A Global Study to Assess the Effects of Durvalumab + Domvanalimab Following Concurrent Chemoradiation in Participants With Stage III Unresectable NSCLC
Domvanalimab: Domvanalimab IV (Intravenous infusion)
Placebo: Placebo IV (Intravenous infusion)
Study 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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy 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.
Primary outcome measure(s)
Progression Free Survival (PFS) — Up to 5 years after randomization 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.
Trial sites (226)
Facility
City
Region
Status
Research Site
Chandler
Arizona
Research Site
Phoenix
Arizona
Research Site
Fountain Valley
California
Research Site
Santa Rosa
California
Research Site
Washington D.C.
District of Columbia
Research Site
Jacksonville
Florida
Research Site
Orlando
Florida
Research Site
Saint Augustine
Florida
Research Site
Macon
Georgia
Research Site
Elmhurst
Illinois
Research Site
Louisville
Kentucky
Research Site
Baltimore
Maryland
Research Site
Silver Spring
Maryland
Research Site
Ann Arbor
Michigan
Research Site
Detroit
Michigan
Research Site
Minneapolis
Minnesota
Research Site
Rochester
Minnesota
Research Site
Reno
Nevada
Research Site
East Brunswick
New Jersey
Research Site
Columbus
Ohio
Research Site
Maumee
Ohio
Research Site
Oklahoma City
Oklahoma
Research Site
Pittsburgh
Pennsylvania
Research Site
Charleston
South Carolina
Research Site
Chattanooga
Tennessee
Research Site
Nashville
Tennessee
Research Site
Nashville
Tennessee
Research Site
Fort Sam Houston
Texas
Research Site
Fairfax
Virginia
Research Site
Fort Belvoir
Virginia
Research Site
Spokane Valley
Washington
Research Site
Appleton
Wisconsin
Research Site
Brussels
Belgium
Research Site
Edegem
Belgium
Research Site
Haine-Saint-Paul
Belgium
Research Site
Leuven
Belgium
Research Site
Liège
Belgium
Research Site
Sint-Niklaas
Belgium
Research Site
Barretos
Brazil
Research Site
Londrina
Brazil
+ 186 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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