Slide 1: Phase 3 Study of Ivonescimab (AK112) vs. Pembrolizumab as First-line Treatment: HARMONi-2
Phase 3 Study of Ivonescimab (AK112) vs. Pembrolizumab as First-line Treatment for PD-L1- positive Advanced NSCLC: HARMONi-2 C. Zhou1,2, J. Chen3, L. Wu3, L. Wang1, A. Xiong1, B. Liu4, J. Yao5, H. Zhong6, J. Li7, Y. Cheng8, Y. Sun9, H. Ge10, Q. Shi11, M. Zhou12, Z. Han13, J. Wang14, Q. Bu15, Y. Zhao
Slide 2: Disclosures
Disclosures • Honoraria as a speaker: Lily China, Sanofi, BI, Roche, MSD, Qilu, Hengrui, Innovent Biologics, C-Stone, LUYE Pharma, TopAlliance Biosciences Inc, Amoy Diagnositics. • Advisor: Innovent Biologics, Hengrui, Qilu, TopAlliance Biosciences Inc. Caicun Zhou | HARMONi-2 2
Slide 3: Background
Background • Anti-PD-1/L1 monotherapy or in combination with chemotherapy has been the standard of care for the first-line treatment of PD-L1 positive aNSCLC without driver gene alterations • Monotherapy with an immune checkpoint inhibitor provides limited clinical benefit for PD-L1 positive aNSCLC1
Slide 4: HARMONi-2 (AK112-303) Study Design
HARMONi-2 (AK112-303) Study Design A randomized, double-blind, phase 3 studya Patient Population Ivonescimab • Stage IIIB-IV aNSCLC 20 mg/kg Q3W (N=198) Treatment until no clinical • No prior systemic therapy R benefit, • No EGFR mutations or ALK 1:1 unacceptable rearrangements toxicity or up to • E
Slide 5: Baseline Characteristics
Baseline Characteristics Characteristics, n (%) Ivonescimab Pembrolizumab Total (n = 198a) (n = 200a) (n = 398a) <65 97 (49.0) 85 (42.5) 182 (45.7) Age (years) ≥65 101 (51.0) 115 (57.5) 216 (54.3) Male 164 (82.8) 169 (84.5) 333 (83.7) Sex Female 34 (17.2) 31 (15.5) 65 (16.3) 0 25 (12.6) 26 (13.0) 51
Slide 6: Primary endpoint: PFS per IRRC
Primary endpoint: PFS per IRRC Ivonescimab Pembrolizumab (n = 198) (n = 200) mPFS, mos 11.14 5.82 (95% CI) (7.33, NE) (5.03, 8.21) Stratified HR 0.51 (95% CI) (0.38, 0.69) p-value <0.0001 9-mo: 56% (47, 64) 9-mo: 40% (32, 48) Median Follow-up: 8.67 months Ivonescimab demonstrated a statistically sig
Slide 7: PFS Subgroup Analyses
PFS Subgroup Analyses Ivonescimab Pembrolizumab Unstratified Hazard Ratio Events/Patients Events/Patients (95% CI) Overall 72/198 112/200 0.51 (0.38, 0.69) Age <65 37/97 50/85 0.53 (0.34, 0.81) ≥65 35/101 62/115 0.52 (0.34, 0.79) Sex Male 58/164 94/169 0.53 (0.38, 0.74) Female 14/34 18/31 0.49 (0.24
Slide 8: Key PFS Subgroup Analyses
Key PFS Subgroup Analyses PD-L1 Low (TPS 1-49%) PD-L1 High (TPS ≥50%) Stratified HR 0.54 Stratified HR 0.46 (95% CI) (0.37, 0.79) (95% CI) (0.28, 0.75) PD-L1 expression Squamous Non-Squamous Stratified HR 0.48 Stratified HR 0.54 (95% CI) (0.31, 0.74) (95% CI) (0.36, 0.82) NSCLC Histology Ivonescimab
Slide 9: ORR, DCR and DoR per IRRC
ORR, DCR and DoR per IRRC Ivonescimab Pembrolizumab (n = 198) (n = 200) ORR, % 50.0 38.5 (95% CI) (42.8, 57.2) (31.7, 45.6) DCR, % 89.9 70.5 (95% CI) (84.8, 93.7) (63.7, 76.7) Median DoR, mos NR NR (95% CI) (NE, NE) (8.28, NE) ORR and DCR were higher with ivonescimab vs. pembrolizumab. Data cut off:
Slide 10: Safety Summary
Safety Summary TRAEs The Most Common TRAEs (incidence ≥10%) Ivonescimab Pembrolizumab Safety Summary, n (%) (n = 197a) (n = 199a) TRAEs (all grades) 177 (89.8) 163 (81.9) Grade≥3 58 (29.4) 31 (15.6) Serious TRAEs 41 (20.8) 32 (16.1) Leading to discontinuation 3 (1.5) 6 (3.0) b Leading to death 1 (0.
Slide 11: Immune-Related and Possible VEGF-Related AEs
Immune-Related and Possible VEGF-Related AEs irAEs Possible VEGF-Related AEs Ivonescimab Pembrolizumab Ivonescimab Pembrolizumab Safety Summary, n (%) Safety Summary, n (%) (n = 197a) (n = 199a) (n = 197a) (n = 199a) Possible VEGF-Related 94 (47.7) 42 (21.1) irAEs (all grades) 59 (29.9) 56 (28.1) AE
Slide 12: Global Health Status – EORTC QLQ-C30
Global Health Status – EORTC QLQ-C30 Time to deterioration of global health status – EORTC QLQ-C30a Stratified HR 0.92 (95% CI) (0.63, 1.33) Median time to deterioration (mos): NR (9.63, NE) Median time to deterioration (mos): 9.92 (8.02, NE) b b Ivonescimab was associated with comparable, numerical
Slide 13: Conclusions
Conclusions • First-line ivonescimab significantly improve IRRC-assessed PFS in patients with aNSCLC and PD-L1 TPS ≥1%, compared with pembrolizumab (median PFS (mos), 11.14 vs. 5.82; HR, 0.51; p<0.0001). • PFS benefit with ivonescimab were consistent across major clinical subgroups: TPS ≥50%, HR =
Slide 14: Acknowledgments
Acknowledgments • We sincerely thank all the participants and their families • Thank you to all of the investigators and study site personnel from 55 sites • Thanks to all personnel of Akeso Biopharma, Inc. who supported the study Caicun Zhou | HARMONi-2 14