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)

Sponsor

AstraZeneca (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05925530

Collaborator

(none)

140

Enrollment

Arm

41.9

Anticipated Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Non-small Cell Lung Cancer	Drug: Durvalumab	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

140 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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)

Anticipated Study Start Date :

Oct 16, 2023

Anticipated Primary Completion Date :

Apr 21, 2026

Anticipated Study Completion Date :

Apr 12, 2027

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Resection rate [At day of surgery (Within 40 days of the last dose of neoadjuvant treatment)]
Resection rate is defined as the proportion of all participants who completed all intended neoadjuvant therapy, MDT re-assessment, and definitive surgical resection of the primary tumour.

Secondary Outcome Measures

Resection rate [At the day of surgery (within 40 days after the last dose of neoadjuvant treatment )]
Resection rate will be further assessed separately in participants deemed resectable at baseline and participants deemed borderline resectable at baseline.
R0, R1, R2 resection rates [At the day of surgery (within 40 days after the last dose of neoadjuvant treatment)]
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.
Pathological complete response (pCR) [At the day of surgery (within 40 days after the last dose of neoadjuvant treatment)]
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.
Overall Survival (OS) [From first dose of study intervention until death, withdrawal of consent, or the end of the study (approximately 3.5 years)]
OS will be defined as the time from first dose of study intervention until the date of death due to any cause.
Overall Survival (OS) rate [At 12 months and 24 months]
The proportion of participants alive at 12 and 24 months.
Event-free survival (EFS) [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)]
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.
Event-free survival (EFS) rate [At 12 months and 24 months]
The proportion of participants alive and event-free at 12 and 24 months.
Progression Free Survival (PFS) [From first dose of study intervention until disease progression, death, withdrawal of consent, or the end of the study (approximately 3.5 years)]
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.
Progression Free Survival (PFS) rate [At 12 months and 24 months]
The proportion of participants alive without disease progression at 12 and 24 months.
Objective response rate (ORR) pre-surgery/pre-chemoradiotherapy (CRT) [From first dose of study intervention until death, surgery/start of CRT]
ORR is defined as the proportion of participants who have complete response or partial response (unconfirmed) as assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
ORR after definitive CRT [From MDT decision timepoint (baseline for this endpoint) until the first tumour assessment after definitive CRT]
ORR is defined as the proportion of participants who have complete response or partial response (unconfirmed) as assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
Percentage of all participants with circulating tumor DNA (ctDNA) clearance [From Cycle 1 Day 1 up to pre-surgery/CRT (within 7 to 14 days pre-surgery/CRT) [Each cycle is of 3 weeks]]
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 participants with ctDNA clearance will be assessed.
Number of participants with adverse events [From time of signature of the ICF up to at least 90 days after last dose of study intervention]
Safety and tolerability will be evaluated in terms of adverse events and serious adverse events.
Surgical safety: Surgical delays [Time from baseline MDT assessment to surgery]
Time from baseline MDT assessment to surgery.
Surgical safety: Duration of surgical procedure [Time from start of surgery to end of surgery]
Time from start of surgery to end of surgery.
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 will be assessed.
Surgical safety: Intention of surgical approach [At baseline]
Intention of surgical approach at baseline (minimally invasive vs open thoracotomy).
Surgical safety: Actual surgical procedure [At surgery]
Actual surgical procedure (minimally invasive vs open thoracotomy).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 130 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Deemed resectable or borderline resectable at baseline, confirmed by MDT evaluation at diagnosis.
Previously untreated 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.