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

NCT05211895 | Active Not Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: D9075C000012021-004327-32
• Study Type: interventional
• Target: 791
• Locations: 28 countries
• Sites: 226

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.

Conditions

Non-Small Cell Lung Cancer

Keywords

non-small cell lung cancer; locally advanced; NSCLC

Outcome Measures

Primary Outcomes (1)

• 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%. Outcomes measures were applicable with the previous version of the protocol. The study objectives are considered descriptive rather than confirmatory according to the protocol amendment.

  Up to 5 years after randomization

Secondary Outcomes (13)

• Progression Free Survival (PFS)

  Up to 5 years after randomization

• Overall Survival (OS)

  Approximately 5 years after randomization

• Objective Response Rate (ORR)

  Approximately 5 years after randomization

• Duration of Response (DoR)

  Approximately 5 years after randomization

• Time from randomization to second progression (PFS2)

  Approximately 5 years after randomization

Study Arms (2)

Arm A: Durvalumab + Domvanalimab

EXPERIMENTAL

Durvalumab and domvanalimab as an IV infusion q4w, starting on Day 1 for up to a maximum of 12 months

Drug: Durvalumab; Drug: Domvanalimab

Arm B: Durvalumab + Placebo

ACTIVE COMPARATOR

Durvalumab + placebo as an IV infusion q4w starting on Day 1 for up to a maximum of 12 months

Drug: Durvalumab; Other: Placebo

Interventions

Durvalumab DRUG

Durvalumab IV (Intravenous infusion)

Arm A: Durvalumab + Domvanalimab; Arm B: Durvalumab + Placebo

Domvanalimab DRUG

Domvanalimab IV (Intravenous infusion)

Arm A: Durvalumab + Domvanalimab

Placebo OTHER

Placebo IV (Intravenous infusion)

Arm B: Durvalumab + Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant must be ≥ 18 years at the time of screening.
• Histologically- or cytologically-documented NSCLC and have been treated with concurrent CRT for locally advanced, unresectable (Stage III) disease
• Provision of a tumour tissue sample obtained prior to CRT
• Documented tumour PD-L1 status ≥ 1% by central lab
• Documented EGFR and ALK wild-type status (local or central).
• Patients must not have progressed following definitive, platinum-based, concurrent chemoradiotherapy
• Participants must have received at least 2 cycles of platinum-based chemotherapy concurrent with radiation therapy
• 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.
• WHO performance status of 0 or 1 at randomization
• Adequate organ and marrow function

You may not qualify if:

• 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.
• Mixed small cell and non-small cell lung cancer histology.
• Participants who receive sequential (not inclusive of induction) chemoradiation therapy for locally advanced (Stage III) unresectable NSCLC.
• Participants with locally advanced (Stage III) unresectable NSCLC who have progressed during platinum-based cCRT.
• Any unresolved toxicity CTCAE \>Grade 2 from the prior chemoradiation therapy (excluding alopecia).
• Participants with ≥ grade 2 pneumonitis from prior chemoradiation therapy.
• 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
• Active or prior documented autoimmune or inflammatory disorders (with exceptions)
• Active EBV infection, or known or suspected chronic active EBV infection at screening
• Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab.

Sponsors & Collaborators

• AstraZeneca: lead
• Arcus Biosciences, Inc.: collaborator

Study Sites (226)

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Chandler, Arizona, 85224, United States

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Phoenix, Arizona, 85054, United States

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Fountain Valley, California, 92708, United States

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Santa Rosa, California, 95403, United States

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Washington D.C., District of Columbia, 20016, United States

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Jacksonville, Florida, 32224, United States

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Orlando, Florida, 32804, United States

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Saint Augustine, Florida, 32086, United States

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Macon, Georgia, 31217, United States

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Elmhurst, Illinois, 60126, United States

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Louisville, Kentucky, 40202, United States

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Baltimore, Maryland, 21224, United States

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Silver Spring, Maryland, 20910, United States

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Ann Arbor, Michigan, 48106-0995, United States

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Detroit, Michigan, 48202, United States

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Minneapolis, Minnesota, 55407, United States

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Rochester, Minnesota, 55905, United States

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Reno, Nevada, 89511, United States

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East Brunswick, New Jersey, 08816, United States

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Columbus, Ohio, 43214, United States

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Maumee, Ohio, 43537, United States

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Oklahoma City, Oklahoma, 73102, United States

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Pittsburgh, Pennsylvania, 15212, United States

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Charleston, South Carolina, 29401, United States

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Chattanooga, Tennessee, 37404, United States

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Nashville, Tennessee, 37203, United States

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Nashville, Tennessee, 37232, United States

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Fort Sam Houston, Texas, 78234, United States

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Fairfax, Virginia, 22031, United States

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Fort Belvoir, Virginia, 22060, United States

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Spokane Valley, Washington, 99216, United States

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Appleton, Wisconsin, 54911, United States

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Brussels, 1160, Belgium

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Edegem, 2650, Belgium

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Haine-Saint-Paul, 7100, Belgium

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Leuven, 3000, Belgium

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Liège, 4000, Belgium

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Sint-Niklaas, 9100, Belgium

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Barretos, 14784-400, Brazil

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Londrina, 86015-520, Brazil

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Porto Alegre, 91350200, Brazil

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Porto Velho, 76834-899, Brazil

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Rio de Janeiro, 20231-050, Brazil

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Santo André, 09060-650, Brazil

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São Paulo, 01221-900, Brazil

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Taubaté, 12030-200, Brazil

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Calgary, Alberta, T2N 5G2, Canada

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Kelowna, British Columbia, V1Y 5L3, Canada

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Laval, Quebec, H7M 3L9, Canada

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Montreal, Quebec, H4A 3J1, Canada

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Las Condes, 7560908, Chile

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Port Montt, 5500243, Chile

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Santiago, 7500713, Chile

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Santiago, 7520426, Chile

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Santiago, 7630370, Chile

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Santiago, 8241479, Chile

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Temuco, 4810218, Chile

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Aix-en-Provence, 13616, France

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Angers, 49055, France

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Bobigny, 93000, France

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Lille, 59000, France

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Paris, 75014, France

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Pau, 6400, France

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Quimper, 29000, France

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Saint-Grégoire, 35760, France

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Saint-Quentin, 02321, France

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Vantoux, 57070, France

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Villeurbanne, 69100, France

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Berlin, 12351, Germany

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Berlin-Zehlendorf, 14165, Germany

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Braunschweig, 38114, Germany

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Chemnitz, 09116, Germany

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Cologne, 51109, Germany

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Erlangen, 91054, Germany

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Essen, 45147, Germany

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Giessen, 35392, Germany

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Halle, 06120, Germany

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Koblenz, 56073, Germany

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Krefeld, 47805, Germany

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Löwenstein, 74245, Germany

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Moers, 47441, Germany

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Regensburg, 93049, Germany

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Regensburg, 93053, Germany

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Tübingen, 72076, Germany

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Athens, 11526, Greece

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Athens, 11527, Greece

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Athens, 12462, Greece

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Athens, 18547, Greece

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Holargos, Athens, 155 62, Greece

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Thessaloniki, 55236, Greece

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Thessaloniki, 56 429, Greece

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Thessaloniki, 57001, Greece

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Hong Kong, 150001, Hong Kong

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Budapest, 1121, Hungary

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Budapest, 1122, Hungary

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Deszk, 6772, Hungary

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Győr, 9024, Hungary

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Salgótarján, 3100, Hungary

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Székesfehérvár, 8000, Hungary

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Törökbálint, 2045, Hungary

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Ahmedabad, 380054, India

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Bangalore, 560027, India

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Bangalore, 560064, India

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Delhi, 110085, India

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Howrah, 711103, India

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Hyderabad, 500032, India

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Jaipur, 302004, India

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Jaipur, 302022, India

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Kolkata, 700160, India

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Marg Jaipur, 302004, India

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Mohali, 160055, India

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Namakkal, 637001, India

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New Delhi, 110005, India

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New Delhi, 110029, India

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Varanasi, 221005, India

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Bergamo, 24127, Italy

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Roma, 00144, Italy

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Rozzano, 20089, Italy

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Bunkyō City, 113-8431, Japan

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Bunkyō City, 113-8603, Japan

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Bunkyō City, 113-8677, Japan

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Chiba, 260-8717, Japan

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Fukuoka, 812-8582, Japan

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Hidaka-shi, 350-1298, Japan

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Hirosaki-shi, 036-8563, Japan

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Itabashi-ku, 173-0003, Japan

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Kashihara-shi, 634-8522, Japan

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Kōtoku, 135-8550, Japan

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Kumamoto, 860-8556, Japan

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Matsuyama, 791-0280, Japan

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Nagoya, 464-8681, Japan

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Osaka, 545-8586, Japan

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Osakasayama-shi, 589-8511, Japan

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Sapporo, 003-0804, Japan

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Sunto-gun, 411-8777, Japan

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Tokyo, 104-0045, Japan

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Yokohama, 221-0855, Japan

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Yokohama, 241-8515, Japan

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Johor Bahru, 81100, Malaysia

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Kuala Lumpur, 59100, Malaysia

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Kuala Selangor, 46050, Malaysia

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Kuching, 93586, Malaysia

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Chihuahua City, 31207, Mexico

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Guadalajara, 44638, Mexico

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Mexico City, 03810, Mexico

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Oaxaca City, 68020, Mexico

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Bodø, 8092, Norway

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Gjøvik, 2819, Norway

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Oslo, 0379, Norway

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Trondheim, 0730, Norway

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City of Muntinlupa, 1780, Philippines

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Iloilo City, 5000, Philippines

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Quezon City, 1100, Philippines

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Quezon City, 1112, Philippines

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Bialystok, 15-027, Poland

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Gliwice, 44-102, Poland

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Katowice, 40-074, Poland

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Lodz, 93-513, Poland

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Warsaw, 02-781, Poland

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Wroclaw, 53-413, Poland

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Bucharest, 022328, Romania

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Bucharest, 050098, Romania

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Craiova, 200542, Romania

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Floreşti, Romania

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Iași, 700483, Romania

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Oradea, 410001, Romania

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Sibiu, 550245, Romania

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Suceava, 720214, Romania

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eManzimtoti, 4126, South Africa

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Parktown, 2193, South Africa

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Pretoria, 0084, South Africa

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Daegu, 42415, South Korea

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Goyang-si, 10408, South Korea

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Incheon, 21431, South Korea

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Incheon, 21565, South Korea

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Jinju, 52727, South Korea

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Seoul, 03722, South Korea

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Seoul, 06273, South Korea

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Seoul, 06351, South Korea

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Seoul, 07061, South Korea

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Suwon, 16247, South Korea

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Bilbao (Vizcaya), 48013, Spain

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Castellon, 12002, Spain

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Córdoba, 14004, Spain

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El Palmar, 30120, Spain

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Palma de Mallorca, 07010, Spain

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Sabadell (Barcelona), 08208, Spain

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Basel, 4031, Switzerland

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Bern, CH-3010, Switzerland

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Lausanne, 1011, Switzerland

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Hsinchu, 300, Taiwan

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New Taipei City, 220216, Taiwan

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Taichung, 40447, Taiwan

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Taichung, 40705, Taiwan

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Tainan, 704, Taiwan

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Taipei, 10002, Taiwan

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Taipei, 10449, Taiwan

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Taipei, 11217, Taiwan

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Taoyuan, 333, Taiwan

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Bangkok, 10300, Thailand

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Bangkok, 10400, Thailand

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Bangkok, 10700, Thailand

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Hat Yai, 90110, Thailand

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Adapazarı, 54290, Turkey (Türkiye)

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Ankara, 06340, Turkey (Türkiye)

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Ankara, 6100, Turkey (Türkiye)

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Antalya, 07058, Turkey (Türkiye)

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Çankaya, 06680, Turkey (Türkiye)

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Edirne, 22030, Turkey (Türkiye)

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Istanbul, 34098, Turkey (Türkiye)

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Istanbul, 34662, Turkey (Türkiye)

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Izmir, 35360, Turkey (Türkiye)

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Konya, 42080, Turkey (Türkiye)

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Birmingham, B9 5SS, United Kingdom

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Brighton, BN2 5BE, United Kingdom

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Cardiff, CF14 2TL, United Kingdom

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Cheltenham, GL53 7AN, United Kingdom

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Edinburgh, EH4 2XR, United Kingdom

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High Heaton/Newcastle Upon Tyn, NE7 7DN, United Kingdom

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Leeds, LS 9 7TF, United Kingdom

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London, SE1 9RT, United Kingdom

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Nottingham, NG5 1PB, United Kingdom

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Truro, TR1 3LJ, United Kingdom

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Hanoi, 100000, Vietnam

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Hanoi, 10000, Vietnam

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Ho Chi Minh City, 700000, Vietnam

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Related Links

• 1-844-432-3892 Lung Cancer Study Locator details to CT.gov for the US sites only

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

durvalumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 11, 2022
• First Posted: January 27, 2022
• Study Start: February 18, 2022
• Primary Completion: August 10, 2026
• Study Completion (Estimated): September 8, 2027
• Last Updated: August 28, 2026

Record last verified: 2026-08

Locations

HK (1); FR (11); BR (8); HU (7); PH (4); IT (3); ES (6); NO (4); RO (8); VN (3); GR (8); IN (15); BE (6); US (32); DE (16); PL (6); KR (10); CH (3); CL (7); ME (4); TW (9); TH (4); TU (10); GB (10); CA (4); ZA (3); MY (4); JP (20)