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)

Non-small Cell Lung Cancer Clinical Trial

— 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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05925530
• Other study ID #: D9106C00002
• Status: Recruiting
• Phase: Phase 2
• Start date: February 22, 2024
• Est. completion date: August 27, 2027

Study information

• Verified date: February 2024
• Source: AstraZeneca
• Contact: AstraZeneca Clinical Study Information Center
• Phone: 1-877-240-9479
• Email: information.center[@]astrazeneca.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 140
• Est. completion date: August 27, 2027
• Est. primary completion date: April 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 130 Years

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-small Cell Lung Cancer

Intervention

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.

Locations

Country	Name	City	State
Austria	Research Site	Klagenfurt
Austria	Research Site	Wien
Austria	Research Site	Wien
Canada	Research Site	Kelowna	British Columbia
Canada	Research Site	Kingston	Ontario
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Montreal	Quebec
Czechia	Research Site	Brno
Czechia	Research Site	Olomouc
Czechia	Research Site	Prague
Czechia	Research Site	Praha 5
France	Research Site	Brest Cedex
France	Research Site	La Tronche
France	Research Site	Marseille
France	Research Site	Montpellier
France	Research Site	Paris Cedex 5
France	Research Site	Poitiers
France	Research Site	Rouen
France	Research Site	Toulouse
France	Research Site	Vesoul
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Esslingen
Germany	Research Site	Gauting
Germany	Research Site	Grosshansdorf
Germany	Research Site	Köln
Germany	Research Site	Luebeck
Germany	Research Site	Moers
Germany	Research Site	München
Germany	Research Site	Offenbach am Main
Germany	Research Site	Wuerzburg
Hungary	Research Site	Törökbálint
Italy	Research Site	Bari
Italy	Research Site	Bologna
Italy	Research Site	Milan
Italy	Research Site	Milano
Italy	Research Site	Napoli
Italy	Research Site	Palermo
Italy	Research Site	Pavia
Italy	Research Site	Peschiera Del Garda
Italy	Research Site	Treviso
Portugal	Research Site	Lisboa
Portugal	Research Site	Lisboa
Portugal	Research Site	Vila Nova De Gaia
Spain	Research Site	Barakaldo
Spain	Research Site	Barcelona
Spain	Research Site	L'Hospitalet de Llobregat
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Valencia
Spain	Research Site	Zaragoza
Sweden	Research Site	Lund
United States	Research Site	Charlottesville	Virginia
United States	Research Site	Chicago	Illinois
United States	Research Site	Saint Petersburg	Florida

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Austria,  Canada,  Czechia,  France,  Germany,  Hungary,  Italy,  Portugal,  Spain,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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 )
Secondary	R0, R1, R2 resection rates	The R0, R1, and R2 resection rates 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)
Secondary	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)
Secondary	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)
Secondary	Overall Survival (OS) rate	The proportion of participants alive at 12 and 24 months.	At 12 months and 24 months
Secondary	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)
Secondary	Event-free survival (EFS) rate	The proportion of participants alive and event-free at 12 and 24 months.	At 12 months and 24 months
Secondary	Progression Free Survival (PFS)	PFS is defined as the time from the first dose of study intervention to 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)
Secondary	Progression Free Survival (PFS) rate	The proportion of participants alive without disease progression at 12 and 24 months.	At 12 months and 24 months
Secondary	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 Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.	From first dose of study intervention until death, surgery/start of CRT
Secondary	ORR after definitive CRT	ORR is defined as the proportion of participants who have unconfirmed complete response or partial response as assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.	From MDT decision timepoint (baseline for this endpoint) until the first tumour assessment after definitive CRT
Secondary	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]
Secondary	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
Secondary	Surgical safety: Surgical delays	Time from last neoadjuvant treatment dose to surgery.	Time from last neoadjuvant treatment dose to surgery
Secondary	Surgical safety: Duration of surgical procedure	Time from start of surgery to end of surgery.	Time from start of surgery to end of surgery
Secondary	Surgical safety: Length of hospital stay	Time from the beginning of the surgery/procedure to the discharge of hospital.	Time from the beginning of the surgery/procedure to the discharge of hospital
Secondary	Surgical safety: Intended surgical approach	Intended surgical approach at baseline (minimally invasive vs open thoracotomy).	At baseline
Secondary	Surgical safety: Actual surgical approach	Actual surgical approach (minimally invasive vs open thoracotomy).	At surgery
Secondary	Surgical safety: Intended surgical procedure	Intended surgical procedure (lobectomy vs bilobectomy vs sleeve resection vs pneumonectomy).	At baseline
Secondary	Surgical safety: Actual surgical procedure	Actual surgical procedure (lobectomy vs bilobectomy vs sleeve resection vs pneumonectomy)	At surgery