Inavolisib (PI3Kα inhibitor/p110α degrader) more than doubles PFS vs placebo in Asian PIK3CA-mut HR+/HER2– aBC

In the Phase 3 INAVO120 trial (NCT04191499), inavolisib (INAVO) is an oral, selective PI3Kα inhibitor that also promotes degradation of mutant p110α, combined with palbociclib (CDK4/6 inhibitor) plus fulvestrant (SERD) in endocrine-resistant, PIK3CA-mutated HR+/HER2– advanced breast cancer. In the Asian subgroup (n=120; 58 INAVO vs 62 placebo), median PFS was 14.8 vs 6.8 months (HR 0.38; 95% CI 0.24–0.59) and ORR was 60.3% vs 27.4% (Δ 32.9%); median OS was 32.7 vs 27.0 months (HR 0.74; 95% CI 0.43–1.27). Grade 3–4 AEs were high (98.3% vs 87.1%) with more serious AEs (29.3% vs 9.7%) and frequent dose interruptions (72.4% vs 27.4%; hyperglycemia interruption 31.0% with INAVO), but discontinuations remained low (3.4% vs 0%); efficacy looks substantially stronger than historical PI3K-pathway endocrine combos like alpelisib+fulvestrant in SOLAR-1 (median PFS 11.0 vs 5.7 months in PIK3CA-mut disease, without CDK4/6) and AKT inhibition with capivasertib+fulvestrant in CAPItello-291 biomarker-positive tumors (median PFS 7.3 vs 3.1 months).