INAVO120: Phase III trial final overall survival (OS) analysis of first-line inavolisib (INAVO)/placebo (PBO) + palbociclib (PALBO) + fulvestrant (FULV) in patients (pts) with <i>PIK3CA</i> -mutated, hormone receptor-positive (HR+), HER2-negative (HER2–), endocrine-resistant advanced breast cancer (aBC).
Bibliographic record
Abstract
1003 Background: INAVO, a highly potent and selective PI3Kα inhibitor that also promotes mutated p110α degradation, is FDA-approved in combination with PALBO + FULV for PIK3CA -mutated, HR+, HER2–, endocrine-resistant aBC, based on the primary analysis of INAVO120 (NCT04191499), which showed a statistically significant and clinically meaningful investigator-assessed progression-free survival (INV-PFS) benefit in the INAVO arm vs. the PBO arm (hazard ratio 0.43; 95% confidence interval [CI] = 0.32–0.59; p < 0.0001). At that analysis, interim OS results were immature. Here we report the final OS analysis, including updated efficacy and safety. Methods: Pts received INAVO (9 mg orally once daily [PO QD]; Days 1–28 of each 28-day cycle)/PBO + PALBO (125 mg PO QD; Days 1–21 of each cycle) + FULV (500 mg intramuscularly; Cycle 1 Days 1 and 15 then every ~4 weeks). OS and objective response rate (ORR) were formally tested; updated INV-PFS and safety analyses are descriptive. Results: Data cut-off was Nov 15, 2024, at 34.2 months (mo) of median follow-up. Median OS was 34.0 mo (95% CI = 28.4–44.8) in the INAVO arm and 27.0 mo (95% CI = 22.8–38.7) in the PBO arm (stratified hazard ratio 0.67; 95% CI = 0.48–0.94; p = 0.0190 [boundary = 0.0469]). The OS benefit was consistent across key subgroups. The survival probability at 6, 12, 18, 24, and 30 mo was 96.8%, 87.0%, 74.3%, 65.8%, and 56.5% in the INAVO arm and 90.1%, 76.7%, 67.2%, 56.3%, and 46.3% in the PBO arm. ORR was 62.7% (95% CI = 54.8–70.2) and 28.0% (95% CI = 21.3–35.6), respectively (p < 0.0001). Median time to chemotherapy (TTC) was 35.6 mo (95% CI = 25.4–not reached) in the INAVO arm and 12.6 mo (95% CI = 10.4–16.1) in the PBO arm (stratified hazard ratio 0.43; 95% CI = 0.30–0.60). Updated median INV-PFS was 17.2 mo (95% CI = 11.6–22.2) in the INAVO arm and 7.3 mo (95% CI = 5.9–9.2) in the PBO arm (stratified hazard ratio 0.42; 95% CI = 0.32–0.55), with landmark analyses supporting durable benefit. 90.7% of pts in the INAVO arm and 84.7% in the PBO arm had grade 3/4 adverse events (AEs); there were no new grade 5 AEs; 63.4% and 13.5% experienced any-grade hyperglycemia (grouped term); and AEs led to INAVO and PBO discontinuation in 6.8% and 0.6% of pts, respectively. Conclusions: INAVO + PALBO + FULV demonstrated a statistically significant and clinically meaningful OS benefit compared with PBO + PALBO + FULV. Improvement in INV-PFS was maintained during longer follow-up, along with a substantial and statistically significant improvement in ORR. TTC was also substantially delayed (by ~2 years) by the addition of INAVO to PALBO + FULV. With longer exposure to INAVO, no new safety signals, nor changes in the safety profile, were noted, supporting good tolerability (reflected in low discontinuation due to AEs). Clinical trial information: NCT04191499 .
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.006 | 0.001 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".