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 wi

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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 .