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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Non-Small Cell Lung Cancer | Drug: Durvalumab Drug: Oleclumab Drug: Monalizumab Other: Placebo | Phase 3 |
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| Study Type : | Interventional (Clinical Trial) |
| EstimatedEnrollment : | 999 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Masking Description: | Double-Blind |
| Primary Purpose: | Treatment |
| Official Title: | A Phase III, Double-blind, Placebo-controlled, Randomised, Multicentre, International Study of Durvalumab Plus Oleclumab and Durvalumab Plus Monalizumab in Patients With Locally Advanced (Stage III), Unresectable Non-small Cell Lung Cancer (NSCLC) Who Have Not Progressed Following Definitive, Platinum-Based Concurrent Chemoradiation Therapy |
| Actual Study Start Date : | February 7, 2022 |
| Estimated Primary Completion Date : | May 29, 2026 |
| Estimated Study Completion Date : | May 31, 2030 |
Resource links provided by the National Library of Medicine 
MedlinePlus Genetics related topics: Lungcancer
MedlinePlus related topics: LungCancer
Drug Information available for: Durvalumab
U.S. FDA Resources
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| Arm | Intervention/treatment |
|---|---|
| Experimental: Arm A: Durvalumab and Oleclumab Durvalumab on Day 1 of each 28-day cycle + Oleclumab on Days 1 and 15 of cycles 1 and 2, then on Day 1 of each subsequent 28-day cycle for up to 12 months | Drug: Durvalumab Durvalumab IV (intravenous infusion) Drug: Oleclumab Oleclumab IV (intravenous infusion) |
| Experimental: Arm B: Durvalumab and Monalizumab Durvalumab + Monalizumab on Day 1 of each 28-day cycle for up to 12 months. Placebo infusion will be administered on Day 15 of cycles 1 and 2 only | Drug: Durvalumab Durvalumab IV (intravenous infusion) Drug: Monalizumab Monalizumab IV (intravenous infusion) Other: Placebo Placebo IV (intravenous infusion) |
| Active Comparator: Arm C: Durvalumab and Placebo Durvalumab on Day 1 of each 28-day cycle + Placebo on Days 1 and 15 of cycles 1 and 2, then on Day 1 of each subsequent 28-day cycle for up to 12 months | Drug: Durvalumab Durvalumab IV (intravenous infusion) Other: Placebo Placebo IV (intravenous infusion) |
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Primary Outcome Measures :
- Progression Free Surival (PFS) [TimeFrame:Up to 5 years after first patient randomized.]
Progression Free Survival (PFS) as assessed by BICR, per RECIST 1.1.
Secondary Outcome Measures :
- Overall Survival (OS) [TimeFrame:Up to 9 years after first patient randomized]
Overall survival (OS)
- Objective response rate (ORR) [TimeFrame: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 [TimeFrame:Up to 9 years after first patient randomized]
Overall survival (OS) at 24 months
- Duration of response (DoR) [TimeFrame: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 [TimeFrame: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) [TimeFrame: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) [TimeFrame: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) [TimeFrame: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 [TimeFrame:Up to 5 years after first patient randomized]
Progression free survival (PFS) as assessed by Investigator
- IHC analysis of PD-L1 TC expression [TimeFrame:Up to 5 years after first patient randomized]
IHC analysis of PD-L1 TC expression relative to efficacy outcomes
- Concentration of Durvalumab [TimeFrame:From date of randomization until 3 months after date of last IP dose]
To assess the Pharmaco*kinetics of Durvalumab when in combination with Monalizumab or Oleclumab - serum peak and trough concentrations
- Anti-drug antibodies (ADAs) [TimeFrame: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) [TimeFrame:Up to 5 years after last patient randomized]
Time to deterioration in pulmonary symptoms (TTFCD)
- Concentration of Oleclumab [TimeFrame:From date of randomization until 3 months after last dose of IP]
To assess the Pharmaco*kinetics of Oleclumab when in combination with Durvulumab - serum peak and trough concentrations
- Concentration of Monalizumab [TimeFrame:From date of randomization until 3 months after last dose of IP]
To assess the Pharmaco*kinetics of Monalizumab when in combination with Durvalumab - serum peak and trough concentrations
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Information from the National Library of Medicine
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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 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.
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Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05221840
Contacts
| Contact: AstraZeneca Clinical Study Information Center | 1-877-240-9479 | information.center@astrazeneca.com |
Locations
Show 233 study locations
Sponsors and Collaborators
AstraZeneca
Investigators
| Principal Investigator: | Fabrice Barlesi, MD | Gustave Roussy, Cancer Campus, Grand Paris |
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Additional Information:
Lung Cancer Study Locator details 
| Responsible Party: | AstraZeneca |
| ClinicalTrials.gov Identifier: | NCT05221840 |
| Other Study ID Numbers: | D9078C00001 2023-503999-24-00 ( Registry Identifier: Clinical Trial Information System (CTIS) ) 2021-004346-37 ( EudraCT Number ) |
| First Posted: | February 3, 2022 Key Record Dates |
| Last Update Posted: | May 17, 2024 |
| Last Verified: | May 2024 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared. |
| Supporting Materials: | Study Protocol Statistical Analysis Plan (SAP) |
| Time Frame: | AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. |
| Access Criteria: | When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. |
| URL: | https://astrazenecagroup-dt.pharmacm.com/DT/Home |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by AstraZeneca:
| Non-Small Cell Lung Cancer Locally Advanced NSCLC |
Additional relevant MeSH terms:
| Lung Neoplasms Carcinoma, Non-Small-Cell Lung Respiratory Tract Neoplasms Thoracic Neoplasms Neoplasms by Site Neoplasms Lung Diseases | Respiratory Tract Diseases Carcinoma, Bronchogenic Bronchial Neoplasms Durvalumab Antineoplastic Agents, Immunological Antineoplastic Agents |
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