Clinical trial NCT05925530: 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)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Non-small Cell Lung Cancer
Keywords: Neoadjuvant
Durvalumab
Chemoradiotherapy
Surgery
Adjuvant
Consolidation
Multidisciplinary team (MDT)
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2023-06-29
Enrollment: 140
Sex: ALL
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Resection rate
timeFrame: At day of surgery (Within 40 days of the last dose of neoadjuvant treatment)
Secondary outcomes:
measure: Resection rate
timeFrame: At the day of surgery (within 40 days after the last dose of neoadjuvant treatment)
measure: R0, R1, R2 resection rates
timeFrame: At the day of surgery (within 40 days after the last dose of neoadjuvant treatment)
measure: Pathological complete response (pCR)
timeFrame: At the day of surgery (within 40 days after the last dose of neoadjuvant treatment)
measure: Overall Survival (OS)
timeFrame: From first dose of study intervention until death, withdrawal of consent, or the end of the study (approximately 3.5 years)
measure: Overall Survival (OS) rate
timeFrame: At 12 months and 24 months
measure: Event-free survival (EFS)
timeFrame: 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)
measure: Event-free survival (EFS) rate
timeFrame: At 12 months and 24 months
measure: Progression Free Survival (PFS)
timeFrame: From first dose of study intervention until disease progression, death, withdrawal of consent, or the end of the study (approximately 3.5 years)
measure: Progression Free Survival (PFS) rate
timeFrame: At 12 months and 24 months
measure: Objective response rate (ORR) pre-surgery/pre-chemoradiotherapy (CRT)
timeFrame: From first dose of study intervention until death, surgery/start of CRT
measure: ORR during study intervention and definitive CRT
timeFrame: From MDT re-assessment timepoint (baseline for this endpoint) until the first tumour assessment after definitive CRT
measure: Percentage of all participants with circulating tumor DNA (ctDNA) clearance
timeFrame: From Cycle 1 Day 1 up to pre-surgery/CRT (within 7 to 14 days pre-surgery/CRT) [Each cycle is of 3 weeks]
measure: Number of participants with adverse events
timeFrame: From enrollment up to at least 90 days after last dose of study intervention
measure: Surgical safety: Duration of surgical procedure
timeFrame: Time from start of surgery to end of surgery
measure: Surgical safety: Length of post operative hospital stay
timeFrame: Time from the beginning of the surgery/procedure to the discharge of hospital
measure: Surgical safety: Intended surgical approach
timeFrame: At baseline
measure: Surgical safety: Actual surgical approach
timeFrame: At surgery
measure: Surgical safety: Intended surgical procedure
timeFrame: At baseline
measure: Surgical safety: Actual surgical procedure
timeFrame: At surgery
measure: Number of participants with delayed surgery
timeFrame: 40 days after last dose of study intervention to surgery
measure: Surgical safety: Length of surgical delays
timeFrame: 40 days after last dose of study intervention to surgery
measure: Number of participants with reason of surgical delay
timeFrame: 40 days after last dose of study intervention to surgery
measure: Time from last neoadjuvant dose to surgery
timeFrame: Time from last neoadjuvant dose of study intervention to surgery
Other outcomes:
Locations:
city: Duarte
country: United States
facility: Research Site
state: California
city: Stuart
country: United States
facility: Research Site
state: Florida
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Bronx
country: United States
facility: Research Site
state: New York
city: Durham
country: United States
facility: Research Site
state: North Carolina
city: Houston
country: United States
facility: Research Site
state: Texas
city: Charlottesville
country: United States
facility: Research Site
state: Virginia
city: Klagenfurt
country: Austria
facility: Research Site
city: Wien
country: Austria
facility: Research Site
city: Wien
country: Austria
facility: Research Site
city: Kelowna
country: Canada
facility: Research Site
state: British Columbia
city: Kingston
country: Canada
facility: Research Site
state: Ontario
city: Chicoutimi
country: Canada
facility: Research Site
state: Quebec
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Brno
country: Czechia
facility: Research Site
city: Olomouc
country: Czechia
facility: Research Site
city: Prague
country: Czechia
facility: Research Site
city: Praha 5
country: Czechia
facility: Research Site
city: Brest Cedex
country: France
facility: Research Site
city: La Tronche
country: France
facility: Research Site
city: Marseille
country: France
facility: Research Site
city: Montpellier
country: France
facility: Research Site
city: Mulhouse
country: France
facility: Research Site
city: Paris Cedex 5
country: France
facility: Research Site
city: Pessac
country: France
facility: Research Site
city: Poitiers
country: France
facility: Research Site
city: Rouen
country: France
facility: Research Site
city: Toulouse
country: France
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Esslingen
country: Germany
facility: Research Site
city: Gauting
country: Germany
facility: Research Site
city: Grosshansdorf
country: Germany
facility: Research Site
city: Heidelberg
country: Germany
facility: Research Site
city: Köln
country: Germany
facility: Research Site
city: Luebeck
country: Germany
facility: Research Site
city: Moers
country: Germany
facility: Research Site
city: München
country: Germany
facility: Research Site
city: Offenbach am Main
country: Germany
facility: Research Site
city: Wuerzburg
country: Germany
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Törökbálint
country: Hungary
facility: Research Site
city: Bari
country: Italy
facility: Research Site
city: Bologna
country: Italy
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Milan
country: Italy
facility: Research Site
city: Napoli
country: Italy
facility: Research Site
city: Padova
country: Italy
facility: Research Site
city: Palermo
country: Italy
facility: Research Site
city: Pavia
country: Italy
facility: Research Site
city: Peschiera Del Garda
country: Italy
facility: Research Site
city: Treviso
country: Italy
facility: Research Site
city: Lisboa
country: Portugal
facility: Research Site
city: Lisboa
country: Portugal
facility: Research Site
city: Vila Nova De Gaia
country: Portugal
facility: Research Site
city: Barakaldo
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: L'Hospitalet de Llobregat
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Pamplona
country: Spain
facility: Research Site
city: Valencia
country: Spain
facility: Research Site
city: Zaragoza
country: Spain
facility: Research Site
city: Lund
country: Sweden
facility: Research Site
city: Solna
country: Sweden
facility: Research Site
city: Uppsala
country: Sweden
facility: Research Site
Study officials:
References: