Recruiting NCT05211895

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

Phase III Interventional Non-Small Cell Lung Cancer

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied: The protocol lists: Durvalumab, Domvanalimab, Placebo.
Who it may be relevant to: Registry conditions: Non-Small Cell Lung Cancer. Basic parameters: from 18 years · All.
What needs checking: Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place: United States, Belgium, Brazil, Canada, Chile +23
Next step: Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

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

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.

Interventions

Drug Durvalumab
Durvalumab IV (Intravenous infusion)
Drug Domvanalimab
Domvanalimab IV (Intravenous infusion)
Other Placebo
Placebo IV (Intravenous infusion)

Primary outcome measures

Progression Free Survival (PFS) [Time frame: Up to 8 years after randomization]

Secondary outcome measures (12)

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]

Eligibility criteria

Inclusion criteria

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

Exclusion criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation: Randomized
Model: Parallel assignment
Masking: Quadruple blind
Primary purpose: Treatment