Study to Assess Neoadjuvant Durvalumab (D) and Platinum-Based Chemotherapy (CT), Followed by Either Surgery and Adjuvant D or CRT and Consolidation D, in Resectable or Borderline Resectable Stage IIB-IIIB NSCLC (MDT-BRIDGE) (MDT-BRIDGE)

A Multicentre, Phase II, Single-Arm, Interventional Study of Neoadjuvant Durvalumab and Platinum-based Chemotherapy (CT), Followed by Either Surgery and Adjuvant Durvalumab or Chemoradiotherapy (CRT) and Consolidation Durvalumab, in Participants With Resectable or Borderline Resectable Stage IIB-IIIB Non-small Cell Lung Cancer (NSCLC)

The purpose of this study is to assess efficacy and safety of neoadjuvant durvalumab in combination with platinum-based chemotherapy (CT) given as initial therapy after cancer diagnosis followed by either surgery and adjuvant durvalumab or chemoradiotherapy (CRT) and consolidation durvalumab given alone as further therapy in participants with resectable and borderline resectable stage IIB-IIIB NSCLC.

Study Overview

• Status: Active, not recruiting
• Conditions: Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: Durvalumab

Detailed Description

This will be a multicentre, Phase II, single-arm, global study assessing the efficacy and safety of neoadjuvant durvalumab and platinum-based CT, given intravenously, followed by either surgery and adjuvant durvalumab or definitive CRT and consolidation durvalumab in participants with resectable and borderline resectable stage IIB-IIIB NSCLC.

Neoadjuvant Period A:

All participants will initially receive 2 cycles of neoadjuvant durvalumab + CT (investigator's choice platinum-based) every three weeks. Participants will be assessed for resectability by a multidisciplinary team.

Neoadjuvant Period B:

Cohort 1: Participants who are deemed eligible for surgery will receive study intervention every three weeks for an additional one and up to two cycles, followed by surgery.

CRT:

Cohort 2: Participants with unresectable tumours (according to MDT re-assessment) will receive definitive CRT (6 one-week cycles) for approximately six weeks.

Both cohorts will then go on to receive durvalumab every four weeks until disease progression or recurrence or up to one year.

• Study Type: Interventional
• Enrollment (Actual): 142
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, 1130
    • Research Site
  • Vienna, Austria, 1140
    • Research Site
• Canada
  • Ontario
    • Kingston, Ontario, Canada, K7L 2V7
      • Research Site
  • Quebec
    • Chicoutimi, Quebec, Canada, G7H 5H6
      • Research Site
    • Montreal, Quebec, Canada, H4A 3J1
      • Research Site
• Czechia
  • Brno, Czechia, 625 00
    • Research Site
  • Olomouc, Czechia, 77900
    • Research Site
  • Prague, Czechia, 12808
    • Research Site
  • Prague, Czechia, 150 06
    • Research Site
• France
  • La Tronche, France, 38700
    • Research Site
  • Marseille, France, 13008
    • Research Site
  • Montpellier, France, 34295
    • Research Site
  • Mulhouse, France, 68070
    • Research Site
  • Paris, France, 75005
    • Research Site
  • Pessac, France, 33604
    • Research Site
  • Poitiers, France, 86000
    • Research Site
  • Toulouse, France, 31059
    • Research Site
• Germany
  • Berlin, Germany, 13125
    • Research Site
  • Cologne, Germany, 51109
    • Research Site
  • Großhansdorf, Germany, 22927
    • Research Site
  • Moers, Germany, 47441
    • Research Site
  • Würzburg, Germany, 97074
    • Research Site
• Hungary
  • Budapest, Hungary, 1122
    • Research Site
  • Törökbálint, Hungary, 2045
    • Research Site
• Italy
  • Bari, Italy, 70124
    • Research Site
  • Bologna, Italy, 40138
    • Research Site
  • Milan, Italy, 20141
    • Research Site
  • Milan, Italy, 20132
    • Research Site
  • Milan, Italy, 20133
    • Research Site
  • Naples, Italy, 80131
    • Research Site
  • Palermo, Italy, 90127
    • Research Site
  • Pavia, Italy, 27100
    • Research Site
  • Peschiera del Garda, Italy, 37019
    • Research Site
• Portugal
  • Lisbon, Portugal, 1500-650
    • Research Site
  • Lisbon, Portugal, 1350-352
    • Research Site
• Spain
  • Barakaldo, Spain, 48903
    • Research Site
  • Barcelona, Spain, 08025
    • Research Site
  • L'Hospitalet de Llobregat, Spain, 08908
    • Research Site
  • Madrid, Spain, 28046
    • Research Site
  • Madrid, Spain, 28027
    • Research Site
  • Madrid, Spain, 28007
    • Research Site
  • Pamplona, Spain, 31008
    • Research Site
  • Valencia, Spain, 46009
    • Research Site
  • Zaragoza, Spain, 50009
    • Research Site
• Sweden
  • Solna, Sweden, 171 64
    • Research Site
  • Uppsala, Sweden, SE-751 85
    • Research Site
• United States
  • New York
    • The Bronx, New York, United States, 10467
      • Research Site
  • Texas
    • Houston, Texas, United States, 77030
      • Research Site
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Deemed resectable or borderline resectable at baseline, confirmed by MDT evaluation at diagnosis.
• Previously untreated and pathologically confirmed Stage IIB to select [i.e.N2] Stage IIIB by AJCC v8.
• Nodal status confirmed with whole body FDG-PET and biopsy via endobronchial ultrasound, mediastinoscopy, or thoracoscopy.
• Mandatory brain MRI.
• EGFR and ALK wild-type.
• Medically operable: adequate cardiac and lung function to undergo resection.
• Participant must be ≥ 18 years, at the time of screening.
• Histologically or cytologically documented NSCLC.
• Minimum life expectancy of 12 weeks.
• Minimum body weight of 30 kg.
• Male and female participants must be willing to use acceptable methods of contraception.
• Female participants of childbearing potential must have negative pregnancy test.

Exclusion Criteria:

• Unresectable NSCLC confirmed by MDT evaluation at baseline
• Stage IIIC patients
• Participants whose planned surgery at enrollment is a wedge resection
• Known EGFR mutation or ALK translocation
• Participants contraindicated for surgical intervention due to comorbid conditions
• Participants who are allergic to study intervention.
• Participants with more than one primary tumour.
• Known active hepatitis infection, positive HCV antibody, HBsAg or HBV core antibody (anti-HBc), at screening.
• Female participants who are pregnant or breastfeeding.
• Judgement by the investigator that the participant should not participate in the study.
• Previously infected or tested positive for human immunodeficiency virus.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Durvalumab; Durvalumab will be administered to the participants via intravenous infusion (IV)

Drug: Durvalumab; Participants that go on to receive surgery, will receive durvalumab for up to four cycles prior to surgery. Participants that go on to receive CRT will receive durvalumab for up to two cycles prior to CRT. All participants will receive durvalumab every four weeks until disease progression or recurrence or up to 12 months following surgery/CRT, unless there is unacceptable toxicity, withdrawal of consent, or another discontinuation criterion is met.; Other Names: MEDI4736

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Resection rate	Resection rate is defined as the proportion of all participants who underwent definitive surgery. Participants who undergo (ie, start) surgery with the goal of complete tumour resection will be counted as meeting this endpoint.	At day of surgery (Within 40 days of the last dose of neoadjuvant treatment)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological complete response (pCR)	pCR will be defined as the proportion of participants who undergo surgery and have 0% residual viable tumour cells in resected lung and lymph nodes.	At the day of surgery (within 40 days after the last dose of neoadjuvant treatment)
Overall Survival (OS)	OS will be defined as the time from first dose of study intervention until the date of death due to any cause.	From first dose of study intervention until death, withdrawal of consent, or the end of the study (approximately 3.5 years)
Overall Survival (OS) rate	The proportion of participants alive at 12 and 24 months.	At 12 months and 24 months
Event-free survival (EFS)	EFS is defined as the time from the first dose of study intervention to any of the following events: PD that precludes surgery, progression or recurrence of disease after surgery, PD in the absence of surgery, disease progression, recurrence, or death due to any cause.	From first dose of study intervention until progression of disease (PD), recurrence or death, withdrawal of consent, or the end of the study (approximately 3.5 years)
Event-free survival (EFS) rate	The proportion of participants alive and event-free at 12 and 24 months.	At 12 months and 24 months
Progression Free Survival (PFS) rate	The proportion of participants alive without disease progression at 12 and 24 months.	At 12 months and 24 months
Percentage of all participants with circulating tumor DNA (ctDNA) clearance	Circulating tumour DNA clearance (ie, cMR) will be defined as a change from detectable ctDNA to undetectable ctDNA (ctDNA concentration less than limit of detection) at specified timepoints. The percentage of all biomarker-evaluable participants with ctDNA clearance will be assessed.	From Cycle 1 Day 1 up to pre-surgery/CRT (within 7 to 14 days pre-surgery/CRT) [Each cycle is of 3 weeks]
Number of participants with adverse events	Safety and tolerability will be evaluated in terms of adverse events and serious adverse events.	From enrollment up to at least 90 days after last dose of study intervention
Surgical safety: Intended surgical approach	Intended surgical approach at baseline (minimally invasive vs open thoracotomy).	At baseline
Surgical safety: Actual surgical approach	Actual surgical approach (minimally invasive vs open thoracotomy).	At surgery
Surgical safety: Intended surgical procedure	Intended surgical procedure (lobectomy vs bilobectomy vs sleeve resection vs pneumonectomy).	At baseline
Surgical safety: Actual surgical procedure	Actual surgical procedure (lobectomy vs bilobectomy vs sleeve resection vs pneumonectomy)	At surgery
Resection rate	Resection rate will be further assessed separately in participants deemed resectable at baseline and participants deemed borderline resectable at baseline.	At the day of surgery (within 40 days after the last dose of neoadjuvant treatment)
R0, R1, R2 resection rates	The R0, R1, and R2 resection rates (assessed separately) are defined as the proportion of resected participants with resection margins assessed as R0, R1, and R2 respectively. R0 corresponds to resection for cure or complete remission, R1 to microscopic residual tumour, R2 to macroscopic residual tumour.	At the day of surgery (within 40 days after the last dose of neoadjuvant treatment)
Progression Free Survival (PFS)	PFS is defined as the time from the first dose of study intervention to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.-defined PD, as assessed by the investigator, or death due to any cause.	From first dose of study intervention until disease progression, death, withdrawal of consent, or the end of the study (approximately 3.5 years)
Objective response rate (ORR) pre-surgery/pre-chemoradiotherapy (CRT)	ORR is defined as the proportion of participants who have unconfirmed complete response or partial response as assessed by the investigator per RECIST 1.1.	From first dose of study intervention until death, surgery/start of CRT
ORR during study intervention and definitive CRT	ORR is defined as the proportion of participants who have unconfirmed complete response or partial response as assessed by the investigator per RECIST 1.1.	From MDT re-assessment timepoint (baseline for this endpoint) until the first tumour assessment after definitive CRT
Surgical safety: Duration of surgical procedure	The safety of study intervention will be evaluated from start to end of surgery	Time from start of surgery to end of surgery
Surgical safety: Length of post operative hospital stay	The safety of study intervention will be evaluated during post operative hospital stay	Time from the beginning of the surgery/procedure to the discharge of hospital
Number of participants with delayed surgery	The safety of study intervention will be evaluated for participants with delayed surgery	40 days after last dose of study intervention to surgery
Surgical safety: Length of surgical delays	The safety of study intervention will be evaluated during the length of the surgical delay	40 days after last dose of study intervention to surgery
Number of participants with reason of surgical delay	The safety of study intervention will be evaluated for participants with reason of surgical delay	40 days after last dose of study intervention to surgery
Time from last neoadjuvant dose to surgery	The safety of the study intervention will be evaluated from last neoadjuvant dose to surgery	Time from last neoadjuvant dose of study intervention to surgery

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): February 22, 2024
• Primary Completion (Actual): January 12, 2026
• Study Completion (Estimated): August 27, 2027

Study Registration Dates

• First Submitted: June 22, 2023
• First Submitted That Met QC Criteria: June 22, 2023
• First Posted (Actual): June 29, 2023

Study Record Updates

• Last Update Posted (Actual): April 16, 2026
• Last Update Submitted That Met QC Criteria: April 15, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Surgery; Neoadjuvant; Adjuvant; Chemoradiotherapy; Durvalumab; Consolidation; Multidisciplinary team (MDT)
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; Antineoplastic Agents, Immunological; Antineoplastic Agents; durvalumab
• Other Study ID Numbers: D9106C00002; 2023-503357-35-00 (Registry Identifier: CTIS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD 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 Vivli.org. 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 approved.

IPD Sharing Time Frame

AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA/PhRMA Data-Sharing Principles. For details of our timelines, please refer to our disclosure commitment at

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No