Celcuity VIKTORIA-1 data show gedatolisib doubles PFS in subgroup

Celcuity's gedatolisib triplet achieved 21.5 months median PFS versus 9.1 months for alpelisib in PIK3CA-mutant breast cancer patients without liver metastases.

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Celcuity has presented updated subgroup analyses from the PIK3CA mutant cohort of its Phase 3 VIKTORIA-1 study at the European Society of Medical Oncology Congress 2026, reporting that its gedatolisib triplet more than doubled median progression-free survival against the comparator arm in patients without liver metastases.

The data, presented by Dr Barbara Pistilli of Gustave Roussy, showed that patients with no liver metastases who received gedatolisib plus fulvestrant plus palbociclib achieved a median PFS of 21.5 months, compared with 11.5 months for the gedatolisib doublet and 9.1 months for alpelisib plus fulvestrant. A hazard ratio of 0.46 against control was reported for the triplet arm. Celcuity notes that patients without liver metastases represent roughly 60 to 70 per cent of those treated in this second-line setting, making this a commercially significant subpopulation.

Efficacy and tolerability

The objective response rate for the gedatolisib triplet in the PIK3CA mutant cohort reached 59 per cent, with a median duration of response of 19.4 months, against 33 per cent and 7.5 months respectively for alpelisib plus fulvestrant. The doublet arm recorded a 43 per cent ORR and a median duration of response of 27.8 months, though the arm enrolled fewer patients.

Tolerability data were a notable feature of the presentation. Discontinuation rates due to treatment-emergent adverse events with the gedatolisib regimens were 5 per cent for the triplet and 4 per cent for the doublet, compared with 19 per cent for alpelisib. Grade 3 stomatitis, a class effect associated with PI3K inhibition, was described as transient: fewer than 3 per cent of patients had Grade 3 events by the second treatment cycle, and all resolved within one to two weeks.

Igor Gorbachevsky, Chief Medical Officer of Celcuity, said the median duration of response exceeded 19 months for the gedatolisib triplet in both the PIK3CA wild-type and mutant cohorts, describing this as, to the company's knowledge, "the longest median duration of response results ever reported for a therapeutic regimen used in the primary analysis for a Phase 3 trial in the second-line HR+/HER2- advanced breast cancer setting."

Market context and competitive landscape

HR+/HER2- advanced breast cancer is the largest breast cancer subtype by volume, accounting for approximately 70 per cent of all cases globally. The second-line setting after CDK4/6 inhibitor and endocrine therapy failure has been a particularly active area of drug development, with PI3K pathway inhibition representing one of the leading mechanistic approaches alongside antibody-drug conjugates and next-generation endocrine agents.

Alpelisib, a PI3K-alpha-selective inhibitor marketed by Novartis, has faced tolerability headwinds in real-world use, with hyperglycaemia and stomatitis contributing to discontinuations above those seen in trial settings. Gedatolisib's pan-PI3K and dual mTORC1/2 profile differentiates it mechanistically, and the tolerability data presented at ESMO appear consistent with earlier readouts. A separate network meta-analysis also presented at the congress, led by Dr Sara Tolaney of Dana-Farber, found gedatolisib regimens demonstrated statistically or numerically superior PFS versus other regimens in the PIK3CA wild-type population, including a comparison with imlunestrant plus abemaciclib.

Gedatolisib already holds FDA approval under the brand name REVTORPYK for the PIK3CA wild-type second-line indication. The PIK3CA mutant cohort data now presented at ESMO will be pivotal in determining whether the company pursues a label expansion. Celcuity's VIKTORIA-2 programme is evaluating gedatolisib combinations in the first-line setting, with readouts from that trial representing the next major catalyst for the asset.

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