FDA Accepts sNDA for Gedatolisib in PIK3CA-Mutant HR+/HER2– Breast Cancer

The FDA has accepted a supplemental new drug application (sNDA) for gedatolisib (Revtorpyk) for the treatment of patients with hormone receptor (HR)–positive, HER2-negative, PIK3CA-mutant locally advanced or metastatic breast cancer following progression on or after at least 1 line of endocrine therapy in the metastatic setting, according to a news release from Celcuity, the agent’s developer.¹

The agency assigned the application a Prescription Drug User Fee Act (PDUFA) target action date of June 25, 2027.

Data supporting the sNDA came from the PIK3CA-mutant cohort (study 2) of the randomized, open-label, phase 3 VIKTORIA-1 trial. Updated results from this cohort were presented by Barbara Pistilli, MD, head of the Breast Cancer Unit at Gustave Roussy, as a late-breaking rapid oral presentation (LBA 16) at the 2026 European Society for Medical Oncology (ESMO) Congress.^2,3 The news release announcing the sNDA acceptance did not specify the combination regimen under review.

VIKTORIA-1 Efficacy Outcomes

In the cohort, patients with HR-positive, HER2-negative, PIK3CA-mutant advanced breast cancer were randomly assigned 3:3:1 to gedatolisib plus fulvestrant and palbociclib (triplet), gedatolisib plus fulvestrant (doublet), or alpelisib (Piqray) plus fulvestrant (control).

The confirmed and unconfirmed objective response rate (ORR) was 59% (78/133) with the triplet, 43% (18/42) with the doublet, and 33% (42/127) with alpelisib plus fulvestrant. The median duration of response was 19.4 months (95% CI, 11.1-25.1) in the triplet arm, 27.8 months (95% CI, 9.2-not reached [NR]) in the doublet arm, and 7.5 months (95% CI, 5.6-16.6) in the control arm.

Progression-free survival (PFS) benefit with gedatolisib was observed across subgroups defined by metastatic sites. Among patients without liver metastases, the median PFS was 21.5 months (95% CI, 11.4-NR) with the triplet (n = 77) vs 9.1 months (95% CI, 5.6-16.9) with the control regimen (n = 76; HR, 0.46; 90% CI, 0.30-0.72; P = .0016). The median PFS was 11.5 months (95% CI, 9.2-NR) with the doublet (n = 28; HR, 0.71; 90% CI, 0.41-1.25; P = .1627).

In patients with liver metastases, the median PFS was 9.1 months (95% CI, 5.7-11.1) with the triplet (n = 78; HR, 0.47; 90% CI, 0.34-0.65; P <.0001) and 11.1 months (95% CI, 3.7-NR) with the doublet (n = 24; HR, 0.38; 90% CI, 0.23-0.62; P = .0006) vs 4.6 months (95% CI, 3.7-5.6) with the control regimen (n = 79).

Among patients with visceral metastases, the median PFS was 9.8 months (95% CI, 7.5-12.9) with the triplet (n = 117; HR, 0.52; 90% CI, 0.39-0.70; P <.0001) and 11.3 months (95% CI, 7.4-22.1) with the doublet (n = 39; HR, 0.53; 90% CI, 0.35-0.79; P = .0042) vs 5.6 months (95% CI, 4.6-7.2) with the control regimen (n = 118). In those without visceral metastases, the median PFS was 21.5 months (95% CI, 9.6-NR) with the triplet (n = 38) and 9.2 months (95% CI, 3.9-16.9) with the control regimen (n = 37; HR, 0.38; 90% CI, 0.21-0.73; P = .0059), NR (95% CI, 1.6-NR) with the doublet (n = 13; HR, 0.40; 90% CI, 0.15-1.1; P = .0703),

Adverse Effects Noted in VIKTORIA-1

Discontinuation due to treatment-emergent adverse effects occurred in 5% of patients in the triplet arm, 4% in the doublet arm, and 19% in the alpelisib arm. Grade 3 stomatitis was transient; by cycle 2, fewer than 3% of patients had grade 3 stomatitis, and all grade 3 events resolved within 1 to 2 weeks. Stomatitis led to discontinuation in 1% of patients receiving the triplet and no patients receiving the doublet.

According to Igor Gorbachevsky, MD, chief medical officer of Celcuity, the median duration of response of more than 19 months observed with the triplet in both VIKTORIA-1 cohorts is, to the company’s knowledge, the longest reported for a phase 3 primary analysis in the second-line HR-positive, HER2-negative setting.

“[The FDA’s acceptance] takes us one step closer to bringing [gedatolisib] to more patients” with HR-positive, HER2-negative disease, said Brian Sullivan, chief executive officer and cofounder of Celcuity, in the news release. Sullivan added that, if approved in this population, gedatolisib would be available as a second-line treatment option regardless of a patient’s tumor PIK3CA status.

Other FDA Actions With Gedatolisib

The application follows an FDA approval granted on July 14, 2026, for gedatolisib in combination with fulvestrant (Faslodex), with or without palbociclib (Ibrance), for adult patients with HR-positive, HER2-negative locally advanced or metastatic breast cancer without a detected PIK3CA mutation following progression on or after at least 1 line of endocrine therapy in the metastatic setting.⁴ That decision was also supported by data from VIKTORIA-1, which is evaluating gedatolisib plus fulvestrant, with or without palbociclib, in patients with HR-positive, HER2-negative advanced breast cancer.

The FDA previously granted breakthrough therapy and fast track designations to gedatolisib on the basis of promising preliminary clinical data.

Warning and Precautions With Gedatolisib

According to the Important Safety Information for the currently approved indication in patients without a detected PIK3CA mutation, warnings and precautions for gedatolisib include stomatitis, dermatologic reactions, hyperglycemia, and embryo-fetal toxicity.

In the PIK3CA wild-type population, stomatitis occurred in 72% of patients who received gedatolisib plus fulvestrant and palbociclib, including grade 3 events in 22%, and in 58% of those who received gedatolisib plus fulvestrant alone, including grade 3 events in 12%. The label recommends a steroid-containing, alcohol-free mouthwash for prophylaxis of stomatitis.

Rash was reported in 30% of patients in the triplet arm (grade 3, 6%) and 40% of patients in the doublet arm (grade 3, 5%). Increased fasting glucose occurred in 46% of patients who received the triplet regimen (grade 3, 0.9%) and 57% of those who received the doublet regimen (grade 3, 1.8%).

Because of the risk of embryo-fetal toxicity, patients are advised to use effective contraception during treatment and for 2 weeks after the final dose.

Beyond the second-line setting, gedatolisib is being evaluated in the first-line treatment of HR-positive, HER2-negative advanced breast cancer in the ongoing phase 3 VIKTORIA-2 program, which consists of 2 studies in treatment-naive patients. The first is assessing gedatolisib plus palbociclib and fulvestrant in patients with endocrine-resistant disease, and the second is assessing gedatolisib plus palbociclib and letrozole in patients with endocrine-sensitive disease.

The agent is also under investigation in combination with darolutamide (Nubeqa) for patients with metastatic castration-resistant prostate cancer in the ongoing phase 1b/2 CELC-G-201 trial.

References

1. Celcuity announces FDA acceptance of sNDA for REVTORPYK™ (gedatolisib). News release. Celcuity. November 9, 2026. Accessed November 9, 2026. https://tinyurl.com/2ze59f86
2. Celcuity presents updated results from PIK3CA mutant cohort of phase 3 VIKTORIA-1 trial at ESMO 2026. News release. Celcuity. October 24, 2026. Accessed November 9, 2026. https://tinyurl.com/bp57sj2j
3. Pistilli B, Curgliano G, Andre F, et al. VIKTORIA-1: Updated results of a randomized, open-label, phase 3 study of gedatolisib (geda) + fulvestrant (fulv) ± palbociclib (palbo) vs standard of care in patients (pts) with HR+/HER2- advanced breast cancer (ABC) (Study 2). Presented at the 2026 European Society for Medical Oncology; October 23-27, 2026; Madrid, Spain. LBA16
4. FDA approves gedatolisib with fulvestrant, with or without palbociclib, for HR-positive, HER2-negative locally advanced or metastatic breast cancer. News release. FDA. July 14, 2026. Accessed November 10, 2026 https://tinyurl.com/yck3eabf