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.

Age: 18 Years to 130 Years old

Gender: All

Start Date: 02/22/2024

Primary Completion Date (Estimated): 01/12/2026

Study Completion Date (Estimated): 08/27/2027

Accepts Healthy Volunteers: No

Trial Purpose and 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

Age: 18 Years to 130 Years old

Gender: All

Accepts 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.