Revtorpyk (gedatolisib) / Pfizer, Celcuity - LARVOL DELTA

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

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) (ESMO 2026) - No abstract available

Clinical • Late-breaking abstract • Metastases • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

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) (ESMO 2026) - No abstract available

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

Gedatolisib (Ged) vs Other Regimens Post-CDK4/6i and Endocrine Therapy (ET) in PIK3CA Wild-Type (WT) HR+/ HER2- Advanced Breast Cancer (aBC): A Network Meta-Analysis (NMA) (ESMO 2026) - No abstract available

Metastases • Retrospective data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • CDK4 • HER-2 • PIK3CA

A Randomized, Open-Label, Phase 3 Study Evaluating Efficacy and Safety of Gedatolisib with Endocrine Therapy (ET) and Palbociclib vs ET and Ribociclib as First-Line (1L) Treatment in Patients With HR-Positive (HR+) HER2-Negative (HER2-) Advanced Breast Cancer (ABC) (VIKTORIA-2) (ESMO 2026) - No abstract available

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

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

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

Phase II study of trastuzumab-pkrb plus gedatolisib in patients with HER2-positive metastatic breast cancer who progressed after two or more HER2-directed therapies. (PubMed, ESMO Open) - "Trastuzumab-pkrb plus gedatolisib demonstrated a 43.2% response rate and manageable toxicity, supporting dual HER2/PI3K pathway targeting in heavily pretreated HER2-positive MBC."

Journal • P2 data • Breast Cancer • Diabetes • HER2 Breast Cancer • HER2 Positive Breast Cancer • Mucositis • Oncology • Solid Tumor • Stomatitis • PIK3CA • PTEN

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

A randomized, open-label, phase 3 study of gedatolisib + fulvestrant ± palbociclib vs standard of care in HR+/HER2−/PIK3CA-mutant (MT) advanced breast cancer (VIKTORIA-1 Study 2). (ASCO 2026) - P3 | "Geda has superior preclinical potency and cytotoxicity compared to alpelisib, capivasertib, and everolimus and demonstrated activity in PIK3CA-MT and wild-type (WT) breast cancer cell lines. These data demonstrate that gedatolisib combination therapies offer a potential new standard of care as 2L treatment of HR+/HER2- ABC, irrespective of PIK3CA mutation status."

Clinical • Late-breaking abstract • Metastases • P3 data • Breast Cancer • Dental Disorders • Diabetes • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • Stomatitis • HER-2 • PIK3CA

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

Dual Targeting of FGFR4 and PI3K-mTOR Suppresses Tumor-Associated Phenotypes in Pancreatic Ductal Adenocarcinoma. (PubMed, Int J Mol Sci) - "PDAC cell lines representing a spectrum of FGFR4 dependence were treated with the selective FGFR4 inhibitor fisogatinib in combination with the clinically relevant PI3K-mTOR inhibitor gedatolisib...Dual pathway inhibition consistently and additively suppressed tumor-associated phenotypes despite compensatory MAPK activation, with the clearest added benefit over fisogatinib alone in migration, cell-cycle control, and 4E-BP1 modulation, supporting translational regulation as a shared therapeutic vulnerability. These findings provide a preliminary rationale for biomarker-guided strategies targeting FGFR4 and PI3K-mTOR signaling in pancreatic cancer."

Journal • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • EIF4EBP1 • FGF19 • FGFR4

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

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) (AACR 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."

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

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

Celcuity Submits sNDA to FDA for REVTORPYK (gedatolisib) for HR+/HER2-, PIK3CA Mutant Locally Advanced or Metastatic Breast Cancer (Celcuity Press Release) - "The application to the FDA is supported by positive results from the PIK3CA mutant cohort of the Phase 3 VIKTORIA-1 clinical trial."

FDA filing • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer

Emerging Strategies Targeting the PI3K/AKT/mTOR Pathway in HR+/HER2- Advanced Breast Cancer. (PubMed, Drugs) - "Isoform-specific PI3K inhibitors, including alpelisib and inavolisib, have demonstrated clinically meaningful progression-free survival benefits in PIK3CA-mutated populations, with inavolisib showing improved tolerability and efficacy. In contrast, pan-PI3K inhibitors such as buparlisib have been constrained by toxicity. Targeting downstream signaling, AKT inhibitors have also shown benefit: capivasertib has demonstrated clinical efficacy leading to US Food and Drug Administration approval, while ipatasertib has yielded encouraging results, particularly in tumors harboring PIK3CA, AKT1, or PTEN alterations. Mammalian target of rapamycin inhibitors, notably everolimus, have shown efficacy irrespective of mutation status. The dual PI3K-mTOR inhibitor (gedatolisib) has also shown promising progression-free survival benefit in a PIK3CA wild-type population...Future directions include rational combination strategies, improved biomarker-driven selection, and novel..."

Journal • Review • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • AKT1 • HER-2 • PIK3CA • PTEN

Newly FDA-Approved REVTORPYK (gedatolisib) Included in the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for HR+/HER2- Locally Advanced or Metastatic Breast Cancer (The Manila Times) - "The NCCN Guidelines play a pivotal role in decision-making processes for individuals involved in cancer care all over the world, including physicians, nurses, pharmacists, payers, and patients and their families. The guidelines present expert recommendations for cancer screening, diagnosis, and treatment, as well as cancer care options, and are utilized in cancer treatment decision-making to drive positive patient outcomes....Based on the company’s commitment to ensuring broad patient access to REVTORPYK, Celcuity has created a comprehensive patient support program. REVTORPYK is expected to be commercially available in the U.S. in the late third quarter of 2026. To make REVTORPYK available to patients prior to commercial launch, those who are eligible will be able to enroll in Celcuity’s expanded access program. Physician requests for participation in Celcuity’s expanded access program..."

Launch US • NCCN guideline • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer

Celcuity…indicated plans to launch the product in late Q3 2026 (MSN News) - "On Tuesday...Celcuity (CELC) became a commercial-stage biotech with U.S. approval of Revtorpyk in combination with fulvestrant for a subset of breast cancer patients as a late-line option. The 'approval was largely expected, but the company delayed the launch until late 3Q26'..."

Launch US • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer

FDA approves gedatolisib with fulvestrant, with or without palbociclib, for HR-positive, HER2-negative locally advanced or metastatic breast cancer (FDA) - "Efficacy was evaluated in Study 1 of VIKTORIA-1 (NCT05501886), an open-label, randomized, multicenter trial that enrolled 392 adults with locally advanced (inoperable) or metastatic HR-positive, HER2-negative breast cancer. Patients were randomized (1:1:1) to receive either gedatolisib in combination with fulvestrant and palbociclib (Arm A), gedatolisib in combination with fulvestrant (Arm B), or fulvestrant alone (Arm C)....The recommended dosage for gedatolisib is 180 mg as an intravenous infusion over 30 minutes once weekly on Days 1, 8, and 15 of every 28-day cycle, in combination with fulvestrant, with or without palbociclib, until disease progression or unacceptable toxicity."

FDA approval • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer

A concise and practical route to Gedatolisib via a continuous-flow Kumada coupling reaction. (PubMed, RSC Adv) - "This approach avoids hazardous reagents as well as high-boiling solvents, thereby improving both safety and scalability. The 100 gram scale synthesis affords Gedatolisib in 66% overall yield (98.9% purity), featuring mild conditions and crystallization-based purification, offering lower costs and better scalability for industrial production."

Journal • Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

RESOLVE: Abemaciclib + Letrozole +/- Metformin or Gedatolisib in Endometrial Cancer (clinicaltrials.gov) - P2 | N=110 | Recruiting | Sponsor: Dana-Farber Cancer Institute | N=180 ➔ 110

Enrollment change • P53WT • Endometrial Cancer • Oncology • Solid Tumor • ER • TP53

TRIM21-mediated ubiquitination of PARP1 regulated by the PI3K/AKT-STAT5A axis suppresses small cell lung cancer. (PubMed, Nat Commun) - "Importantly, combining the PI3K/AKT inhibitor PKI-587 with the PARP inhibitor BMN673 synergistically inhibits tumor growth across multiple SCLC models, including cell lines, patient-derived organoids, and xenograft models. Collectively, our findings define a "PI3K/AKT-STAT5A-TRIM21-PARP1" axis critical for SCLC progression and propose its dual inhibition as a promising therapeutic strategy."

Journal • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • Targeted Protein Degradation • PARP1 • STAT5 • STAT5AWqe • TRIM21

Proteasome inhibition overcomes TRAIL resistance and enhances MSC-sTRAIL activity in malignant pleural mesothelioma (EACR 2026) - "The cytotoxicity of sTRAIL was assessed alone or in combination with bortezomib, venetoclax or gedatolisib. These data support proteasome-mediated priming as a promising strategy to enhance TRAIL-based therapies in resistant tumors."

Malignant Pleural Mesothelioma • Mesothelioma • Pleural Mesothelioma • Solid Tumor

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