Perioperative durvalumab plus chemotherapy plus new agents for resectable non-small-cell lung cancer: the platform phase II NeoCOAST-2 trial
Mené sur 202 patients atteints d'un cancer du poumon non à petites cellules de stade IIA-IIIB et résécable, cet essai de phase II évalue l'efficacité, du point de vue du taux de réponse complète, et la toxicité de l'ajout du durvalumab à un traitement périopératoire combinant une chimiothérapie et un autre agent (oléclumab, monalizumab ou datopotamab déruxtécan)
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.
Nature Medicine , résumé, 2025