In the Phase 3 VIKTORIA-1 trial for HR+/HER2-, PIK3CA-mutant advanced breast cancer, the triplet regimen of gedatolisib plus palbociclib and fulvestrant cut progression-free survival (PFS) to a median of 11.1 months from 5.6 months with alpelisib plus fulvestrant, reducing the risk of progression or death by 50% (HR 0.50; P<.0001).

Celcuity disclosed detailed VIKTORIA-1 results for the PIK3CA-mutant cohort, highlighting gedatolisib in combination regimens and superiority over the single-target approach.

Gedatolisib, in both the triplet and the doublet regimens, demonstrated statistically significant PFS improvements versus alpelisib plus fulvestrant in HR+/HER2-, PIK3CA-mutant disease.

Limitations include that regulatory approval is not guaranteed and future safety and efficacy data could alter the outcomes.

The data reinforce gedatolisib’s multi-target PAM inhibition of PI3K/mTORC1/2, with potential to become a new standard of care pending regulatory approvals and ongoing sNDA submissions to the FDA and other authorities.

Results will be presented at ASCO 2026 in a late-breaking session, framing gedatolisib as a multitarget PAM inhibitor that outperforms alpelisib in this setting.

The press release casts these results as potentially establishing a new standard of care for post-CDK4/6 inhibitor and aromatase inhibitor–treated HR+/HER2-, PIK3CA-mutant ABC, with implications for both first-line and later-line contexts in VIKTORIA-2.

Safety data showed consistent tolerability with prior cohorts; discontinuation rates due to adverse events were low across gedatolisib regimens.

Across regimens, discontinuation due to adverse events was lower for gedatolisib (2.6% for triplet, 3.8% for doublet) than control (7.1%), with common Grade 3+ toxicities including neutropenia, stomatitis, rash, and hyperglycemia.

Gedatolisib’s safety profile appeared more favorable than alpelisib, with notably lower hyperglycemia and diarrhea rates.

Gedatolisib targets multiple PAM pathway components, including all four PI3K isoforms and mTORC1/2, aiming to overcome resistance seen with single-target inhibitors, and is positioned as a first-in-class or best-in-class option in this patient population.

In addition to PIK3CA-mutant disease, there is signal of activity in PIK3CA wild-type disease, suggesting broader potential of pan-PAM inhibition.