durvalumab Drug: Domvanalimab Other: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 860 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Double-blind
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : February 18, 2022
Estimated Primary Completion Date : June 2, 2027
Estimated Study Completion Date : September 28, 2029

Resource links provided by the National Library of Medicine

Drug Information available for: Durvalumab

Arm Intervention/treatment
Experimental: Arm A: Durvalumab + Domvanalimab
Durvalumab and domvanalimab as an IV infusion q4w, starting on Day 1 for up to a maximum of 12 months
Drug: Durvalumab
Durvalumab IV (Intravenous infusion)

Drug: Domvanalimab
Domvanalimab IV (Intravenous infusion)

Active Comparator: Arm B: Durvalumab + Placebo
Durvalumab + placebo as an IV infusion q4w starting on Day 1 for up to a maximum of 12 months
Drug: Durvalumab
Durvalumab IV (Intravenous infusion)

Other: Placebo
Placebo IV (Intravenous infusion)




Primary Outcome Measures :
  1. Progression Free Survival (PFS) [ Time Frame: Up to 8 years after first patient randomised ]
    Defined as time from randomisation until progression per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR), or death due to any cause in participants with PD-L1 TC ≥ 50%.


Secondary Outcome Measures :
  1. Progression Free Survival (PFS) [ Time Frame: Up to 8 years after first patient randomised ]
    Defined as time from randomisation until progression per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR), or death due to any cause in participants with PD-L1 TC ≥ 1%

  2. Overall Survival (OS) [ Time Frame: Approximately 8 years after first patient randomized ]
    Overall Survival (OS)

  3. Objective Response Rate (ORR) [ Time Frame: Approximately 8 years after first patient randomized ]
    Objective Response Rate (ORR) per RECIST 1.1 as assessed by BICR

  4. Duration of Response (DoR) [ Time Frame: Approximately 8 years after first patient randomized ]
    Duration of Response (DoR) using BICR assessment according to RECIST 1.1

  5. Time from randomization to second progression (PFS2) [ Time Frame: Approximately 8 years after first patient randomized ]
    Time from randomization to second progression (PFS2)

  6. Time from randomization to first date of distant metastasis or death (TTDM) [ Time Frame: Approximately 8 years after first patient randomized ]
    Time from randomization until the first date of distant metastasis or death in the absence of distant metastasis (TTDM).

  7. Time to first subsequent therapy (TFST) [ Time Frame: Approximately 8 years after first patient randomized ]
    Time to first subsequent therapy (TFST)

  8. Concentration of Durvalumab and Domvanalimab [ Time Frame: Approximately 12 weeks after last IP dose ]
    The pharmacokinetics (PK) of Durvalumab and Domvanalimab as determined by concentration

  9. PFS6, PFS12, PFS18, PFS24 [ Time Frame: Approximately 6, 12, 18 and 24 months after last patient randomized ]
    PFS at 6, 12, 18 and 24 months (proportion per Kaplan-Meier)

  10. Anti-Drug Antibodies (ADAs) [ Time Frame: Approximately 12 weeks after last IP dose. ]
    The immunogenicity of Durvalumab and domvanalimab as assessed by presence of Anti-Drug Antibodies (ADAs)

  11. Time to deterioration in pulmonary symptoms (TTFCD) [ Time Frame: Approximately 8 years after first patient randomized ]
    Time to deterioration in pulmonary symptoms (TTFCD)



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
  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

EXCLUSION CRITERIA:

  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, basal cell carcinoma of the skin, squamous cell carcinoma of the skin or lentigo maligna that has undergone potentially curative therapy, 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, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis, ILD, pleural effusion, or pulmonary fibrosis diagnosed in the past 6 months prior to randomization.
  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.

    Reproduction

  11. Negative pregnancy test (serum) for WOCBP:
  12. Female participants must be 1 year post menopausal, surgically sterile, or using 1 highly effective form of birth control
  13. Male participants who intend to be sexually active with a WOCBP must be surgically sterile or using an acceptable method of contraception

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05211895


Contacts
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Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com

Locations
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Sponsors and Collaborators
AstraZeneca
Arcus Biosciences, Inc.
Investigators
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Principal Investigator: Hidehito Horinouchi, MD, PhD National Cancer Center Hospital
Principal Investigator: Alexander Spira, MD, PhD Virginia Cancer Specialists Research Institute
Principal Investigator: Jinming Yu, MD, PhD Shandong Cancer Hospital and Institute
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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT05211895    
Other Study ID Numbers: D9075C00001
2021-004327-32 ( EudraCT Number )
First Posted: January 27, 2022    Key Record Dates
Last Update Posted: November 23, 2022
Last Verified: November 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by AstraZeneca:
non-small cell lung cancer
locally advanced
NSCLC
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Durvalumab
Antineoplastic Agents, Immunological
Antineoplastic Agents