Non-Small Cell Lung Cancer
Conditions
Keywords
Non-Small Cell Lung Cancer, Locally Advanced NSCLC
Brief summary
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.
Interventions
DRUGDurvalumab
Durvalumab IV (intravenous infusion)
DRUGOleclumab
Oleclumab IV (intravenous infusion)
DRUGMonalizumab
Monalizumab IV (intravenous infusion)
OTHERPlacebo
Placebo IV (intravenous infusion)
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double-Blind
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Surival (PFS) | Up to 5 years after first patient randomized. | Progression Free Survival (PFS) as assessed by BICR, per RECIST 1.1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Up to 9 years after first patient randomized | Overall survival (OS) |
| Objective response rate (ORR) | Up to 5 years after first patient randomized | Objective response rate (ORR) per RECIST 1.1 as assessed by BICR |
| Overall survival (OS) at 24 months | Up to 9 years after first patient randomized | Overall survival (OS) at 24 months |
| Duration of response (DoR) | Up to 5 years after first patient randomized | Duration of response (DoR) per RECIST 1.1 as assessed by BICR |
| Progression free survival (PFS) at 6, 12, 18, and 24 months | From date of randomization until 24 months | Progression free survival (PFS) at 6, 12, 18, and 24 months respectively, per RECIST 1.1 as assessed by BICR |
| Time from randomization to second progression (PFS2) | Up to 5 years after first patient randomized | Time from randomization to second progression (PFS2) |
| Time from randomization to first date of distant metastasis or death (TTDM) | Up to 5 years after first patient randomized | Time from randomization to first date of distant metastasis or death (TTDM) |
| Time from randomization to start date of first subsequent therapy (TFST) | Up to 9 years after first patient randomized | Time from randomization to start date of first subsequent therapy (TFST) |
| Progression free survival (PFS) as assessed by Investigator | Up to 5 years after first patient randomized | Progression free survival (PFS) as assessed by Investigator |
| IHC analysis of PD-L1 TC expression | Up to 5 years after first patient randomized | IHC analysis of PD-L1 TC expression relative to efficacy outcomes |
| Concentration of Durvalumab | From date of randomization until 3 months after date of last IP dose | To assess the Pharmacokinetics of Durvalumab when in combination with Monalizumab or Oleclumab - serum peak and trough concentrations |
| Anti-drug antibodies (ADAs) | From date of randomization until 3 months after date of last IP dose | The immunogenicity of durvalumab, oleclumab, and monalizumab as assessed by presence of anti-drug antibodies (ADAs) |
| Time to deterioration in pulmonary symptoms (TTFCD) | Up to 5 years after last patient randomized | Time to deterioration in pulmonary symptoms (TTFCD) |
| Concentration of Oleclumab | From date of randomization until 3 months after last dose of IP | To assess the Pharmacokinetics of Oleclumab when in combination with Durvulumab - serum peak and trough concentrations |
| Concentration of Monalizumab | From date of randomization until 3 months after last dose of IP | To assess the Pharmacokinetics of Monalizumab when in combination with Durvalumab - serum peak and trough concentrations |
Countries
Australia, Brazil, Canada, China, Colombia, France, Germany, Italy, Japan, Peru, Poland, Portugal, South Korea, Spain, Taiwan, Thailand, Turkey (Türkiye), United Kingdom, United States, Vietnam
Contacts
PRINCIPAL_INVESTIGATORFabrice Barlesi, MD
Gustave Roussy, Cancer Campus, Grand Paris
Outcome results
None listed