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.
Brief Title
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)
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.
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.
Categories
Central Contacts
Central Contact Role
Contact
Central Contact Phone
1-877-240-9479
Central Contact Email
information.center@astrazeneca.com
Completion Date
Completion Date Type
Estimated
Conditions
Non-small Cell Lung Cancer
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.
* 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.
Inclusion 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.
* 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.
Gender
All
Gender Based
false
Keywords
Neoadjuvant
Durvalumab
Chemoradiotherapy
Surgery
Adjuvant
Consolidation
Multidisciplinary team (MDT)
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
130 Years
Minimum Age
18 Years
NCT Id
NCT05925530
Org Class
Industry
Org Full Name
AstraZeneca
Org Study Id
D9106C00002
Overall Status
Recruiting
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Estimated
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)
Primary Outcomes
Outcome Description
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.
Outcome Measure
Resection rate
Outcome Time Frame
At day of surgery (Within 40 days of the last dose of neoadjuvant treatment)
Secondary Ids
Secondary Id
2023-503357-35-00
Secondary Outcomes
Outcome Description
Resection rate will be further assessed separately in participants deemed resectable at baseline and participants deemed borderline resectable at baseline.
Outcome Time Frame
At the day of surgery (within 40 days after the last dose of neoadjuvant treatment)
Outcome Measure
Resection rate
Outcome Description
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.
Outcome Time Frame
At the day of surgery (within 40 days after the last dose of neoadjuvant treatment)
Outcome Measure
R0, R1, R2 resection rates
Outcome Description
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.
Outcome Time Frame
At the day of surgery (within 40 days after the last dose of neoadjuvant treatment)
Outcome Measure
Pathological complete response (pCR)
Outcome Description
OS will be defined as the time from first dose of study intervention until the date of death due to any cause.
Outcome Time Frame
From first dose of study intervention until death, withdrawal of consent, or the end of the study (approximately 3.5 years)
Outcome Measure
Overall Survival (OS)
Outcome Description
The proportion of participants alive at 12 and 24 months.
Outcome Time Frame
At 12 months and 24 months
Outcome Measure
Overall Survival (OS) rate
Outcome Description
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.
Outcome Time Frame
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)
Outcome Measure
Event-free survival (EFS)
Outcome Description
The proportion of participants alive and event-free at 12 and 24 months.
Outcome Time Frame
At 12 months and 24 months
Outcome Measure
Event-free survival (EFS) rate
Outcome Description
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.
Outcome Time Frame
From first dose of study intervention until disease progression, death, withdrawal of consent, or the end of the study (approximately 3.5 years)
Outcome Measure
Progression Free Survival (PFS)
Outcome Description
The proportion of participants alive without disease progression at 12 and 24 months.
Outcome Time Frame
At 12 months and 24 months
Outcome Measure
Progression Free Survival (PFS) rate
Outcome Description
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.
Outcome Time Frame
From first dose of study intervention until death, surgery/start of CRT
Outcome Measure
Objective response rate (ORR) pre-surgery/pre-chemoradiotherapy (CRT)
Outcome Description
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.
Outcome Time Frame
From MDT re-assessment timepoint (baseline for this endpoint) until the first tumour assessment after definitive CRT
Outcome Measure
ORR during study intervention and definitive CRT
Outcome Description
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.
Outcome Time Frame
From Cycle 1 Day 1 up to pre-surgery/CRT (within 7 to 14 days pre-surgery/CRT) [Each cycle is of 3 weeks]
Outcome Measure
Percentage of all participants with circulating tumor DNA (ctDNA) clearance
Outcome Description
Safety and tolerability will be evaluated in terms of adverse events and serious adverse events.
Outcome Time Frame
From enrollment up to at least 90 days after last dose of study intervention
Outcome Measure
Number of participants with adverse events
Outcome Description
The safety of study intervention will be evaluated from start to end of surgery
Outcome Time Frame
Time from start of surgery to end of surgery
Outcome Measure
Surgical safety: Duration of surgical procedure
Outcome Description
The safety of study intervention will be evaluated during post operative hospital stay
Outcome Time Frame
Time from the beginning of the surgery/procedure to the discharge of hospital
Outcome Measure
Surgical safety: Length of post operative hospital stay
Outcome Description
Intended surgical approach at baseline (minimally invasive vs open thoracotomy).
Outcome Time Frame
At baseline
Outcome Measure
Surgical safety: Intended surgical approach
Outcome Description
Actual surgical approach (minimally invasive vs open thoracotomy).
Outcome Time Frame
At surgery
Outcome Measure
Surgical safety: Actual surgical approach
Outcome Description
Intended surgical procedure (lobectomy vs bilobectomy vs sleeve resection vs pneumonectomy).
Outcome Time Frame
At baseline
Outcome Measure
Surgical safety: Intended surgical procedure
Outcome Description
Actual surgical procedure (lobectomy vs bilobectomy vs sleeve resection vs pneumonectomy)
Outcome Time Frame
At surgery
Outcome Measure
Surgical safety: Actual surgical procedure
Outcome Description
The safety of study intervention will be evaluated for participants with delayed surgery
Outcome Time Frame
40 days after last dose of study intervention to surgery
Outcome Measure
Number of participants with delayed surgery
Outcome Description
The safety of study intervention will be evaluated during the length of the surgical delay
Outcome Time Frame
40 days after last dose of study intervention to surgery
Outcome Measure
Surgical safety: Length of surgical delays
Outcome Description
The safety of study intervention will be evaluated for participants with reason of surgical delay
Outcome Time Frame
40 days after last dose of study intervention to surgery
Outcome Measure
Number of participants with reason of surgical delay
Outcome Description
The safety of the study intervention will be evaluated from last neoadjuvant dose to surgery
Outcome Time Frame
Time from last neoadjuvant dose of study intervention to surgery
Outcome Measure
Time from last neoadjuvant dose to surgery
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
130
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Brendon M Stiles
Investigator Email
brstiles@montefiore.org