Neoadjuvant (neoadj) osimertinib (osi) ± chemotherapy (CT) vs CT alone in resectable (R) epidermal growth factor receptor-mutated (EGFRm) NSCLC: NeoADAURA.

8001 Background: Based on the Ph 3 ADAURA study, adjuvant (adj) treatment (Tx) with osi, a 3rd-generation, EGFR-TKI, is SoC for resected EGFRm stage (stg) IB–IIIA NSCLC (AJCC 7th ed). Neoadj Tx may improve surgical and long-term outcomes. NeoADAURA (NCT04351555) is a global, Ph 3, randomized, controlled, 3-arm study assessing outcomes with neoadj osi ± CT vs CT alone, in EGFRm R-NSCLC. Methods: Eligible pts: aged ≥18 yrs; WHO PS ≤1; EGFRm (Ex19del/L858R) stg II–IIIB (AJCC 8th ed) R-NSCLC. Pts were stratified (stg II vs III; non-Asian vs Chinese vs other Asian; Ex19del vs L858R) and randomized 1:1:1 to neoadj osi 80 mg QD (≥9 wks) + CT (cis/carboplatin + pemetrexed; 3 cycles, Q3W), osi monotherapy (mono) 80 mg QD (≥9 wks) or placebo (PBO) QD + CT (3 cycles, Q3W). Osi/PBO + CT: double blind; osi mono: open label, sponsor blind. Adj osi was offered to all pts who completed surgery (Sx). Primary endpoint: major pathological response (MPR) by blinded central pathology review. Secondary endpoints included pathological complete response (pCR), event-free survival (EFS), and safety. Data cut-off: Oct 15, 2024. Results: Overall, 358 pts were randomized: osi + CT n=121/osi mono n=117/PBO + CT n=120; baseline characteristics were generally balanced across the respective arms (stg II: 49%/50%/51%; non-Asian: 27%/26%/25%; Ex19del: 50%/51%/51%). After neoadj Tx, 92%/97%/89% of pts underwent Sx in the osi + CT/osi mono/PBO + CT arms. Osi + CT (MPR rate 26%) and osi mono (25%) showed statistically significant improvement in MPR vs PBO + CT (2%): odds ratios were 19.8 (p<0.0001) and 19.3 (p<0.0001), respectively. Interim EFS (15% maturity) trended in favor of osi + CT and osi mono vs PBO + CT (Table); ≥80% of pts in each arm received adj osi. In the neoadj period, grade ≥3 all-cause AEs and AEs leading to discontinuation of any Tx occurred in 36%/13%/33% and 9%/3%/5% of pts, respectively, for osi + CT/osi mono/PBO + CT. No pts died within 30 days of Sx. Conclusions: Neoadj osi with or without CT showed statistically significant improvement in the MPR rate over CT alone. EFS data were immature and trended in favor of the osi containing arms. There were no new safety concerns. Neoadj osi ± CT should be considered when planning Tx for pts with EGFRm stg II–IIIB R-NSCLC. Clinical trial information: NCT04351555 . Osi + CT (n=121) Osi mono(n=117) PBO + CT(n=120) MPR rate, % (95% CI)Difference vs PBO + CT, % (95% CI)Odds ratio vs PBO + CT (adjusted 100×[1−alpha]% CI)p-value 26 (18, 34)24 (15, 32)19.8 (4.6, 85.3 a ) <0.0001 25 (17, 34)23 (15, 32)19.3 (1.7, 217.4 b ) <0.0001 2 (<1, 6)––– pCR rate, % (95% CI) 4 (1, 9) 9 (4, 15) 0 (0, 3) 12-mo EFS rate, % (95% CI)EFS hazard ratio vs PBO + CT (CI)p-valueMedian EFS follow-up, mos (range) f 93 (87, 97)0.50 (0.17, 1.41 c ) 0.0382 e 16 (0–42) 95 (89, 98)0.73 (0.40, 1.35 d ) –18 (2–42) 83 (75, 89)––19 (2–42) a 95.002% CI; b 99.9% CI; c 99.8% CI; d 95% CI; e p-value ≤0.002 required for statistical significance at interim analysis; f censored pts.