- |||||||||| Nubeqa (darolutamide) / Bayer, Orion Corp, gedatolisib (PF-05212384) / Celcuity
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). (Hall A; Poster Bd #: 514a) - Apr 24, 2024 - Abstract #ASCO2024ASCO_2291; P1/2 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).
- |||||||||| parsaclisib (INCB50465) / Incyte, gedatolisib (PF-05212384) / Celcuity, buparlisib (AN2025) / Novartis, Adlai Nortye
Journal: A Long Way to Go: A Scenario for Clinical Trials of PI3K Inhibitors in Treating Cancer. (Pubmed Central) - Mar 22, 2024 Not yet recruiting --> Recruiting The establishment of development indicators based on clinical trials for cancer treatment was useful to highlight the clinical investment in 3 new PI3K drugs and the advantages of combine therapy using FDA-approved drugs.
- |||||||||| Ibrance (palbociclib) / Pfizer, gedatolisib (PF-05212384) / Celcuity
Trial completion date, Trial primary completion date, Combination therapy, Metastases: 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) - Feb 15, 2024 P1, N=96, Recruiting, Trial completion date: Dec 2023 --> Mar 2024 | Trial primary completion date: Dec 2023 --> Mar 2024 Trial completion date: Jan 2025 --> Jan 2026 | Trial primary completion date: Jan 2024 --> Jan 2025
- |||||||||| Ibrance (palbociclib) / Pfizer, gedatolisib (PF-05212384) / Celcuity, Mektovi (binimetinib) / Ono Pharma, Pierre Fabre, Pfizer
Combined inhibition of CDK4/6 and signal transduction: activity beyond ER+ breast cancer (Ballroom 6 DE - Upper Level - Convention Center) - Feb 5, 2024 - Abstract #AACR2024AACR_1213; The palbociclib-binimetinib combination has recently been incorporated into the NCI Precision Medicine Initiative as part of ComboMATCH, where investigation is ongoing in low-grade serous ovarian cancer, pancreatic cancer, and other RAS-mutant tumors. Such combinations hold substantial promise for extending the use of the CDK4/6 inhibitor drug class beyond ER+ breast cancer.
- |||||||||| gedatolisib (PF-05212384) / Celcuity
GEDATOLISIB ASSOCIATED ACUTE MYOCARDITIS IN A PATIENT WITH BREAST CANCER (Hall B4-5) - Jan 26, 2024 - Abstract #ACC2024ACC_3273; A high index of suspicion for cardiotoxicity is needed when evaluating patients receiving novel cancer therapies. The integration of multimodality imaging including CMR is instrumental.
- |||||||||| gedatolisib (PF-05212384) / Celcuity
And gedatolisib (Twitter) - Jul 18, 2023
- |||||||||| gedatolisib (PF-05212384) / Celcuity, Hexalen (altretamine) / Ipsen, Eisai, Idhifa (enasidenib) / BMS, Servier
Review, Journal: Antitumor Activity of s-Triazine Derivatives: A Systematic Review. (Pubmed Central) - Jun 14, 2023 The medicinal chemistry of s-triazine derivatives as anticancer agents was summarized, including discovery, structure optimization, and biological applications. This review will provide a reference to inspire new and original discoveries.
- |||||||||| gedatolisib (PF-05212384) / Celcuity
Journal: Design, Synthesis and Phenotypic Profiling of Simplified Gedatolisib Analogues. (Pubmed Central) - Jun 1, 2023 Compound 5f (LASSBio-2252) stood out as the most promising of the series, showing good aqueous solubility (42.38 ?M (pH = 7.4); 39.33 ?M (pH = 5.8)), good partition coefficient (cLogP = 2.96), cytotoxic activity on human leukemia cell lines (CCRF-CEM, K562 and MOLT-4) and an excellent metabolic stability profile in rat liver microsomes (t = 462 min; Clapp = 0.058 mL/min/g). The ability of 5f to exert its cytotoxic effect through modulation of the PI3K pathway was demonstrated by flow cytometry analysis in a comparative manner to gedatolisib.
- |||||||||| gedatolisib (PF-05212384) / Celcuity, brivanib alaninate (BMS-582664) / ZAI Lab, Idhifa (enasidenib) / BMS, Servier
Review, Journal: Recent updates on 1,2,3-, 1,2,4-, and 1,3,5-triazine hybrids (2017-present): The anticancer activity, structure-activity relationships, and mechanisms of action. (Pubmed Central) - Mar 2, 2023 This review focuses on the anticancer activity of 1,2,3-, 1,2,4-, and 1,3,5-triazine hybrids, together with the structure-activity relationships and mechanisms of action developed from 2017 to the present. The enriched structure-activity relationships may be useful for further rational drug development of triazine hybrids as potential clinical candidates.
- |||||||||| gedatolisib (PF-05212384) / Celcuity
Journal: An integrative approach for exploring the nature of fibroepithelial neoplasms. (Pubmed Central) - Feb 27, 2023 The enriched structure-activity relationships may be useful for further rational drug development of triazine hybrids as potential clinical candidates. This study revealed the molecular profiles of MPT that can lead to molecular classification and potential targeted therapy, and suggested that the MPT PDX model can be a useful tool for studying the pathogenesis of fibroepithelial neoplasms and for preclinical drug screening to find new therapeutic strategies for MPT.
- |||||||||| Journal: Selective Eradication of Colon Cancer Cells Harboring PI3K and/or MAPK Pathway Mutations in 3D Culture by Combined PI3K/AKT/mTOR Pathway and MEK Inhibition. (Pubmed Central) - Jan 22, 2023
We found profound tumor cell destruction under treatment with a combination of Torin 1 (inhibiting mTOR), MK2206 (targeting AKT) and selumetinib (inhibiting MEK) in 3D but not in 2D...Gedatolisib, a dual PI3K/mTOR inhibitor, could replace Torin1/MK2206 with similar efficiency...Here, we identified a novel, efficient therapy, which induced proliferation stop and tumor cell destruction in vitro based on the genetic background. These preclinical findings show promise to further test this combi-treatment in vivo in mice and to potentially develop a mutation specific targeted therapy for CRC patients.
- |||||||||| Ibrance (palbociclib) / Pfizer, gedatolisib (PF-05212384) / Celcuity
Trial completion date, Trial primary completion date, Combination therapy, Metastases: 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) - Jan 10, 2023 P1, N=96, Recruiting, Gedatolisib as a single agent and in combination with other therapies reported promising preliminary efficacy and safety in various solid tumor types. Trial completion date: Jan 2024 --> Jan 2025 | Trial primary completion date: Jan 2023 --> Jan 2024
- |||||||||| gedatolisib (PF-05212384) / Celcuity
Journal: BPTF promotes the progression of distinct subtypes of breast cancer and is a therapeutic target. (Pubmed Central) - Dec 20, 2022 BPTF targeting with the bromodomain inhibitor bromosporine, alone or in combination with the PI3K pathway inhibitor gedatolisib, produced significant anti-tumor effects against TNBC cells in vitro and in vivo. These studies demonstrate BPTF activation in distinct breast cancer subtypes, identify pathways by which BPTF promotes breast cancer progression, and suggest BPTF as a rational target for breast cancer therapy.
- |||||||||| Talzenna (talazoparib) / Pfizer, gedatolisib (PF-05212384) / Celcuity
Enrollment change, Trial completion date, Trial primary completion date, Metastases: BTCRC-BRE18-337: Gedatolisib Plus Talazoparib in Advanced Triple Negative or BRCA1/2 Positive, HER2 Negative Breast Cancers (clinicaltrials.gov) - Dec 19, 2022 P1/2, N=37, Recruiting, These studies demonstrate BPTF activation in distinct breast cancer subtypes, identify pathways by which BPTF promotes breast cancer progression, and suggest BPTF as a rational target for breast cancer therapy. N=54 --> 37 | Trial completion date: Dec 2023 --> Jun 2023 | Trial primary completion date: Dec 2022 --> Jun 2023
- |||||||||| Ibrance (palbociclib) / Pfizer, gedatolisib (PF-05212384) / Celcuity
A Phase 3 study of gedatolisib plus fulvestrant with and without palbociclib in patients with HR+/HER2- advanced breast cancer previously treated with a CDK4/6 inhibitor plus a non-steroidal aromatase inhibitor (VIKTORIA-1) (Hall 1) - Oct 28, 2022 - Abstract #SABCS2022SABCS_1978; Background: Gedatolisib is a potent reversible dual inhibitor that selectively targets all Class I isoforms of phosphoinositide 3-kinase (PI3K) and mechanistic target of rapamycin (mTOR)...Study 2 will include up to 350 subjects randomized in a 3:3:1 ratio to Arm D (gedatolisib, palbociclib, and fulvestrant), Arm E (alpelisib plus fulvestrant), or Arm F (gedatolisib plus fulvestrant)...Secondary endpoints included overall survival (OS), safety and tolerability, ORR, duration of response, time to response, CBR, quality of life, and pharmacokinetics. This trial is open for enrollment.
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