Akeso (9926) WCLC 2024 Presentation summary

Study background and design

• Anti-PD-1/L1 monotherapy or with chemotherapy is standard for first-line PD-L1+ advanced NSCLC, but monotherapy offers limited benefit.

• Ivonescimab is a bispecific antibody targeting PD-1 and VEGF, showing promising efficacy and safety in phase 2.

• HARMONI-2 is a randomized, double-blind, phase 3 trial comparing ivonescimab to pembrolizumab in first-line PD-L1+ advanced NSCLC.

• 398 patients with stage IIIB-IV aNSCLC, no EGFR/ALK alterations, and PD-L1 TPS ≥1% were randomized 1:1.

• Primary endpoint was PFS by IRRC; secondary endpoints included OS, ORR, DCR, DoR, TTR, safety, and QoL.

Patient characteristics

• Median age was balanced; 54.3% were ≥65 years, and 83.7% were male.

• Most patients had ECOG PS 1 (87.2%) and stage IV disease (92.2%).

• 45.5% had squamous histology; 42.2% had PD-L1 TPS ≥50%.

• 13.3% had liver metastases, and 18.1% had brain metastases.

Efficacy results

• Ivonescimab significantly improved PFS vs. pembrolizumab (median 11.14 vs. 5.82 months; HR 0.51; p<0.0001).

• PFS benefit was consistent across subgroups, including age, sex, ECOG, smoking status, metastases, stage, histology, and PD-L1 expression.

• Subgroup analysis: HR 0.46 for PD-L1 ≥50%, HR 0.54 for PD-L1 1-49%, HR 0.48 for squamous, HR 0.54 for non-squamous.

• ORR was 50.0% for ivonescimab vs. 38.5% for pembrolizumab; DCR was 89.9% vs. 70.5%.

• Median DoR was not reached in either arm at data cutoff.