Summit Therapeutics Inc. · NASDAQ:SMMT
Summit Therapeutics — WCLC 2025 (IASLC World Conference on Lung Cancer) Presidential Presentation
15 slides from Summit Therapeutics's conference presentation, Sep 5, 2025
Slide 1: Ivonescimab vs Placebo Plus Chemo, Phase 3 in EGFR+ NSCLC: HARMONi
Ivonescimab vs Placebo Plus Chemo, Phase 3 in Patients with EGFR+ NSCLC Progressed with 3rd gen EGFR-TKI Treatment: HARMONi Jonathan W. Goldman1, Antonio Passaro2, Janessa Laskin3, Delvys Rodrigues-Abreu4, Antonio Calles5, Lyudmila Bazhenova6, Giuseppe Lo Russo7, Natasha Leighl8, Frederico Cappuzzo9
Slide 2: Phase 3 Study Design
Phase 3 Study Design Ivonescimab + Endpoints: Key Eligibility Criteria Chemotherapy Primary Locally advanced or (N = 219) • OS, PFS by IRRC per RECIST 1.1 metastatic NSCLC: • EGFR sensitizing R Secondary mutation+ 1:1 • ORR by IRRC, DoR, safety and • Progressed on 3rd gen tolerability EGFR-TKI N=438
Slide 3: Demographic and Baseline Characteristics
Demographic and Baseline Characteristics Arms were well-balanced; majority were females, ECOG 1, never smokers; 25% with brain mets Ivonescimab+chemo Placebo+chemo Characteristic, n (%) (N=219) (N=219) Age – Median (range) 62 (32-84) 60 (36-84) ≥65 yr 83 (37.9) 88 (40.2) Female 130 (59.4) 127 (58.0)
Slide 4: Primary Endpoint: PFS by IRRC
Primary Endpoint: PFS by IRRC Statistically significant and clinically meaningful benefit with ivonescimab 100 median FU: 22.3 mo Events, n (%) Median HR P Value (mo) (95% CI) 80 Ivonescimab+chemo 129 (75.0) 6.8 0.52 <0.0001 Placebo+chemo 146 (84.4) 4.4 (0.41-0.66) 60 PFS (%) 54.0% 40 34.7% Ivonesci
Slide 5: PFS by IRRC – Subgroup Analysis
PFS by IRRC – Subgroup Analysis Consistent across pre-defined subgroups Ivonescimab Placebo + Favors Ivonescimab Favors Placebo Hazard Ratio + chemo chemo + chemo + chemo (95% CI) Ivo + chemo Pbo + chemo HR (Events/N) (Events/N) Overall population 129/172 146/173 0.52 (0.41-0.66) Age <65 years 89/11
Slide 6: PFS by Presence or Absence of Brain Mets
PFS by Presence or Absence of Brain Mets 100 100 Pts with Brain Mets at Baseline: Pts with No Brain Mets at Baseline: HR = 0.34 (95% CI: 0.20-0.57) HR = 0.59 (95% CI: 0.45-0.77) 80 80 60 Ivonescimab+chemo Ivonescimab+chemo PFS (%) 60 PFS (%) Placebo+chemo Placebo+chemo 40 40 20 20 0 0 0 3 6 9 12 15
Slide 7: PFS by IRRC: Primary Analysis vs Longer Term Follow-Up (LTF)
PFS by IRRC: Primary Analysis vs Longer Term Follow-Up (LTF) Consistent PFS between primary and LTF including all NA & EU patients 100 Primary analysis (median FU: 22.3 mo, N=345): Ivonescimab+chemo (Primary) HR = 0.52 (95% CI: 0.41-0.66) Placebo+chemo (Primary) 80 LTF analysis (median FU: 29.7 mo,
Slide 8: Primary Endpoint: Overall Survival
Primary Endpoint: Overall Survival Favorable Trend Observed; NA & EU Follow-up Not Yet Mature 100 Events, n Median HR P Value (%) (mo) (95% CI) 80 Ivonescimab + chemo 122 (55.7) 16.8 0.79 0.0570 (0.62-1.01) Placebo + chemo 140 (63.9) 14.0 60 OS (%) Ivonescimab+chemo 40 Placebo+chemo Median FU: 20 Ov
Slide 9: Overall Survival: Longer Term Western Follow-up
Overall Survival: Longer Term Western Follow-up OS stable with longer term Western data, nominal p=0.0332 Events, n Median HR P Value 100 (%) (mo) (95% CI) Ivonescimab + chemo 134 (61.2) 16.8 0.78 0.0332 (0.62-0.98) 80 Placebo + chemo 157 (71.7) 14.0 Region Median FU Median OS (mo) (mo) 60 OS (%) NA
Slide 10: Overall Survival Subgroup Analysis – Longer Term FU
Overall Survival Subgroup Analysis – Longer Term FU Consistent across pre-defined subgroups Ivonescimab Placebo Favor Ivonescimab Favor Placebo Hazard Ratio + chemo + chemo + chemo + chemo (95% CI) (Events/N) (Events/N) Overall population 134/219 157/219 0.78 (0.62-0.98) Age <65 years 90/136 99/131
Slide 11: Overall Response Rate and Duration of Response
Overall Response Rate and Duration of Response By IRRC 100% 80% 84% DCR 73% 60% ORR/DCR DCR DoR (mo) Ivonescimab + Placebo + 40% chemo chemo 45% ORR n 98 75 34% 20% ORR Median (95% CI) 7.6 (5.5-10.6) 4.2 (2.9-4.7) 0% Ivonescimab+chemo Placebo+chemo 11 CI=confidence interval; DCR=disease control rate
Slide 12: Treatment-Related Adverse Events (TRAEs)
Treatment-Related Adverse Events (TRAEs) Most common were lab abnormalities, nausea, decreased appetite 50.0 95.0 Ivonescimab + Placebo + Total 42.2 93.1 TRAE, n(%) chemo chemo Anemia 10.1 12.4 49.1 56.4 (N=218) (N=218) 12.8 45.0 WBC count decreased 11.0 44.0 Any Grade 207 (95.0) 203 (93.1) Neutroph
Slide 13: Immune-related and VEGF-related TRAEs
Immune-related and VEGF-related TRAEs Most common irAEs: hypo/hyperthryroidism, transaminase elevation, rash; mostly low grade Most common VEGF-related TRAEs: proteinuria, hypertension, hemorrhage; mostly low grade irAE VEGF-related 9.6 33.0 7.3 33.5 Total 6.0 17.9 Total 3.2 15.1 Hypothyroidism 0.5
Slide 14: Summary
Summary • Ivonescimab had a significant and clinically meaningful PFS benefit in EGFRm+ NSCLC patients post-3rd gen TKI • Reduced risk of progression or death by 48% vs chemotherapy, HR=0.52 • Consistent efficacy across pre-defined subgroups • Increased ORR and DoR • OS final analysis showed favorab
Slide 15: Acknowledgements
Acknowledgements Thank you to everyone who made this trial possible: • The patients and their families • The personnel at all the clinical study sites • The scientists, regulatory, operations, and other teams within Summit and Akeso who helped develop ivonescimab and supported the study The study wa