Neoadjuvant durvalumab plus chemotherapy in resectable or borderline resectable non-small-cell lung cancer: the phase 2 MDT-BRIDGE trial
The phase 2 MDT-BRIDGE study is investigating perioperative durvalumab plus neoadjuvant chemotherapy (AEGEAN regimen) in resectable and borderline resectable non-small-cell lung cancer and chemoradiotherapy (CRT) followed by consolidation durvalumab (PACIFIC regimen) in patients who become unresectable after neoadjuvant chemoimmunotherapy guided by multidisciplinary team assessments during the neoadjuvant period. The primary endpoint was the overall resection rate (descriptive with no formal hypothesis testing). Secondary endpoints included event-free survival, progression-free survival, pathological complete response rate (resectable patients cohort), circulating tumor DNA clearance between baseline and presurgery/pre-CRT and safety. Overall, 142 patients received neoadjuvant treatment; 64.8% and 35.2% were deemed resectable and borderline resectable at baseline, respectively. The overall resection rate (95% confidence interval) was 74.6% (66.7‒81.6) in a population that included more than one-third of patients with borderline resectable disease. R0 resection rate was 96.2% (90.6‒99.0) in those who underwent surgery. Overall, 131 (92.3%) patients had surgery (n = 106) or CRT (n = 25) after neoadjuvant treatment, and 117 (82.4%) patients received adjuvant (n = 94) or consolidation (n = 23) durvalumab. During adjuvant or consolidation durvalumab, maximum grade 3/4 adverse events occurred in 7.4% of resected patients and 17.4% of CRT-treated patients, with 8.5% and 13.0% discontinuing treatment due to adverse events. This multidisciplinary team-guided approach was feasible and enabled delivery of curative-intent treatment (surgery or CRT), followed by durvalumab in most patients, and demonstrated encouraging preliminary efficacy with a manageable adjuvant or consolidation safety profile that was consistent with prior studies. ClinicalTrials.gov identifier: NCT05925530 . As presented at the ESMO Congress 2026: In the global phase 2 MDT-BRIDGE trial, neoadjuvant durvalumab plus chemotherapy in patients with resectable and borderline resectable non-small-cell lung cancer, followed by multidisciplinary reassessment, enabled surgery in most patients, leading to encouraging pathological complete response rates, and no additional safety concerns were reported when patients with unresectable tumors continued with chemoradiotherapy and consolidative durvalumab.
Authors
- Maximilian Diehn (ORCID: https://orcid.org/0000-0003-2032-0581)
- Ilaria Attili (ORCID: https://orcid.org/0000-0003-1333-6622)
- Ignacio Diaz Perez
- Ernest Nadal (ORCID: https://orcid.org/0000-0002-9674-5554)
- Andrea Riccardo Filippi (ORCID: https://orcid.org/0000-0001-7159-7869)
- Andrew Robinson (ORCID: https://orcid.org/0000-0003-3219-6936)
- Ugochinyere Emeribe (ORCID: https://orcid.org/0009-0000-8251-6163)
- Benoît Roch (ORCID: https://orcid.org/0000-0002-4064-7621)
- Andrea Ardizzoni (ORCID: https://orcid.org/0000-0003-2678-0714)
- David Allan Cairns (ORCID: https://orcid.org/0000-0002-2338-0179)
- Linda W. Martin (ORCID: https://orcid.org/0000-0002-7951-5677)
- Martin Reck (ORCID: https://orcid.org/0000-0002-5348-4462)
- Jonathan David Spicer (ORCID: https://orcid.org/0000-0003-2708-1309)
- Matteo Giaj Levra (ORCID: https://orcid.org/0000-0002-9015-6871)
- Carl Michael Gay (ORCID: https://orcid.org/0000-0002-4907-0718)
- Margarita Majem (ORCID: https://orcid.org/0000-0002-9919-7485)
- David Matthew Kurtz (ORCID: https://orcid.org/0000-0002-6382-4651)
- Cordula Petersen (ORCID: https://orcid.org/0000-0003-0754-7730)
- Davina Gillian Gale (ORCID: https://orcid.org/0000-0002-4521-8199)
- Rosa Maria Alvarez (ORCID: https://orcid.org/0000-0003-0935-8298)
- Nefeli Georgoulia
- Nicolas Girard (ORCID: https://orcid.org/0000-0002-7636-6688)
- Arnaud Boyer
- Zhou Zhu
Institutions
- AstraZeneca (United Kingdom) (GB)
- University of Leeds (GB)
- The University of Texas MD Anderson Cancer Center (US)
- University of Milan (IT)
- Université de Versailles Saint-Quentin-en-Yvelines (FR)
- Kingston General Hospital (CA)
- Cancer Research UK (GB)
- Hospital de Sant Pau (ES)
- Hospital General Universitario Gregorio Marañón (ES)
- Institut d'Investigació Biomédica de Bellvitge (ES)
- Centre Hospitalier Universitaire de Montpellier (FR)
- IRCCS Azienda Ospedliero-Universitaria di Bologna Policlinico di Sant'Orsola (IT)
- Institut Català d'Oncologia (ES)
- University Medical Center Hamburg-Eppendorf (DE)
- Hôpital Saint Joseph (FR)
- German Center for Lung Research (DE)
- Stanford Medicine (US)
- AstraZeneca (United States) (US)
- Fondazione IRCCS Istituto Nazionale dei Tumori (IT)
- Institut de Recerca Sant Pau (ES)
- McGill University (CA)
- University of Virginia (US)
- European Institute of Oncology (IT)
- Institut Curie (FR)
- University of Bologna (IT)
- Stanford University (US)
Publication Details
- Journal
- Nature Medicine
- Published
- 2026-10-26
- DOI
- https://doi.org/10.1038/s41591-026-04742-7
- Primary Topic
- Lung Cancer Diagnosis and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- AstraZeneca