115TiP - MDT-BRIDGE: A phase 2 study of neoadjuvant durvalumab (D) + chemotherapy (CT) followed by either surgery and adjuvant D or chemoradiotherapy (CRT) and consolidation D in patients (pts) with resectable or borderline resectable stage IIB-IIIB NSCLC

Background

In the phase 3 AEGEAN study, neoadjuvant D + platinum-based CT followed by adjuvant D, versus neoadjuvant CT alone, significantly improved pathological complete response (pCR) and event-free survival (EFS) in pts with resectable NSCLC. In the placebo-controlled phase 3 PACIFIC study, consolidation D significantly improved outcomes for pts with unresectable stage III NSCLC after CRT. The strong pathological and clinical outcomes seen with CT + immunotherapy (IO) have generated interest in its use to enable pts with borderline resectable NSCLC to undergo surgery (Sx). In parallel, for pts who are initially deemed resectable but later become unresectable/inoperable during neoadjuvant treatment (Tx), the safety and efficacy of initial neoadjuvant IO + CT, followed by CRT and consolidation IO should be explored. To inform clinical practice, MDT-BRIDGE (NCT05925530) assesses the efficacy and safety of neoadjuvant D + CT followed by either Sx and adjuvant D or CRT and consolidation D in pts with resectable/borderline resectable Stage IIB–IIIB NSCLC.

Trial Design

This is a global, phase 2, non-randomized study of pts aged ≥18 yr with ECOG PS 0/1 and histologically/cytologically confirmed, Tx-naïve, EGFR/ALK wild-type, Stage IIB to select IIIB [N2] NSCLC (AJCC 8th ed). Initially deemed resectable/borderline resectable by a multidisciplinary team (MDT), ∼140 pts will receive 2 cycles of neoadjuvant D + investigator’s choice platinum-based CT Q3W IV, followed by MDT assessment of resectability. Pts deemed resectable will receive a further 1–2 cycles of neoadjuvant D + CT followed by Sx (Cohort 1); pts deemed unresectable will receive CRT for ∼6 wk (Cohort 2). Pts in Cohort 1 who become ineligible for Sx can enter Cohort 2. After Sx/CRT, all pts will receive D Q4W IV for up to 1 yr. The primary endpoint is the resection rate in all pts. Secondary endpoints include resection rates in the subsets of pts deemed resectable or borderline resectable at baseline; R0, R1, and R2 resection outcomes; pCR; EFS; progression-free survival; overall survival; objective response rate; ctDNA clearance; and safety.

Clinical trial identification

NCT05925530 (Release date June 29, 2023).

Editorial acknowledgement

Medical writing support for this abstract, under the direction of the authors, was provided by Werner Gerber, PhD, (Fourways, South Africa) and Aaron Korpal, PhD, (Macclesfield, UK) of Ashfield MedComms, an Inizio Company, and was funded by AstraZeneca.

Legal entity responsible for the study

AstraZeneca, Sweden.

Funding

AstraZeneca.

Disclosure

M. Reck: Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, BMS, Boehringer Ingelheim, Daiichi Sankyo, GSK, Lilly, MSD, Merck, Mirati, Novartis, Pfizer, Roche, Regeneron, Sanofi; Financial Interests, Personal, Speaker’s Bureau: Amgen, AstraZeneca, BMS, Boehringer Ingelheim, Daiichi Sankyo, GSK, Lilly, MSD, Merck, Mirati, Novartis, Pfizer, Roche, Regeneron, Sanofi; Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, BMS, Boehringer Ingelheim, Daiichi Sankyo, GSK, Lilly, MSD, Merck, Mirati, Novartis, Pfizer, Roche, Regeneron, Sanofi; Non-Financial Interests, Personal and Institutional, Officer: ESMO; Non-Financial Interests, Institutional, Research Grant: BMS, Boehringer Ingelheim; Non-Financial Interests, Institutional, Principal Investigator: Amgen, AstraZeneca, BMS, Boehringer Ingelheim, Daiichi Sankyo, BeiGene, GSK, Lilly, MSD, Merck, Mirati, Novartis, Roche. E. Nadal: Financial Interests, Personal, Invited Speaker: Roche, Bristol Myers Squibb, Merck Sharp & Dohme, Merck Serono, Sanofi, Pfizer, Lilly, Amgen, Janssen, Daiichi Sankyo, Boehringer Ingelheim, AstraZeneca, Qiagen, Pierre Fabre, Takeda; Financial Interests, Personal, Advisory Board: Roche, Bristol Myers Squibb, Merck Sharp & Dohme, Sanofi, Pfizer, Lilly, Amgen, Janssen, Daiichi Sankyo, Boehringer Ingelheim, AstraZeneca, Qiagen, Pierre Fabre, Takeda, Bayer; Non-Financial Interests, Personal, Funding: Roche, Pfizer, Merck Serono, Bristol Myers Squibb. N. Girard: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, MSD, Roche, Pfizer, Mirati, Amgen, Novartis, Sanofi, Gilead; Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, MSD, Roche, Pfizer, Janssen, Boehringer, Novartis, Sanofi, AbbVie, Amgen, Lilly, Grunenthal, Takeda, Owkin, Leo Pharma, Daiichi Sankyo, Ipsen; Financial Interests, Institutional, Research Grant, Local: Roche, Sivan, Janssen; Financial Interests, Institutional, Funding: BMS, Leo Pharma; Financial Interests, Institutional, Research Grant: MSD; Non-Financial Interests, Personal, Officer, International Thymic malignancy interest group, president: ITMIG; Other, Personal, Other, Family member is an employee: AstraZeneca. A.R.R. Filippi: Financial Interests, Personal, Invited Speaker: AstraZeneca, Roche; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Research Grant: AstraZeneca; Financial Interests, Personal, Principal Investigator: AstraZeneca; Financial Interests, Personal, Advisory Role: Radiomics; Financial Interests, Personal, Funding: AstraZeneca, MSD, Roche. L.W. Martin: Financial Interests, Personal, Speaker’s Bureau: Genentech, Ethicon; Financial Interests, Personal, Advisory Board: AstraZeneca, Genentech; Non-Financial Interests, Personal, Officer: General Thoracic Surgical Club; Financial Interests, Personal, Full or part-time Employment: University of Virginia School of Medicine; Non-Financial Interests, Personal, Principal Investigator: Alliance Foundation Trial 46; Financial Interests, Personal, Advisory Role: OnTarget Laboratories; Non-Financial Interests, Personal, Leadership Role: Alliance for Clinical Trials. C.M. Gay: Financial Interests, Personal, Invited Speaker: Aptitude Health, Dava Oncology, MJH Healthcare, OncLive, Peer View Institute; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, BeiGene; Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Daiichi Sankyo, Jazz, MonteRosa; Financial Interests, Personal, Research Grant: AstraZeneca; Financial Interests, Personal, Advisory Role: AstraZeneca, Catalyst, Roche/Genentech, STCube. C. Petersen: Non-Financial Interests, Personal, Invited Speaker: Brainlab, Siemens/Varian, AstraZeneca, Novocure; Non-Financial Interests, Personal, Research Grant: Siemens; Financial Interests, Personal, Principal Investigator: MSD, Merck ; Non-Financial Interests, Personal, Training: Brainlab. D. Gale: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca, GSK; Financial Interests, Personal, Other: Co-founder of Inivata (acquired by NeoGenomics in 2021). H.R. Bridge, N. Donner, N.E. Georgoulia : Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. J. Spicer: Financial Interests, Personal, Other, Honoraria: Amgen, AstraZeneca, Bristol Myers Squibb/Medarex, Chemocentryx, Merck, Novartis; Financial Interests, Personal, Advisory Role: AstraZeneca, Bristol Myers Squibb/Medarex, Merck, Protalix Biotherapeutics, Regeneron, Xenetic Biosciences; Financial Interests, Institutional, Research Funding: AstraZeneca, Bristol Myers Squibb/Medarex, CLS-Therapeutics, CLS-Therapeutics, Merck, Protalix Biotherapeutics, Roche; Financial Interests, Personal, Other, Travel and Accommodations: AstraZeneca, Bristol Myers Squibb/Medarex, Merck.