A Global Study to Assess the Effects of Durvalumab With Oleclumab or Durvalumab With Monalizumab Following Concurrent Chemoradiation in Patients With Stage III Unresectable Non-Small Cell Lung Cancer

Phase 3Active Not RecruitingNCT05221840

AstraZeneca1,051 enrolled

Overview

This is a Phase III, randomised, double-blind, multicentre, international study assessing the efficacy and safety of durvalumab (MEDI4736) in combination with oleclumab (MEDI9447) or durvalumab (MEDI4736) with monalizumab (IPH2201) in adults with locally advanced (Stage III), unresectable NSCLC, who have not progressed following platinum-based cCRT.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

1,051

Conditions

Non-Small Cell Lung Cancer

Interventions

DurvalumabDRUG

Durvalumab IV (intravenous infusion)

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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 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 malignancy treated with curative intent with no known active disease ≥5 years before the first dose of study intervention and of low potential risk for recurrence, adequately resected non-melanoma skin cancer and curatively treated in situ disease, or adequately treated carcinoma in situ or Ta tumours 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 - diagnosed in the past 6 months prior to randomization. * Active or prior documented autoimmune or inflammatory disorders (with exceptions) * Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab.

Locations (202)

Research Site

San Diego, California, United States

Research Site

New Haven, Connecticut, United States

Research Site

Stuart, Florida, United States

Research Site

Urbana, Illinois, United States

Research Site

New Albany, Indiana, United States

Research Site

Outcomes

Primary Outcomes

Progression Free Surival (PFS)

Progression Free Survival (PFS) as assessed by BICR, per RECIST 1.1.

Time frame: Up to 5 years after first patient randomized.

Secondary Outcomes

Overall Survival (OS)

Overall survival (OS)

Time frame: Up to 9 years after first patient randomized

Objective response rate (ORR)

Objective response rate (ORR) per RECIST 1.1 as assessed by BICR