CodeBreaK 300 Trial

[Slide 1] Pietrantonio et al A Sotorasib 100 960 mg-panitumumab Investigator's choice (n 53) (n 54) 90 Median os, months NE 10.3 80 HR (95% CI) 0.70 (0.41, 1.18) 70 Pvalue (2-sided) .20 60 50 40 30 20 10 Sotorasib 960 mg-panitumumab 0 Investigator's choice T 0 2 4 6 8 10 12 14 16 18 20 22 Time Since Random Assignment (months) Number at risk: Sotorasib 960 mg- 53 51 46 41 36 31 20 12 4 3 0 panitumumab Investigator's choice 54 49 44 36 30 22 16 9 3 2 1 0 B Sotorasib 100 240 mg-panitumumab Investigator's choice (n - 53) (n 54) 90 Median os, months 11.9 10.3 80 HR (95% CI) 0.83 (0.49, 1.39) 70 Pvalue (2-sided) .50 60 50 40 30 20 10 Sotorasib 240 mg-panitumumab 0 Investigator's choice 0 2 4 6 8 10 12 14 16 18 20 22 Time Since Random Assignment (months) Number at risk: Sotorasib 240 mg- 53 53 44 36 34 25 19 14 6 2 0 panitumumab Investigator's choice 54 49 44 36 30 22 16 9 3 2 1 0 --- [Slide 2] C D Investigator's Sotorasib 960 mg- HR for disease Investigator's Sotorasib 240 mg- HR for disease choice panitumumab progression choice panitumumab progression Subgroup Number of patients or death (95% CI) Number of patients or death (95% CI) All randomly assigned patients 54 53 0.70 (0.41, 1.18) 54 53 0.83 (0.49, 1.39) Age, years <65 26 32 1.10 (0.54, 2.22) 26 39 1.36 (0.70, 2.63) >65 28 21 0.34 (0.14, 0.85) 28 14 0.40 (0.13, 1.25) Sex Male 24 29 0.84 (0.41, 1.76) 24 26 0.90 (0.43, 1.90) Female 30 24 0.53 (0.25, 1.09) 30 27 0.80 (0.38,1.69) Time from initial diagnosis of metastatic disease to random assignment >18 months 31 29 0.59 (0.27, 1.30) 31 29 0.74 (0.35, 1.57) <18 months 23 24 0.74 (0.36, 1.54) 23 22 0.92 (0.45, 1.91) Sidedness Right sided 16 24 0.82 (0.36, 1.88) 16 17 0.63 (0.23, 1.69) Left sided 37 28 0.67 (0.32, 1.40) 37 36 1.01 (0.55, 1.86) Primary tumor location Colon 37 37 0.87 (0.46, 1.63) 37 32 10 0.72 (0.36, 1.43) Rectum 17 16 0.41 (0.15, 1.10) 17 21 1.00 (0.46, 2.16) Number of prior therapy lines for metastatic disease 1-2 27 36 0.76 (0.38, 1.51) 27 29 Hot 0.88 (0.45, 1.75) >3 27 17 0.85 (0.38, 1.92) 27 24 0.78 (0.36, 1.67) Liver metastasis Yes 38 38 0.66 (0.36, 1.23) 38 36 0.97 (0.53, 1.75) No 16 15 0.39 (0.10, 1.49) 16 17 0.41 (0.13, 1.23) - 0.01 1 100 0.01 1 100 Sotorasib 960 mg- Investigator's Choice Sotorasib 240 mg- Investigator's Choice Panitumumab Better Better Panitumumab Better Better FIG 2. os of sotorasib-panitumumab versus investigator's choice. (A) Kaplan-Meier curves of os for sotorasib 960 mg-panitumumab (full analysis set). (B) Kaplan-Meier curves of os for sotorasib 240 mg-panitumumab (full analysis set). (C) Forest plot of sotorasib 960 mg-panitumumab treatment effect on os in subgroup analyses. (D) Forest plot of sotorasib 240 mg-panitumumab treatment effect (continued on following page) --- [Slide 3] 8 Overall Survival Analysis of the Phase III CodeBreaK 300 Study of Sotorasib Plus Panitumumab Versus Investigator's Choice in Chemorefractory KRAS G12C Colorectal Cancer Filippo Pietrantonio, MD ; Lisa Salvatore, MD²,³ ; Taito Esaki, MD4 ; Dominik Paul Modest, MD5 : David Paez Lopez-Bravo, MD6; Julien Taieb, MD7 ID ; Michalis V. Karamouzis, MD8 ; Erika Ruiz-Garcia, MD ID ; Tae Won Kim, MD¹⁰ ; Yasutoshi Kuboki, MD¹¹ ; Fausto Meriggi, MD¹²; David Cunningham, MD¹³ : Kun-Huei Yeh, MD, PhD,¹⁴,¹⁵ ID ; Emily Chan, MD, PhD16; Joseph Chao, MD¹⁶ : Qui Tran, PhD¹⁶ ; Chiara Cremolini, MD¹⁷ ; and Marwan Fakih, MD¹⁸ DOI https://doi.org/10.1200/JCO-24-02026 ABSTRACT ACCOMPANYING CONTENT In the phase III CodeBreaK 300 study, sotorasib 960 mg-panitumumab significantly pro- Appendix longed progression-free survival (PFS) versus investigator's choice (trifluridine/tipiracil or \ Data Sharing regorafenib) in patients with KRAS G12C-mutated chemorefractory metastatic colorectal Statement cancer (mCRC). One hundred sixty patients were randomly assigned 1:1:1 to receive sotorasib / Protocol 960 mg-panitumumab (n = 53), sotorasib 240 mg-panitumumab (n = 53), or investigator's ded from ascopubs.org by 78.175.224.177 on April 12, 2025 from 078.175.224.177 choice (n = 54; crossover permitted after primary analysis). Overall survival (OS) analysis, a Accepted February 21, 2025 key secondary end point, although not adequately powered, was prespecified at 50% ma- pyright c 2025 American Society of Clinical Oncology. All rights reserved. Published April 11, 2025 turity (after approximately 80 deaths). In this study, we report the os, updated overall response rates (ORRs), and data for safety. After a median follow-up of 13.6 months, J Clin Oncol 00:1-8 24, 28, and 30 deaths occurred in the sotorasib 960 mg-panitumumab, sotorasib 240 mg- c 2025 by American Society of panitumumab, and investigator's choice arms, respectively; updated objective response Clinical Oncology rates (ORRs; 95% CI) were 30.2% (95% CI, 18.3 to 44.3), 7.5% (95% CI, 2.1 to 18.2), and 1.9% (95% CI, 0.0 to 9.9), respectively. Compared with investigator's choice, the hazard ratios (HRs [95% CI]) for OS were 0.70 (95% CI, 0.41 to 1.18; two-sided P = .20) with sotorasib View Online Article 960 mg-panitumumab and 0.83 (95% CI, 0.49 to 1.39; two-sided P = .50) with sotorasib 240 mg-panitumumab. No new safety signals were observed. Although not statistically significant, the observed OS HR and ORR along with prior PFS and safety findings support sotorasib 960 mg-panitumumab as a standard of care in patients with chemorefractory KRAS G12C mCRC. Creative Commons Attribution Non-Commercial No Derivatives 4.0 License

[Slide 1] FDA U.S. FOOD & DRUG Q Search Menu ADMINISTRATION Home / Drugs / Development & Approval Process I Drugs / Drug Approvals and Databases / Resources for Information I Approved Drugs / FDA approves sotorasib with panitumumab for KRAS G12C-mutated colorectal cancer FDA approves sotorasib with panitumumab for KRAS G12C-mutated colorectal cancer f Share X Post in Linkedin Email Print On January 16, 2025, the Food and Drug Administration approved sotorasib (Lumakras, Resources for Information Content current as of: I Approved Drugs Amgen Inc.) with panitumumab (Vectibix, Amgen Inc.) for adult patients with KRAS G12C- 01/16/2025 mutated metastatic colorectal cancer (mCRC), as determined by an FDA-approved test, Oncology who have received prior fluoropyrimidine-, oxaliplatin-, and irinotecan-based Regulated Product(s) (Cancer)/Hematologic chemotherapy. Drugs Malignancies Approval Oncology Notifications Today, the FDA also approved the therascreen KRAS RGQ PCR Kit (QIAGEN GmbH) as a companion diagnostic device to aid in identifying patients with colorectal cancer whose Ongoing Cancer tumors harbor KRAS G12C mutations and who may be eligible for Lumakras with Vectibix. Accelerated Approvals

[Slide 1] FDA U.S. FOOD & DRUG ADMINISTRATION

[Slide 1] OncLive ON AIR® Insight Into the Latest FDA Approvals Dr Fakih discusses the significance of the FDA approval of sotorasib plus panitumumab for the treatment of adult patients with KRAS G12C-mutated mCRC, key findings from the pivotal CodeBreaK 300 trial, and how this combination fits into the current KRAS G12C-mutated mCRC treatment paradigm. Marwan G. Fakih, MD #OncLiveOnAir City of Hope Download episodes from iTunes or onclive.com/podcasts

[Slide 1] Secondary Endpoint: Protocol-Specified Final OS in Intent- to-Treat Population - Solorasib 960 mg Botorasib 240 mg Investigator's I I 2 " - Panitumumab + Panitumumab Choice M (s* 53) in 53) in 54) 0 - Median (95% CI) 05, Soloras $60 mg . Paniumumab NE (B.6-NE) 11.9(7,5-NE) 103(7.0-NE) months' . investigator's Choice - , , - HR (95% City 0.70 (0.41-1.15) 0.83 (0.49-1.39) - . - : . a 4 Months From Randomization - / - - " - - - - . . . . Pivalue (2-sided) 0.20 0.50 - 1 - - - . . I . . - - - - - - Number of deaths (%) 24(45) 28 (53) 30(56) - I I 2 a - $ - After a median follow-up of 13.6 months, sotorasib (240 mg - - and 960 mg) . panitumumab showed a trend of improved Solorasb 240 mg . Panitumab os versus Investigator's choice, with 30% reduction In risk . Investigator's Choice a . - 4 1 - 16 - . of death for sotorasib 960 mg . panitumumab . - From - - - - . : - 1 . . . : - - - I . - . - - - - father - extrat, - W&Ch - - by - - = - - - or Ch , - dated - proportional - - - - node or - 112 - adcass - - - supe os - - Information and grad registered) $ almoted any - - exampled - Date - M December - a - and MR Asset - ASCO - - - - Marwan 0. Faith MD ENDOLEDGE CANCER 2024 ASCO #ASCO24 - - - . | ANNUAL MEETING - -