Slide 1: Ivonescimab combined with chemotherapy in EGFR-mutant non-squamous NSCLC (HARMONi-A)
Ivonescimab combined with chemotherapy in patients with EGFR-mutant non-squamous non-small cell lung cancer who progressed on EGFR-TKIs treatment: a randomized, double-blind, multi-center, phase 3 trial (HARMONi-A study) Li Zhang1, Wenfeng Fang1, Yuanyuan Zhao1, Yongzhong Luo2, Runxiang Yang3, Yan H
Slide 2: Background
2 Background • For patients with EGFR-mutant NSCLC, upfront treatment with tyrosine kinase inhibitors is standard. However, drug resistance remains a challenge, and an effective therapy after progression is needed. • Each slide: • No more than 30-40 words • Ivonescimab per slide (AK112/SMT112) is an
Slide 3: HARMONi-A Study Design
3 HARMONi-A Study Design Ivonescimab Ivonescimab Key Eligibility Criteria 20mg/kg 20mg/kg Q3W + + Treatment until: • nsq-NSCLC (Stage IIIB/C ineligible for surgery or Pemetrexed 500 mg/m2 Pemetrexed 500 local therapy and IV ) Carboplatin AUC5 • Intolerable toxicity mg/m2 Q3W • EGFR sensitive mutatio
Slide 4: Statistical Analyses
4 Statistical Analyses • Estimated sample size: • Each slide: ▪ 320 patients (assuming HR=0.65, overall α=0.025 [one-side], power=89% for PFS) • No more than 30-40 words per slide • No more • Analysis than 6 lines of text methods: ▪• A Include stratified citations, log-rank testwhere applicable was
Slide 5: Disposition of Study Treatment
5 Disposition of Study Treatment 501 patients assessed for eligibility 179 ineligible 169 violated inclusion or met exclusion criteria 5 withdrawal of consent 1 loss to follow-up 4 others 322 enrolled and randomly assigned 161 ivonescimab plus chemotherapy 161 placebo plus chemotherapy 77 discountin
Slide 6: Baseline Characteristics
6 Baseline Characteristics Ivonescimab + Chemotherapy (N=161） Placebo + Chemotherapy (N=161) Age, n(%) Median (rang)，years 59.6 (32.3, 74.9) 59.4 (36.2, 74.2) <65 111 (68.9) 110 (68.3) ≥65 50 (31.1) 51 (31.7) Sex, n(%) Male 77 (47.8) 79 (49.1) Female 84 (52.2) 82 (50.9) ECOG, n(%) 0 24 (14.9) 34 (21
Slide 7: Study Met Primary Endpoint of PFS per IRRC
7 Study Met Primary Endpoint of PFS per IRRC HR and P-value were stratified by previous 3rd Gen EGFR-TKI ues (yes vs. no) and presence of brain metastases (yes vs. no), and were calculated with stratified Cox model and log rank test. The two-sided P-value boundary is 0.024 as calculated using Lan-De
Slide 8: Subgroup Analysis of PFS per IRRC
8 Subgroup Analysis of PFS per IRRC No. of events/No. of patients HR (95% CI) No. of events/No. of patients HR (95% CI) Ivonescimab Placebo Ivonescimab Placebo + Chemo + Chemo + Chemo + Chemo Ivonescimab is an investigational therapy not approved by any regulatory authority other 8 than China’s Nati
Slide 9: PFS of 19del and L858R
9 PFS of 19del and L858R PFS Kaplan Meier Curve Evaluated by IRRC PFS Kaplan Meier Curve Evaluated by IRRC with 19del with L858R Probability of Progression-free survival (%) Probability of Progression-free survival (%) HR (95% CI): 0.48 (0.32, 0.73) HR (95% CI): 0.43 (0.27, 0.67) Ivonescimab is an i
Slide 10: PFS by Presence of Brain Metastases
10 PFS by Presence of Brain Metastases PFS Kaplan Meier Curve Evaluated by IRRC PFS Kaplan Meier Curve Evaluated by IRRC without Brain Metastasis with Brain Metastasis Probability of Progression-free survival (%) Probability of Progression-free survival (%) HR HR (95% CI): 0.48 (0.34, 0.69) HR(95% (
Slide 11: ORR, DCR and DoR per IRRC
ORR, DCR and DoR per IRRC Ivonescimab Placebo + Chemo + Chemo 3 3 ORR, % 50.6 35.4 (95% CI) (42.6, 58.6) (28.0, 43.3) DCR, % 93.1 83.2 (95% CI) (88.0, 96.5) (76.5, 88.6) 3 3 33 Median DoR, 6.6 4.2 month (4.3, 7.6) (3.0, 4.7) (95% CI) RD, rate difference; CI, confidence interval. RD and CI were calcu
Slide 12: Overall Survival (at 30% of data maturity)
12 Overall Survival (at 30% of data maturity) HR: 0.72 (0.48, 1.09) after 96 events, 30% data maturity Two OS analyses were performed per request by Chinese Regulatory Authority (1st analysis at 30% and 2nd at 52% of data maturity) Data cutoff date: June 25, 2023 (median follow-up of 10.2 months) HR
Slide 13: Overall Survival (at 52% of Data Maturity)
13 Overall Survival (at 52% of Data Maturity) HR: 0.80 (0.59, 1.08) after 52% of data maturity OS is consistent for both analysis Data cutoff date: December 2023 (median follow-up of 17.6 months) HR, hazard ratio; CI, confidence interval. Ivonescimab is an investigational therapy not approved by any
Slide 14: Safety Summary
14 Safety Summary Ivonescimab + Placebo + TRAE, n(%) Chemotherapy Chemotherapy (N=161） (N=161) Any grade 158 (98.1) 153 (95.0) Grade≥3 87 (54.0) 69 (42.9) Serious* 46 (28.6) 26 (16.1) Led to discontinuation of ivonescimab/placebo 9 (5.6) 4 (2.5) Led to death 0 (0.0) 0 (0.0) G d ≥3 u -related 10 (6.2
Slide 15: Treatment-Related Adverse Events Grade ≥3
15 T M Ad E d ≥ WBC count decreased Neutrophil count decreased Platelet count decreased Ivonescimab is an investigational therapy not approved by any regulatory authority other 15 than China’s National Medical Products Administration (NMPA) Presented by Dr. Li Zhang, MD / ASCO 2024
Slide 16: Immune-related Adverse Events (irAE)
16 Immune-related Adverse Events (irAE) Categories Ivonescimab + Chemotherapy (N=161） Placebo + Chemotherapy (N=161) Preferred Term, n(%) Any grade G d ≥3 Any grade G d ≥3 irAE 39 (24.2) 10 (6.2) 10 (6.2) 4 (2.5) Hypothyroidism 17 (10.6) 1 (0.6) 0 0 Hyperthyroidism 9 (5.6) 0 0 0 Rash 6 (3.7) 4 (2.5)
Slide 17: Adverse Events of Special Interest (AESI)
17 Adverse Events of Special Interest (AESI) Categories Ivonescimab + Chemotherapy (N=161） Placebo + Chemotherapy (N=161) Preferred Term, n(%) Any grade G d ≥3 Any grade G d ≥3 AESI 48 (29.8) 5 (3.1) 25 (15.5) 4 (2.5) Proteinuria 28 (17.4) 1 (0.6) 13 (8.1) 0 Haemorrhage 11 (6.8) 0 8 (5.0) 0 Urinary
Slide 18: Conclusions
18 Conclusions • Ivonescimab plus chemotherapy significantly improved PFS in patients who progressed on prior EGFR-TKIs treatments: PFS HR 0.46 (95% CI: 0.34, 0.62), P<0.001 • The prespecified subgroup analysis showed PFS benefit favoring patients receiving ivonescimab over those receiving the place
Slide 19: Acknowledgement
19 Acknowledgement We thank all the patients and their families, investigators and all team members for supporting this trial. The study was supported by Akeso Biopharma, Inc., Zhongshan, China. 19 Presented by Dr. Li Zhang, MD / ASCO 2024
Slide 20: Ivonescimab is an investigational therapy not approved by any regulatory authority other than China’s
Ivonescimab is an investigational therapy not approved by any regulatory authority other 20 than China’s National Medical Products Administration (NMPA) Presented by Dr. Li Zhang, MD / ASCO 2024