INAVO120 phase 3 trial: Subgroup analyses of Asian patients (pts) with PIK3CA -mutated (mut), hormone receptor-positive, HER2-negative (HER2–), endocrine-resistant advanced breast cancer (aBC) treated with inavolisib (INAVO)/placebo (PBO) + palbociclib (PALBO) + fulvestrant (FULV).

28 Background: INAVO is an oral, highly potent, and selective PI3Kα inhibitor that also promotes mut p110α degradation. In INAVO120 (NCT04191499), INAVO + PALBO + FULV showed statistically significant and clinically meaningful improvements in investigator-assessed progression-free survival (PFS; hazard ratio HR at primary analysis 0.43; 95% confidence interval CI = 0.32–0.59; p < 0.0001) and overall survival (OS; HR at final analysis 0.67; 95% CI = 0.48–0.94; p = 0.0190) v PBO + PALBO + FULV. We report subgroup analyses of Asian pts. Methods: Pts received INAVO (9 mg orally once daily PO QD) + PALBO (125 mg PO QD; Days 1–21 of each 28-day cycle) + FULV (500 mg intramuscularly; Cycle 1 Days 1 and 15 then every ~4 weeks) or PBO (PO QD) + PALBO + FULV. PFS, OS, duration of response (DoR), time to first subsequent chemotherapy (CT)/death, objective response rate (ORR), safety, and post-progression treatment (tx) were analyzed. Results: At clinical cut-off (Nov 15, 2024), 120 Asian pts were randomized (58 to INAVO; 62 to PBO). Median INAVO and PBO tx duration was 13.0 months (mo; range 0.9–52.3) v 6.2 mo (0.1–40.3), respectively. Median age was 52 years (range 27–77) in the INAVO arm v 50 years (33–79) in the PBO arm; 22.4 v 32.2% of pts had body mass index ≥25.0. Efficacy is shown in the Table. Grade 3–4 AEs occurred in 98.3 v 87.1% of pts; serious AEs, in 29.3 v 9.7% (most common: pyrexia 5.2% and febrile neutropenia 5.2% with INAVO v vomiting 3.2% with PBO). AEs leading to INAVO/PBO discontinuation occurred in 3.4% (transitional cell carcinoma 1.7%, acute kidney injury 1.7%) v 0% of pts; AEs leading to INAVO/PBO dose reduction, in 13.8 v 1.6% (most common: stomatitis 3.4% v rash 1.6%); AEs leading to INAVO/PBO dose interruption, in 72.4 v 27.4% (most common: hyperglycemia 31.0% v neutrophil count decreased 8.1%). The most common post-progression tx was CT (50.0 v 76.7% at second line). Conclusions: Consistent with the intention-to-treat (ITT) population, INAVO + PALBO + FULV showed a clinically meaningful efficacy benefit in Asian pts, with no new safety signals and numerically lower INAVO discontinuation and dose reduction rates v the ITT population. These data further support the benefit of the INAVO120 regimen in PIK3CA mut, hormone receptor-positive, HER2–, endocrine-resistant aBC. Clinical trial information: NCT04191499 . INAVO arm(n = 58) PBO arm(n = 62) HR (95% CI) Median PFS, mo (95% CI) 14.8 (9.3–21.1) 6.8 (5.4–9.2) 0.38 (0.24–0.59) Median OS, mo (95% CI) 32.7 (20.5–NR) 27.0 (20.1–NR) 0.74 (0.43–1.27) Median time to first subsequent CT/death, mo (95% CI) 19.2 (12.5–32.7) 10.6 (6.7–14.1) 0.47 (0.30–0.74) (n = 35) (n = 17) Median DoR, mo (95% CI) 18.8 (14.7–NR) 10.7 (7.5–NR) (n = 58) (n = 62) Δ, % (95% CI) ORR, % 60.3 27.4 32.9 (16.1, 49.7) NR, not reached.