On March 2, 2023 Pediatric reported that solid tumors make up approximately 40% of all childhood cancers (Press release, Children’s Hospital Los Angeles, MAR 2, 2023, View Source [SID1234628104]). While pediatric cancer is rare, children can develop a wide range of tumor types, located in different parts of the body, which can make the differential diagnosis challenging. Investigators at Children’s Hospital Los Angeles have developed a liquid biopsy for solid tumors that has the potential to aid in reaching a specific diagnosis when surgery or a tissue biopsy is not feasible. The study findings were published on February 23 in the journal npj Precision Oncology.

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"This is one of the first clinically validated liquid biopsy tests to be launched at a pediatric academic medical center," says Jaclyn Biegel, PhD, Chief of Genomic Medicine and Director of the Center for Personalized Medicine at CHLA.

"We created a test that may be helpful in making a diagnosis, determining prognosis, and potentially identifying an effective therapy for children with solid tumors," says Fariba Navid, MD, Medical Director of Clinical Research in the Cancer and Blood Disease Institute at CHLA. Dr. Navid and Dr. Biegel are co-senior authors of this study.

A specific test for pediatric tumors is required because the genetics of tumors that affect adults differ from those in children. Adult tumors tend to be caused by mutations—sequence-based changes in a gene—so most liquid biopsy tests have been developed specifically to identify these mutations. However, pediatric tumors arising from mutations are less common. In children, copy number changes—losing or having extra copies of one or more genes—or rearrangements of genes that result in gene fusions, are more characteristic. For their research study, the CHLA team combined a technique known as Low-Pass Whole Genome Sequencing (LP-WGS) with targeted sequencing of cell-free DNA from plasma to detect copy number changes, as well as mutations and gene fusions, that are characteristic of pediatric solid tumors. An important feature of the study was that it required a much smaller volume of sample than is required for liquid biopsy studies in adults. Since an infant or young child has a smaller blood volume, the assays needed to be scaled down to accommodate this difference.

To create the test, the researchers collaborated with clinical teams and research investigators at CHLA including Jesse Berry, MD, Director of Ocular Oncology and CHLA’s Retinoblastoma Program, as well as investigators involved in Oncology, Neurosurgery and Pathology and Laboratory Medicine. Leo Mascarenhas, MD, MS, Deputy Director of the Cancer and Blood Disease Institute at CHLA was also involved in the design and support of the project.

The first version of the test, launched in Nov. 2022, evaluates chromosomal copy number changes in blood samples, cerebrospinal fluid and the aqueous humor of the eye to aid in the clinical diagnosis for patients with solid tumors, brain tumors and retinoblastoma, respectively.

The next version of the clinical assay, available in about six months, will include detection of mutations and gene fusions.

The liquid biopsy-based genetic tests join the CHLA-developed OncoKids cancer panel, a next-generation sequencing-based assay designed to detect changes in DNA or RNA that are associated with pediatric leukemias, brain and solid tumors; the CHLA Cancer Predisposition Panel; RNAseq for cancer, a transcriptome-based assay using RNA sequencing; VMD4Kids, a panel for vascular and mosaic disorders; as well as methylation array-based profiling for pediatric brain tumors.

Eirini Christodoulou, PhD, and Venkata Yellapantula, PhD, both at CHLA, are co-lead authors on the study. Additional authors, all at CHLA, include: Jennifer Cotter MD, Xiaowu Gai PhD, Dejerianne Ostrow, PhD, and Moiz Bootwalla, MS, of the Department of Pathology and Laboratory Medicine; Katrina O’Halloran MD, James Amatruda MD, PhD, Anya Zdanowicz of the Cancer and Blood Disease Institute; and Liya Xu, PhD, of The Vision Center.

On March 2, 2023 Natera, Inc. (NASDAQ: NTRA), a global leader in cell-free DNA testing, reported the Company’s first commercial coverage policies for its molecular residual disease test, Signatera, including its first pan-cancer coverage policy for adjuvant, recurrence monitoring, and treatment monitoring (Press release, Natera, MAR 2, 2023, View Source [SID1234628103]).

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Effective March 1, 2023, Blue Shield of California now provides commercial coverage of Signatera for plan members diagnosed with any solid tumors. Specifically, the policy describes tumor-informed ctDNA testing with Signatera as medically necessary for patients with stage I-IV cancer to provide information for (1) adjuvant or targeted therapy; and/or (2) monitoring for relapse or progression, including but not limited to the use of immunotherapy.

In addition, effective January 1, 2023, Blue Cross and Blue Shield of Louisiana is providing coverage of serial testing with Signatera for plan members diagnosed with colorectal and muscle invasive bladder cancer and for pan-cancer immunotherapy monitoring.

"Following the recent breast cancer coverage decision by Medicare, achieving our first commercial coverage policies for Signatera – including one that encompasses pan-cancer coverage – is another major milestone for Natera and the patients who will now have enhanced access to tumor-informed ctDNA testing," said John Fesko, chief business officer. "These developments underscore the medical necessity of Signatera to inform critical treatment decisions and detect recurrence earlier."

Data supporting the clinical validity and utility of Signatera has been published in approximately 40 peer-reviewed publications, including validation across multiple cancer types to detect recurrence earlier than standard diagnostic tools1,2 and to improve the assessment of treatment response in conjunction with imaging.3

About Signatera

Signatera is a custom-built circulating tumor DNA (ctDNA) test for treatment monitoring and molecular residual disease (MRD) assessment in patients previously diagnosed with cancer. The test is available for both clinical and research use, and has been granted three Breakthrough Device Designations by the FDA for multiple cancer types and indications. The Signatera test is personalized and tumor-informed, providing each individual with a customized blood test tailored to fit the unique signature of clonal mutations found in that individual’s tumor. Signatera is intended to detect and quantify cancer left in the body, at levels down to a single tumor molecule in a tube of blood, to identify recurrence earlier and to help optimize treatment decisions.

On March 2, 2023 Prostate Cancer Foundation reported that Immunotherapies have successfully treated many types of cancer with the exception of advanced prostate cancer that has become resistant to treatment, known as metastatic castration-resistant prostate cancer (mCRPC) (Press release, Prostate Cancer Foundation, MAR 2, 2023, View Source [SID1234628102]). New findings from a Prostate Cancer Foundation (PCF)-funded investigator reveal the mechanism by which prostate cancer cells reprogram the immune system to promote rather than suppress cancer, as well as a promising new combination therapy that could prevent them from developing this ability.

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The research led by 2016 Izzy Englander – PCF Challenge Award recipient Akash Patnaik, MD, PhD, MMSc, and his team at the University of Chicago was recently published in the peer-reviewed journal Clinical Cancer Research.

"These findings represent an exciting new opportunity to prevent prostate cancer cells from evading the immune system and a promising combination therapy for metastatic castration-resistant prostate cancer," said Howard R. Soule, PhD, Executive Vice President and Chief Science Officer of the Prostate Cancer Foundation. "PCF commends Dr. Patnaik and the research team on their achievement and proudly supports their work to bring us closer to our mission to eliminate death and suffering from prostate cancer."

Researchers found that by recruiting abnormal tumor-associated macrophages (TAM) that express PD-1 into the tumor microenvironment, the immune system promotes the growth of prostate cancer.

Androgen deprivation therapy (ADT) and chemotherapy are first-line treatment options for metastatic prostate cancer. However, patients often relapse and the disease advances. Nearly 35,000 men in the U.S. are projected to die of prostate cancer in 2023.

Approximately 50% to 75% of mCRPC patients have a mutation in the tumor suppressor gene PTEN which drives the PI3K tumor growth and survival pathway; in patients with PTEN-mutated tumors, the normal anti-tumor immune response is often suppressed. Alterations of the PTEN/PI3K pathway are known drivers of advanced prostate cancer. Clinical trials of single drugs to target this pathway and combinations of PI3K inhibitors and ADT have shown limited benefit in patients with mCRPC.

Patnaik and his team performed a series of experiments using PTEN-mutated mouse models. They found that following treatment with a combination of ADT and copanlisib, a PI3K inhibitor, PD-1-expressing immunosuppressive TAM blocked the anti-cancer immunity mediated by macrophages; the cancer cells forced the macrophages into tumor-promoting mode by binding to the protein PD-1 on their surface. The researchers hypothesized that adding a third drug to block PD-1 would unleash the ability of the macrophages to kill the cancer. The triple combination of PD-1 checkpoint immunotherapy plus ADT hormone therapy plus a PI3K inhibitor yielded a response rate 60% greater among treated mice than among untreated control mice. These data suggest that the three-drug approach is needed to overcome treatment resistance in PTEN-mutated prostate cancer.

As part of the PCF Challenge Award, a phase 1b clinical trial will be conducted to test the safety and efficacy of copanlisib in combination with an anti-PD-1 drug in patients with PTEN-deficient mCRPC. If successful, the research could result in a new precision immunotherapy regimen for these patients.

On March 2, 2023 Arcus Biosciences (NYSE:RCUS), a clinical-stage, global biopharmaceutical company focused on developing differentiated molecules and combination therapies for people with cancer, reported that its management team will participate in a fireside chat at the upcoming Barclays Global Healthcare Conference in Miami Beach, Florida (Press release, Arcus Biosciences, MAR 2, 2023, View Source [SID1234628101]). The fireside chat will take place on Tuesday, March 14th, 2023 at 8:30 a.m. ET.

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A live webcast of the fireside chat will be available by visiting the "Investors & Media" section of the Arcus Biosciences website at www.arcusbio.com. A replay of the webcast will be available following the live event.

On March 2, 2023 Personalis, Inc. (Nasdaq: PSNL), a leader in advanced genomics for precision oncology, reported that its Board of Directors has appointed Christopher Hall as Chief Executive Officer (CEO) and a member of the Board, effective immediately, in addition to his role as President (Press release, Personalis, MAR 2, 2023, View Source [SID1234628100]). Hall will lead the Company’s efforts to drive a new paradigm for the active management of cancer with the aim of guiding care from biopsy throughout the life of the patient. Hall joined Personalis in October 2022 and became President at the end of December 2022.

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The Board also promoted Aaron Tachibana to the extended leadership position of Chief Operating Officer (COO), effectively immediately, in addition to his role as Chief Financial Officer (CFO). Tachibana served as Interim CEO since the end of December 2022, and has served as CFO since joining Personalis in 2019, when he led the Company through its initial public offering. In addition, Dr. Richard Chen has been promoted to the position of Executive Vice President, R&D, effective immediately, in addition to his role as Chief Medical Officer (CMO). Dr. Chen, who joined Personalis in 2011 as Chief Scientific Officer, was previously Senior Vice President, R&D and CMO.

"This is a momentous time for Personalis, and we are confident that with this leadership team, we can deliver on our potential to create a new paradigm for the way cancer is actively managed," said Karin Eastham, Board Chair of Personalis. "The Board thanks Aaron for his role as Interim CEO for the past two months. He, Chris, and Rich led a strategic overhaul to focus on three core areas: winning in the minimal residual disease (MRD) space, enabling customers to develop personalized cancer vaccines, and supporting biopharmaceutical customers with their clinical trials. They have also taken prudent steps to reduce our cash burn, focus on improving margins, and work toward future profitability."

Added Eastham, "We are thrilled to welcome Chris, Aaron, and Rich into their new roles, building upon a strong foundation as Personalis evolves into a diagnostic product company and as a critical partner in cancer recurrence detection and therapy monitoring."

"Since its founding, Personalis has emerged as a genomics technology leader, a sequencing powerhouse, and as a trusted partner to many of the world’s leading pharmaceutical companies," said Hall, Personalis’ President and CEO. "I’m excited about the future of this company and honored to be appointed as CEO to lead us into our next chapter. We believe we have one of the most discerning technologies to both characterize and monitor cancer, setting us up to become the leader in MRD detection and, ultimately, to help usher in a new standard of care in oncology."

Hall has several decades of experience in the diagnostic space, previously serving as CEO of Naring Health, a multi-omics company; President and COO of Veracyte; and as SVP and Chief Business Officer of Celera’s cardiovascular testing business. Hall earned an M.B.A. from Harvard University and a B.A. from DePauw University.

Tachibana has served in CFO and operational leadership roles in multiple public companies, focusing on improving gross margins and profitability. Tachibana holds a B.S. in Business Administration and Finance from San Jose State University.

Dr. Chen has decades of industry and academic experience in clinical medicine and oncology, innovative diagnostic and scientific product development, data science and genomics. He has co-founded several companies in the life sciences, including Ingenuity Systems, a pioneer in genomics and systems biology analytics for biopharma. Dr. Chen received a B.S. in Computer Science, an M.S. in Biomedical Informatics, and an M.D. from Stanford University.

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