Non-small Cell Lung Cancer
Conditions
Keywords
Neoadjuvant, Durvalumab, Chemoradiotherapy, Surgery, Adjuvant, Consolidation, Multidisciplinary team (MDT)
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.
Interventions
DRUGDurvalumab
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.
Sponsors
AstraZeneca
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 130 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 underwent definitive surgery. Participants who undergo (ie, start) surgery with the goal of complete tumour resection will be counted as meeting this endpoint. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 (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. |
| 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 Response Evaluation Criteria in Solid Tumors (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 unconfirmed complete response or partial response as assessed by the investigator per RECIST 1.1. |
| ORR during study intervention and definitive CRT | From MDT re-assessment timepoint (baseline for this endpoint) until the first tumour assessment 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 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 biomarker-evaluable participants with ctDNA clearance will be assessed. |
| Number of participants with adverse events | From enrollment 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: Duration of surgical procedure | Time from start of surgery to end of surgery | The safety of study intervention will be evaluated from start to end of surgery |
| Surgical safety: Length of post operative hospital stay | Time from the beginning of the surgery/procedure to the discharge of hospital | The safety of study intervention will be evaluated during post operative hospital stay |
| Surgical safety: Intended surgical approach | At baseline | Intended surgical approach at baseline (minimally invasive vs open thoracotomy). |
| Surgical safety: Actual surgical approach | At surgery | Actual surgical approach (minimally invasive vs open thoracotomy). |
| Surgical safety: Intended surgical procedure | At baseline | Intended surgical procedure (lobectomy vs bilobectomy vs sleeve resection vs pneumonectomy). |
| Surgical safety: Actual surgical procedure | At surgery | Actual surgical procedure (lobectomy vs bilobectomy vs sleeve resection vs pneumonectomy) |
| Number of participants with delayed surgery | 40 days after last dose of study intervention to surgery | The safety of study intervention will be evaluated for participants with delayed surgery |
| Surgical safety: Length of surgical delays | 40 days after last dose of study intervention to surgery | The safety of study intervention will be evaluated during the length of the surgical delay |
| Number of participants with reason of surgical delay | 40 days after last dose of study intervention to surgery | The safety of study intervention will be evaluated for participants with reason of surgical delay |
| Time from last neoadjuvant dose to surgery | Time from last neoadjuvant dose of study intervention to surgery | The safety of the study intervention will be evaluated from last neoadjuvant dose to surgery |
Countries
Austria, Canada, Czechia, France, Germany, Hungary, Italy, Portugal, Spain, Sweden, United States
Outcome results
None listed