Perioperative durvalumab plus chemotherapy plus new agents for resectable non-small-cell lung cancer: the platform phase 2 NeoCOAST-2 trial
Published report from the NeoCOAST-2 trial registered as NCT05061550, in Nature Medicine (2025), chosen as the most cited paper whose own text cites the registry id.
Overview
In the phase II NeoCOAST-2 platform study, 202 patients with untreated, resectable stage IIA-IIIB non-small-cell lung cancer (NSCLC) were randomized to receive neoadjuvant durvalumab plus platinum-doublet chemotherapy with oleclumab, a CD73 inhibitor (Arm 1), or with monalizumab, a NKG2A inhibitor (Arm 2), or neoadjuvant durvalumab plus single-agent platinum chemotherapy with the TROP-2 antibody-drug conjugate (ADC) datopotamab deruxtecan (Arm 4), followed by surgical resection and adjuvant durvalumab with oleclumab or monalizumab (Arms 1 and 2) or durvalumab alone (Arm 4). Primary endpoints were pathological complete response (pCR) rate and safety; secondary endpoints included feasibility of surgery and major pathological response (mPR) rate. In the modified intention-to-treat population (n = 198; Arm 1, n = 74; Arm 2, n = 70; Arm 4, n = 54), pCR rates were 20.3% (15/74; 95% CI, 11.8-31.2), 25.7% (18/70; 95% CI, 16.0-37.6) and 35.2% (19/54; 95% CI, 22.7-49.4), and mPR rates were 41.9% (31/74; 95% CI, 30.5-53.9), 50.0% (35/70; 95% CI, 37.8-62.2) and 63.0% (34/54; 95% CI, 48.7-75.7) in arms 1, 2, and 4, respectively. In the safety population, 69/74 (93.2%), 66/71 (93.0%), and 51/54 (94.4%) patients underwent surgery, respectively. Overall, grade ≥3 treatment-related adverse events occurred in 27/74 (36.5%), 29/71 (40.8%) and 11/54 (20.4%) patients, respectively. In NeoCOAST-2, the first neoadjuvant trial examining an ADC plus chemo-immunotherapy in resectable NSCLC, pCR rates were highest in the datopotamab-deruxtecan-containing arm, warranting further investigation in larger trials of ADCs and checkpoint inhibition in the neoadjuvant setting. ClinicalTrials.gov identifier: NCT05061550.
Indexed on Europe PMC as PubMed record 40450142 (DOI 10.1038/s41591-025-03746-z). Its abstract cites the registry id NCT05061550, which is how it was matched to this trial; no figure has been checked by an editor.
This is the paper Europe PMC returns for registry id NCT05061550 with the most citations, so it is the natural first reading for anyone following the NeoCOAST-2 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.
- Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.