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

Phase 3Active Not RecruitingNCT05211895

AstraZeneca791 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

791

Conditions

Non-Small Cell Lung Cancer

Interventions

DurvalumabDRUG

Durvalumab IV (Intravenous infusion)

DomvanalimabDRUG

Domvanalimab IV (Intravenous infusion)

PlaceboOTHER

Placebo IV (Intravenous infusion)

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (226)

Outcomes

Primary Outcomes

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.

Time frame: Up to 5 years after randomization

Secondary Outcomes

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 ≥ 1% 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.

Time frame: Up to 5 years after randomization

Overall Survival (OS)

Overall Survival (OS) 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.

Time frame: Approximately 5 years after randomization

Objective Response Rate (ORR)

Objective Response Rate (ORR) per RECIST 1.1 as assessed by BICR 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.

Time frame: Approximately 5 years after randomization

Duration of Response (DoR)

Duration of Response (DoR) using BICR assessment according to RECIST 1.1 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.

Data from ClinicalTrials.gov

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Research Site

Chandler, Arizona, United States

Research Site

Phoenix, Arizona, United States

Research Site

Fountain Valley, California, United States

Research Site

Santa Rosa, California, United States

Research Site

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

Research Site

Jacksonville, Florida, United States

Research Site

Orlando, Florida, United States

Research Site

Saint Augustine, Florida, United States

Research Site

Macon, Georgia, United States

Research Site

Elmhurst, Illinois, United States

...and 216 more locations