2024年米国臨床腫瘍学会（ASCO）肺がんまとめ

テキスト全文

• #1.

  My Best of ASCO 2024 @M_Torasawa

• #2.

  MARIPOSA #8504 @M_Torasawa PALOMA-3 NSCLC Oral (N = 43) Pickup #LBA8505 EGFR 1 HARMONi-A #8508 1 CHRYSALIS-2 n=2 MPM ADRIATIC #LBA5 n=4 #8001 CheckMate77T #LBA8007 AEGEAN #8011 #LBA8503 ROS1 Driver NSCLC n = 16 SCLC BEAT-SC CROWN ALK n=3 TRUST-1 #8520 CodeBreaK 101 KRAS NSCLC n=5 NSCLC n=6 CheckMate816 / Driver NSCLC n=5 #LBA8010 EVOKE-01 #LBA8500 #8516 #8512 KRYSTAL-12 HER2 #LBA8509 FGFR EGFR ALK Beamion LUNG-1 #8514 LAURA ADAURA #8005 #LBA4

• #3.

  Agenda 01 EGFR NSCLC 02 EGFR NSCLC 03 SCLC @M_Torasawa 04 NSCLC ( / )

• #4.

  Agenda 6 @M_Torasawa pickup 01 EGFR NSCLC ü LAURA III (#LBA4) ü ADAURA (#8005) ü MARIPOSA ü HARMONi-A ü PALOMA-3 (#8504) (#8508) (#LBA8505) Uncommon ü CHRYSALIS-2 (#8516) 02 EGFR NSCLC 03 SCLC 04 NSCLC ( / )

• #5.

  I III EGFR NSCLC EGFR NSCLC @M_Torasawa EGFR NSCLC IA1 2 IIA IIIA IA3 IB IV 2023 IIA UFT 2cm 1A 1A 2cm 2C 1A 3 1C 1B ( Pickup #LBA4 LAURA III EGFRm NSCLC 2023 EGGR 2B ) ASCO 2024 CRT Pickup ASCO 2024 #8005 ADAURA ADAURA MRD

• #6.

  EGFR NSCLC @M_Torasawa ± FLAURA 1A REVEL, JVCG 1A ICI + ICI ± + IMpower150, KEYNOTE-789, ORIENT-31, CheckMate722, ATTLAS 2A RELAY + + Dato-DXd, TROP2 ± TROPION-Lung05 MARIPOSA-2 2B ARCHER1050 KEYNOTE-010, CheckMate-057, OAK HER3-Dxd + + HERTHENA-Lung01 FLAURA2 + + MARIPOSA Pickup Pickup ASCO 2024 #8504 MARIPOSA EGFRm + MARIPOSA 2023 ( + NSCLC ド ASCO 2024 Pickup ASCO 2024 #8508 HARMONi-A #LBA8505 PALOMA-3 EGFR-TKI EGFR-TKI, ) EGFRm Non-sq NSCLC PD-1/VEGF 2023 vs. EGFRm NSCLC

• #7.

  Uncommon EGFR NSCLC Exon 20ins Exon18-21 Uncommon EGFR-TKI 2C [1] ORR PFS 10.7 71% PFS 9.4 [2] ORR 55% + PAPILLON + Pickup #8516 WU-KONG1 (abst#8513) ASCO 2024 CHRYSALIS-2 Uncommon EGFRm NSCLC 2023 2023 @M_Torasawa [1] Yang JCH, et al. Lancet Oncol. 2015;16(7):830-838.,[2] Okuma Y, et al. JAMA Oncol. 2024;10(1):43-51. Pickup

• #8.

  Pickup テ III EGFRm NSCLC CRT LAURA #LBA 4 (Plenary session) S. Ramalingam, et al. Lu Shun, Kato Terufumi, Dong Xiaorong, et al. Osimertinib after Chemoradiotherapy in Stage III EGFR-Mutated NSCLC. N Engl J Med. 0(0). doi:10.1056/NEJMoa2402614 @M_Torasawa

• #9.

  Pickup テ LAURA N =143 III EGFRm NSCLC Ex19del/L858R PS 0-1 CRT ( IIIB IIIC 9 7 @M_Torasawa 80mg PFS (BICR) R 2:1 OS CRT N = 73 6 (IIIA vs IIIB/IIIC) / ) 8 (49 ) IIIA (35 ) (16 ) cCRT RT IMRT ( 8 12 48 CT, MRI) PFS (BICR PFS 13% PD 25% AE final OS ) f/u PFS 22.0 28% (n = 15) PD ASCO2024, abst #LBA4, Lu Shun, et al. N Engl J Med. 2024. doi:10.1056/NEJMoa2402614 Osi positive 7% PD 74% α maturity 60% f/u AE PFS 5.6 81% (n = 50) PD Osi

• #10.

  Pickup テ LAURA PFS (BICR) 60 @M_Torasawa 2 PFS 0.16, (95%CI 0.10 0.24) p < 0.001 48 65% OS 60 13% 48 36 24 12 0.81, (95%CI 0.42 1.56) p = 0.53 36 39.1 5.6 0 24 1 PFS 12 74% 54.0 0 22% Maturity 20% ( PFS HR EGFR <65 65 CRT Never L858R IIIA cCRT CR Ever Ex19del IIIIB/IIIC sCRT PR PFS ASCO2024, abst #LBA4, Lu Shun, et al. N Engl J Med. 2024. doi:10.1056/NEJMoa2402614 SD 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 60% )

• #11.

  Pickup テ LAURA @M_Torasawa 68% 22% -40 21% 48% -20 0 8% 29% 6% 29% 1% 7% 3% 7% 16% 37% 1% 1% ü ASCO2024, abst #LBA4, Lu Shun, et al. N Engl J Med. 2024. doi:10.1056/NEJMoa2402614 20 40 60 80 (%)

• #12.

  Pickup テ LAURA 29% 56% @M_Torasawa n = 63* 28 44% 12 19% 16 25% 15 24% 1 2% 0 0% 8 13% 21 33% 19 30% 5 8% 21 33% 2 3% EGFR-TKI 1/2G TKI 3G TKI - Osimertinib - Aumolertinib - Furmonertinib VEGF 78% 10% n = 66* 57 86% 7 11% 52 79% 51 77% 1 2% 1 2% 5 8% 11 17% 7 11% 1 2% 5 8% 2 3% * 8 ü ü RT beyond = 8.3 24 35% G3 ILD 8% G1/2, G5 1 13% 12% 48% G3 AE ILD 1% G1/2 G3 2% ASCO2024, abst #LBA4, Lu Shun, et al. N Engl J Med. 2024. doi:10.1056/NEJMoa2402614 5% 38% AE G1 G1/2

• #13.

  Pickup テ @M_Torasawa 10.9mo CRT 18.9mo Ami (SC) + Laz Cb + PEM Osi 6.1mo 4.2mo Ami (SC) + Laz Cb + PEM + Osi 23.7mo CRT 1 380 168,120 4.2mo Cb + PEM Ami + Laz G3 AE 6.1mo 25.5mo CRT 3 / 93,000 145 83,430 39.1mo 4 63 4 44,000 8.3mo Cb + PEM + Ami + Laz CRT Osi 6.3mo Cb + PEM + Ami CRT Osi PFS ( ) LAURA

• #14.

  Pickup テ LAURA Summary Discussion points EGFR 01 02 03 NSCLC PFS @M_Torasawa CRT 84% OS 20% MRD TKI PACIFIC . 80% (ADAURA . / PACIFIC-R EGFR subset ASCO2024, abst #LBA4, Lu Shun, et al. N Engl J Med. 2024. doi:10.1056/NEJMoa2402614 ( 40% ) )

• #15.

  Pickup EGFRm IB-IIIA ADAURA NSCLC MRD #8005 (Oral abstract) T. John, et al. @M_Torasawa

• #16.

  Pickup デ ADAURA @M_Torasawa N = 339 IB-IIIA EGFRm NSCLC 3 R 24 1:1 Ex19del/L858R PS 0-1 MRD (IB / II / IIIA) (Ex19del / L858R) / ) 12, 24 ctDNA ASCO2024, abst #8005 , ctDNA 1 5 24 24 24 12, 24 12 3 Germline variant CHIP , Follow-up Adjuvant MRD WES 12, 24 5 1 N = 343 EGFR ( ctDNA 80mg ctDNA 52 , 52 24 5 MRD

• #17.

  Pickup デ ADAURA MRD @M_Torasawa N = 220 8% (n = 112) MRD ü Stage I 0% 92% ü Stage II 8% ü Stage III 13% MRD (17/18 MRD 2.2 5.6 1 MRD MRD (18/220 ) ( ) DFS 49% 80% 0% 4/5 8% MRD 17% 0/13 31% 75% 80% 2 MRD 66% 57% 1 ASCO2024, abst #8005 13% 5% 4.7 DFS MRD 7% (n = 108) (3 )

• #18.

  Pickup デ ADAURA MRD MRD/DFS MRD 01 02 03 Summary Discussion points DFS 4.7 MRD IMpower010 MRD MRD 62% MRD MRD 4/5 MRD MRD ASCO2024, abst #8005 / MRD @M_Torasawa

• #19.

  Pickup EGFRm NSCLC MARIPOSA ト + #8504 (Oral abstract) E. Felip, et al. @M_Torasawa

• #20.

  Pickup ト MARIPOSA @M_Torasawa Ami + N = 429 ( EGFR+ NSCLC PS 0 1 L858R, Ex19 del AMI 1050mg 1400mg 4 1 Laz 1 240mg R Osi ü ü ü OS ORR DoR PFS2 ) 1 80mg EGFR Ex19del / L858R / TP53 N = 216 ( ctDNA NGS Ex19del L858R ctDNA TP53mt (n = 293, 54%) TP53wt (n = 247, 46%) ASCO2024, abst #8504 PFS (Ami + Laz vs Osi) 2 N = 429 ( 2:2:1 ü ü 80kg ) Guardant360 CDx EGFRm ctDNA EGFRm ctDNA ) C3D1 Biodesix ddPCR ctDNA TP53 50% vs 30% C3D1 70% EGFR 100% 80% 60% 40% 20% 0% 85% 9

• #21.

  Pickup ト MARIPOSA PFS @M_Torasawa PFS ( ) HR 0.69, p = 0.010 41% HR 0.69, p = 0.005 16% HR 0.58, p = 0.017 HR 0.74, p = 0.004 54% 70% TP53mt HR 0.65, p = 0.003 TP53wt HR 0.75, p = 0.114 ctDNA+ HR 0.68, p = 0.002 ctDNA- HR 0.72, p = 0.132 HR 0.49, p = 0.015 15% HR 0.64, p = 0.004 0 5 10 Ami+Laz ASCO2024, abst #8504 15 Osi 20 25 30

• #22.

  Pickup ト MARIPOSA Summary + 02 FLAURA2 03 Molecular FLAURA2 PFS ASCO2024, abst #8504 @M_Torasawa PFS Front line 01 Discussion points 25.5 . MET .

• #23.

  Pickup EGFR-TKI ド EGFRm Non-sq NSCLC HARMONi-A #8508 (Oral abstract) L. Zhang, et al. HARMONi-A Study Investigators, Fang W, Zhao Y, et al. Ivonescimab Plus Chemotherapy in Non-Small Cell Lung Cancer With EGFR Variant: A Randomized Clinical Trial. JAMA. Published online May 31, 2024. doi:10.1001/jama.2024.10613 @M_Torasawa

• #24.

  Pickup ド HARMONi-A @M_Torasawa + CBDCA +PEM N = 161 EGFR+ NSCLC + PEM R EGFR 1:1 PS 0-1 EGFR-TKI ü ü + CBDCA + PEM N = 161 24 + PEM 3G TKI PFS (IRRC) AK112/SMT112 PD-1/VEGF VEGF PD-1 10 (J Immunother Cancer. 2023) OS ORR DoR TTR EGFR-TKI 3G 3 1/2G 3G 5 f/u 2 7.89 ASCO2024, abst #8508, Fang W, et al. JAMA. Published online May 31, 2024. doi:10.1001/jama.2024.10613, https://www.smmttx.com/wp-content/uploads/2023/12/Ivonescimab-Overview-HCPs-INVESTORS-MEDIA-12.7.23.pdf

• #25.

  Pickup ド HARMONi-A @M_Torasawa 6 PFS PFS 0.46, (95%CI 0.34 0.62) p < 0.0001 12 PFS EGFR 55% 10 <65 8 65 6 4 2 DCR OS 24 20 51% 35% 93% Ever Ex19del 33% 0 ORR L858R Other 4.8 7.1 Never 3G-TKI 83% 52%Maturity (f/u 0.80, (95%CI 0.59 1.08) 16 17.6 HR 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 ) G3 irAE 6% 3% G3 VEGF 3% 3% 12 8 4 0 17.1 14.5 ASCO2024, abst #8508, Fang W, et al. JAMA. Published online May 31, 2024. doi:10.1001/jama.2024.10613, https://www.smmttx.com/wp-content/uploads/2023/12/Ivonescimab-Overview-HCPs-INVESTORS-MEDIA-12.7.23.pdf

• #26.

  Pickup ド EGFRm NSCLC ICI PFS ( @M_Torasawa ) CBDCA+PTX+BEV+Atezo CBDCA+PTX+Atezo CBDCA+PTX+BEV IMpower150 71% 36% 42% 48% 35% 29% CBDCA+PTX (PEM) +BEV+Atezo IMpower151 CBDCA+PTX (PEM) CDDP+PEM+sintilimab IBI305 CDDP+PEM+sintilimab CDDP+PEM Orient-31 CBDCA+PTX+BEV+Atezo ATTLAS CBDCA+PEM+Nivo CBDCA+PEM CheckMate722 CBDCA+PEM+Pembro CBDCA+PEM KEYNOTE-789 CBDCA+PEM+Ivonescimab HARMONi-A 51% CBDCA+PEM 0 2 42% 70% CBDCA (CDDP)+PEM 4 Chemo+ICI+VEGFi 6 Chemo+ICI 8 Chemo ASCO2024, abst #8508, Fang W, et al. JAMA. Published online May 31, 2024. doi:10.1001/jama.2024.10613 10 12 PFS 31% 27% 29% 27% 35%

• #27.

  Pickup ド HARMONi-A Summary Discussion points EGFR-TKI 01 02 03 策 VEGF PD-L1 @M_Torasawa PFS VEGF+PD-1 ABCP OS MARIPOSA-2 PFS ICI MARIPOSA-2 [Ami + Chemo]: 6.3 , HARMONi-A: 7.1 ASCO2024, abst #8508, Fang W, et al. JAMA. Published online May 31, 2024. doi:10.1001/jama.2024.10613, https://www.smmttx.com/wp-content/uploads/2023/12/Ivonescimab-Overview-HCPs-INVESTORS-MEDIA-12.7.23.pdf

• #28.

  Pickup ナ EGFRm NSCLC vs. PALOMA-3 #LBA8505 (Oral abstract) LB. Neighl, et al. Leighl NB, Akamatsu H, Lim SM, et al. Subcutaneous versus Intravenous Amivantamab, both in Combination with Lazertinib, in Refractory EGFRmutated NSCLC: Primary Results from the Phase 3 PALOMA-3 Study. J Clin Oncol. Published online June 10, 2024:JCO2401001. @M_Torasawa

• #29.

  Pickup PALOMA-3 @M_Torasawa Ami ( EGFR+ NSCLC ・ R PS 0 1 L858R, Ex19 del )+ N = 206 4 1:1 Ami ( )+ N = 212 2 AUC ORR PFS ( DoR ) AMI ü ü EGFR ü ü / Osi / Ex19del / L858R 4 Ami 1600mg 2240mg 80kg 1 1050mg 1400mg 80kg Laz 1 240mg 2 OS 7.0 7 GMR 6 35% 2 C trough C2D1 C trough C4D1 C2 AUCD1-D15 1.15 (90 CI 1.04 1.26) 1.43 (90 CI 1.27 1.61) 1.03 (90 CI 0.98 1.09) ü ASCO2024, abst #LBA8505, Leighl NB, et al. J Clin Oncol. Published online June 10, 2024:JCO2401001.

• #30.

  Pickup PALOMA-3 @M_Torasawa PFS 100 Best reponse (%) 30 45 50 18 12 CR 32 10 PR 8 SD 4 6 2 PD 38 OS 20 IV SC IV Confirmed 27% (21 33) 27% (21 33) SC 4.3 SC IV 0.62, (95%CI 0.42 0.92) p = 0.017 ORR PFS, OS 6.1 0 NE 0 SC 0.84, (95%CI 0.64 1.10) p = 0.20 1 OS 12 10 8 ASCO2024, abst #LBA8505, Leighl NB, et al. J Clin Oncol. Published online June 10, 2024:JCO2401001. SC IV 65% 51% SC IV

• #31.

  Pickup PALOMA-3 @M_Torasawa IRR VTE 66% 70 50 40 20 10 13% G1 2 15 G3 10 SC IV 0 IRR 70 26% 12% 9% G1 7% G2 G3 SC SC IV IV SC IV 65% 60 G1 50 40 ( Grade) ( Grade) G2 30 10 (42/39) 17% 14% 5 0 20 (164/171) (206/210) 20 60 30 8 12.5% 0 C1 C2 C3 C4 54% 51% 46% 43% SC IV SC IV Grade 3: 4% Grade 3: 1% ASCO2024, abst #LBA8505, Leighl NB, et al. J Clin Oncol. Published online June 10, 2024:JCO2401001. Grade 3: 4% Grade 3: 4% AE

• #32.

  Pickup 1 st line @M_Torasawa Ami + Laz 2024/4/8 2nd line G3 AE MARIPOSA Cb + PEM Ami + Laz Cb + PEM + Ami + Laz 3rd line Cb + PEM + Ami Osi PALOMA-3 Cb + PEM Ami (SC) + Laz 25.5mo 6.1mo Ami (SC) + Laz Cb + PEM + Osi PFS ( 63% 92% 34% 58% 72% 18% 56% 52% 13% 13% 6.1mo 4.2mo 18.9mo Osi 35% 6.3mo 18.9mo Ami + Chemo 2024/5/31 75% 8.3mo 18.9mo Osi IRR 4.2mo 23.7mo MARIPOSA-2 AE ) ü Ami (SC)+ Laz Cho BC, et al. LBA14. Ann Oncol. 2023;34:S1306.Passaro A, et al. Ann Oncol. 2024;35(1):77-90. Leighl NB, et al. J Clin Oncol. Published online June 10, 2024:JCO2401001.

• #33.

  Pickup PALOMA-3 DoR 01 PFS Summary OS C1D1 4 6 Discussion points PK SC C1D2 6 8 7 02 03 IRR ORR VTE 2 VTE MARIPOSA, MARIPOSA-2 ASCO2024, abst #LBA4, Lu Shun, et al. N Engl J Med. 2024. doi:10.1056/NEJMoa2402614 @M_Torasawa

• #34.

  Pickup ニ Uncommon EGFRm NSCLC CHRYSALIS-2 #8516 (Rapid oral abstract) BC. Cho, et al. @M_Torasawa

• #35.

  Pickup ニ 策 ORR CHRYSALIS-2 I/ Ib @M_Torasawa Cohort A EGFR Ex19 del or L858R Osi Cohort B EGFR Ex20ins SoC Cohort C Uncommon EGFR Cohort D EGFR Ex19 del or L858 Cohort E EGFR Ex19 del or L858R Osi IHC validation Cohort F EGFR Ex19 del or L858R IHC validation R2PD OS CBR PFS ASCO2024, abst #8516, * 3G-EGFRTKI f/u 1/2G EGFR-TKI 規 Osi Osi * validation 1050 mg IV 240 mg 13.8 2 Ami N = 105 ü ü (Afa 47% 53% S768X 32%) G719X L861X G719X L861X S768X E709K E709A L833V R776C R776H R831H V744M V789L V774M Other

• #36.

  Pickup ニ CHRYSALIS-2 n = 49 n = 56 57% PFS L861X (n = 15) 48% 33% 7.8 + ASCO2024, abst #8516 G719 (n = 33) S768X (n = 12) 48% 19.5 PAPILLON @M_Torasawa Uncommon EGFR Uncommon 50%

• #37.

  Agenda 5 @M_Torasawa pickup 02 01 EGFR NSCLC EGFR 02 NSCLC ALK ü CROWN Nivo (#LBA8503) vs Pembro ROS1 ü TRUST-1 (#8520) KRAS ü CodeBreak 101 ü KRYSTAL-12 (#8512) (#LBA8509) HER2 ü Beamion-lung1 (#8514) 03 SCLC 04 NSCLC ( / )

• #38.

  ALK NSCLC @M_Torasawa PFS 9.3 10.9 10.2 11.1 3 (CROWN)1 (ALEX)2 (J-ALEX)3 (ALTA-1L)4 ( ) ( ) ( ) 34.1 34.8 1A 46% 19% ) ( PFS (ALTA-1L) (J-ALEX)3 (ALEX)2 ( ) ( ) (ALEX) 43% 24.1 (ALTA-1L)4 ( 64% ) 2B (ALTA-1L) (CROWN) (CROWN)1 ( 2B 0 6 12 18 24 30 36 ) 5 42 PFS 2023 Pickup #LBA8503 (CROWN) ALK+ NSCLC ASCO 2024 vs. 5 (CROWN) [1] Solomon BJ, et al. Lancet Respir Med. 2023;11(4):354-366.. [2] Mok T, et al. Ann Oncol. 2020;31(8):1056-1064.[3] Nakagawa K, et al. Lung Cancer. 2020;139:195-199 [4] Camidge DR, et al. J Thorac Oncol. 2021;16(12):2091-2108.

• #39.

  ROS1, HER2 NSCLC ROS-1 @M_Torasawa HER2 1C 1C ASCO 2024 Pickup #8520 (TRUST-1) / ROS1+ NSCLC (abst#8519) Pickup 1C ASCO 2024 Pickup #8514 (Beamion LUNG-1 ) HER2 2023 2023

• #40.

  KRAS NSCLC @M_Torasawa KRAS ASCO 2024 + CBDCA + PEM Pickup #8512 (CodeBreaK101) KRAS G12C NSCLC + (abst#8510) Pickup + (abst#LBA8511) Pickup 1B ASCO 2024 Pickup 11 #LBA8509 (KRYSTAL-12) NSCLC KRAS G12C vs. / 2023 2023

• #41.

  Pickup ALK CROWN NSCLC vs. 5 #LBA8503 (Oral abstract) BJ. Solomon, et al. Solomon BJ, Liu G, Felip E, et al. Lorlatinib Versus Crizotinib in Patients With Advanced ALK-Positive Non-Small Cell Lung Cancer: 5-Year Outcomes From the Phase III CROWN Study. J Clin Oncol. Published online May 31, 2024:JCO2400581. @M_Torasawa

• #42.

  Pickup CROWN IIIB/IV @M_Torasawa 100mg 1 1 N = 149 ALK+ NSCLC R PS 0 2 わ 1:1 250mg 1 1 N = 147 ü ü 7 PS 2 : L vs C; 2 vs 6% ASCO2024, abst #LBA8503 OS PFS (investigator) ORR 5 ü PFS ü ORR, ORR ü DOR, DOR ü TTP ü ü / PFS 25% PFS (BICR) 50% f/u PD AE PFS 60.2 50% (n = 74) 5% f/u PD AE 55.1 5% (n = 7)

• #43.

  Pickup CROWN PFS @M_Torasawa PFS 0.19, (95%CI 0.13 0.27) ( ) 100 80 60 48 60% 60 36 24 40 9.1 12 8% 20 0 0 1 2 3 4 5 5 0.06, (95%CI 0.03 0.12) ü 60 ü 16 48 36 24 12 0 ASCO2024, abst #LBA8503 16.4 92% 21% ü ALK variant (1 3), TP53 PFS (TP53mt LOR PFS PFS NR vs 51.6 ) [1] Solomon BJ, et al. Lancet Respir Med. 2023;11(4):354-366.. [2] Mok T, et al. Ann Oncol. 2020;31(8):1056-1064.[3] Nakagawa K, et al. Lung Cancer. 2020;139:195-199 [4] Camidge DR, et al. J Thorac Oncol. 2021;16(12):2091-2108.

• #44.

  Pickup CROWN @M_Torasawa (n = 31) (N = 29) (n = 31) (n = 90) (n = 87) (n = 89) 100% ALK 48 19 52 33 ALK 3 3 6 12 TP53 48 52 30 26 70 MAPK 0 10 4 4 60 PIK3/MTOR/PTEN 3 10 1 0 50 RTK 3 19 3 6 40 Cell cycle 13 16 4 6 39 45 40 31 16 26 19 32 ctDNA ü ALK ASCO2024, abst #LBA8503. Solomon BJ, et al. J Clin Oncol. Published online May 31, 2024:JCO2400581. 90 80 30 20 10 0

• #45.

  Pickup CROWN @M_Torasawa CNS Grade Grade 3/4 Grade 5 AE Any AE AE AE Grade -100 ü ü ü ü -80 -60 -40 0 20 40 60 80 Grade 1 100 (%) Grade 2 Grade 3 25% 23% Grade 4 21% 12% 0 CNS AE (2 -20 1 ) 3 HLGT HLGT HLGT SMQ ASCO2024, abst #LBA8503. Solomon BJ, et al. J Clin Oncol. Published online May 31, 2024:JCO2400581. 10 NEC 20 30 40 50 (%)

• #46.

  Pickup AE @M_Torasawa * * * CNS 25mg or 25mg 25mg * ü ü CNS AE Liu G, et al. A pragmatic guide for management of adverse events associated with lorlatinib. Lung Cancer. 2024;191:107535.

• #47.

  Pickup @M_Torasawa CNS CROWN 25% 37 ; 192 44 ; 63 60.2mo 4.2mo 105 ; 221 34.8mo 5.5mo ALEX 42% L 34.8mo 4.2mo Cb PEM ü 29% B Cb PEM 5.5mo 4.2mo L Cb PEM 59% 2 ü ü 30.8mo 1 CNS 7.1mo 4.2mo 61% ALTA-1L 42% Cb PEM 229 155 ; CNS AE 2 ALK-TKI ALK-TKI

• #48.

  Pickup CROWN Summary 5 5 01 02 PFS Discussion points 92 % CNS ALK 16 PFS 100mg 03 ASCO2024, abst #LBA4, Lu Shun, et al. N Engl J Med. 2024. doi:10.1056/NEJMoa2402614 PFS @M_Torasawa

• #49.

  Pickup / ROS1 ネ NSCLC TRUST-1 #8520 (Rapid Oral abstract) W. Li, et al. Li W, Xiong A, Yang N, et al. Efficacy and Safety of Taletrectinib in Chinese Patients With ROS1+ Non-Small Cell Lung Cancer: The Phase II TRUST-I Study. J Clin Oncol. Published online June 1, 2024:JCO2400731. @M_Torasawa

• #50.

  Pickup ネ TRUST-1 IIIB/IV @M_Torasawa TKI naïve ROS1+ NSCLC DOR IC-ORR BOR DOR TTR PFS ORR (IRC) 600mg PS 0 1 TKI ROS1 TKI N = 106 TKI ORR N = 67 TKI (%) (%) (%) 56 51 56 61 0: 78% 1 2: 99% 21 34 17 42 91% 600mg ORR G2032R PFS ORR 88% N = 12 TKI 52% 75% 23.5 f/u 9.7 7.6 67% 0 ASCO2024, abst #8520, Li W, et al. J Clin Oncol. Published online June 1, 2024:JCO2400731. f/u 10 20 30 ( )

• #51.

  Pickup ネ ROS-1 Study TRIDENT-1 [2] [3]* STARTRK-2 [4] [5] PROFILE1001 [6] 106 71 21 53 30 50 91 79 62 68 67 42 19.3 19.2 (88%) IC-ORR (%) ) G2032R ( (23.5 ) ASCO2024 ü (89%) (64%) 35.7 21.0 (59% [10/17]) (0% [0/6]) ) (67% [8/12]) AST * @M_Torasawa TRUST-1 [1] ORR (%) PFS ( TKI (76%) (70%) (21%) 10% ROS1 (62%) (53%) 15% Chol (80%) (36%) (27%) (55%) 19.0 (38%) (44%) #8519 TRK (TrkB) ROS1 CNS [1] Li W, et al. J Clin Oncol. Published online June 1, 2024:JCO2400731. [2] Drilon A, et al. N Engl J Med. 2024;390(2):118-131. [3] Shaw AT, et al. Lancet Oncol. 2019;20(12):1691-1701. [4] Drilon A, et al. Lancet Oncol. 2020;21(2):261-270. [5] Lim SM, et al. J Clin Oncol. 2017;35(23):2613-2618. [6] Shaw AT, et al. N Engl J Med. 2014;371(21):1963-1971.

• #52.

  Pickup ネ TRUST-1 Summary Discussion points G2032R 01 02 ROS1 TKI AE Phase 3 Phase 2 vs vs TRIDENT 3 NCT06140836 NCT04603807 TRUST-II NCT04919811 ASCO2024, abst #LBA4, Lu Shun, et al. N Engl J Med. 2024. doi:10.1056/NEJMoa2402614 @M_Torasawa

• #53.

  Pick Up HER2 (HER2 TKI: BI 1810631) Beamion LUNG-1 #8514 (Rapid oral abstract) J. Heymach, et al. @M_Torasawa

• #54.

  Pickup Beamion lung-1 HER2 Rationale I/ TKI HER2 TKI HER2 HER2 / / NSCLC 2 HER2 52% 56% 57% BID 15 30 60 100 150 QD 60 120 180 240 300 MTD 120/240 mg QD ASCO2024, abst #8514 HER2 Phase 1b Phase 1a N = 83 @M_Torasawa 360 HER2 NSCLC 策 1: HER2 TKD 2: HER2 TKD 3: HER2 non-TKD 4: 5: HER2 TKD HER2 TKD HER2 ADC ORR n = 42 TKD Sq

• #55.

  Pickup Beamion lung-1 Phase1a ORR 74 NSCLC (n = 41) (n = 74) HER2 44% 35% Phase1b ORR T-Dxd HER2 TKD A775_G776insYVMA (n = 32) (n = 12) (n = 34) 38% 36% 62% (n = 16) 69% Phase1b (n = 42) (n = 23) 74% ALT ASCO2024, abst #8514 @M_Torasawa Any G3 67% 10% 29% 21% 10% HER2 HER2 NSCLC T-Dxd 2

• #56.

  Pickup KRAS G12C 10 NSCLC (CodeBreaK101 ) #8512 (Targeting KRAS in Non Small Cell Lung Cancer) BT. Li, et al. @M_Torasawa

• #57.

  Pickup 10 CodeBreaK101 Ib Induction KRAS G12C+ NSCLC PS 0 2 CBDCA PEM @M_Torasawa Maintenance PEM 960 mg 960 mg Until PD 4 TTR PFS OS PK ORR DCR DOR Grade 3 N = 37 N = 21 TRAE (%) ICI 64 67 41 52 (%) (%) ASCO2024, abst #8514 86 16 21 92% 95% ALT AST G3 49% 62% FN -40 -30 -20 -10 0 10 20 30 40 (%)

• #58.

  Pickup 10 CodeBreaK101 @M_Torasawa CodeBreaK202 PFS ORR DCR f/u 64% 100% 10.8 f/u 42% 84% PD-L1 ASCO2024, abst #8514 PS 0 1 PD-L1 CBDCA+PEM + R + 4 1:1 4.4 + 2 4 6 8 10 12 ( PFS 11.9 KRAS G12C ü ü ü ) ( CBDCA+PEM + PFS ) KEYNOTE-189 PD-L1 NSCLC CodeBreaK202 PEM Until PD 8.3 0 PD-L1 KRAS G12C+ NSCLC 9.2 PFS 6.2 PEM

• #59.

  Pickup 11 KRAS G12C NSCLC vs. (KRYSTAL-12 ) #LBA8509 (Targeting KRAS in Non Small Cell Lung Cancer) T. Mok, et al. @M_Torasawa

• #60.

  Pickup 11 IIIB/IV KRYSTAL12 @M_Torasawa KRAS G12C NSCLC R PS 0 1 2:1 /ICI 75 mg/m2 N = 152 / ADA (% Chemo+ICI (%) (%) (chemo/ICI PD ) DOC ADA (%) , ORR (BICR) DoR OS PRO PFS ( BICR) 600mg BID N =301 64 65 64 72 26 26 73 73 17 18 TRAE 94% ADA DOC DOC G1 86% G2 AST G3 ALT G3 47% 46% -60 -50 -40 -30 -20 -10 0 10 20 30 40 50 60 (%) ASCO2024, abst #8514

• #61.

  Pickup 11 KRYSTAL12 PFS (BICR) 6 0.58, (95%CI 0.45 0.76) p < 0.0001 10 @M_Torasawa CodeBreaK200 PFS ADA DOC 45% 34% 8 6 4 2 5.5 3.8 0 ADA DOC ü ü ü ü ü ü 7.2 ORR (BICR) ADA 32% ORR DOC 9% ADA 24% KRAS G12C PFS ASCO2024, abst #8514, [1] de Langen AJ, et al. Lancet. 2023;401(10378):733-746. ORR DOC 11% NSCLC ORR n = 171 PFS 5.6 ORR 28.1% ORR 33.3% 34% ( Grade) ALT 10% ( Grade) AST 10% ( Grade) n = 174 ü ü ü ü ü [1] PFS 4.5 ORR 13.2% ORR 15.4% 19% ( Grade) 18% ( Grade)

• #62.

  Agenda @M_Torasawa 2 pickup 03 01 EGFR NSCLC 02 EGFR NSCLC SCLC ü ADRIATIC ü BEAT-SC #LBA5 #8001 04 NSCLC ( / )

• #63.

  SCLC @M_Torasawa SCLC LD-SCLC ED-SCLC I IIA CASPIAN I IIA + ETP + Durva IMpower133 CBDCA + ETP + Atezo CRT (cCRT > sCRT) CR ASCO 2024 PS SoC PCI Durva CBDCA + ETP + Atezo ± BEV Pickup 13 #8001 BEAT-SC ES-SCLC + ± Durva+Treme ASCO 2024 Pickup 2023 12 #LBA5 ADRIATIC LS-SCLC ± CRT 2023

• #64.

  Pickup LS-SCLC (ADRIATIC 12 cCRT ) #LBA5 (Plenary) DR. Spigel, et al. @M_Torasawa

• #65.

  Pickup 12 ADRIATIC LS-SCLC (I III PS 0-1 cCRT cCRT PCI @M_Torasawa 1500mg q4w N = 264 ) R D q4w N = 266 1:1:1 SD 24 1500mg+ 75mg (4 1500mg q4w 24, 36 18, 24 ORR TTDM PFS2 ) (I/II vs III), PCI ( Durva CDDP+ETP (%) CRT CR/PR (%) 1 1 (%) PCI (%) ASCO2024, abst #LBA5 Placebo 62 62 66 67 84 88 74 70 54 54 PBO PFS, OS (Dual primary) OS PFS ) Disposition 2 2 34% 46% 26% PD 58% AE 18% ICI PD AE 24.4% ICI

• #66.

  Pickup 12 ADRIATIC PFS (BICR) 24 @M_Torasawa 18 0.76, (95%CI 0.61 0.95) p = 0.01 49% 20 OS PFS 36% 16 12 8 4 16.6 24 9.2 48 24 34% 12 OS 68% 60 36 55.9 59% OS 33.4 57% 0 27.6 48% 37.2 OS OS PS HR cCRT CRT <65 0 <14 CDDP/ETP 1 1 CR 65 1 14 28 CBDCA/ETP 1 2 PR 28 ASCO2024, abst #LBA5 24 36 PFS 46% 0 0.73, (95%CI 0.57 0.93) p = 0.0104 SD PCI 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1

• #67.

  Pickup 12 ADRIATIC @M_Torasawa G3 24% 24% 23.4 22.9 10.7 38.2 / Grade 32% 10% 5% ASCO2024, abst #LBA5 2% 30.2 G3/4 / 3 3 G5 / 0.4 0 8.8 / -40 Grade 3 6 ü -30 -20 -10 G2 3 0 10 20 30 40 (%)

• #68.

  Pickup 12 ADRIATIC LS-SCLC OS 01 PFS LS-SCLC ICI LS-SCLC Discussion points cCRT 27% , 2 (OS, ED-SCLC: 2 OS 2 03 ICI cCRT BiTE ASCO2024, abst #LBA5 @M_Torasawa OS ; LS-SCLC: 2 SCLC-I 02 04 Summary ICI DLL-3 2 ICI ICI KEYLYNK-013 NCT04624204 DeLLPhi-306 NCT06117774 [24%] 18% NRG-LU005 NCT03811002 )

• #69.

  Pickup ES-SCLC + (BEAT-SC 13 ± ) #8001 (Oral abstract) Y. Ohe, et al. @M_Torasawa

• #70.

  Pickup 13 BEAT-SC @M_Torasawa / PFS ( ES-SCLC PS 0 1 N = 166 R BEV fit OS, ORR, DoR Until PD 1:1 ) / ü ü PS ü PFS 10.2 N = 164 BEV Placebo BEV (%) (%) (%) CBDCA (%) BEV ASCO2024, abst #8001 65 40 13 23 92 7 65 45 12 16 92 G3 AE ü 89% Placebo 90% BEV AE 21% Placebo 17%

• #71.

  Pickup 13 BEAT-SC PFS (investigator) @M_Torasawa 6 0.70, (95%CI 0.54 0.90) p = 0.006 6 OS PFS BEV 45% 27% 12 1.22, (95%CI 0.89 1.67) p = 0.2212 OS BEV 54% 24 69% 5 4 12 3 5.7 2 1 4.4 0 PFS 12 13.0 20% 11% 28% 0 BEV BEV 48% 264 (160 ) ORR BEV 82% (%) (%) 73% (%) ICI (%) (%) ASCO2024, abst #8001 24 16.0 57 72 26 29 24 22 3 4 10 20 ü OS 34%

• #72.

  Pickup 13 BEAT-SC PFS Summary + + OS 01 02 Discussion points @M_Torasawa + 0.7 OS OS OS ASCO2024, abst #8001 PFS 1 benefit

• #73.

  Agenda @M_Torasawa 4 pickup 04 01 EGFR NSCLC 02 EGFR NSCLC 03 SCLC NSCLC ( / ) ü CheckMate816 ü AEGEAN ü CheckMate77T #LBA8010 #8011 #LBA8007 ü EVOKE-01 #LBA8500

• #74.

  NSCLC @M_Torasawa Neoadjuvant ASCO 2024 C C Optional chemo/RT C 14 #LBA8010 (CheckMate816) NSCLC CheckMate 816 4 N N N CM816 (IB-IIIA) Pickup up to 4 cycles vs Perioperative KN-671 (IIB-IIIA) AEGEAN (IIA-IIIB) CheckMate77T (IIA-IIIB) P P P P C C C C D D D D C C C C N N N N C NEOTORCH (IIA-IIIB) C C C P ( 9 months, Q3W 13 cycles) (abst#8012) Pickup ASCO 2024 S U R G E R Y D ( 12 months, Q4W 12 cycles) N ( 12 months, Q4W 12 cycles) T T T T C C C C T ( 9 months, Q3W 13 cycles) Pickup 15 #8011 (AEGEAN) N2 R-NSCLC AEGEAN ASCO 2024 Pickup 16 #LBA8007 (CheckMate77T) III NSCLC CheckMate77T Adjuvant C IMpower010 (IB-IIIB) up to 4 cycles Optional chemo KN-091 (IIB-IIIB) up to 4 cycles 2023 A ( 12 months, Q3W 16 cycles) P ( 12 months, Q3W 18 cycles) 3 weeks N Nivo T Tori A Atezo P Pembro D Durva C Chemo

• #75.

  NSCLC Status ICI @M_Torasawa KEYNOTE-671[1] AEGEAN[2] NEOTORCH[3] CheckMate77T[4] CheckMate816[5] 797 740 501 (only Chinese) 461 358 (%) 70.3 68.9 89.6 72.9 71.5 PS 0 (%) 63.7 68.6 34.7 64.2 69.3 Sq (%) 43.1 46.2 77.7 50.7 48.6 (AJCC8th) 29.7 28.4 35.4 - (AJCC 7th) Stage A (AJCC8th) 54.7 47.3 67.3 63.8 - (AJCC 7th) Stage B (AJCC8th) 15.6 24.0 31.9 ICI N Stage EGFR/ALK (ITT ( ) - (AJCC 7th) ) Only CDDP base CDDP < CBDCA base CDDP < CBDCA base CDDP < CBDCA base CDDP > CBDCA base cycle 4 4 3 4 3 cycle (chemo) 0 0 1 0 (optional) cycle (IO) Q3W×13 Q4W×12 Q3W×13 Q4W×12 - EFS, OS (dual) pCR, EFS (mITT) EFS pCR, EFS 25.2 11.7 25.4 57.6 ( ) Perioperative EFS, mPR ( 18.3 ) Neoadjuvant [1] Wakelee Heather, et al. N Engl J Med. 2023;389(6):491-503. [2] Heymach John V., et al. N Engl J Med. 2023;389(18):1672-1684. [3] Lu S, et al. JAMA. 2024;331(3):201-211. [4] Cascone T, et al. N Engl J Med. 2024;390(19):175

• #76.

  NSCLC @M_Torasawa NSCLC ICI ICI 1A ± 1A 1A S-1 Pickup 17 ASCO 2024 1A TROP2 2023 2023 #LBA8500 (EVOKE-01) NSCLC vs PD(L)-1

• #77.

  Pickup 14 NSCLC + (CheckMate816 4 vs. ) #LBA8010 (Rapid oral abstract) J Spicer, et al. @M_Torasawa

• #78.

  Pickup 14 CheckMate816 IB IIIA NSCLC R AJCC 7 PS 0 1 EGFR/ALK ü ü @M_Torasawa + Chemoa N = 179 1:1 (6 pCR (BICR) EFS (BICR Adjuvant (optional) ) MPR (BICR) OS TTDM Chemob ü PD-L1 IB II / IIIA <1 / 1% Nivo a) N = 179 Non-Sq CDDP + PEM or CBDCA + PTX Sq CDDP + GEM or CBDCA + PTX b) CDDP + VNR, CDDP + GEM Disposition IB/ II IIIA Sq PD-L1 < 1% PD-L1 1% CDDP CBDCA 64 36.3 63.1 48.6 43.6 49.7 69.3 21.8 65 34.6 64.2 53.1 43.0 49.7 74.9 18.4 ASCO2024, abst #LBA8010, Forde et al.. N Engl J Med. 2022;386(21):1973-1985. 94% 16% PD 7% AE 1% ( 98% 83% 8% 77%, 17% ( 98% 85% 75% 21% PD 10% AE 1% 10% 61%, 25%

• #79.

  Pickup 14 EFS 57.6 48 42 36 30 24 18 12 6 0 CheckMate816 @M_Torasawa 36 0.66, (95%CI 0.49 0.90) P = 0.0451 EFS OS Nivo 53% *OS 40% p = 0.0164 0.671 (95%CI 0.47 1.07) P = 0.0451* 57.6 77% 60 43.8 36 EFS 48 24 18.4 49% 12 38% Nivo Nivo OS (%) (%) Chemo (%) VEGF EGFR/ALK TKI EGFR/ALK ASCO2024, abst #LBA8010 53 23 7 40 21 15 3 71 35 7 39 42 15 10 CDDP HR 0.79 CBDCA HR 0.36 40 60 95% 80 ( 58% 48 OS Non-pCR pCR NC 20 OS Nivo HR 0.71 0 64% 71% 0 Nivo OS Nivo 48 48 36 ) 63%

• #80.

  Pickup 14 CheckMate816 @M_Torasawa ctDNA 86 (24%) ü AE Nivo 56% vs OS HR 0.31 (0.10-0.64) 24/43 35% Nivo ctDNA 36 48 6 5 7 AE SAE vs -100 11 -80 -60 -40 -20 15/43 pCR ctDNA ASCO2024, abst #LBA8010 3 84 8 AE OS HR 0.58 (0.20 1.64) 38 52 EFS OS 34 34 0 2 0 15 G1 2 G3 4 20 40 60 80 100 (%)

• #81.

  Pickup N2 15 NSCLC AEGEAN #8011 (Rapid oral abstract) J Heymach, et al. @M_Torasawa

• #82.

  Pickup 15 AEGEAN IIA IIIB[N2] @M_Torasawa NSCLC R AJCC 8 PS 0 1 EGFR/ALK ü ü PD-L1 + Chemo N = 181 pCR (BICR) EFS (BICR 1:1 II / III <1 / 49.5% 366/740 N2 ASCO2024, abst #8011 1 ) MPR (BICR) DFS + Chemo N = 185 1% Durva N2 N2 (40 (n =181) 100 (n =185) Disposition 80 IIIA IIIB Sq N2 single N2 multi PD-L1 < 1% CBDCA 62 51.9 48.1 45.9 77.9 18.8 32.6 70.2 65 46.5 53.0 55.1 71.4 21.6 33.5 73.5 (%) 60 40 20 0 Durva D-N2 ü N2 ITT D-ITT R0 PBO-N2 PBO-ITT disposition

• #83.

  Pickup 15 AEGEAN @M_Torasawa pCR, mPR 100 40 80 (%) 17.5% 30 60 (%) 40 20 11.7% 13.0% 20 10 0 0 D-N2 D-ITT PBO-N2 PBO-ITT ü N2 D-N2 ü N2 EFS ITT HR 0.68 (0.53 0.88) 25.9 mf/u 11.7 N2 HR 0.63 (0.43 0.9) 19.5 mf/u 11.8 0 pCR 6 ASCO2024, abst #8011 12 18 24 30 36 ( ) MPR ü N2 N2 MPR D-ITT PBO-N2 PBO-ITT pCR MPR rate ITT G3 / 4 NSCLC 21%

• #84.

  Pickup 16 III NSCLC (CheckMate77T ) #8070 (Oral abstract) MP Pulla, et al. @M_Torasawa

• #85.

  Pickup 16 CheckMate77T IIA (>4cm) IIIB[N2] NSCLC III Nivo IIIA IIIB PS 0 Sq PD-L1 < 1% PD-L1 1 49 % PD-L1 50% ASCO2024, abst #LBA8007 + 1:1 II / III ü PD-L1 (Sq / non-Sq) N2 Chemo N = 181 R AJCC 8 PS 0 1 EGFR/ALK ü ü @M_Torasawa 66 53 47 74 44 45 40 13 <1 / EFS (BICR (6 ) Nivo (n =55) 13 + Chemo N = 185 1% pCR (BICR) MPR (BICR) OS 360 mg Q3W (n =91) (n =90) 64 63 37 66 42 39 32 24 III non-N2 IIIA IIIB PS 0 Sq PD-L1 < 1% PD-L1 1 49 % PD-L1 50% 66 100 0 56 56 44 27 27 (n =57) 65 100 0 58 60 49 30 19 ü non-N2 N2 N2 PS0 non-Sq

• #86.

  Pickup 16 CheckMate77T @M_Torasawa pCR 40 37.5% 24.4% 21% EFS 20 EFS) HR 0.32 (0.19 0.54) III non-N2 HR 0.61 (0.30 1.24) HR 0.40 (0.20 0.78) HR 0.23 (0.09 0.58) III single-N2 10 III multi-N2 0 (%) ( III N2 13.6% 30 mf/u25.4 III N2 III non-N2 III single-station N2 III 0 multi- station N2 ü N2 Nivo ypN0 ypN0 ASCO2024, abst #LBA8007 36% 57% 12 18 24 Nivo 30 benefit III Nivo Nivo 46% N2 6 N2 Nivo 44% 1% 14% 36 ( )

• #87.

  Pickup 16 / N0 T1–2 @M_Torasawa N2 single Discrete/non-bulky N2 multi Discrete/non-bulky N2 Bulky (N2a/b) N2 Invasive (N2a/b) N3 切除可能 切除可能な 可能性あり 不明 切除不能 切除不能 切除可能 切除可能 切除可能な 可能性あり 切除不能 切除不能 切除不能 N1 III T3 T4 切除可能 切除可能 切除可能 切除可能な 可能性あり 切除不能 切除不能 切除不能 T4 invasion* 切除可能な 可能性あり 切除可能な 可能性あり 切除可能な 可能性あり 切除可能な 可能性あり 切除不能 切除不能 切除不能 p PACIFIC p ICI (neoadjuvant +/- adjuvant ICI) WCLC 2023 abst# OA06.05

• #88.

  Pickup 16 CheckMate77T Summary N2 N2 01 02 03 Discussion points III @M_Torasawa NSCLC ypN0 ICI N2 non-N2 . Nivo N2 EFS N2 non-N2 N2-multi NCCN, ESMO N2 single-station N2 pCR 策 ASCO2024, abst #LBA8007 EFS pCR Nivo EFS

• #89.

  Pickup 17 PD(L)-1 NSCLC vs (EVOKE-01 ) #LBA8500 (Oral abstract) Paz-Ales LG, et al. Paz-Ares LG, Juan-Vidal O, Mountzios GS, et al. Sacituzumab Govitecan Versus Docetaxel for Previously Treated Advanced or Metastatic Non-Small Cell Lung Cancer: The Randomized, Open-Label Phase III EVOKE-01 Study. J Clin Oncol. Published online May 31, 2024:JCO2400733. @M_Torasawa

• #90.

  Pickup 17 EVOKE-01 @M_Torasawa Stage IV NSCLC PS 0 1 Actionable 1 Topo1 N = 299 R ICI PFS, ORR, DoR, DCR (investigator) 1:1 N = 304 TROP2 ü ü ü 66 55.9 34.4 9.7 11.7 QOL : (Sq / Non-sq) ICI (CR/PR, PD/SD) 64 54.9 33.2 11.8 12.8 Non-Sq (%) ICI; CR+PR (%) ICI; SD+PD (%) EGFR-TKI (%) ALK-TKI (%) 71.9 35.5 64.2 2.0 0.3 ASCO2024, abst #LBA8500, Paz-Ares LG, et al. J Clin Oncol. Published online May 31, 2024:JCO2400733. p α 0.0223 Disposition SG SG 1 (%) 2 (%) 3 (%) (%) OS SG 73.7 37.2 62.8 4.3 0.3 (n =296*) 12.8% 67.9% * (n = 288*) 4.9% 60.4%

• #91.

  Pickup 17 OS 12.7 EVOKE-01 @M_Torasawa PFS 0.84, (95%CI 0.68 1.04) P = 0.0534 12 SG EFS 12.7 DOC 12 47% 8 6 2 SG 10 37% 14% 8 6 11.1 9.8 4.1 4 2 0 18% 3.9 0 SG SG OS OS HR PS <65 65 *PD/SD DOC 12 10 4 ORR 0.92, (95%CI 0.77 1.11) ICI Sq 0 PD/SD* Non-Sq 1 CR/PR HR 0.75 (95%CI: 0.58 0.97) 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 ASCO2024, abst #LBA8500, Paz-Ares LG, et al. J Clin Oncol. Published online May 31, 2024:JCO2400733. ICI SD/PD Nonresponsive (non-responsive) HR 0.75 Responsive CR/PR HR 1.09 Non-Sq (non-responsive) HR 0.79 Sq (non-responsive) HR 0.62 ICI 0 2 4 6 8 10 12

• #92.

  Pickup 17 G3 AE EVOKE-01 @M_Torasawa DOC SG SG DOC 67% 76% 17% 10% AE SG Overall DOC 33 44 40 -60 1 1 2 1 34 6 6 13 25 37 -40 -20 0 G3 ü 46 30 10 4 43 -80 22 13 10 42 -100 76 67 29 ü 25 G1 2 25 G3 6 20 40 60 80 ASCO2024, abst #LBA8500, Paz-Ares LG, et al. J Clin Oncol. Published online May 31, 2024:JCO2400733. 100 ü AE SG SG

• #93.

  Pickup 17 TROPION-Lung01 EVOKE-01 Status TROPION-Lung01[1] EVOKE-01[2] N 299 299 TROP2 ADC @M_Torasawa HR 0.92 PFS Deruxtecan derivaive SN-38 4 7.6 6mg/kg day1 q3w 10mg/kg day1/8 q3w 61 65 Non-Sq(%) 76 72 (%) 17 DAR (%) 1(%) 56 12 56 2(%) 36 34 7 10 99 100 88 100 15 6 PFS, OS OS 3(%) (%) ICI (%) (%) Primary Endpoint [1] ESMO 2023 #LBA12. [2] ASCO2024, abst #LBA8500. SG DOC (EVOKE-01) Dato-Dxd DOC (TROPION-Lung01) HR 0.75 HR 0.84 OS HR 0.90* 0 *74% 2 4 6 8 10 12 OS 2024.5.27 ü 2 PFS, OS DOC 14 ( )

• #94.

  Pickup 17 EVOKE-01 Summary Discussion points @M_Torasawa OS 1 OS 10% ICI 01 02 ICI TOROPION Lung01 PFS Biological TROPION-Lung01 03 ASCO2024, abst #LBA8007 TROPION-Lung01 OS efflux