A Phase II Clinical Study on Precision Treatment of Rare Tumours in China Guided by Patient-Derived Tumor Organoids (PDO) and Next-Generation Sequencing (NGS)

The objective of this Phase II, open-label, multicenter, non-randomised controlled clinical trial is to guide precision treatment for patients with rare tumours based on Patient-Derived Organoids/Next-Generation Sequencing drug screening.

Start Date01 Jan 2025

Sponsor / Collaborator

Peking University Shenzhen Hospital

ChiCTR2400085888

/ RecruitingNot ApplicableIIT

The establishment of a PRO-based PARPi maintenance treatment management system for patients with epithelial ovarian cancer

Start Date20 Jun 2024

Sponsor / Collaborator-

NCT06387056

/ RecruitingPhase 2IIT

An Exploratory Study of the Safety and Efficacy of Genomic Biomarker-guided Neoadjuvant Therapy for Locally Advanced and Oligometastatic Prostate Cancer (SEGNO)

To evaluated the safety and efficacy of genomic biomarker-guided neoadjuvant therapy for locally advanced and oligometastatic prostate cancer.

Start Date01 Apr 2024

Sponsor / Collaborator

The First Affiliated Hospital of Xiamen University

100 Clinical Results associated with Pamiparib

100 Translational Medicine associated with Pamiparib

100 Patents (Medical) associated with Pamiparib

1,500

Literatures (Medical) associated with Pamiparib

01 Mar 2025·CURRENT PHARMACEUTICAL DESIGN

PARP Pioneers: Using BRCA1/2 Mutation-targeted Inhibition to Revolutionize Breast Cancer Treatment

Article

Author: Shah, Kamal ; Bhati, Akash ; Dewangan, Hitesh Kumar ; Aggarwal, Shagun ; Sharma, Navneet

Abstract::

Breast cancer stands on the second position in the world in being common and women happen to have it with high rate of about five-folds around the world. The causes of occurrence can matter with different humans be it external factors or the internal genetic ones. Breast cancer is primarily driven by mutations in the BRCA1 and BRCA2 susceptibility genes. These BC susceptibility genes encode proteins critical for DNA homologous recombination repair (HRR). Poly (ADP ribose) polymerases (PARP) are the essential enzymes involved in the repairing of the damaged DNA. So the inhibition of these inhibitors can be considered as the promising strategy for targeting cancers with defective damage in the deoxyribonucleic acid. Olaparib and talazoparib are PARP inhibitors (PARPi) are being employed for the monotherapies in case of the deleterious germline HER2-negative and BRCA-mutated breast cancer. The potency of PARP for trapping on DNA and causes cytotoxicity may have difference in the safety and efficacy with the PARPi. The PARPi have been found its place in the all different types of breast cancers and have shown potential benefits. The purpose of this review is to provide an update on the oral poly(ADP-ribose) polymerase (PARP) inhibitors for the improvement in the treatment and management of breast cancer.

01 Mar 2025·CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY

Efficacy and safety of PARP inhibitors in prostate cancer: An umbrella review of systematic reviews and meta-analyses

Review

Author: Li, Yong-Tang ; Lee, Chen-Yu ; Kang, Yuan-Fu ; Luo, Chiao-An ; Tzang, Bor-Show ; Tzang, Chih-Chen ; Wu, Hui-Wen ; Hsu, Tsai-Ching ; Hsieh, Chia-Ming

Prostate cancer is a significant cause of cancer-related deaths in men. Poly (ADP-ribose) polymerase inhibitors (PARPi) have been shown to improve progression-free survival, especially in patients with BRCA1/2 mutations and deficiencies in homologous recombination repair (HRR). We conducted systematic reviews and meta-analyses and found that PARPi, combined with androgen receptor inhibitors, significantly improved overall survival (OS) and progression-free survival (PFS) in BRCA1/2-mutant and HRR-deficient patients. PARPi therapies increased the incidence of adverse events (AEs), including fatigue, nausea, anemia, neutropenia, and thrombocytopenia. Among different PARP inhibitors, Olaparib, Talazoparib, and Rucaparib demonstrated the strongest efficacy in improving OS and PFS but were also linked to higher rates of AEs. Combination therapies with PARPi and hormonal treatments proved more effective than monotherapy, especially in genetically targeted subgroups like BRCA1/2-mutant patients. This umbrella review demonstrates that PARPi treatment significantly improves clinical outcomes, particularly in BRCA1/2-mutant and HRR-deficient mCRPC patients.

01 Feb 2025·Translational Oncology

CDK4/6 inhibitors promote PARP1 degradation and synergize with PARP inhibitors in non-small cell lung cancer

Article

Author: Yin, Yi ; Ghosh, Anwesha B ; Raj, Ganesh V ; Roggero, Carlos M ; Devineni, Anvita ; Blatt, Eliot ; Ma, Shihong

Despite widespread deregulation of CDK4/6 activity in non-small cell lung cancer (NSCLC), clinical trials with CDK4/6 inhibitor (CDK4/6i) as a monotherapy have shown poor antitumor activity. Preclinical studies indicate that CDK4/6i may collaborate by influencing DNA damage repair pathways during radiotherapy. Since PARP1 expression was also significantly upregulated in NSCLC, we analyzed the efficacy of combining PARP1 and CDK4/6 inhibition in NSCLC models. We found that CDK4/6is synergize with PARP1 inhibitors (PARPis) to inhibit the clonogenic growth of RB-proficient NSCLC models. This synergy correlates with increased accumulation of DNA damage, interrupted cell-cycle checkpoints, and enhanced apoptotic cell death. Mechanistically, we showed that CDK4/6is promote PARP1 protein degradation, which lead to decreased availability of DNA repair factors involved in homologous recombination and suppression of DNA repair competency. Furthermore, we showed that PARP trapping is engaged in this synergy. We then confirmed that combining PARPi and CDK4/6i blocked the growth of NSCLC xenografts in vivo and patient-derived explant models ex vivo. Our data reveal a previously uncharacterized impact of CDK4/6i on PARP1 levels in RB-proficient NSCLC models and the engagement of PARP trapping in the synergy between CDK4/6i and PARPi. Our findings suggest combining CDK4/6i with PARPi could be a viable therapeutic strategy for patients with RB-proficient NSCLC.

News (Medical) associated with Pamiparib

15 Jul 2024

·www.businesswire.com

Breast Cancer Canada Launches $1M Fellowship To Expand Research Funding

TORONTO--( BUSINESS WIRE )--Today, Breast Cancer Canada , a national charity dedicated to saving lives through breast cancer research, is proud to announce a series of initiatives to support the progress of breast cancer research. The announcements include the introduction of a $1 million Canadian fellowship, as well as three diverse investments into breast cancer research. The grants are generously funded by AstraZeneca Canada and Breast Cancer Canada’s annual Precision Oncology Research Grants. “ As the breast cancer landscape evolves and we continue to push the boundaries of what’s possible, it’s important that we diversify our funding to ensure we keep up with research needs right here in Canada. Right now, that looks like investing in the next generation of Canadian breast cancer specialists, partnering with industry stakeholders to co-fund research grants, and continuing financial support for research in precision oncology,” said Kimberly Carson, CEO of Breast Cancer Canada. “ Through strategic partnerships and targeted funding, we are driving innovation and improving health outcomes for the breast cancer patients of tomorrow.” Canadian Breast Cancer Clinical Scientist Fellowship Program With early-age incidence of breast cancer on the rise 1 and the demand for specialized oncology expertise increasing 2 , the development of top-tier Canadian specialists is critical, including a focus on research learning. Breast Cancer Canada is proud to introduce the Canadian Breast Cancer Clinical Scientist Fellowship Program to support and attract the next generation of breast cancer specialists. This funding initiative will provide a significant investment of $1 million into advancing the future of breast cancer training, development, research, and care in Canada. More details on the Fellowship program process and competitive candidate application process will be released in the fall by Breast Cancer Canada at breastcancerprogress.ca . NeoAdjuvant Equity and Outcomes Research Matching Grants In partnership with AstraZeneca Canada, a global, science-led biopharmaceutical company, Breast Cancer Canada is also launching a $200,000 call for grants in solutions to equitable access for pre-surgery chemotherapy (neoadjuvant chemotherapy) and outcomes including the patient lived experience. In a co-sponsored grant of $100,000 each from Breast Cancer Canada and AstraZeneca Canada, two research grants will be awarded. As breast cancer care needs continue to evolve for stage II and III patients, Breast Cancer Canada is proud to partner with industry stakeholders to support progress through research programs that will expand knowledge on pre-surgery therapy planning and uses in Canada. “ There have been tremendous advances in breast cancer care, and we’re proud of the role that AstraZeneca continues to play in delivering these innovations to change the way breast cancer is treated and pursue our goal of eliminating breast cancer as a cause of death,” says Brian Seguin, AstraZeneca Canada, Head – Breast Cancer. “ This transformative work can’t be done alone, which is why we’re excited to build on our partnership with BCC and work collaboratively to support leading-edge Canadian health outcomes research that will not only help to enable access to neo-adjuvant treatment options earlier, but also contribute to greater health equity and health system sustainability over the patient’s lifetime.” The contributions from AstraZeneca Canada are unrestricted, which enables Breast Cancer Canada to allocate funds strategically and under the comprehensive review of a Scientific Advisory Committee. Applications are being accepted for the NeoAdjuvant Equity and Outcomes Research Matching Grants from now until August 2, 2024. For application details please visit: https://breastcancerprogress.ca/apply-for-grant-funding/ . Precision Oncology Research Grants The Fellowship funding initiative and AstraZeneca Canada research partnership come on the heels of Breast Cancer Canada’s third annual Precision Oncology Research Grants program. Breast cancer researchers from across Canada were invited to submit projects in December 2024 for funding consideration. Breast Cancer Canada’s Scientific Advisory Committee awards funding across the spectrum of breast cancer research – from basic discovery studies to accelerating the translation of results into clinical practice. The selected projects undergo a rigorous peer review process and focus on the four divisions of precision oncology research pillars: basic science, screening and detection, personalized treatment, and patient-reported outcomes. The following are the selected grant recipient researchers for Breast Cancer Canada research funding: $75,000 Dr. David Lim, Women's College Hospital Identifying a prognostic gene signature for invasive lobular breast carcinoma. $50,000 Dr. Saima Hassan Centre de Recherche de Centre Hospitalier de l’Université de Montréal Researching dissecting tumor and microenvironment influences in PARPi response in BRCA-mutant and BRCA-wild type breast cancer patients $75,000 Dr. Lisa Porter WE-SPARK Health Institute, University of Windsor Establishing a Biomarker Platform for Postpartum Breast Cancer $50,000 Dr. Ives Levesque McGill University Exploring the validation of FxMammo, AI Assistant for Breast Cancer Screening, in the Canadian Population $75,000 Dr. Rodney Ouelette Centre de Médecine de Précision du Nouveau Brunswick Exploring extracellular-vesicle-based liquid biopsy profiles in early-stage triple-negative breast (TNBC) cancer and their response to neoadjuvant chemotherapy $50,000 Dr. Mark Vincent London Health Sciences Evaluating small molecule RAD51 inhibitors $75,000 Dr. Caroline Hamm We-SPARK Health Institute Windsor Regional Hospital Assessing the effectiveness and implementation of the CTN program, using a navigator-assisted clinical trial enrollment platform $50,000 Dr. Edward Chow Sunnybrook Research Institute Preventing Radiation Dermatitis in Large-Breasted Patients: A Randomized Phase III Trial Breast Cancer Canada remains dedicated to progress through breast cancer research, advocacy for access to the best care, and elevating the patient voice to improve the lives of Canadians affected by breast cancer. Through strategic investments and collaborative partnerships, we continue to drive progress so that the more we know, the sooner we can end breast cancer. To know more about how Breast Cancer Canada powers progress through research, visit: breastcancerprogress.ca/progress-and-research/ . About Breast Cancer Canada Breast Cancer Canada is a national charity dedicated to saving lives through breast cancer research. With a focus on precision oncology (personalized care), it is the only national breast cancer organization in Canada that has a clear mandate to raise money for research and advocate and educate on the progress of new research evidence. The organization receives no government funding, meaning all research is funded through the generosity of donors. For more information visit, breastcancerprogress.ca. About AstraZeneca Canada AstraZeneca is a global, science-led biopharmaceutical business whose innovative medicines are used by millions of patients worldwide. The company’s core areas of scientific focus are Oncology; Cardiovascular, Renal and Metabolic (CVRM); Rare Disease; Respiratory & Immunology; and Vaccine & Immune Therapies. In Canada, the company employs approximately 1,800 people and recently announced a major expansion of its research footprint in Mississauga – including the expansion of its AstraZeneca R&D Hub and the creation of a new Alexion Development Hub for Rare Diseases. AstraZeneca was recently recognized as one of Canada’s Top 100 Employers, one of Canada’s Most Admired Corporate Cultures, and a Greater Toronto Top Employer. AstraZeneca is committed to contributing to a more sustainable future for people, society and planet taking important steps to help tackle some of the most pressing sustainability challenges globally – from climate and biodiversity loss, to health equity and health system resilience. AstraZeneca was one of the first seven companies globally to have its net zero targets verified by the Science-Based Targets initiative (SBTi) Corporate Net-Zero Standard. For more information, please visit the company’s website at www.astrazeneca.ca . ______________________________________ 1 https://www.uottawa.ca/about-us/media/news-all/breast-cancer-rates-rising-among-canadian-women-their-20s-30s-40s#:~:text=For%20women%20in%20their%20Thirties,2019%20for%20a%2012.5%25%20increase . 2 https://www-ncbi-nlm-nih-gov.libproxy1.nus.edu.sg/pmc/articles/PMC10742250/

Phase 3

01 May 2023

·www.prnewswire.com

Significant Positive Shift in the Glioma Market with 13% CAGR During the Study Period (2019-2032) Expected by Analysts at DelveInsight

The dynamics of the glioma market are anticipated to change in the coming years owing to the positive outcomes of the emerging pipeline candidates during the developmental stage by key players, such as Bayer, VBL Therapeutics, Candel Therapeutics, AstraZeneca, DNAtrix, DelMar Pharmaceuticals, Chimerix, KaryoPharma, VBI Vaccines, Kazia Therapeutics, and others LAS VEGAS, May 1, 2023 /PRNewswire/ -- DelveInsight's Glioma Market Insights report includes a comprehensive understanding of current treatment practices, glioma emerging drugs, market share of individual therapies, and current and forecasted market size from 2019 to 2032, segmented into 7MM [the United States, the EU-4 (Italy, Spain, France, and Germany), the United Kingdom, and Japan]. Key Takeaways from the Glioma Market Report As per DelveInsight analysis, the glioma market size in the 7MM was approximately USD 1 billion in 2022. According to the assessment done by DelveInsight, the estimated total incident glioma cases in the 7MM were approximately 47K in 2022. Leading glioma companies such as Bayer, Chimerix, Aivita Biomedical, Denovo Biopharma, Northwest Therapeutics, VBL Therapeutics, Laminar Pharmaceuticals, MedImmune, DNAtrix, Immunomic Therapeutics, Imvax, MimiVax, CNS Pharmaceuticals, Epitopoietic Research Corporation (ERC), Istari Oncology, SonALAsense, Kintara Therapeutics, Bristol Myers Squibb, Medicenna Therapeutics, BioMimetix, Eisai and Merck Sharp & Dohme, Kazia Therapeutics, Oblato, Genenta Science, Enterome, Inovio Pharmaceuticals, Karyopharm Therapeutics, VBI Vaccines, TME Pharma, Day One Biopharmaceuticals, Servier, Orbus Therapeutics, TVAX Biomedical, AnHeart Therapeutics, Beigene, SpringWorks Therapeutics, Forma Therapeutics, Hoffmann-La Roche, Incyte Corporation, Eli Lilly, and others are developing novel glioma drugs that can be available in the glioma market in the coming years. The promising glioma therapies in the pipeline include Regorafenib, ONC201, AV-GBM-1, Enzastaurin (DB-102), DCVax-L, Ofranergene Obadenovec (VB-111), LAM561 (2-OHOA), MEDI4736 (durvalumab), Tasadenoturev (DNX-2401), ITI-1000 (pp65 DC Vaccine), IGV-001, SurVaxM, Berubicin, GLIOVAC (Sitoiganap), Lerapolturev + Pembrolizumab, SONALA-001 + Exablate 2.0 Device, VAL-083 (dianhydrogalactitol), Pomalidomide, MDNA55, BMX-001, Lenvatinib ± Pembrolizumab, Paxalisib (GDC-0084), OKN-007, Temferon, EO2401, INO-5401+ INO-9012+ LIBTAYO (cemiplimab), Selinexor (KPT-330), Olutasidenib (FT-2102), VBI-1901, NOX-A12 (Olaptesed Pegol), Tovorafenib (DAY101), Vorasidenib (AG-881), Eflornithine, TVI-Brain-1, AB-218, BGB-290, Mirdametinib, FT-2102 (Olutasidenib), Vinblastine + Bevacizumab, Cobimetinib, PEMAZYRE (Pemigatinib), VERZENIO (abemaciclib) , and others. In December 2022, Chimerix announced the successful launch of the ONC201 Phase III ACTION study in patients with H3 K27M-mutant glioma. In June 2022, Day One Biopharmaceuticals announced positive initial data from its pivotal Phase II (FIREFLY-1) study with tovorafenib (DAY101) in relapsed pediatric low-grade glioma (pLGG). Discover which therapies are expected to grab the major glioma market share @ Glioma Market Report Glioma Overview Glioma is the most common kind of glial cell tumor in the central nervous system (CNS). Gliomas are infiltrative tumors that affect the brain tissue surrounding them. Glioblastoma is the most hazardous type of brain tumor, whereas pilocytic astrocytomas are the least dangerous. Previously, diffuse gliomas were classified into subgroups and grades depending on histopathologies, such as diffuse astrocytomas, oligodendrogliomas, or mixed gliomas/oligoastrocytomas. The specific etiology of glioma, like other primary brain tumors, remains unknown. However, certain variables may increase the risk of getting a brain tumor. Glioma symptoms vary depending on tumor type, size, location, and growth rate. Some common glioma symptoms include headache, nausea or vomiting, memory loss, urine incontinence, speech problems, and others. A medical history and a physical examination are used for glioma diagnosis. Glioma Epidemiology Segmentation DelveInsight estimates that there were approximately 47K incident cases of glioma in the 7MM in 2022. As per our analysis, the United States contributed to the largest incident population of glioma, acquiring ~40% of the 7MM in 2022. The glioma market report proffers epidemiological analysis for the study period 2019–2032 in the 7MM segmented into: Total glioma incident cases Glioma grade-specific cases Glioma age-specific cases Glioma type-specific cases Download the report to understand which factors are driving glioma epidemiology trends @ Glioma Epidemiological Insights Glioma Treatment Market Glioma treatment is based on the type of glioma, its size and location, and the patient's unique characteristics. Chemotherapy and radiation therapy will be administered after surgery, particularly in individuals when the tumor cannot be removed entirely because it has invaded critical parts of the brain or is inaccessible. The typical glioma treatment protocol comprises surgery, chemotherapy, and radiation. Chemotherapy may include carmustine (BCNU), lomustine (CCNU), or gleostine (generic), cisplatin, carboplatin, etoposide, and irinotecan in case of low-grade glioma whereas temozolomide (TEMODAR) is the standard chemotherapy used in case of high-grade glioma majorly, Gliadel wafer implants (biodegradable discs injected with BCNU) are usually given as adjunctive treatment after surgery, although usage of Gliadel wafers remains a point of controversy due to its questionable survival benefits. Avastin (Genentech) and Temodar/Temodal (Merck), among others, are approved medications for HGG. However, due to patent expiration, the generic version of Temodar and biosimilars of Avastin are available on the glioma market. As generics and biosimilars are more cost-effective for patients than new medicines, intense competition exists among them. Furthermore, due to a lack of knowledge concerning bevacizumab's overall survival benefit, it is not recommended in unselected patients with newly diagnosed GBM. Currently, only one medication for LGG is approved, Tafinlar (dabrafenib) plus Mekinist (trametinib). Moreover, the current therapeutic market lacks a viable method for curing glioblastoma; therefore, the survival rate of people diagnosed with glioma remains poor. Glioma is incurable, and treatment choices are limited. Furthermore, the tumor has a high recurrence rate and a poor patient prognosis. In addition, there is currently no approved therapy for the unmethylated MGMT patient pool. To know more about glioma treatment guidelines, visit @ Glioma Management Glioma Therapies and Key Companies Regorafenib: Bayer ONC201: Chimerix AV-GBM-1: Aivita Biomedical Enzastaurin (DB-102): Denovo Biopharma DCVax-L: Northwest Therapeutics Ofranergene Obadenovec (VB-111): VBL Therapeutics LAM561 (2-OHOA): Laminar Pharmaceuticals MEDI4736 (durvalumab): MedImmune Tasadenoturev (DNX-2401): DNAtrix ITI-1000 (pp65 DC Vaccine): Immunomic Therapeutics IGV-001: Imvax SurVaxM: MimiVax Berubicin: CNS Pharmaceuticals GLIOVAC (Sitoiganap): Epitopoietic Research Corporation (ERC) Lerapolturev + Pembrolizumab: Istari Oncology SONALA-001 + Exablate 2.0 Device: SonALAsense VAL-083 (dianhydrogalactitol): Kintara Therapeutics Pomalidomide: Bristol Myers Squibb MDNA55: Medicenna Therapeutics BMX-001: BioMimetix Lenvatinib ± Pembrolizumab: Eisai and Merck Sharp & Dohme Paxalisib (GDC-0084): Kazia Therapeutics OKN-007: Oblato Temferon: Genenta Science EO2401: Enterome INO-5401+ INO-9012+ LIBTAYO (cemiplimab): Inovio Pharmaceuticals Selinexor (KPT-330): Karyopharm Therapeutics VBI-1901: VBI Vaccines NOX-A12 (Olaptesed Pegol): TME Pharma Tovorafenib (DAY101): Day One Biopharmaceuticals Vorasidenib (AG-881): Servier Eflornithine: Orbus Therapeutics TVI-Brain-1: TVAX Biomedical AB-218: AnHeart Therapeutics BGB-290: Beigene Mirdametinib: SpringWorks Therapeutics FT-2102 (Olutasidenib): Forma Therapeutics Vinblastine + Bevacizumab: Hoffmann-La Roche Cobimetinib: Hoffmann-La Roche PEMAZYRE (Pemigatinib): Incyte Corporation VERZENIO (abemaciclib): Eli Lilly Learn more about the FDA-approved drugs for glioma @ Drugs for Glioma Treatment Glioma Market Dynamics Glioma market growth can be ascribed to various factors, including an aging population, evolving research, better diagnostic tests, developing surgical procedures, improved radiotherapy techniques, and novel systemic medicines. Commercially, there is a greater emphasis on high-grade glioma than low-grade glioma because patients with low-grade glioma often live longer than those with high-grade glioma. As a result, just a few therapies are in late-stage studies, while the majority are in early-stage trials. In the case of GBM, on the other hand, the pipeline is robust, with numerous potential therapies in late and mid-stage research that have yet to be marketed. The pipeline includes drugs with varied modes of action and administration routes. It is interesting to note that the emerging market of glioma includes budding gene therapy, i.e., ofranergene obadenovec (VB-111) by VBL Therapeutics, followed by four vaccine/immunotherapy candidates such as VBI-1901, AV-GBM-1 and ITI-1000 (pp65 DC Vaccine), tasadenoturev (DNX-2401) by VBI Vaccines, Aivita Biomedical, Immunomic Therapeutics, and DNAtrix, respectively, and these therapies are going to alter the glioma market dynamics in the upcoming years. The current glioma market has been categorized based on the dominant treatment pattern across the 7MM, which shows slight variances in the overall prescription pattern. The forecast model considers surgery, chemotherapy/radiation therapy, bevacizumab + radiotherapy/chemotherapy, and OPTUNE with temozolomide. The anticipated launch of new therapies and improved integration of early patient screening, medication in secondary care and other clinical settings, research on optimum implementation methods, and increased awareness may eventually facilitate the development of successful treatment alternatives. However, there are a few challenges to the timely identification and treatment of these patients, such as a lack of a reliable biomarker that can aid in diagnosis and patient classification and identifying recurrence and signaling medication response. Furthermore, the failure rate of high-phased drug trials is significant, making it impossible to predict trial success, exacerbating the need for medicines that could assist ease the patient segment with this severe kind of cancer. Scope of the Glioma Market Report Therapeutic Assessment: Glioma current marketed and emerging therapies Glioma Market Dynamics: Conjoint Analysis of Emerging Glioma Drugs Competitive Intelligence Analysis: SWOT analysis and Market entry strategies Unmet Needs, KOL's Views, Analyst's Views, Glioma Market Access and Reimbursement Discover more about glioma drugs in development @ Glioma Clinical Trials Table to Contents Related Reports Glioma Epidemiology Forecast Glioma Epidemiology Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted glioma epidemiology in the 7MM, i.e., the United States, EU5 (Germany, Spain, Italy, France, and the United Kingdom), and Japan. Glioma Pipeline Glioma Pipeline Insight – 2023 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key glioma companies, including PTC Therapeutics, Ono Pharmaceuticals, Philogen, SpringWorks Therapeutics, Xennials Therapeutics, AnHeart Therapeutics, Istari Oncology, among others. High-Grade Glioma Pipeline High-Grade Glioma Pipeline Insight – 2023 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key high-grade glioma companies, including PTC Therapeutics, Aadi, Lee's Pharmaceutical, among others. Malignant Glioma Pipeline Malignant Glioma Pipeline Insight – 2023 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key malignant glioma companies, including Bexion Pharmaceuticals, Inc., Lee's Pharmaceutical Limited, Merck & Co, Oblato, Inc., OncoSynergy, Inc, among others. Recurrent Malignant Glioma Pipeline Recurrent Malignant Glioma Pipeline Insight – 2023 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key recurrent malignant glioma companies, including Bexion Pharmaceuticals, Inc., Merck, Oblato, OncoSynergy, Inc, among others. Glioblastoma Pipeline Glioblastoma Pipeline Insight – 2023 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key glioblastoma companies, including AstraZeneca, BioNTech, Merck, Pfizer, Roche, among others. 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It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . Connect with us on LinkedIn |Facebook|Twitter Contact Us Shruti Thakur [email protected] +1(919)321-6187 Logo: SOURCE DelveInsight Business Research, LLP

Phase 3Phase 2VaccineImmunotherapy

15 Nov 2022

·www.sciencedaily.com

Unraveling the biology behind aggressive pediatric brain tumor reveals potential new treatment avenue

Researchers have identified a novel treatment approach to an aggressive type of pediatric brain cancer, using therapies already approved to treat cancer. The team developed a mouse model of pediatric glioma with a histone mutation called H3.3-G34, which allowed them to study the tumor's biology in the presence of a functional immune system, revealing a promising outlook for long-term survival. Researchers at the University of Michigan Rogel Cancer Center have identified a novel treatment approach to an aggressive type of pediatric brain cancer, using therapies already approved to treat cancer. "Our findings have immediate translational potential, which is very exciting," said senior study author Maria Castro, Ph.D., R. C. Schneider Collegiate Professor of Neurosurgery and professor of cell and developmental biology at Michigan Medicine. The team developed a mouse model of pediatric glioma with a histone mutation called H3.3-G34. The mutation is seen in about half of children with brain cancer. The mouse model allowed researchers to study the tumor's biology in the presence of a functional immune system, revealing a promising outlook for long-term survival. Tumors with the H3.3 mutation have a defect in how they repair DNA. This means the tumors are more responsive to radiation therapy, a treatment that works by damaging DNA. Combined with surgery, radiation has been the standard therapy for pediatric high-grade glioma. The finding also suggested synergizing the effect by pairing radiation with a small-molecule inhibitor that even further impairs the DNA damage response. They tested this in both human cell cultures and mice using pamiparib, a PARP inhibitor that has been shown to cross the blood-brain barrier. "If we combine small molecules that inhibit the repair of DNA with radiotherapy, the radiation becomes much more effective. We saw this approach not only improved median survival of mice, but also gave us long term survivors," said Santiago Haase, Ph.D., a postdoctoral fellow in the Castro-Lowenstein lab. Haase is first author on the paper, published in the Journal of Clinical Investigation. What's more, when the researchers injected another tumor into the mice that had received the combination treatment and survived long-term, 80% of the mice were able to eliminate the new tumor without any additional treatment. This suggests immune memory, which could prove crucial in preventing cancer recurrence. "That's critical," Castro said. "This particular tumor can often be removed with surgery. But around a year later, the tumor comes back -- and that's what kills the patient. By combining radiation with a small molecule that inhibits DNA repair, we not only eliminate the primary tumor mass, but we enlist immunological memory to protect these animals from tumor recurrence. That's an important consideration." A previous clinical trial tested a different PARP inhibitor in pediatric high-grade glioma, but it was halted due to poor response. The researchers looked at the inhibitor used, veliparib, and found it was not as effective as pamiparib at crossing the blood-brain barrier. In addition, it was not as effective at killing the tumor cells. When tested in the animal model, it did not provide survival benefit in combination with radiation. The trial also did not select patients based on genetic mutations. "This is a beautiful example of how precision medicine can work. When we can do the molecular profiling of tumors, it can show us what therapy to implement in relation to the mutations the tumor cells are harboring. One size does not fit all," said Pedro Lowenstein, M.D., Ph.D., Richard C. Schneider Collegiate Professor of Neurosurgery and professor of cell and developmental biology at Michigan Medicine. Going one step further, the researchers also observed pieces of DNA outside the cell's nucleus in the cytoplasm, an unusual phenomenon that suggests viral infection or cell damage. Pursuing this, they found DNA in the cytoplasm stimulates a pathway called STING, which acts as an alarm bell to the immune system, signaling something is wrong. "The STING pathway was activated in these tumor cells, which suggests another new therapeutic angle by which we can treat these tumors, which is blocking the STING pathway," Castro said. Combining a STING agonist with radiation led to long-term survival and immunological memory in 60% of mice treated. The H3.3 mutation is routinely screened for in pediatric cancer patients. In addition, all the therapies tested are already FDA approved. The researchers are currently working to translate their findings into two clinical trials, one to test pamiparib with radiation and the other using a STING agonist with radiation.

Radiation TherapyClinical Study

100 Deals associated with Pamiparib

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KEGG	Wiki	ATC	Drug Bank
D11426	-	L01XE	DB14769

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Approved

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Indication	Country/Location	Organization	Date
BRCA-mutated Fallopian Tube Carcinoma	CN	BeiGene (Suzhou) Co. Ltd.	30 Apr 2021
BRCA-mutated Fallopian Tube Carcinoma	CN	BeOne Medicines Ltd.	30 Apr 2021
BRCA-mutated Ovarian Cancer	CN	BeOne Medicines Ltd.	30 Apr 2021
BRCA-mutated Ovarian Cancer	CN	BeiGene (Suzhou) Co. Ltd.	30 Apr 2021
BRCA-mutated Peritoneal Neoplasms	CN	BeOne Medicines Ltd.	30 Apr 2021
BRCA-mutated Peritoneal Neoplasms	CN	BeiGene (Suzhou) Co. Ltd.	30 Apr 2021

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Advanced cancer	Phase 3	US	BeOne Medicines Ltd.	19 Dec 2019
Advanced cancer	Phase 3	CN	BeOne Medicines Ltd.	19 Dec 2019
Advanced cancer	Phase 3	JP	BeOne Medicines Ltd.	19 Dec 2019
Advanced cancer	Phase 3	AU	BeOne Medicines Ltd.	19 Dec 2019
Advanced cancer	Phase 3	FR	BeOne Medicines Ltd.	19 Dec 2019
Advanced cancer	Phase 3	IT	BeOne Medicines Ltd.	19 Dec 2019
Advanced cancer	Phase 3	MY	BeOne Medicines Ltd.	19 Dec 2019
Advanced cancer	Phase 3	NZ	BeOne Medicines Ltd.	19 Dec 2019
Advanced cancer	Phase 3	PL	BeOne Medicines Ltd.	19 Dec 2019
Advanced cancer	Phase 3	KR	BeOne Medicines Ltd.	19 Dec 2019

Clinical Result

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Phase

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03914742 (CTgov)	Phase 1/2	Recurrent Glioma \| Recurrent WHO Grade II Glioma \| Recurrent Glioblastoma	67	PARP Inhibitor BGB-290+Temozolomide (Phase 1: Dose Finding)	bjdhppyoht(ezvybwajpf) = zkyicpzeni nhozoltjbo (xpfqkzhajz, qmpfdsvbov - iehiqsqsdb) View more	-	16 Dec 2024
				PARP Inhibitor BGB-290+Temozolomide (Phase 2: Arm A Alkylator-resistant)	vslqepyoiv(uwwajparvl) = gnufxurgvv xtyyaalltt (nlbjsbgmdx, vlfetdxdvs - cdfpnoufzk) View more
NCT05489926 (ESMO2024) Manual	Phase 2	Recurrent ovarian cancer Third line BRCA1/2 mutation	15	Pamiparib 60 mg po BID	ukazbzoxit(euirrikqgk) = rtnmztvhxq oeixxigaly (tsdbnbxspo ) View more	Negative	14 Sep 2024
				Pamiparib 60 mg po BID (BRCAmut pts)	ukazbzoxit(euirrikqgk) = jijebcvzhs oeixxigaly (tsdbnbxspo )
ASCO2024	Not Applicable	Invasive Mammary Carcinoma	-	PARPi (Patients with TNBC)	pwxfxtufsb(rksbnbbjks) = vjpmpdwlxz uoxsdyrume (dcqjsagoeh )	-	24 May 2024
				PARPi (Patients with ER+HER2- breast cancer)	pwxfxtufsb(rksbnbbjks) = isziofmsqn uoxsdyrume (dcqjsagoeh ) View more
SNO2023	Phase 2	Glioma IDH1-mutant \| MGMT methylated	39	Pamiparib 60 mg BID + Temozolomide 20 mg daily	rotamfgiah(itcleybszj) = gyczaeeexp amsgkilnso (dtrokhbjyp ) View more	Negative	10 Nov 2023
				Placebo	jihexkxvzs(pbzktxwpew) = jitbnatsan hbiimybmzq (ohzjuozwyd ) View more
NCT05652283 (ESMO 12023 \| ESMO 22023) Manual	Phase 2	Ovarian Cancer Neoadjuvant myChoice HRD Positive \| BRCA1 mutations \| BRCA2 mutations	20	Pamiparib+ Surufatinib	egqtscfecg(abjywhemcs) = zamnnmiufu wdmdyxpywy (cmjuuataom )	Positive	22 Oct 2023
				Pamiparib+ Surufatinib (completed NAT)	lbpmerdyht(hbfcbpkflo) = ghpbwaksmy rqkzujuutq (dpowwgmfhg ) View more
ASTRO2023	Not Applicable	Recurrent Glioblastoma	-	Pamiparib	smyczkagbp(vpufxliofs) = No grade 3+ toxicities were documented in the olaparib arm mmchneacrb (afsytkawdx ) View more	-	01 Oct 2023
				Olaparib
#201 (ESGO2023)	Not Applicable	Ovarian Cancer Adjuvant BRCA mutation	291	Platinum-based CT (PBC)	wmsoffnbbp(kuzsfmcaox) = frjzsvgvip twlzdijidx (ronijgcwtt )	Negative	27 Sep 2023
				Non-platinum-based CT (nPBC)	wmsoffnbbp(kuzsfmcaox) = zrfcrnhspw twlzdijidx (ronijgcwtt )
#763 (ESGO2023)	Not Applicable	Ovarian Cancer Maintenance	-	Met Group	eursijcfed(wjqxstgozm) = yhdqipmnsh bwbgpbxezc (hofztlnuqy )	-	27 Sep 2023
NCT03427814 (PARALLEL303, CTgov)	Phase 2	Advanced gastric carcinoma	136	Pamiparib (Pamiparib)	tushmawjeh(zbxyvdtygg) = afxsgyguaq rktlscqdpc (xtxtsrgwmv, wmfldxrkwn - qymqifdxvc) View more	-	21 Sep 2023
				Placebo (Placebo)	tushmawjeh(zbxyvdtygg) = pkbrkaatjp rktlscqdpc (xtxtsrgwmv, kdsheyggnx - vpndntthrl) View more

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