Latest news with #fulvestrant
Medscape
2 days ago
- Health
- Medscape
Tibremciclib for Advanced Breast Cancer: Is It Worth It?
Adding the novel CDK4/6 inhibitor tibremciclib (Betta Pharmaceuticals) to second-line fulvestrant significantly extended progression-free survival (PFS) in patients with HR-positive/HER2-negative advanced breast cancer, but with the tradeoff of increased toxicity, new data suggest. Compared with fulvestrant alone, the combination prolonged median PFS for these patients by 11 months, according to results from the phase 3 TIFFANY trial. However, similar to existing CDK4/6 inhibitors, the tibremciclib-fulvestrant combination added to treatment side effects — including substantially higher rates of diarrhea, hematologic toxicities, and hypokalemia. The authors of the analysis, published in JAMA Oncology , described the toxicities as "manageable," emphasizing that few patients stopped treatment because of them. Study author Xichun Hu, MD, of Fudan University Shanghai Cancer Center, told Medscape Medical News that tibremciclib compares favorably with other CDK4/6 inhibitors in terms of dose reduction and discontinuation rates. However, Hu noted, that's based on cross-trial comparisons, which have to be interpreted with caution. Kathy Miller, MD, who was not involved in the trial, had a similar take. 'Toxicity actually looks similar to ribociclib and palbociclib, with primarily myelosuppression and little non-heme toxicity,' Miller, of the Melvin and Bren Simon Comprehensive Cancer Center at Indiana University, told Medscape Medical News. Tibremciclib plus fulvestrant was recently approved in China for HR-positive/HER2-negative advanced breast cancer following results from the trial, but the combination has yet to be approved in the US. The Benefits vs the Risks In the trial, Hu and colleagues studied the safety and efficacy of the new agent among patients from 69 centers in China who had experienced progression while on endocrine therapy and had received no more than one line of chemotherapy. A total of 274 patients were randomized (2:1) to receive either tibremciclib (400 mg orally, once daily) or placebo plus fulvestrant until disease progression, death, or treatment discontinuation over a median follow-up of 13 months. Eighty patients (43.5%) in the tibremciclib arm and 64 (71.1%) in the placebo arm experienced a PFS event (disease progression or death). Tibremciclib plus fulvestrant significantly improved PFS to 16.5 months versus 5.6 months with fulvestrant alone, reducing the risk of progression by 63% (hazard ratio [HR], 0.37; P < .001). As for safety, adverse events were higher in the treatment arm. The most common treatment-emergent adverse events were diarrhea (79.3% in the tibremciclib arm vs 13.3% in placebo arm), neutropenia (75.5% vs 15.6%), leukopenia (73.9% vs 16.7%), and anemia (69% vs 21.1%). Nausea and vomiting were also more common with tibremciclib, at 37% and 40.2%, respectively — versus 18.9% and 11.1% in the placebo group. Most often, those adverse events were grade 1 or 2. However, 50.5% of patients in the tibremciclib group had a grade 3 or higher treatment-emergent adverse event, versus 21.1% in the placebo group. The most common were neutropenia (15.2% vs 5.6%), anemia (12.0% vs 4.4%), and hypokalemia (12% vs 0%). Hypokalemia was often due to diarrhea and was managed with electrolyte monitoring and potassium supplementation, Hu said. One-third of patients in the tibremciclib arm developed hypertriglyceridemia (5.4% grade 3 or higher) — a rate higher than that seen with other CDK4/6 inhibitors. Cases were managed with lipid-lowering agents such as atorvastatin. More patients on tibremciclib experienced dosing interruptions due to adverse events (54% vs 23%), and dose reductions were also more common with the combination therapy (18.5% vs 4.4%). However, only four patients (all in the tibremciclib arm) discontinued treatment due to side effects. Overall, the adverse event profile of tibremciclib lines up with that of other CDK4/6 inhibitors and comes with better PFS, Hu said, noting that "the benefit-risk balance of tibremciclib plus fulvestrant appears highly favorable." In TIFFANY, the authors note d that cases of neutropenia and leukopenia were numerically lower than in trials of abemaciclib, dalpiciclib, and palbociclib plus fulvestrant. According to Hu, tibremciclib is structurally different from other drugs in its class, with a greater selectivity for CDK4 and less inhibition of CDK6 and CDK9, which may reduce the incidence of neutropenia as well as severe diarrhea. Plus, the PFS improvement seen in TIFFANY was greater, Hu said. Pa lbociclib in PALOMA-3 showed a median PFS of 9.5 months vs 4.6 months for fulvestrant alone (HR, 0.46); abemaciclib in MONARCH led to a PFS of 11.5 months vs 5.6 months (HR, 0.38, a Chinese population); and dalpiciclib in DAWNA-1 achieved 16.6 months vs 7.2 months (HR, 0.50, also in Chinese patients). While these are cross-trial comparisons, it's still unclear exactly how tibremciclib stacks up against other drugs in its class (including its impact on overall survival). The authors also caution that, because the trial exclusively enrolled Chinese patients without prior CDK4/6 inhibitor exposure, the findings may not be generalizable to broader populations, particularly in regions like North America and Europe. Miller pointed to the generalizability question as well, noting that fulvestrant monotherapy is typically not the standard of care in the US and other Western countries. 'This [study] joins a long list of second-line endocrine studies that show drug activity but don't compare to standard of care and don't really tell us how to best use the drug,' Miller said.
Yahoo
05-08-2025
- Business
- Yahoo
Atavistik doses first subject in trial of ATV-1601 for solid tumours
Atavistik Bio has dosed the first subject in its Phase I clinical trial of ATV-1601, an allosteric selective AKT1 E17K inhibitor, designed to treat adults with solid tumours. The trial uses a dose escalation and expansion phase, with the therapy as a single agent, followed by a similar phase in combination with fulvestrant at one location in the US. It is an open-label study and aims to assess the preliminary antitumor activity, tolerability, pharmacokinetics, and safety of the therapy in those with advanced or metastatic AKT1 E17K-mutant solid tumours. ATV-1601will be assessed in conjunction with fulvestrant in individuals with AKT1 E17K-mutant hormone receptor-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Atavistik Bio CEO Bryan Stuart said: 'Dosing the initial patient in our first-in-human study of ATV-1601 represents a significant milestone as we transition to a clinical stage biotechnology company and an important step forward in our efforts to develop innovative treatments for patients. 'As a selective allosteric AKT1 E17K inhibitor, ATV-1601 has generated a highly differentiated preclinical profile, which we believe has the potential to address significant unmet needs for patients. We look forward to evaluating ATV-1601 in the clinic and moving rapidly toward early proof-of-concept data for this programme.' According to the company, the pan-AKT inhibitor is designed to prevent all three AKT isoforms: AKT1, AKT2, and AKT3. Despite this, these inhibitors are often less effective for those with AKT1 E17K-driven mutant tumours and can lead to adverse events, resulting in the discontinuation of treatment or reduced doses in many individuals. Developed using the company's AMPS technology and integrated with the AI-enabled drug discovery engine, ATV-1601 is part of the company's larger pipeline of in-house discovered allosteric oncology candidates. "Atavistik doses first subject in trial of ATV-1601 for solid tumours" was originally created and published by Clinical Trials Arena, a GlobalData owned brand. The information on this site has been included in good faith for general informational purposes only. It is not intended to amount to advice on which you should rely, and we give no representation, warranty or guarantee, whether express or implied as to its accuracy or completeness. You must obtain professional or specialist advice before taking, or refraining from, any action on the basis of the content on our site. Sign in to access your portfolio
Yahoo
28-07-2025
- Business
- Yahoo
Celcuity Announces Clinically Meaningful Improvement in Both Progression-Free Survival ('PFS') Primary Endpoints from PIK3CA Wild-Type Cohort of Phase 3 VIKTORIA-1 Trial
Hazard Ratios and Improvements in Median PFS areUnprecedented in HR+/HER2- Advanced Breast Cancer ('ABC') Gedatolisib + palbociclib + fulvestrant ('gedatolisib triplet') reduced the risk of disease progression or death by 76% vs. fulvestrant (HR=0.24; 95% CI: 0.17–0.35; p<0.0001). Median PFS was 9.3 months with the gedatolisib triplet versus 2.0 months with fulvestrant Gedatolisib + fulvestrant ('gedatolisib doublet') reduced the risk of progression or death by 67% vs. fulvestrant (HR=0.33; 95% CI: 0.24–0.48; p<0.0001). Median PFS was 7.4 months with the gedatolisib doublet versus 2.0 months with fulvestrant The efficacy results establish several new milestones in the history of drug development for HR+/HER2- advanced breast cancer Treatment discontinuation due to a treatment-related adverse event for the gedatolisib triplet and gedatolisib doublet was lower than was observed in Arm D of Celcuity's Phase 1b trial in ABC patients and lower than observed in any Phase 3 trials for currently approved drug combinations in HR+/HER2- ABC The favorable safety profile with the gedatolisib triplet and gedatolisib doublet was better than observed in the Phase 1b trial in ABC, including lower rates of hyperglycemia and stomatitis Full data from the PIK3CA wild-type cohort of the VIKTORIA-1 clinical trial will be presented at an upcoming medical conference later this year. Celcuity expects to submit a New Drug Application for gedatolisib to the U.S. Food and Drug Administration in the fourth quarter of 2025. Topline data for the VIKTORIA-1 PIK3CA mutation cohort is expected by the end of 2025. Management to host webcast and conference call today, July 28, 2025, at 8:00 a.m. ET MINNEAPOLIS, July 28, 2025 (GLOBE NEWSWIRE) -- Celcuity Inc. (Nasdaq: CELC), a clinical-stage biotechnology company pursuing development of targeted therapies for oncology, today announced positive topline results from the PIK3CA wild-type cohort of the Phase 3 VIKTORIA-1 clinical trial evaluating gedatolisib plus fulvestrant with and without palbociclib versus fulvestrant in adults with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, PIK3CA wild-type, locally advanced or metastatic breast cancer, following progression on, or after, treatment with a CDK4/6 inhibitor and an aromatase inhibitor. In the trial, the gedatolisib triplet demonstrated a statistically significant and clinically meaningful improvement in PFS among patients, reducing the risk of disease progression or death by 76% compared to fulvestrant (based on a hazard ratio [HR] of 0.24, 95% confidence interval [CI] 0.17-0.35; p<0.0001). The mPFS, as assessed by blinded independent central review ('BICR'), was 9.3 months with the gedatolisib triplet versus 2.0 months with fulvestrant, an incremental improvement of 7.3 months. The gedatolisib doublet also demonstrated a statistically significant and clinically meaningful improvement in PFS among patients, reducing the risk of disease progression or death by 67% compared to fulvestrant (HR of 0.33, 95% CI 0.24-0.48; p<0.0001). The mPFS, as assessed by BICR, was 7.4 months with the gedatolisib doublet versus 2.0 months with fulvestrant, an incremental improvement of 5.4 months. The topline efficacy data from the VIKTORIA-1 PIK3CA wild-type cohort established several new milestones in the history of drug development for HR+/HER2- advanced breast cancer: The hazard ratios for the gedatolisib triplet and doublet are more favorable than have ever been reported by any Phase 3 trial for patients with HR+/HER2- ABC. The 7.3- and 5.4-months incremental improvements in median PFS for the gedatolisib triplet and gedatolisib doublet over fulvestrant, respectively, are higher than have ever been reported by any Phase 3 trial for patients with HR+/HER2- ABC receiving at least their second line of therapy. Gedatolisib is the first inhibitor targeting the PI3K/AKT/mTOR pathway to demonstrate positive Phase 3 results in patients with HR+/HER2-/PIK3CA wild-type ABC whose disease progressed on or after treatment with a CDK4/6 inhibitor. Sara Hurvitz, MD, Senior Vice President, Clinical Research Division, Fred Hutchinson Cancer Center, Professor and Head, Division of Hematology and Oncology, University of Washington, Department of Medicine and co-principal investigator for the trial said: 'Patients with HR-positive, HER2-negative, PIK3CA wild-type advanced breast cancer whose disease has progressed while on, or after, treatment with a CDK4/6 inhibitor typically derive limited benefit from subsequent endocrine-based therapy. The topline data for both gedatolisib regimens from VIKTORIA-1 are potentially practice-changing. To my knowledge, we have not seen Phase 3 results in patients with HR-positive, HER2-negative advanced breast cancer before where there was a quadrupling of the likelihood of survival without disease progression relative to the study control.' Treatment discontinuation due to a treatment-related adverse event for the gedatolisib triplet and gedatolisib doublet was lower than was observed in Arm D of the Phase 1b trial in patients with ABC, and lower than observed in any Phase 3 trials for currently approved drug combinations in HR+/HER2- ABC. Additionally, the gedatolisib triplet and gedatolisib doublet were better tolerated than was observed in the Phase 1b trial in patients with ABC, including lower rates of hyperglycemia and stomatitis. Igor Gorbatchevsky, MD, Chief Medical Officer of Celcuity said: 'The topline data from VIKTORIA-1 demonstrate the potential for gedatolisib to become a transformative new medicine for the treatment of patients with HR-positive, HER2-negative, PIK3CA wild-type advanced breast cancer whose disease progressed on or after treatment with CDK4/6 inhibitors. The 7.3 and 5.4-months incremental improvement in median PFS relative to fulvestrant for the gedatolisib regimens are potentially paradigm shifting results. We are also very excited that treatment with gedatolisib combined with fulvestrant with or without palbociclib was well-tolerated by the VIKTORIA-1 patients and that only a few patients discontinued treatment due to an adverse event.' Brian Sullivan, Chairman, Chief Executive Officer and co-founder of Celcuity said, 'The efficacy improvement relative to the control that each of the gedatolisib regimens demonstrated was historic for this patient population. We are excited about the potential opportunity to provide a breakthrough therapeutic option for patients with HR-positive, HER2-negative, PIK3CA wild-type advanced breast cancer.' Full data from the PIK3CA wild-type cohort of the VIKTORIA-1 clinical trial will be presented at an upcoming medical conference later this year. Celcuity expects to submit a New Drug Application for gedatolisib to the U.S. Food and Drug Administration in the fourth quarter of 2025. Topline data for the VIKTORIA-1 PIK3CA mutation cohort is expected by the end of 2025. Webcast and Conference Call InformationThe Celcuity management team will host a webcast/conference call on Monday, July 28, 2025, at 8:00 a.m. ET to discuss the topline results from the Phase 3 VIKTORIA-1 trial. Those who would like to participate may access the live webcast here, or register in advance for the teleconference here. A replay of the webcast will be available on the Celcuity website following the live event. Notes HR+/HER2- Breast cancer Breast cancer is the second most common cancer and one of the leading causes of cancer-related deaths worldwide.1 More than two million breast cancer cases were diagnosed globally in 2022.1 While survival rates are high for those diagnosed with early breast cancer, only approximately 30% of patients who are diagnosed with or who progress to metastatic disease are expected to live five years after their diagnosis.2 HR+/HER2- breast cancer is the most common subtype of breast cancer, accounting for approximately 70% of all breast cancers.2 Three interconnected signaling pathways, estrogen, cyclin D1-CDK4/6, and PI3K/AKT/mTOR (PAM), are primary oncogenic drivers of HR+, HER2- breast cancer.3 Therapies inhibiting these pathways are approved and used in various combinations for advanced breast cancer. Currently approved inhibitors of the PAM pathway for breast cancer target a single PAM pathway component, such as PI3Kα, AKT, or mTORC1.4,5,6,7 However, resistance to CDK4/6 inhibitors and current endocrine therapies develops in many patients with advanced disease.8 Survival rates are low with 30% of patients anticipated to live beyond five years after diagnosis.2 Optimizing the inhibition of the PAM pathway is an active area of focus for breast cancer research. VIKTORIA-1VIKTORIA-1 is a Phase 3 open-label, randomized clinical trial to evaluate the efficacy and safety of gedatolisib in combination with fulvestrant with or without palbociclib in adults with HR+/HER2- ABC whose disease progressed on or after prior CDK4/6 therapy in combination with an aromatase inhibitor. The clinical trial is enrolling subjects regardless of PIK3CA status while enabling separate evaluation of subjects according to their PIK3CA status. Subjects who meet eligibility criteria and do not have confirmed PI3KCA mutations (WT) were randomly assigned (1:1:1) to receive a regimen of either gedatolisib, palbociclib, and fulvestrant, gedatolisib and fulvestrant, or fulvestrant. Subjects who meet eligibility criteria and have confirmed PI3KCA mutations (MT) are randomly assigned (3:3:1) to receive a regimen of either the gedatolisib triplet, alpelisib and fulvestrant, or the gedatolisib doublet. GedatolisibGedatolisib is an investigational, multi-target PAM inhibitor that potently targets all four class I PI3K isoforms, mTORC1, and mTORC2 to induce comprehensive blockade of the PAM pathway.9,10,11 As a multi-target PAM inhibitor, gedatolisib's mechanism of action is highly differentiated from currently approved single-target inhibitors of the PAM pathway.11 Inhibition of only a single PAM component gives tumors an escape mechanism through cross-activation of the uninhibited targets. Gedatolisib's comprehensive PAM pathway inhibition ensures full suppression of PAM activity by eliminating adaptive resistance cross-activation that occurs with single-target inhibitors. Unlike single-target inhibitors of the PAM pathway, gedatolisib has demonstrated equal potency and comparable cytotoxicity in PIK3CA-mutant and -wild-type breast tumor cells in nonclinical studies and early clinical data.11,12 About CelcuityCelcuity is a clinical-stage biotechnology company pursuing development of targeted therapies for treatment of multiple solid tumor indications. The company's lead therapeutic candidate is gedatolisib, a potent, pan-PI3K and mTORC1/2 inhibitor that comprehensively blockades the PAM pathway. Its mechanism of action and pharmacokinetic properties are differentiated from other currently approved and investigational therapies that target PI3Kα, AKT, or mTORC1 alone or together. A Phase 3 clinical trial, VIKTORIA-1, evaluating gedatolisib in combination with fulvestrant with or without palbociclib in patients with HR+/HER2- advanced breast cancer is currently enrolling patients. A Phase 1/2 clinical trial, CELC-G-201, evaluating gedatolisib in combination with darolutamide in patients with metastatic castration resistant prostate cancer, is ongoing. A Phase 3 clinical trial, VIKTORIA-2, evaluating gedatolisib plus a CDK4/6 inhibitor and fulvestrant as first-line treatment for patients with HR+/HER2- advanced breast cancer is currently enrolling patients. More detailed information about Celcuity's active clinical trials can be found at Celcuity is headquartered in Minneapolis. Further information about Celcuity can be found at Follow us on LinkedIn and X. Forward-Looking StatementsThis press release contains statements that constitute "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995 including statements relating to the potential therapeutic benefits of gedatolisib; the size, design and timing of our clinical trials; our interpretation of topline clinical trial data; the ability of our data to support the filing of an NDA with the FDA; our expectations regarding the timing of and our ability to obtain FDA approval to commercialize gedatolisib; and other expectations with respect to gedatolisib. Words such as, but not limited to, 'look forward to,' 'believe,' 'expect,' 'anticipate,' 'estimate,' 'intend,' "confidence," "encouraged," 'potential,' 'plan,' 'targets,' 'likely,' 'may,' 'will,' 'would,' 'should' and 'could,' and similar expressions or words identify forward-looking statements. The forward-looking statements included in this press release are based on management's current expectations and beliefs which are subject to a number of risks, uncertainties and factors, including that our topline results are based on a preliminary analysis of key efficacy and safety data, and such data may change following a more comprehensive review of the data related to the clinical trial; unforeseen delays in our planned NDA for gedatolisib; and our ability to obtain and maintain regulatory approvals to commercialize gedatolisib. In addition, all forward-looking statements are subject to other risks detailed in our Annual Report on Form 10-K for the year ended December 31, 2024, and our Quarterly Report on Form 10-Q for the quarter ended March 31, 2025, as such risks may be updated in our subsequent filings with the Securities and Exchange Commission. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. All forward-looking statements are qualified in their entirety by these cautionary statements, and we undertake no obligation to revise or update this press release to reflect events or circumstances after the date hereof. References: Sung H, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;10.3322/caac.21660. National Cancer Institute. Surveillance, Epidemiology and End Results Program (Accessed July 2025). Alves, C. L., & Ditzel, H. J. Drugging the PI3K/AKT/mTOR Pathway in ER+ Breast Cancer. Int J Mol Sci, 2023;24(5),4522. United States Package Insert, US FDA, ITOVEBI United States Package Insert, US FDA, PIQRAY United States Package Insert, US FDA, TRUCAP United States Package Insert, US FDA, AFINITOR Lloyd M R, et al. Mechanisms of Resistance to CDK4/6 Blockade in Advanced Hormone Receptor-positive, HER2-negative Breast Cancer and Emerging Therapeutic Opportunities. Clin Cancer Res. 2022;28(5):821-30 Venkatesan, A. M., et al. Bis(morpholino-1,3,5-triazine) derivatives: potent adenosine 5'-triphosphate competitive phosphatidylinositol-3-kinase/mammalian target of rapamycin inhibitors: discovery of compound 26 (PKI-587), a highly efficacious dual inhibitor. J Med Chem, 2010;53(6), 2636-2645. Mallon, R., et al. Antitumor efficacy of PKI-587, a highly potent dual PI3K/mTOR kinase inhibitor. Clin Cancer Res, 2011;17(10), 3193-3203. Rossetti, S., et al. Gedatolisib shows superior potency and efficacy versus single-node PI3K/AKT/mTOR inhibitors in breast cancer models. NPJ Breast Cancer, 2024;10(1), 40. Layman, R., et al. 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. Lancet Oncol, 2024;25(4), 474-487. View source version of release on Contacts: Celcuity Inc. Brian Sullivan, bsullivan@ Vicky Hahne, vhahne@ (763) 392-0123 ICR HealthcarePatti Bank, (415) 513-1284Fehler beim Abrufen der Daten Melden Sie sich an, um Ihr Portfolio aufzurufen. Fehler beim Abrufen der Daten Fehler beim Abrufen der Daten Fehler beim Abrufen der Daten Fehler beim Abrufen der Daten
