NAUTIKA1 ALK Cohort

[Slide 1] NAUTIKA1: study schema and baseline characteristics (WCLC 2026 presentation MO06.01, Sept 14, 2026; vision-transcribed from @UrsWeberMD's session photo) Phase II umbrella study of targeted neoadjuvant tx in patients with early-stage NSCLC harbouring study-eligible oncogenic drivers; primary analysis of the ALK+ cohort. Key eligibility: stage IB-IIIA/select IIIB (T3N2 only) NSCLC (AJCC 8th ed); ALK+; eligible for R0 resection; local molecular testing (CLIA-certified lab via FISH, IHC or NGS). ALK+ cohort: neoadjuvant alectinib (600 mg BID; 8 weeks) -> surgery and pathologic response assessment by local review -> adjuvant tx: <=4 cycles SOC platinum-based chemotherapy, then <=2 years alectinib. Key endpoints - Primary: MPR (locally assessed; defined as <=10% residual viable tumour cells). Secondary: MPR (centrally assessed), pCR, pathologic regression, ORR, DFS, EFS, OS, nodal downstaging, ctDNA clearance rate. Exploratory: ctDNA status over time, correlation with outcomes. Footnote: at the cutoff, 33 patients had received chemotherapy then alectinib while 3 had received only chemotherapy at that point. One patient withdrew consent after discontinuing neoadjuvant treatment due to adverse event. --- [Slide 2] Pathologic and radiographic responses and 2-year time-to-event outcomes (WCLC 2026 MO06.01; data snapshot 30 June 2026; median follow-up 23.0 months) Pathological response (n=43): MPR 24 (56%) [95% CI 40, 71]; pCR 8 (19%) [95% CI 8, 33]. Radiographic response (n=45; locally assessed, unconfirmed): ORR 27 (60%) [95% CI 44, 74] - all PR 27 (60%) [44, 74]; SD 16 (36%) [22, 51]; PD 1 (2%) [<1, 12]; NE 1 (2%) - the same all-PR pattern as the WCLC 2025 interim. 2-year event rates, % (95% CI): EFS (n=45) 90 (81, 99); DFS (n=39) 97 (91, 100); OS (n=45) 98 (93, 100). Weighted percentage pathologic regression waterfall (n=40), colour-coded pCR / MPR / non-MPR with baseline disease stage, baseline nodal stage, histology and neoadjuvant best overall response tracks; no point estimates read from the waterfall bars. Banner: Robust pathologic regression and radiographic responses were observed with neoadjuvant alectinib. Footnotes: adjuvant treatment was chemotherapy and alectinib in 33 patients (73%) and chemotherapy only in 3 (7%). DFS assessed in the efficacy-evaluable population who had R0 resection and were deemed disease-free (n=39). Weighted % viable tumour regression values set to "missing" for patients without primary tumour R0 resection. --- [Slide 3] Surgical outcomes, safety and nodal downstaging (WCLC 2026 MO06.01) Surgical outcomes (n=42): median time from last neoadjuvant tx to surgery 1 day (range 1-49); surgical delays - AEs 2 (5%) | scheduling 3 (7%); surgery duration median 224 min (range 60-659); days in hospital median 3 (range 0-13; n=41); resection R0 40 (95%) | no resection 2 (5%); intraoperative complications 1 (2%); peri-hilar/lobar adhesions 6 (14%). Alectinib safety, n (%) - Neoadjuvant (N=48) | Adjuvant (n=33): any-grade TRAE 43 (90) | 30 (91); grade 3/4 TRAE 3 (6) | 3 (9); SAE 1 (2) | 1 (3); dose reduction/interruption 15 (31) | 14 (42); treatment discontinuation 3 (6) | 4 (12). Pathologic nodal downstaging post surgery Sankey (n=45): clinical staging at BL cN2 26 / cN1 11 / cN0 8 -> post-surgical N staging ypN0 20 / ypN1 9 / ypN2 10 / ypN3 1 (upstaged/stable/downstaged flows per legend). Banner: 14/45 pts (31%) downstaged to ypN0. Footnotes: surgery after Day 67 from start of neoadjuvant treatment was considered delayed. No resection: required pneumonectomy (n=1), pleural disease found at time of surgery (n=1). Treatment discontinuation included pneumonitis after completion of neoadjuvant alectinib (n=1). Banner: R0 resection rates were high and neoadjuvant alectinib was well tolerated. --- [Slide 4] ctDNA clearance status post neoadjuvant tx and pathologic/clinical outcomes (WCLC 2026 MO06.01) Plasma-only/tumour-agnostic ctDNA was analysed by PredicineWES+ (BL) and PredicineBEACON (MRD) with whole blood germline control subtraction. BEP included 39/45 patients (87% of eligible and efficacy-evaluable patients). 77% of BEP (30/39) was ctDNA+ at BL. ALK fusions detected in 26% of BEP (10/39). ctDNA clearance prior to surgery was observed in 86% of patients (24/28) who were ctDNA+ at BL. All patients who had MPR (n=13) or pCR (n=6) were either ctDNA- at BL or cleared ctDNA prior to surgery [ns are the biomarker-evaluable subset with longitudinal ctDNA data, not the full-cohort pathologic response counts]. All patients who were event free at 2 years (n=16) were either ctDNA- at BL or cleared ctDNA prior to surgery. Sankey (patients with BL and longitudinal ctDNA data): BL ctDNA+ (n=28) / ctDNA- (n=9) -> last sample pre-surgery ctDNA- (n=33) / ctDNA+ (n=4) -> pathologic response non-MPR (n=18) / MPR (n=13) / pCR (n=6) -> EFS at 2 years: event (n=4) / censored (n=17) / no event (n=16). Banner: These data suggest that ctDNA MRD clearance after neoadjuvant alectinib may be associated with favourable outcomes. Footnotes: 1 patient was excluded from outcomes analysis due to missing MPR/pCR. Censored: last disease assessment date not yet 2 years from first treatment date, but event-free at the snapshot. Last sample collected post-BL during the neoadjuvant phase before surgery; 2 patients only had a Cycle 2 Day 1 sample.

[Slide 1] WCLC 2026 Mini Oral MO06.01 title slide (photographed and shared by @HHorinouchi on Aug 27, 2026, ahead of the Sept 14 session; author list transcribed and normalized from the photographed slide) MO06.01. NAUTIKA1: Primary Analysis of Neoadjuvant Alectinib in Resectable Stage IB-IIIB ALK+ NSCLC J.M. Lee (UCLA), A. Cummings (UCLA), N. Florez (Dana-Farber), N. Mohindra (Northwestern), D. Wigle (Mayo Clinic), J. Lin (Michigan), C.A. Shu (Columbia), A. Saltos (Moffitt), E. Shum (NYU Perlmutter), M.V. Negrao (MD Anderson), T. Patil (Colorado), L. Sholl, A. Saqi, E. Kadel, B. Ding, C. Ngiam, I. Bara (Genentech), J. Chaft (MSK)

[Slide 1] Pathologic and radiographic response (WCLC 2025, ALK+ cohort; DCO 02-Sep-2024) Weighted % viable tumor regression waterfall in the pathologic response analysis population (n=25), with per-patient baseline disease stage, baseline nodal stage, and neoadjuvant best overall response; -90% MPR threshold marked. No point estimates read from the waterfall bars. Pathologic response (N=28): MPR 17 (60.7); pCR 7 (25.0). Radiographic response (N=30): ORR 19 (63.3); PR 19 (63.3); SD 9 (30.0); PD 1 (3.3); NE 1 (3.3). Banner: Robust pathologic regression and radiographic responses were observed with neoadjuvant alectinib. --- [Slide 2] NAUTIKA1: study schema and baseline characteristics (WCLC 2025, ALK+ cohort) NAUTIKA1 (NCT04302025) is a phase II umbrella study investigating targeted neoadjuvant treatments in early-stage NSCLC with study-eligible oncogenic drivers. Clinical and surgical outcomes for the ALK+ cohort; clinical data cutoff September 02, 2024. Key eligibility: resectable stage IB-IIIB (T3N2 only; AJCC 8th ed) NSCLC; local molecular testing in a CLIA-certified lab via FISH, IHC, or NGS. ALK+ cohort: neoadjuvant alectinib 600 mg BID for 8 weeks -> surgery and pathologic response assessment (local review) -> adjuvant <=4 cycles SoC platinum-based chemotherapy, then <=2 years of alectinib. Flow: enrolled N=33 -> eligible N=30 -> received neoadjuvant alectinib N=30 -> underwent surgery N=27 (did not: disease progression 1, withdrew consent 2) -> resection not performed 2 (surgeon decision 1, pleural metastasis 1) -> received adjuvant treatment N=21. Baseline (N=33): median age 59.0 (35-80); F/M 19 (57.6)/14 (42.4); tobacco current/former/never 0/6 (18.2)/27 (81.8); ECOG 0/1 23 (69.7)/10 (30.3); histology non-sq/sq 31 (93.9)/2 (6.1); stage IB/IIA/IIB/IIIA/IIIB 3/2/3/23 (69.7)/2; nodal N0/N1/N2 5 (15.2)/7 (21.2)/21 (63.6). --- [Slide 3] Tumor and lymph node downstaging (WCLC 2025, ALK+ cohort) Radiographic downstaging Sankey (baseline stage IB/IIA/IIB/IIIA/IIIB -> post-alectinib IA through IVB): 43.3% (13/30) of patients experienced radiographic downstaging (per AJCC 8th ed). Pathologic nodal downstaging Sankey (cN0 5 / cN1 7 / cN2 18 -> ypN0 13 / ypN1 4 / ypN2 7 / ypN3 1): 33.3% (10/30) of patients achieved pathologic nodal downstaging. Assessed in all eligible and treated patients (N=30).

Same WCLC 2025 deck as the @bensolomon1 capture above (single source, photographed independently) plus the Conclusions slide. --- [Slide 4] Conclusions (WCLC 2025, ALK+ cohort) Alectinib is globally approved in the adjuvant setting for patients with resected ALK+ NSCLC, based on results from the phase III ALINA study (NCT03456076) [Wu et al. NEJM 2024]. The results presented here from the NAUTIKA1 study suggest there is a potential role for neoadjuvant alectinib alongside the ALINA regimen, as a promising perioperative approach for patients with resectable, stage IB-IIIB ALK+ NSCLC.

[Slide 1] WCLC 2025 Mini Oral abstract screenshot (ALK+ cohort; DCO 02-Sep-2024) Introduction: Alectinib is globally approved in the adjuvant setting for resected ALK+ stage IB-IIIB (AJCC 8th ed) NSCLC. NAUTIKA1 (NCT04302025) is a phase II umbrella study investigating targeted treatments in the neoadjuvant/adjuvant setting in early-stage NSCLC with study-eligible alterations (e.g., ALK, ROS1, NTRK and KRAS G12C). New clinical and surgical outcomes from 33 patients in the ALK+ cohort. Methods: Stage IB, II, IIIA or selected IIIB (T3N2 only) ALK+ NSCLC, ECOG PS 0/1. Neoadjuvant alectinib 600 mg BID for 8 weeks, then surgery, platinum-based chemotherapy (<=4 cycles) unless refused/not indicated/contraindicated, then adjuvant alectinib 600 mg BID for two years. Primary endpoint: locally assessed MPR (<=10% residual viable tumor cells). Secondary: pCR, radiographic response, nodal downstaging, safety. Results (abstract, DCO 02-Sep-2024): 33 patients enrolled. MPR 17/28 (60.7%); pCR 7/28 (25.0%). Radiographic objective response 19/30 (63.3%); nodal downstaging 8/30 (26.7%) [abstract figure; the WCLC25 presentation slides report pathologic nodal downstaging 10/30 (33.3%)]. No intraoperative complications. R0 resections in 25/27 (92.6%) of patients who underwent surgery. AEs led to dose reduction/interruption in 12/33 (36.4%) and discontinuation in 3/33 (9.1%) [abstract; N=33 includes 3 ineligible patients in the AE summary]. Neoadjuvant alectinib was well tolerated with no new safety signals. Conclusions: Neoadjuvant alectinib achieved clinically meaningful MPR/pCR rates with no new safety signals, and can be added to ALINA as a promising perioperative approach. Below: weighted % viable tumor regression waterfall (n=25), MPR / non-MPR / pCR color-coded; -90% MPR threshold. No point estimates read from the waterfall bars.