docetaxel (CPC634) / Cristal Therap - LARVOL DELTA

The translational journey of cancer nanomedicines: biological and entrepreneurial lessons learned. (PubMed, Drug Deliv Transl Res) - "Whilst Doxil and covid-19 vaccines demonstrated certain benefits, many NM failed in clinical development...This note describes the translational journey of CPC634 (docetaxel entrapping core-crosslinked polymeric micelles) and illustrates lessons learned in drug product development...A goal-oriented product design which is validated by external experts increases chances of development success and assures investor-readiness. NM development will progress by aligning fundamental biological insights with industrial product requirements, driving therapeutic breakthroughs."

Journal • Infectious Disease • Novel Coronavirus Disease • Oncology

Drug release from docetaxel-entrapped core-crosslinked polymeric micelles: A population pharmacokinetic modelling approach based on clinical data. (PubMed, Biomed Pharmacother) - "Achieving a balance between nanoparticle stability in the circulation and efficient intratumoural release is critical for improving therapeutic efficacy. This underscores the importance of pH in the design of nanoparticles with temporarily covalently bound drugs."

Clinical data • Journal • PK/PD data • Oncology

Efficacy and Safety of Darolutamide (DARO) in Combination With Androgen-­Deprivation Therapy (ADT) and Docetaxel (DOC) by Disease Volume and Risk in the Phase 3 ARASENS S­tudy (DGU 2023) - No abstract available.

P3 data

Dosing, safety, and pharmacokinetics (PK) of combination therapy with darolutamide (DARO), androgen-deprivation therapy (ADT), and docetaxel (DOC) in patients with metastatic hormone-sensitive prostate cancer (mHSPC) in the ARASENS study (DGU 2023) - No abstract available.

Clinical

Targeted Therapy Options in Advanced CRPC (Targeted Oncology) - "AGGARWAL: The PROfound study [NCT02987543]…led to the initial FDA approval of olaparib.1 This is a study that was randomized 2:1 in an open-label fashion. Patients had to have had 1 prior novel hormonal agent [NHA], so they could have had either abiraterone [Zytiga] or enzalutamide [Xtandi], and they had to have a mutation of either [BRCA1, BRCA2, ATM, BARD1, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, PPP2R2A, RAD51B, RAD51C, RAD51D, and/or RAD54L]....AGGARWAL: The key [takeaway from the study] is that not all DNA repair mutations are created equal…. [We know now that] the mutations that are most sensitive to PARP inhibition tend to be those that [harbor] BRCA2 and then BRCA1, perhaps to a slightly lesser degree, whereas mutations like ATM have limited activity. In fact, [there was] no difference in [rPFS]."

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Effective Treatment Options and Sequencing for Patients With Castration-Resistant Prostate Cancer (Medscape) - "Sandhya Srinivas, MD: Hello. I'm Sandy Srinivas. I'm host of the Medscape InDiscussion podcast series on prostate cancer. Today we're going to be discussing an important topic. All patients with prostate cancer who undergo androgen deprivation therapy will ultimately develop castrate resistance, and that's defined as castrate-resistant prostate cancer (CRPC) - patients having a low level of testosterone and having progressive disease either by prostate-specific antigen (PSA) or by imaging studies....Shilpa Gupta, MD: Thank you...I am really honored to be with you to discuss these topics. I was drawn to oncology because of how dynamic the field was at the time, back in 2011 or so, when newer targeted therapies were coming around, and I wanted something where one could always be learning in the field with new treatment options. Urologic oncology was almost a coincidence. I was working in a prostate cancer lab, and at the time I remember that docetaxel was..."

Audio

STARTAR: AR inhibition + ADT + apalutamide + RT + docetaxel for salvage in PSA recurrent PC after RP (YouTube) - "Andrew J. Armstrong, MD...the primary analysis of the Phase II STARTAR (NCT03311555) salvage trial of androgen receptor (AR) inhibition with androgen deprivation therapy (ADT) and apalutamide with radiation therapy (RT) followed by docetaxel in men with PSA recurrent prostate cancer (PC) after radical prostatectomy (RP). The primary endpoint was 36-month progression-free survival (PFS)....This interview took place at the American Society of Clinical Oncology (ASCO) 2023 Annual Congress in Chicago, IL."

Interview • Video

Treating Stage 4 Prostate Cancer (Everydayhealth) - "Stage 4 prostate cancer is considered incurable. But there is good news: New therapies have extended the lives of men with stage 4 prostate cancer. About a decade ago, the length of time men lived after a diagnosis of stage 4 prostate cancer was 18 months to two years, but with the inclusion of newer therapies, three to five years is not uncommon, according to William Dahut, MD...'Men are definitely living longer, but they're not being cured of the cancer,' he says."

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Chemotherapy Utilized in Pretreated Metastatic Castration-Resistant Prostate Cancer : Episode 8: Physicians Discuss the Addition of Cabizatxel to Treatment in mCRPC (Targeted Oncology) - "JOSHUA LANG, MD, MS: How do you select next-line treatment for a patient with metastatic castration-resistant prostate cancer [mCRPC] who has received docetaxel and an androgen receptor [AR]-targeted therapy...But that 25 mg/m2 dose, the incidence of infectious neutropenia was approaching 10%, which is so terrible. And the toxicity death rates, people dying from infectious complications, was around 5%. [In that case, it was] very high risk, especially at that 25 mg/m2 dose."

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Exploring Darolutamide’s Impact on Time to Pain Progression Based on Disease Volume in the ARASENS Study - Matthew Smith (Urotoday) - "Matthew Smith: Yeah, happy to do so. We designed ARASENS at a time soon after the first observations that docetaxel improved survival in patients with metastatic castration-sensitive prostate cancer, and elected to use the winning arm of the previous trial as the control group....A little bit different than some of the other agents where that does occur and there might be more of an inclination to do stepwise treatment. But I'm very comfortable starting ADT and darolutamide at the same time."

Interview • Video

Recent advancements in treating mCSPC disease landscape - "Recent advancements in treating mCSPC disease landscape...Review key learnings for practical implementation of multi-modal therapy."

Live event

Recent advancements in treating mCSPC disease landscape (McGill University) - "Recent advancements in treating mCSPC disease landscape...Review key learnings for practical implementation of multi-modal therapy."

Live event

STARTAR: ADT with apalutamide, radiation therapy and docetaxel in prostate cancer (YouTube) - "Tian Zhang, MD...discusses findings from the Phase II STARTAR trial (NCT03311555) of androgen receptor inhibition with androgen deprivation therapy (ADT) and apalutamide with radiation therapy followed by docetaxel in patients with PSA recurrent prostate cancer. 3-year progression-free survival was increased after treatment, demonstrating the clinical feasibility of intensifying systemic treatments for PSA recurrent prostate cancer. "

Interview • Video

Podcast: ARASENS, TRITON3, and Other Key Advances at GU23 (ASCO Daily News) - "Guest host Dr. Neeraj Agarwal and Dr. Jeanny Aragon-Ching discuss several crucial studies that will be presented at the 2023 ASCO Genitourinary Cancers Symposium, including ARASENS, TRITON3, and others in prostate cancer, as well as novel therapies in mRCC and urothelial carcinoma."

Audio • Renal Cell Carcinoma

Roundtable Discussion: Dorff Reviews Factors for Selecting Chemotherapy and Other Later-Line mCRPC Treatments (Targeted Oncology) - "During a Targeted Oncology Case-Based Roundtable event, Tanya B. Dorff, and participants, discussed the case of a patient with metastatic castration-resistant prostate cancer who has already received enzalutamide and docetaxel....That is a good point. It could be not only another primary, but neuroendocrine differentiation, which classically doesn't express PSMA. Himisha Beltran, MD...has done some work showing that some neuroendocrine prostate cancers still do express PSMA."

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CINOVA: a phase II study of CPC634 (nanoparticulate docetaxel) in patients with platinum resistant recurrent ovarian cancer. (PubMed, Int J Gynecol Cancer) - "Treatment with CPC634 was feasible, but without apparent clinical activity in patients with recurrent platinum-resistant ovarian cancer. Side effects were mainly gastrointestinal in 24 (96%) patients, including nausea, vomiting, and decreased appetite, fatigue, anemia, and dyspnea."

Journal • P2 data • Cardiovascular • Chronic Kidney Disease • Fatigue • Febrile Neutropenia • Gastrointestinal Disorder • Gynecology • Hematological Disorders • Hypertension • Infectious Disease • Nephrology • Neutropenia • Obstetrics • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Pulmonary Disease • Renal Disease • Solid Tumor

Triplet therapy including darolutamide should be standard of care in mCSPC, data indicate (Urology Times) - "The regimen should be considered the new standard of care for this patient population, according to findings presented at the 2023 American Society of Clinical Oncology Genitourinary Cancers Symposium. The authors were led by Maha H.A. Hussain, MD...Patients were randomized 1:1 to 600 mg of darolutamide twice daily or placebo, in combination with ADT plus docetaxel."

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Phase IIR trial of docetaxel and HER2 targeted therapies in HER2+ recurrent/metastatic salivary duct/SGC (NRG Winter 2023) - No abstract available.

A 67-Year-Old-Man with Metastatic Prostate Cancer - Episode 2: Available Systemic Therapy Options for Metastatic Castration-Resistant Prostate Cancer (mCRPC) After Docetaxel and AR-Targeted Therapy (Urology Times) - "Dr Stephen J. Freedland reviews the available treatment options for patients with metastatic castration-resistant prostate cancer (mCRPC), visceral disease, and no actionable genomic alterations, who received prior treatment with docetaxel and AR-targeted therapy."

Video

DORA Trial (NCT03574571) Reaches Key Milestone (YouTube) - "Dr. Michael J. Morris...PI of the Phase III Trial of Docetaxel vs. Docetaxel and Radium-223 for Metastatic Castration-Resistant Prostate Cancer (mCRPC), also known as the DORA Trial, discusses the study's important 50% accrual milestone."

Video

Pre‐Clinical Studies to Advance Zilovertamab‐Based, Anti‐ROR1 CAR‐T cell Therapy for Metastatic Prostate Cancer. (SBUR 2022) - "ROR1 was expressed at high levels on castration resistant small cell PCa and neuroendocrine PCa cell lines and PDX models. Zilovertamab synergized with docetaxel to inhibit tumor growth in patient derived xenograft in vivo and in organoid cultures. Zilovertamab-based CART cells durably eradicated ROR1+ prostate cancer xenograft tumors. These studies supported the recently launched Phase 1b clinical trial of Zilovertamab plus docetaxel in metastatic CRPC patients. Clinical development of GMP Zilovertamab CART cells for a clinical trial in CLL is in progress and may lead to rapid progression to a clinical trial for metastatic CRPC and NEPC."

NICE recommends new treatment for EGFR-positive lung cancer (European Pharmaceutical Review) - "Professor Sanjay Popat...stated: 'Mobocertinib [is] not only a proven effective targeted treatment but one that can be taken orally at home...This positive decision from NICE means that clinical management of this devastating type of lung cancer is brought more in line with other forms of the disease where targeted treatments are already routinely available.'"

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NRG-HN010 Study Overview (YouTube) - "Dr. Stuart Wong...discussed NRG-HN010: A Controlled, Randomized Phase II Trial of Docetaxel Plus Trastuzumab Versus Ado-Trastuzumab Emtansine for Recurrent, Metastatic, or Treatment-Naive, Unresectable HER2-Positive Salivary Gland Cancer."

Video

Design, Development and Clinical Translation of CriPec®-based Core-Crosslinked Polymeric Micelles. (PubMed, Adv Drug Deliv Rev) - "The frontrunner formulation CPC634, which refers to 65 nm-sized CCPM entrapping the chemotherapeutic drug docetaxel, showed excellent pharmacokinetic properties, safety, tumor accumulation and antitumor efficacy in multiple animal models...Altogether, the preclinical and clinical results obtained to date demonstrate that mPEG-b-pHPMAmLac CCPM based on CriPec® technology are a potent, tunable, broadly applicable and well-tolerable platform for targeted drug delivery and improved anticancer therapy. ADDR Theme Issue: Image-Guided Drug Delivery (IGDD)."

Journal • Review • Oncology

Bimodal Vs Trimodal Therapy in Patients With Metastatic Hormone-Sensitive Prostate Cancer (Targeted Oncology) - "During a case-based roundtable event, Ashley Evan Ross, MD, PhD, reviewing therapeutic options for a patient with metastatic hormone-sensitive prostate cancer."

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