gedatolisib (PF-05212384) / Pfizer, Celcuity - LARVOL DELTA

Unifying molecular structure and cellular morphology to enhance drug-target interaction modeling in cancer (AACR 2026) - "Among the top-ranking DTI pairs, gedatolisib and PIK3CB showed a similarity of 0.95, consistent with the drug's known activity as a PI3K/mTOR pathway inhibitor...In contrast, low-similarity ones involved molecules whose size, polarity, or geometry posed challenges for targets such as metabolic enzymes and heme-binding proteins. Overall, this study highlights the promise of integrating molecular and morphological representations via contrastive learning, providing a powerful framework for advancing DTI modeling and precision cancer therapeutic discovery."

Oncology • PIK3CB

Fourth Quarter and Full Year 2025 Financial Results (GlobeNewswire) - "Research and development ('R&D') expenses were $37.6 million for the fourth quarter of 2025, compared to $33.5 million for the prior-year period. Of the $4.1 million increase in R&D expenses, $8.6 million was related to increased employee and consulting expenses, of which $5.3 million related to commercial headcount additions and other launch-related activities. These amounts were partially offset by a $4.5 million decrease primarily related to costs supporting ongoing activities for the VIKTORIA-1 Phase 3 trial."

Commercial • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer

Topline results from the PIK3CA mutant cohort of the Phase 3 VIKTORIA-1 study are expected to be released in the second quarter of 2026 (GlobeNewswire)

P3 data: top line • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer

Gedatolisib (geda) + fulvestrant ± palbociclib (palbo) vs fulvestrant in patients (pts) with HR+/ HER2-/PIK3CA wild-type (WT) advanced breast cancer (ABC): First results from VIKTORIA-1 (ESMO 2025) - "Hyperglycemia incidence was 9.2% and 11.5%, respectively, with grade 3 severity in 2.3% of pts in both geda groups. Conclusions These data support gedatolisib combination therapy as a potential new standard of care for the 2L treatment of pts with HR+/HER2-/PIK3CA WT ABC."

Clinical • Late-breaking abstract • Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • PIK3CA

Gedatolisib, a multi-target PI3K/AKT/mTOR (PAM) inhibitor, plus fulvestrant with or without palbociclib for second-line (2L) treatment of patients with HR+/HER2-/PIK3CA-wild type (WT) advanced breast cancer (ABC): updated results from the randomized, phase 3 VIKTORIA-1 trial (SABCS 2025) - "In preclinical studies, gedatolisib demonstrated superior potency and cytotoxicity compared to alpelisib, capivasertib, and everolimus, regardless of PI3K-pathway mutation status, and combinations of gedatolisib + fulvestrant, with and without palbociclib, were active in treatment-naive and resistant cell lines. These updated results support gedatolisib combination therapy as a potential new standard of care for the 2L treatment of patients with HR+/HER2-/PIK3CA WT ABC."

Clinical • Metastases • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • PIK3CA

Gedatolisib, a Multitarget PI3K/AKT/mTOR (PAM) Inhibitor, Plus Fulvestrant With or Without Palbociclib for Second-line (2L) Treatment of Patients with HR+/HER2-/ PIK3CA-Wild Type (WT) Advanced Breast Cancer (ABC): Topline Results from VIKTORIA-1 (MBCC 2026) - No abstract available

Clinical • Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • PIK3CA

Gedatolisib, a Multitarget PI3K/AKT/mTOR (PAM) Inhibitor, Plus Fulvestrant With or Without Palbociclib for Second-line (2L) Treatment of Patients with HR+/HER2-/ PIK3CA-Wild Type (WT) Advanced Breast Cancer (ABC): Updated Results from VIKTORIA-1 (MBCC 2026) - No abstract available

Clinical • Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • PIK3CA

Gedatolisib Combined with Palbociclib and Letrozole in Patients with No Prior Systemic Therapy for Hormone Receptor Positive, HER2 Negative Advanced Breast Cancer. (PubMed, Clin Cancer Res) - "Gedatolisib plus palbociclib and letrozole demonstrated preliminary efficacy in patients with no prior systemic therapy for ABC. These results warrant further evaluation of gedatolisib added to standard-of-care, first-line therapy for HR+/HER2- ABC."

Journal • Breast Cancer • Dental Disorders • Hematological Disorders • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Neutropenia • Oncology • Solid Tumor • Stomatitis • ER • HER-2 • PIK3CA

VIKTORIA-1 Trial of Gedatolisib Plus Fulvestrant With or Without Palbociclib in Hormone Receptor-Positive/HER2-/PIK3CA Wild-Type Advanced Breast Cancer. (PubMed, J Clin Oncol) - P3 | "The addition of gedatolisib to fulvestrant, with or without palbociclib, significantly reduced the risk of disease progression or death in patients with hormone receptor-positive/HER2-, PIK3CA WT advanced breast cancer."

Journal • Breast Cancer • Dental Disorders • Diabetes • Hematological Disorders • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Neutropenia • Oncology • Solid Tumor • Stomatitis • HER-2 • PIK3CA

A phase 1/2, open-label, randomized, dose-finding and dose expansion study of gedatolisib in combination with darolutamide in metastatic castration-resistant prostate cancer (mCRPC). (ASCO-GU 2026) - P1/2 | "Results of a randomized Phase (Ph) 2 trial showed improved median radiographic progression-free survival (rPFS) when samotolisib, a dual PI3K-mTOR inhibitor, was added to enzalutamide in pts with mCRPC that progressed on abiraterone (Sweeney et al...Key inclusion criteria: men ≥ 18 years with progressive mCRPC on or after treatment with at least one next-generation ARPI (eg, abiraterone, enzalutamide, apalutamide, darolutamide); ECOG 0-1; measurable disease per RECIST 1.1/PCWG3...Primary objectives for Ph 2 are to assess the antitumor activity of the combination as demonstrated by rPFS. This trial (NCT06190899) is currently open for enrollment across 13 sites in four countries: United States, Spain, France, and United Kingdom."

Clinical • Combination therapy • Metastases • P1/2 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Synergistic efficacy of gedatolisib and darolutamide in prostate cancer to overcome resistance to androgen-targeted therapy. (ASCO-GU 2026) - "The combination of gedatolisib and darolutamide shows a combinatorial benefit in multiple AR-positive PC cell models, regardless of PTEN status or sensitivity to AR inhibitors. These results provide a strong mechanistic rationale for clinical studies evaluating gedatolisib in combination with AR inhibitors in CRPC."

Clinical • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • AR

Synergistic Efficacy of Gedatolisib and Darolutamide in Prostate Cancer to Overcome Resistance to Androgen-Targeted Therapy. (PubMed, Int J Mol Sci) - No abstract available

Journal • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Celcuity Announces Publication of Results from PIK3CA Wild-Type Cohort of Phase 3 VIKTORIA-1 Study of Gedatolisib Regimens in HR+/HER2- Advanced Breast Cancer in Journal of Clinical Oncology (GlobeNewswire) - "In the PIK3CA WT cohort of the Phase 3 VIKTORIA-1 trial, median progression-free survival ('PFS') with the gedatolisib triplet was 9.3 months versus 2.0 months with fulvestrant, an incremental improvement of 7.3 months (HR=0.24; 95% CI: 0.17-0.35; p<0.0001). The objective response rate ('ORR') of the gedatolisib triplet was 31.5% compared to 1% with fulvestrant and the median duration of response ('DOR') was 17.5 months. For the gedatolisib doublet, the median PFS was 7.4 months versus 2.0 months with fulvestrant, an incremental improvement of 5.4 months (HR=0.33; 95% CI: 0.24-0.48; p<0.0001)."

P3 data • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer

Phase II study of trastuzumab-pkrb plus gedatolisib in patients with HER2-positive metastatic breast cancer who progressed after 2 or more HER2-directed chemotherapies (KM-10A/KCSG BR18-13). (ASCO 2025) - P2 | "In this phase II study, the combination of trastuzumab-pkrb and gedatolisib demonstrated a 43.2% response rate with manageable toxicity in patients with HER2 positive MBC and PIK3CA mutations. A translational research study focused on the analysis of cfDNA and PBMC is currently being planned."

Clinical • Metastases • P2 data • Breast Cancer • Diabetes • HER2 Breast Cancer • HER2 Positive Breast Cancer • Mucositis • Oncology • Palliative care • Solid Tumor • Stomatitis • PIK3CA • PTEN

Gedatolisib (Geda), a Multitarget PI3K/AKT/mTOR (PAM) Inhibitor, Plus Fulvestrant (Fulv) ± Palbociclib (Palbo) for Second-line (2L) Treatment of Patients (Pts) with HR+/HER2-/PIK3CA-Wild Type (WT) Advanced Breast Cancer (ABC): Topline Results from VIKTORIA-1 (ESMO-BC 2026) - No abstract available

Clinical • Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • PIK3CA

Gedatolisib (Geda), a Multitarget PI3K/AKT/mTOR (PAM) Inhibitor, Plus Fulvestrant (Fulv) ± Palbociclib (Palbo) for Second-line (2L) Treatment of Patients (Pts) with HR+/HER2-/PIK3CA-Wild Type (WT) Advanced Breast Cancer (ABC): Updated Results from VIKTORIA-1 (ESMO-BC 2026) - No abstract available

Clinical • Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • PIK3CA

New Dual Pan-PI3K/mTOR Inhibitor: Design, Synthesis, Cytotoxic Action, Permeation, Metabolic Stability, and In Silico Protein-Ligand Interaction. (PubMed, ACS Omega) - "Dual PI3K/mTOR inhibitors such as gedatolisib have shown clinical promise, but they still face challenges, including low solubility, poor metabolic stability, and limited activity against resistant tumor phenotypes...Although aqueous insoluble, 9a displayed moderate PAMPA-GIT permeability and low metabolic stability in rat liver microsomes, underscoring its potential as a lead for further optimization. This integrated study provides structural, mechanistic, and pharmacokinetic insights to guide next-generation PI3K/mTOR inhibitor design."

Journal • Hematological Malignancies • Leukemia • Oncology

Study of the CDK4/6 Inhibitor Palbociclib (PD-0332991) in Combination With the PI3K/mTOR Inhibitor Gedatolisib (PF-05212384) for Patients With Advanced Squamous Cell Lung, Pancreatic, Head & Neck and Other Solid Tumors (clinicaltrials.gov) - P1 | N=75 | Suspended | Sponsor: Dana-Farber Cancer Institute | Trial completion date: Jan 2026 ➔ Jan 2027 | Recruiting ➔ Suspended | Trial primary completion date: Dec 2025 ➔ Dec 2026

Trial completion date • Trial primary completion date • Trial suspension • Endometrial Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Oropharyngeal Cancer • Pancreatic Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • PIK3CA • PTEN

A phase 1/2, open-label, randomized, dose-finding and dose expansion study of gedatolisib in combination with darolutamide in metastatic castration-resistant prostate cancer (mCRPC). (ASCO 2024) - P1/2 | "A Phase 2 trial in 129 patients with mCRPC who progressed on abiraterone demonstrated improved median radiographic progression-free survival (rPFS) when samotolisib, a dual PI3K-mTOR inhibitor, was added to enzalutamide. Secondary endpoints include rPFS rates at 9 and 12 months, overall rPFS, prostate-specific antigen response of ≥50% decrease from baseline at 4, 8, 12, and 16 weeks, overall response rate, duration of response, clinical benefit rate, overall survival rate at 18 and 24 months, and safety. The trial is currently open for enrollment (NCT06190899)."

Clinical • Combination therapy • Metastases • P1/2 data • Diabetes • Genito-urinary Cancer • Metabolic Disorders • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

Gedatolisib in combination with palbociclib and endocrine therapy in women with hormone receptor-positive, HER2-negative advanced breast cancer: results from the dose expansion groups of an open-label, phase 1b study. (PubMed, Lancet Oncol) - P1b | "Gedatolisib plus palbociclib and endocrine therapy showed a promising objective response rate compared with the published results for standard-of-care therapies and had an acceptable safety profile."

Combination therapy • Journal • Metastases • P1 data • Breast Cancer • Dental Disorders • Diabetes • Hematological Disorders • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Neutropenia • Oncology • Solid Tumor • Stomatitis • HER-2 • PIK3CA

Celcuity Announces FDA Acceptance of New Drug Application for Gedatolisib in HR+/HER2-/PIK3CA Wild-Type Advanced Breast Cancer (GlobeNewswire) - "The FDA granted Priority Review and assigned a Prescription Drug User Fee Act ('PDUFA') goal date of July 17, 2026. The NDA was submitted under the FDA’s Real-Time Oncology Review ('RTOR') program....The submission is based on clinical data from the PIK3CA wild-type cohort of the Phase 3 VIKTORIA-1 clinical trial."

FDA filing • PDUFA • Priority review • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer

Functional analysis of gedatolisib combined with fulvestrant and/or palbociclib in breast cancer cell models adapted to estrogen receptor and/or CDK4/6 inhibitors (SABCS 2025) - " Gedatolisib (pan-PI3K, mTORC1/2 inhibitor), inavolisib (PI3Kα inhibitor), capivasertib (AKT inhibitor) were tested as single agents or in combination with fulvestrant and/or palbociclib in treatment-naïve BC cell lines with or without PIK3CA mutations as well as in BC cell lines adapted to long-term treatment with fulvestrant and/or palbociclib. These results indicate that gedatolisib plus fulvestrant, with and without palbociclib, effectively controls the growth of treatment-naïve BC cells as well as BC cells adapted to palbociclib/fulvestrant treatment. Moreover, in contrast to the currently approved PI3Kα and AKT inhibitors, the gedatolisib/palbociclib/fulvestrant triplet is effective in BC cells with or without PIK3CA mutations. The combination of gedatolisib with ET and a CDK4/6 inhibitor is being evaluated in two ongoing Phase 3 clinical trials as first-line (VIKTORIA-2) or second-line (VIKTORIA-1) treatment of HR+/HER2- ABC with or without PIK3CA..."

Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PIK3CA

Gedatolisib Plus Fulvestrant With or Without Palbociclib vs Standard-of-Care for the Treatment of Patients With Advanced or Metastatic HR+/HER2- Breast Cancer (VIKTORIA-1) (clinicaltrials.gov) - P3 | N=701 | Active, not recruiting | Sponsor: Celcuity Inc | Recruiting ➔ Active, not recruiting | Trial primary completion date: Jun 2025 ➔ Jun 2026

Enrollment closed • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PGR • PIK3CA

Celcuity Presents Updated Results from the PIK3CA Wild-Type Cohort of the Phase 3 VIKTORIA-1 Trial at the 2025 San Antonio Breast Cancer Symposium (GlobeNewswire) - "For patients whose time to progression on immediate prior therapy was >18 months, representing nearly half of those enrolled, median PFS was 12.4 months (HR=0.17; 95% CI: 0.11-0.28) with the gedatolisib triplet and 10.0 months (HR=0.19; 95% CI: 0.12-0.31) with the gedatolisib doublet versus 1.9 months for fulvestrant. For patients enrolled in the U.S., Canada, Western Europe, and Asia Pacific, representing nearly 60% of those enrolled, median PFS was 16.6 months (HR=0.14; 95% CI: 0.09-0.26) with the gedatolisib triplet and 7.1 months (HR=0.36; 95% CI: 0.24-0.57) with the gedatolisib doublet versus 1.9 months for fulvestrant....The median time to definitive deterioration was 23.7 months (HR=0.39; 95% CI: 0.25-0.67; p = 0.0003) for patients treated with the gedatolisib triplet and not reached for the gedatolisib doublet (HR=0.37; 95% CI: 0.24-0.66; p = 0.0003) versus 4.0 months for fulvestrant."

P3 data • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer

Celcuity to Present Updated Data from the PIK3CA Wild-Type Cohort of the Phase 3 VIKTORIA-1 Trial at the 2025 San Antonio Breast Cancer Symposium (GlobeNewswire) - "The presentation will include additional sub-group efficacy analyses and safety data."

P3 data • Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer