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RecruitingInterventionalPhase 3

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

NCT ID: NCT05211895Sponsor: AstraZenecaLast updated: 2026-06-10

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.

Arms & interventions

  • DrugDurvalumab

    Durvalumab IV (Intravenous infusion)

  • DrugDomvanalimab

    Domvanalimab IV (Intravenous infusion)

  • OtherPlacebo

    Placebo IV (Intravenous infusion)

Outcome measures

Primary

  • Progression Free Survival (PFS)

    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%.

    Time frame: Up to 8 years after randomization

Secondary

  • Progression Free Survival (PFS)

    Time frame: Up to 8 years after randomization

  • Overall Survival (OS)

    Time frame: Approximately 8 years after randomization

  • Objective Response Rate (ORR)

    Time frame: Approximately 8 years after randomization

  • Duration of Response (DoR)

    Time frame: Approximately 8 years after randomization

  • Time from randomization to second progression (PFS2)

    Time frame: Approximately 8 years after randomization

  • Time from randomization to first date of distant metastasis or death (TTDM)

    Time frame: Approximately 8 years after randomization

  • Time to first subsequent therapy (TFST)

    Time frame: Approximately 8 years after randomization

  • Concentration of Durvalumab and Domvanalimab

    Time frame: Approximately 12 weeks after last IP dose

  • PFS6, PFS12, PFS18, PFS24

    Time frame: Approximately 6, 12, 18 and 24 months after randomization

  • Anti-Drug Antibodies (ADAs)

    Time frame: Approximately 12 weeks after last IP dose.

  • Time to deterioration in pulmonary symptoms (TTFCD)

    Time frame: Approximately 8 years after randomization

  • PFS investigator

    Time frame: Up to 8 years after randomization

  • OS 24

    Time frame: Approximately 24 months after randomization

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No
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 EXCLUSION CRITERIA: 1. History of another primary malignancy, except for: * Malignancies treated with curative intent and adequate follow-up with no known active disease and have not required active treatment within the past 3 years before the first dose of study intervention and of low potential risk of recurrence. * Adequately resected non melanoma skin cancer or lentigo maligna without evidence of disease . * Adequately treated carcinoma in situ, including Ta tumors 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.

Study locations (43)

Research Site

Chandler, Arizona, 85224

Recruiting

Research Site

Phoenix, Arizona, 85054

Suspended

Research Site

Fountain Valley, California, 92708

Recruiting

Research Site

Santa Rosa, California, 95403

Recruiting

Research Site

Washington D.C., District of Columbia, 20016

Recruiting

Research Site

Jacksonville, Florida, 32224

Suspended

Research Site

Orlando, Florida, 32804

Recruiting

Research Site

Saint Augustine, Florida, 32086

Recruiting

Research Site

Macon, Georgia, 31217

Suspended

Research Site

Elmhurst, Illinois, 60126

Suspended

Research Site

Maywood, Illinois, 60153

Withdrawn

Research Site

Naperville, Illinois, 60540

Withdrawn

Research Site

Louisville, Kentucky, 40202

Suspended

Research Site

Baltimore, Maryland, 21224

Recruiting

Research Site

Silver Spring, Maryland, 20910

Suspended

Research Site

Ann Arbor, Michigan, 48106-0995

Recruiting

Research Site

Detroit, Michigan, 48202

Completed

Research Site

Minneapolis, Minnesota, 55407

Recruiting

Research Site

Rochester, Minnesota, 55905

Suspended

Research Site

Reno, Nevada, 89511

Recruiting

Research Site

East Brunswick, New Jersey, 08816

Recruiting

Research Site

Florham Park, New Jersey, 07932

Withdrawn

Research Site

Buffalo, New York, 14221

Withdrawn

Research Site

Johnson City, New York, 13790

Withdrawn

Research Site

Asheville, North Carolina, 28805

Withdrawn

Research Site

Asheville, North Carolina, 28806

Withdrawn

Research Site

Charlotte, North Carolina, 28204

Withdrawn

Research Site

Winston-Salem, North Carolina, 27157

Withdrawn

Research Site

Columbus, Ohio, 43214

Recruiting

Research Site

Columbus, Ohio, 43219

Withdrawn

Research Site

Maumee, Ohio, 43537

Recruiting

Research Site

Oklahoma City, Oklahoma, 73102

Recruiting

Research Site

Pittsburgh, Pennsylvania, 15212

Recruiting

Research Site

Charleston, South Carolina, 29401

Suspended

Research Site

Chattanooga, Tennessee, 37404

Recruiting

Research Site

Nashville, Tennessee, 37203

Recruiting

Research Site

Nashville, Tennessee, 37232

Recruiting

Research Site

Fort Sam Houston, Texas, 78234

Recruiting

Research Site

Kingwood, Texas, 77339

Withdrawn

Research Site

Arlington, Virginia, 22205

Recruiting

Research Site

Fort Belvoir, Virginia, 22060

Recruiting

Research Site

Spokane Valley, Washington, 99216

Recruiting

Research Site

Appleton, Wisconsin, 54911

Recruiting