DAROSTEP: Evaluating Step Counts as a Biomarker and Its Relationship on Treatment Outcomes in Vulnerable Patients With Metastatic Hormone-Sensitive Prostate Cancer on Darolutamide and Androgen Deprivation Therapy

This prospective clinical trial aims to investigate the impact of darolutamide in combination with standard-of-care androgen deprivation on physical activity, specifically step count, and its correlation with important markers of safety in vulnerable adults who screen positive by a brief geriatric assessment (GA) and metastatic hormone-sensitive prostate cancer.

Start Date01 Nov 2025

Sponsor / Collaborator

The University of Chicago

NCT06592924

/ Not yet recruitingPhase 3IIT

A Randomized Clinical Trial for the Addition of Docetaxel to Androgen Receptor Pathway Inhibitors in Patients With Metastatic Castration Sensitive Prostate Cancer Without Deep PSA Response

This study is being done to answer the following question: can the chance of prostate cancer growing or spreading be lowered by adding a drug to the usual combination of drugs?
This study would like to find out if this approach is better or worse than the usual approach for prostate cancer.
The usual approach for patients who are not in a study is hormone treatment with Androgen Deprivation Therapy (ADT) and Androgen-Receptor Pathway Inhibitor (ARPI).

Start Date15 Jan 2025

Sponsor / Collaborator

Canadian Cancer Trials Group

[+4]

NCT06625970

/ Not yet recruitingPhase 3IIT

A Randomized Phase III Trial With a Factorial Design Evaluating the Efficacy and Safety of Darolutamide and Stereotactic Dose Escalated Radiotherapy in Patients With Localized Prostate Cancer and High-risk Features of Relapse, From the Prostate Cancer Consortium in Europe (PEACE)

PEACE 7 is an international, multicenter, randomized, open-label phase III study that aims at evaluating the efficacy and safety of darolutamide and of stereotactic dose escalated prostate radiotherapy in patients with localised prostate cancer and high-risk features of relapse (defined as patients with at least 2 high-risk criteria from National Comprehensive Cancer Network (NCCN) classification) using a factorial (2x2) design.
The primary objective of this study is to assess the efficacy of darolutamide and of a stereotactic dose escalated radiotherapy targeting prostate in combination with ADT and pelvic nodal radiotherapy in terms of metastasis-free survival (MSF).
Patients will be randomized (1:1:1:1) to receive either:
* Arm A (Standard arm): ADT + conventional fractionated or moderately hypo-fractionated prostate radiotherapy including pelvic nodal radiotherapy
* Arm B (Experimental arm): ADT + conventional fractionated or moderately hypo-fractionated prostate radiotherapy including pelvic nodal radiotherapy + darolutamide
* Arm C (Experimental arm): ADT + conventional fractionated or moderately hypo-fractionated pelvic nodal radiotherapy + Prostate SBRT
* Arm D (Experimental arm): ADT + conventional fractionated or moderately hypo-fractionated pelvic nodal radiotherapy + Prostate SBRT + darolutamide
Patient will receive systemic treatments (ADT and/or darolutamide) during 2 years where visits on site are planned at D45, D90, D180 and then every 3 months for checkups and follow prostate specific antigen (PSA) level.
Metastasis-free survival (MFS) is defined as the time interval from randomization to the date of the appearance of metastasis (on next generation imaging) or death (from any cause), whichever occurs first. Radiographic evaluation will be carried out at the time of biochemical failure (Phoenix criteria) or in case of clinical suspicion. After biochemical failure (Phoenix criteria) radiographic evaluation on next generation imaging (prostate-specific membrane antigen (PSMA) positron emission tomography (PET) scan (any European Medicines Agency (EMA) approved PSMA tracer)) will be performed every 6 months until a metastatic site of relapse is identified and will be repeated at each subsequent PSA progression.

Start Date01 Jan 2025

Sponsor / Collaborator

UNICANCER

[+1]

100 Clinical Results associated with Darolutamide

100 Translational Medicine associated with Darolutamide

100 Patents (Medical) associated with Darolutamide

352

Literatures (Medical) associated with Darolutamide

01 Feb 2025·Clinical Genitourinary Cancer

Central Nervous System Toxicity in Prostate Cancer Patients Treated with Androgen Receptor Signaling Inhibitors: A Systematic Review, Meta-analysis, and Network Meta-analysis

Review

Author: Laukhtina, Ekaterina ; Parizi, Mehdi Kardoust ; Kimura, Takahiro ; Matsukawa, Akihiro ; Rajwa, Pawel ; Klemm, Jakob ; Chiujdea, Sever ; Yanagisawa, Takafumi ; Kimura, Shoji ; Miki, Jun ; Shariat, Shahrokh F. ; Tsuboi, Ichiro ; Mancon, Stefano ; Shariat, Shahrokh F ; Karakiewicz, Pierre I. ; Mori, Keiichiro ; Miszczyk, Marcin ; Fazekas, Tamás ; Karakiewicz, Pierre I

BACKGROUND:

Androgen-receptor signaling inhibitors (ARSIs) significantly improve survival in systemic therapy for advanced/metastatic prostate cancer (PCa) patients; however possible central nervous system (CNS) toxicity is an unaddressed concern. We aimed to assess and compare the incidence of CNS-related adverse events (AEs) secondary to the treatment of PCa patients with different ARSIs.

MATERIALS:

In August 2023, a comprehensive seach was conducted in three databases for randomized controlled trials (RCTs) of PCa patients receiving ARSIs plus ADT. The primary endpoints included mental impairment, cognitive impairment, seizure, fatigue, and falls.

RESULTS:

Twenty-six RCTs, comprising 20,328 patients, were included in meta-analyses and network meta-analyses (NMAs). ARSIs increased the risk of mental impairment (RR: 1.72; 95% CI, 1.09-2.71), cognitive impairment (RR: 2.25; 95% CI, 1.78-2.86), seizure (RR: 2.20, 95% CI, 1.09-4.45), fatigue (RR: 1.31, 95% CI, 1.20-1.43), and falls (RR: 2.07, 95% CI, 1.60-2.67) compared to standard of care (SOC). Based on NMAs, Enzalutamide showed a significant increase in risk for all assessed CNS-related AEs, while Abiraterone demonstrated significant risk increases in cognitive impairment, fatigue, and falls. Conversely, Darolutamide did not exhibit significant increases in risk for any CNS-related AEs, except for fatigue.

CONCLUSIONS:

The addition of ARSIs to ADT increased all examined CNS-related AEs compared to SOC. Each ARSI is associated with a distinct profile of CNS-related AEs. Careful patient selection and monitoring for CNS sequelae is necessary to achieve the best quality of life in patients on ARSI + ADT for PCa.

01 Jan 2025·EUROPEAN UROLOGY

Prostate Cancer Therapy Cardiotoxicity Map (PROXMAP) for Advanced Disease States: A Systematic Review and Network Meta-analysis with Bayesian Modeling of Treatment Histories

Review

Author: Rivas, Alexis ; Plana, Juan ; Xiao, Daniel ; Tilki, Derya ; Oprea-Lager, Daniela ; van den Bergh, Roderick ; Deng, Brett ; De Santis, Maria ; Guhan, Maya ; Brunckhorst, Oliver ; Canfield, Steven ; Jones, William ; Oldenburg, Jan ; Ploussard, Guillaume ; Mody-Bailey, Neal ; Molony, Donald ; Sanchez, Darren ; Gandaglia, Giorgio ; Thames, Emma ; Owen, Chris ; Magill, Resa ; Swaby, Justin ; van Oort, Inge ; Sommer, Silke Gillessen ; Ranganath, Shreyas ; Iacobucci, Alexander ; Schoots, Ivo ; Galan, Jacob ; Cornford, Philip ; Song, Jeffrey ; Zarker, Andrew ; Holder, Travis ; Aziz, Moez Karim ; Choi, Lily ; Imber, Jared ; Ziaolhagh, Ali ; Fatakdawala, Mariya ; Jacob, Jerril ; Koutroumpakis, Efstratios ; Ali, Abdelrahman ; Howell, Skyler ; Iliescu, Cezar ; Roberts, Matthew ; Desai, Shubh ; Hartshorne, Taylor ; Monlezun, Dominique ; Briers, Erik ; Roland, Jerry ; Zhang, Allan ; Higgason, Noel ; Rouviere, Olivier ; Nichols, Alexis ; Wamique Yusuf, Syed ; Stranne, Johan

BACKGROUND AND OBJECTIVE:

Recommendations of first-line therapies for metastatic hormone-sensitive (mHSPC), nonmetastatic castrate-resistant (M0CRPC), and metastatic castrate-resistant (mCRPC) prostate cancer do not account for cardiotoxicity due to a lack of clear prior evidence. This manuscript assesses cardiotoxicity of these therapies.

METHODS:

We searched Ovid Medline, Elsevier Embase, and the Cochrane Library for randomized clinical trials (RCTs) from database inception to January 14, 2024. Network meta-analyses of first-line mHSPC, M0CRPC, and mCRPC therapies were constructed for the five cardiotoxicity metrics defined by the International Cardio-Oncology Society: heart failure, myocarditis, vascular toxicity, hypertension, and arrhythmias. Additional Bayesian network meta-analyses also accounted for prior treatment history.

KEY FINDINGS AND LIMITATIONS:

Thirteen RCTs (16 292 patients) were included. For mHSPC, androgen deprivation therapy (ADT) plus docetaxel (DTX) plus abiraterone acetate (AA) with prednisone (P) demonstrated a significant increase in hypertension and arrhythmias versus ADT + DTX (risk ratio [RR] 2.85, 95% confidence interval [CI] 1.67-4.89, and RR 2.01, 95% CI 1.17-3.44, respectively); however, no corresponding differences were observed between ADT + DTX plus darolutamide (DAR) and ADT + DTX (RR 1.55, 95% CI 0.73-3.30, and RR 0.94, 95% CI 0.63-1.40, respectively). For mCRPC assuming a history of mHSPC treatment, ADT + AA + P plus olaparib (OLA) demonstrated a statistically significant decrease in hypertension versus ADT + AA + P (RR 0.20, 95% CI 0.16-0.26). M0CRPC results were unremarkable.

CONCLUSIONS AND CLINICAL IMPLICATIONS:

For mHSPC, ADT + DTX + DAR demonstrates less cardiotoxicity than ADT + DTX + AA + P due to a lower risk of hypertension and arrhythmias from decreased mineralocorticoid excess. In addition, OLA counterintuitively offers decreased hypertension when superimposed on ADT + AA + P for mCRPC treatment after prior androgen deprivation from mHSPC therapy.

01 Jan 2025·Molecular Oncology

Assessments of prostate cancer cell functions highlight differences between a pan‐PI3K/mTOR inhibitor, gedatolisib, and single‐node inhibitors of the PI3K/AKT/mTOR pathway

Article

Author: Seibel, Megan ; Kopher, Ross ; Rossetti, Stefano ; Molden, Jhomary ; Laing, Lance ; Sen, Adrish ; DeLaForest, Ann ; Schulz, Stephen ; Iversrud, Charles ; Khan, Salmaan ; MacNeil, Ian ; Broege, Aaron ; Davis, Laura

Metastatic castration‐resistant prostate cancer (mCRPC) is characterized by loss of androgen receptor (AR) sensitivity and oncogenic activation of the PI3K/AKT/mTOR (PAM) pathway. Loss of the PI3K regulator PTEN is frequent during prostate cancer (PC) initiation, progression, and therapeutic resistance. Co‐targeting the PAM/AR pathways is a promising mCRPC treatment strategy but is hampered by reciprocal negative feedback inhibition or feedback relief. Most PAM inhibitors selectively spare (or weakly inhibit) one or more key nodes of the PAM pathway, potentiating drug resistance depending on the PAM pathway mutation status of patients. We posited that gedatolisib, a uniformly potent inhibitor of all class I PI3K isoforms, as well as mTORC1 and mTORC2, would be more effective than inhibitors targeting single PAM pathway nodes in PC cells. Using a combination of functional and metabolic assays, we evaluated a panel of PC cell lines with different PTEN/PIK3CA status for their sensitivity to multi‐node PAM inhibitors (PI3K/mTOR: gedatolisib, samotolisib) and single‐node PAM inhibitors (PI3Kα: alpelisib; AKT: capivasertib; mTOR: everolimus). Gedatolisib induced anti‐proliferative and cytotoxic effects with greater potency and efficacy relative to the other PAM inhibitors, independent of PTEN/PIK3CA status. The superior effects of gedatolisib were likely associated with more effective inhibition of critical PAM‐controlled cell functions, including cell cycle, survival, protein synthesis, oxygen consumption rate, and glycolysis. Our results indicate that potent and simultaneous blockade of all class I PI3K isoforms, mTORC1, and mTORC2 could circumvent PTEN‐dependent resistance. Gedatolisib, as a single agent and in combination with other therapies, reported promising preliminary efficacy and safety in various solid tumor types. Gedatolisib is currently being evaluated in a Phase 1/2 clinical trial in combination with darolutamide in patients with mCRPC previously treated with an AR inhibitor, and in a Phase 3 clinical trial in combination with palbociclib and fulvestrant in patients with HR+/HER2− advanced breast cancer.

139

News (Medical) associated with Darolutamide

13 Jan 2025

·investors.oricpharma.com

ORIC® Pharmaceuticals Provides Early Phase 1b Combination Data for ORIC-944, Operational Highlights for 2024, and Anticipated Upcoming Milestones

Announces encouraging early safety and efficacy data in ongoing dose escalation trial for ORIC-944 in combination with apalutamide in patients with mCRPC Entered into clinical trial collaboration and supply agreement with Johnson & Johnson to evaluate ORIC-114 in combination with subcutaneous amivantamab for the first-line treatment of NSCLC patients with EGFR exon 20 insertion mutations Expects to report seven data readouts across ORIC-114 and ORIC-944 clinical programs over the next 18 months, with potential initiation of registrational trials in 2H25 and early 2026 Cash and investments expected to fund operating plan into late 2026 SOUTH SAN FRANCISCO and SAN DIEGO, Jan. 13, 2025 (GLOBE NEWSWIRE) -- ORIC Pharmaceuticals, Inc. (Nasdaq: ORIC), a clinical stage oncology company focused on developing treatments that address mechanisms of therapeutic resistance, today provided early Phase 1b combination data for ORIC-944, operational highlights for 2024, and anticipated upcoming milestones. “We made strong progress on multiple fronts in 2024, most notably with the initiation of multiple cohorts for ORIC-114 in NSCLC and ORIC-944 in mCRPC. We also forged three strategic collaborations with leading pharma partners, strengthened our leadership team to expand functional capabilities, and completed a $125 million PIPE financing, extending our cash runway into late 2026,” said Jacob M. Chacko, M.D., president and chief executive officer. “These accomplishments position us well for 2025 and beyond, with seven anticipated data readouts over the next 18 months as we advance toward potentially initiating registrational studies for ORIC-114 in the second half of 2025 and for ORIC-944 in early 2026.” Updated Phase 1b Combination Data for ORIC-944 ORIC-944 is a potent and selective allosteric inhibitor of the polycomb repressive complex 2 (PRC2) via allosteric targeting of the embryonic ectoderm development (EED) subunit. ORIC-944 was initially evaluated as a single agent in a Phase 1b trial in patients with advanced prostate cancer and demonstrated potential best-in-class drug properties, including a clinical half-life of approximately 20 hours, robust target engagement, and a favorable safety profile. In mid-2024, the Company initiated once daily dosing of ORIC-944 in combination with 240 mg QD apalutamide or with 600 mg BID darolutamide, as part of the ongoing Phase 1b trial in patients with metastatic castration resistant prostate cancer (mCRPC). As of the December 10, 2024 data cut-off, the Company completed the first two ORIC-944 dose escalation cohorts (n=6 patients) for the apalutamide combination. This initial experience demonstrated: Deep prostate-specific antigen (PSA) decreases across both the 600 mg and 800 mg dose cohorts; 3 of 6 patients achieved confirmed PSA50 responses, of which 2 achieved confirmed PSA90 responses. All the PSA responses were maintained at ≥12 weeks, including a durable confirmed PSA90 response ongoing at 38 weeks. Well-tolerated safety, with primarily Grade 1 and Grade 2 treatment related adverse events (TRAE), consistent with PRC2 and androgen receptor (AR) inhibition, and one Grade 3 TRAE of fatigue (patient remains on treatment without dose modification). The first two dose levels cleared without dose limiting toxicities or treatment discontinuations related to safety. Dose escalation is ongoing. Dose escalation for the combination of ORIC-944 with darolutamide is also ongoing with the first dose cohort completed and the second enrolling. Preliminary clinical activity seen to date is consistent with the apalutamide combination cohort. 2024 Key Accomplishments ORIC-114: a brain penetrant, orally bioavailable, irreversible EGFR/HER2 inhibitor Entered into a clinical trial collaboration and supply agreement with Johnson & Johnson to evaluate ORIC-114 in combination with subcutaneous (SC) amivantamab for the 1L treatment of NSCLC patients with EGFR exon 20 insertion mutations. Initiated a cohort to evaluate ORIC-114 monotherapy for the treatment of patients with 1L treatment-naïve EGFR exon 20 insertion NSCLC. Announced the completion of the dose escalation portion of the Phase 1b trial of ORIC-114 and the selection of two provisional recommended phase 2 doses; after which, first patients were dosed across three expansion cohorts in the Phase 1b trial of ORIC-114 in patients with mutated non-small cell lung cancer (NSCLC), including 2L EGFR exon 20 insertion (EGFR exon 20 inhibitor naïve), 2L+ HER2 exon 20 insertion, and 2L+ EGFR atypical mutations. Presented preclinical data demonstrating potential best-in-class properties, including potency and selectivity, of ORIC-114 to treat NSCLC harboring EGFR exon 20 insertions and other atypical EGFR mutations at the EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics. ORIC-944: a potent and selective allosteric inhibitor of PRC2 Initiated dosing of ORIC-944 in combination with ERLEADA® (apalutamide) and in combination with NUBEQA® (darolutamide) in mid-2024 in the ongoing Phase 1b trial for prostate cancer. Entered into clinical trial collaboration and supply agreements with Johnson & Johnson and Bayer to support the ongoing Phase 1b trial of ORIC-944 in combination with AR inhibitors for the treatment of prostate cancer. Reported initial Phase 1b single agent data for ORIC-944 in metastatic prostate cancer supporting advancement into combination development and demonstrating the potential as a best-in-class PRC2 inhibitor, including a clinical half-life of ~20 hours, robust target engagement, no signs of CYP autoinduction that was observed with first-generation PRC2 inhibitors, and a generally well-tolerated safety profile. Presented preclinical data at the 2024 AACR Annual Meeting demonstrating superior drug properties and synergy data in prostate cancer models, reinforcing the promise of ORIC-944 as a potential best-in-class treatment for combination with AR inhibitors. Corporate Highlights: Strengthened cash position and runway with a $125 million private placement financing from new and existing healthcare specialist funds. Expanded the leadership team with the appointment of industry veteran Keith Lui as Senior Vice President of Commercial and Medical Affairs. Anticipated Program Milestones ORIC anticipates the following upcoming data milestones: ORIC-114 (NSCLC): 1H 2025: 2L EGFR exon 20 and 2L+ HER2 exon 20 2H 2025: 2L+ EGFR atypical 1H 2026: 1L EGFR exon 20 Mid-2026: 1L EGFR exon 20 combination with SC amivantamab and 1L EGFR atypical ORIC-944 (mCRPC): 4Q 2025 / 1H 2026: Combination with AR inhibitors 1H 2025: 2L EGFR exon 20 and 2L+ HER2 exon 20 2H 2025: 2L+ EGFR atypical 1H 2026: 1L EGFR exon 20 Mid-2026: 1L EGFR exon 20 combination with SC amivantamab and 1L EGFR atypical 4Q 2025 / 1H 2026: Combination with AR inhibitors Financial Guidance As of September 30, 2024, cash, cash equivalents and investments totaled $282.4 million, which the company expects will be sufficient to fund its operating plan into late 2026. Presentation and Webcast Jacob M. Chacko, M.D., president and chief executive officer, will present a company overview at the 43rd Annual J.P. Morgan Healthcare Conference on Tuesday, January 14, 2025, at 11:15 a.m. PT. A live webcast will be available through the investor section of the company’s website at www.oricpharma.com. A replay of the webcast will be available for 90 days following the event. About ORIC Pharmaceuticals, Inc. ORIC Pharmaceuticals is a clinical stage biopharmaceutical company dedicated to improving patients’ lives by Overcoming Resistance In Cancer. ORIC’s clinical stage product candidates include (1) ORIC-114, a brain penetrant inhibitor that selectively targets EGFR exon 20, HER2 exon 20 and EGFR atypical mutations, being developed across multiple genetically defined cancers, and (2) ORIC-944, an allosteric inhibitor of the polycomb repressive complex 2 (PRC2) via the EED subunit, being developed for prostate cancer. Beyond these two product candidates, ORIC® is also developing multiple precision medicines targeting other hallmark cancer resistance mechanisms. ORIC has offices in South San Francisco and San Diego, California. For more information, please go to www.oricpharma.com, and follow us on X or LinkedIn. Cautionary Note Regarding Forward-Looking Statements This press release contains forward-looking statements as that term is defined in Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Statements in this press release that are not purely historical are forward-looking statements. Such forward-looking statements include, among other things, statements regarding the continued clinical development of ORIC-114 and ORIC-944; statements regarding the potential best-in-class properties of ORIC-114 and ORIC-944; clinical outcomes from combination studies with ORIC-944, which may materially change as patient enrollment continues or more patient data become available; the development plans and timelines for ORIC-114, ORIC-944 and ORIC’s other product candidates; the potential advantages of ORIC-114, ORIC-944 and ORIC’s other product candidates and programs; plans underlying ORIC’s clinical trials and development; anticipated program milestones, including timing of program and data updates and the initiation of registrational studies; the period over which ORIC estimates its existing cash, cash equivalents and investments will be sufficient to fund its current operating plan; and statements by the company’s chief executive officer. Words such as “believes,” “anticipates,” “plans,” “expects,” “intends,” “will,” “goal,” “potential” and similar expressions are intended to identify forward-looking statements. The forward-looking statements contained herein are based upon ORIC’s current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results could differ materially from those projected in any forward-looking statements due to numerous risks and uncertainties, including but not limited to: risks associated with the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics and operating as an early clinical stage company; ORIC’s ability to develop, initiate or complete preclinical studies and clinical trials for, obtain approvals for and commercialize any of its product candidates; changes in ORIC’s plans to develop and commercialize its product candidates; the potential for clinical trials of ORIC’s product candidates to differ from preclinical, initial, interim, preliminary or expected results; negative impacts of health emergencies, economic instability or international conflicts on ORIC’s operations, including clinical trials; the risk of the occurrence of any event, change or other circumstance that could give rise to the termination of ORIC’s license and collaboration agreements or its clinical trial collaboration and supply agreements; the potential market for ORIC’s product candidates, and the progress and success of competing therapeutics currently available or in development; ORIC’s ability to raise any additional funding it will need to continue to pursue its business and product development plans; regulatory developments in the United States and foreign countries; ORIC’s reliance on third parties, including contract manufacturers and contract research organizations; ORIC’s ability to obtain and maintain intellectual property protection for its product candidates; the loss of key scientific or management personnel; competition in the industry in which ORIC operates; general economic and market conditions; and other risks. Information regarding the foregoing and additional risks may be found in the section titled “Risk Factors” in ORIC’s Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (the “SEC”) on November 12, 2024, and ORIC’s future reports to be filed with the SEC. These forward-looking statements are made as of the date of this press release, and ORIC assumes no obligation to update the forward-looking statements, or to update the reasons why actual results could differ from those projected in the forward-looking statements, except as required by law. Contact: Dominic Piscitelli, Chief Financial Officer dominic.piscitelli@oricpharma.com info@oricpharma.com

Phase 1Clinical ResultAACR

11 Dec 2024

·www.globenewswire.com

Celcuity Presents Overall Survival Data from Phase 1b Study Evaluating Gedatolisib in Combination with Palbociclib and Endocrine Therapy at the 2024 San Antonio Breast Cancer Symposium

Median overall survival (OS) among patients with HR+, HER2- advanced breast cancer who were treatment-naïve in the advanced setting was 77.3 months Median OS among patients previously treated with a CDK4/6 inhibitor was 33.9 months MINNEAPOLIS, Dec. 11, 2024 (GLOBE NEWSWIRE) -- Celcuity Inc. (Nasdaq: CELC), a clinical-stage biotechnology company pursuing development of targeted therapies for oncology, today announced overall survival (OS) data from two patient cohorts evaluated in a Phase 1b trial with gedatolisib, a pan-PI3K/mTORC1/2 inhibitor, in combination with palbociclib and either letrozole or fulvestrant, in patients with HR+, HER2-advanced or metastatic breast cancer. Results will be presented in a poster session at the San Antonio Breast Cancer Symposium (SABCS) being held December 10-13 at the Henry B. Gonzalez Convention Center in San Antonio, Texas. The poster presents overall survival data among patients with HR+, HER2- advanced breast cancer who were either treatment-naïve (N=41) or whose disease progressed during prior treatment with a CDK4/6 inhibitor (N=27). For the treatment-naïve patient cohort (Escalation Arm A and Expansion Arm A), median OS was 77.3 months (95% CI, 50.3 to 89.0). For the patients previously treated with a CDK4/6 inhibitor and who received the Phase 3 dose of gedatolisib (Expansion Arm D), median OS was 33.9 months (95% CI, 17.8 to 52.3). “The median OS results reported for gedatolisib in combination with palbociclib and endocrine therapy are encouraging and compare favorably to published data for currently available first- or second-line standard-of-care regimens for patients with HR+/HER2- advanced breast cancer,” said Igor Gorbatchevsky, MD, Chief Medical Officer of Celcuity. “These results highlight the promising clinical development strategy of simultaneously blocking the ER, CDK4/6, and PAM (PI3K/AKT/mTOR) signaling pathways. This approach provided the rationale for our two Phase 3 clinical trials, the ongoing VIKTORIA-1 and planned VIKTORIA-2, which are and will be evaluating this treatment strategy in patients with HR+, HER2- advanced breast cancer in the second- and first-line setting, respectively.” This poster, and two additional posters presenting nonclinical data for gedatolisib at the SABCS, are available on the publications page of the Celcuity website. About Gedatolisib Gedatolisib is a potent, reversible inhibitor that selectively targets all Class I PI3K isoforms and mTORC1 and mTORC2 to blockade PI3K/AKT/mTOR signaling activity. Its mechanism of action and pharmacokinetic properties are highly differentiated from other currently approved and investigational therapies that target PI3K, AKT, or mTOR alone or together. Inhibiting all four Class I PI3K isoforms and mTORC1/2 limits the potential development of drug resistance compared with isoform-specific PI3K, AKT or mTOR specific inhibitors. A robust response rate and a manageable side effect profile were reported for the Phase 1b clinical trial that evaluated gedatolisib in combination with palbociclib and endocrine therapy in patients with HR+/HER2- advanced breast cancer. Gedatolisib, in combination with palbociclib and fulvestrant, has been granted U.S. Food and Drug Administration (FDA) Breakthrough Therapy designation for the treatment of HR+/HER2- advanced breast cancer that has progressed following treatment with a CDK4/6 inhibitor in combination with an aromatase inhibitor. About Celcuity Celcuity is a clinical-stage biotechnology company focused on development of targeted therapies for treatment of multiple solid tumor indications. The company's lead therapeutic candidate is gedatolisib, a potent, pan-PI3K and mTOR inhibitor. Its mechanism of action and pharmacokinetic properties are highly differentiated from other currently approved and investigational therapies that target PI3K or mTOR 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. More detailed information about the VIKTORIA-1 study can be found at ClinicalTrials.gov. A Phase 1b/2 clinical trial, CELC-G-201, evaluating gedatolisib in combination with darolutamide in patients with metastatic castration resistant prostate cancer, is enrolling patients. 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 expected to begin enrolling patients in the second quarter of 2025. Celcuity is headquartered in Minneapolis. Further information about Celcuity can be found at www.celcuity.com. Follow us on LinkedIn and Twitter. Forward-Looking Statements This press release contains statements that constitute "forward-looking statements" including, but not limited to, the design of our clinical trials; the timing of initiating and enrolling patients in, and receiving results and data from, our clinical trials; the costs and expected results from any ongoing or planned clinical trials; the market opportunity for gedatolisib; revenue expectations; our strategy, marketing and commercialization plans, including the benefits of strategic decisions regarding studies and trials; other expectations with respect to Celcuity's lead product candidate, gedatolisib, and its CELsignia platform; our anticipated use of cash; and the strength of our balance sheet. In some cases, you can identify forward-looking statements by terminology such as "may," "should," "expects," "plans," "anticipates," "believes," "estimates," "predicts," "potential," "intends" or "continue," and other similar expressions that are predictions of or indicate future events and future trends, or the negative of these terms or other comparable terminology. Forward-looking statements are subject to numerous risks, uncertainties, and conditions, many of which are beyond the control of Celcuity. These include, but are not limited to, unforeseen delays in our clinical trials, our ability to obtain and maintain regulatory approvals to commercialize our products, and the market acceptance of such products, the development of therapies and tools competitive with our products, our ability to access capital upon favorable terms or at all, and those risks set forth in the Risk Factors section in Celcuity's Annual Report on Form 10-K for the year ended December 31, 2023 filed with the Securities and Exchange Commission on March 27, 2024. Readers are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. Celcuity undertakes no obligation to update these statements for revisions or changes after the date of this press release, except as required by law. View source version of release on GlobeNewswire.com Contacts: Celcuity Inc. Brian Sullivan, bsullivan@celcuity.comVicky Hahne, vhahne@celcuity.com(763) 392-0123 ICR HealthcarePatti Bank, patti.bank@icrhealthcare.com (415) 513-1284

Phase 1Phase 3Breakthrough TherapyClinical ResultPhase 2

25 Nov 2024

·www.echemi.com

Bayer's New Drug Nubeqa Significantly Extends Survival Time for Prostate Cancer Patients

On November 21, 2024, Bayer announced that a Supplemental New Drug Application (sNDA) for its product darotamine (trade name: Nubeqa) in combination with androgen deprivation therapy (ADT) for the treatment of patients with metastatic hormone-sensitive prostate cancer (mHSPC) has been accepted by the U.S. Food and Drug Administration (FDA). The sNDA application is based on the positive results of the Phase III ARANOTE study. The study was a randomized, double-blind, placebo-controlled clinical trial (n=669) designed to evaluate the efficacy and safety of darotamine (600mg twice daily) in combination with ADT compared with placebo and ADT in the treatment of patients with mHSPC. The primary endpoint of the study was radiologic progression-free survival (rPFS) at 36 months. The results showed that patients in the darotamine group had significantly longer rPFS than those in the placebo group (less than vs 25.0 months, hazard ratio HR=0.54, P<0.0001), and a higher proportion of patients achieved rPFS at 24 months (70.3% vs 52.1%). In addition, progression to metastatic castration-resistant prostate cancer (mCRPC) was significantly delayed in the darotamine group (vs 13.8 months, HR=0.40). In terms of overall survival (OS), a similar proportion of patients reached 24 months in the darotamine and placebo groups (79.8% vs 75.5%). Darotamine, an oral androgen receptor inhibitor, was first approved for marketing in July 2019. To date, darotamine has been approved for two indications, including ① as a monotherapy in adult patients with non-metastatic castration-resistant prostate cancer (nmCRPC) and ② in combination with docetaxel in adult patients with mHSPC.

Clinical ResultPhase 3Drug Approval

100 Deals associated with Darolutamide

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KEGG	Wiki	ATC	Drug Bank
D11045	Darolutamide	L02BB06	DB12941

R&D Status

Approved

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Indication	Country/Location	Organization	Date
Metastatic Prostate Carcinoma	JP	Bayer AG	24 Feb 2023
Metastatic castration-resistant prostate cancer	US	Bayer HealthCare Pharmaceuticals, Inc.	05 Aug 2022
Prostatic Cancer	BR	Bayer AG	01 Jan 2020
Castration-Resistant Prostatic Cancer	US	Bayer HealthCare Pharmaceuticals, Inc.	30 Jul 2019

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Indication	Highest Phase	Country/Location	Organization	Date
Hormone-dependent prostate cancer	NDA/BLA	CN	Orion Pharma Ltd.	08 Jan 2025
Hormone-dependent prostate cancer	NDA/BLA	CN	Bayer Healthcare Co., Ltd.	08 Jan 2025
Hormone-dependent prostate cancer	NDA/BLA	CN	Bayer HealthCare Pharmaceuticals, Inc.	08 Jan 2025
Castration-sensitive prostate cancer	NDA/BLA	US	Bayer AG	26 Sep 2024
Localized Prostate Carcinoma	Phase 3	-	Bayer AG	01 Jan 2025
Recurrent Prostate Carcinoma	Phase 3	US	Bayer AG	03 Apr 2023
Recurrent Prostate Carcinoma	Phase 3	CN	Bayer AG	03 Apr 2023
Recurrent Prostate Carcinoma	Phase 3	JP	Bayer AG	03 Apr 2023
Recurrent Prostate Carcinoma	Phase 3	AU	Bayer AG	03 Apr 2023
Recurrent Prostate Carcinoma	Phase 3	AT	Bayer AG	03 Apr 2023

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05249712 (Pubmed \| World J Urol)	Phase 2	Locally Advanced Prostate Carcinoma Neoadjuvant ctDNA	30	Darolutamide + ADT	ppgbhcuuay(ixddiaymum) = bivvsnidks vxtaiqgkxd (chfkmrornm, 74.4 - 96.5) View more	Positive	03 Jan 2025
NCT04736199 (ARANOTE, Pubmed \| J Clin Oncol)	Phase 3	Hormone-dependent prostate cancer	669	Darolutamide 600 mg	zmiigjjwve(pnaezavvwr): HR = 0.54 (95% CI, 0.41 - 0.71) View more	Positive	20 Dec 2024
				Placebo
NCT04736199 (ARANOTE, ESMO2024 \| NEWS) Manual	Phase 3	Hormone-dependent prostate cancer	669	darolutamide+androgen-deprivation therapy	gmqykoqhsr(pjvuopgckx): HR = 0.54 (95% CI, 0.41 - 0.71), P-Value = <0.0001 View more	Positive	16 Sep 2024
				Placebo+androgen-deprivation therapy
NCT02200614 \| NCT01946204 (SPARTAN \| ARAMIS, ESMO2024)	Phase 3	Castration-Resistant Prostatic Cancer First line serum testosterone	-	ADT+apalutamide	qpdavdvmmi(iodbcoabyg): HR = 0.67 (95% CI, 0.44 - 0.99)	Negative	15 Sep 2024
				ADT+darolutamide
NCT04736199 (ARANOTE, PipelineReview) Manual	Phase 3	Hormone-dependent prostate cancer	669	darolutamide	oiyegdyfhn(amcofuepwk) = Has met its primary endpoint of radiological progression-free survival (rPFS). zuwscxrpne (gyrbumlwlo ) Met View more	Positive	17 Jul 2024
ASCO2024	Not Applicable	Castration-sensitive prostate cancer	10	Darolutamide + Chemotherapy + ADT	hgpmatfzje(qdnlwkpkvu) = 5 patients (50%) presented asthenia ymjpxxuzxl (tcmfjchicn ) View more	Positive	24 May 2024
NCT02799602 (ARASENS, ASCO2024)	Phase 3	Hormone-dependent prostate cancer	1,305	Darolutamide 600 mg	yjdhuuixws(qqrwogavvn) = yislfwuozm yupfcivtyj (atibdcbavn )	Positive	24 May 2024
				Placebo	yjdhuuixws(qqrwogavvn) = qydjxoduuu yupfcivtyj (atibdcbavn )
NCT04122976 (DAROL, AUA2024) Manual	Not Applicable	Castration-Resistant Prostatic Cancer	550	Darolutamide	skdlzbemuh(zucwzyenia) = nrznbndzaa zhgpencfci (bvnnznukac ) View more	Positive	01 May 2024
MP60-18 (AUA2024)	Not Applicable	Castration-sensitive prostate cancer	319	DARO plus ADT (doublet therapy [DT])	zdxnltoero(hwadxuxecc) = dyvssbbzrw nmowluyach (dhavpdmuej ) View more	Positive	01 May 2024
NCT02799602 (ARASENS, ASCO_GU2024) Manual	Phase 3	Castration-sensitive prostate cancer	-	DarolutamiDocetaxeltaxel + ADT	eyjvnhywnk(lpstxapsbh) = kthuyjqxkp clhmniqrcc (ehkqayaans, 6.54 - 9.14) View more	Positive	25 Jan 2024
				DarolutamidecetDocetaxelT	eyjvnhywnk(lpstxapsbh) = wofmdrwugt clhmniqrcc (ehkqayaans, 4.92 - 6.96) View more

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