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Real-World Study of 6,000+ Medicare Patients with Advanced Prostate Cancer Shows Adding PROVENGE® (sipuleucel-T) to Treatment Regimen Reduced Risk of Death by 45%

On February 13, 2020 Dendreon Pharmaceuticals, a commercial-stage biopharmaceutical company and pioneer in the development of immunotherapy, reported results of a first-of-its-kind study examining survival outcomes in men with metastatic castrate-resistant prostate cancer (mCRPC) who were treated with PROVENGE (sipuleucel-T) and oral agents in a real-world treatment setting (Press release, Dendreon, FEB 13, 2020, View Source [SID1234554313]).

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According to a retrospective analysis of medical and pharmacy claims data from more than 6,000 Medicare Fee for Service beneficiaries, the addition of PROVENGE to either Zytiga (abiraterone acetate) or Xtandi (enzalutamide), at any point in a patient’s mCRPC treatment regimen, reduced the risk of death by 45% and extended median overall survival (OS) by 14.5 months.1 These findings were presented in a poster session at the 2020 ASCO (Free ASCO Whitepaper) Genitourinary (GU) Cancers Symposium in San Francisco (abstract #42, Poster Session A, 11:30 a.m. PST).

"Based on our analysis of these real-world data, men with mCRPC who had immunotherapy added to their treatment regimen had a significant reduction in the risk of death at three years, regardless of the sequencing," said Rana R. McKay, M.D., lead study author, and medical oncologist and assistant professor of medicine at Moores Cancer Center, University of California, San Diego. "This magnitude of risk reduction is a compelling finding, and additional analyses are underway looking at other variables that could impact outcomes."

Based upon the real-world use and survival outcomes associated with the utilization of PROVENGE and oral agents Zytiga or Xtandi in men receiving treatment for mCRPC, the study authors found that:

In mCRPC patients treated with Zytiga or Xtandi, the median OS was significantly higher among men who also were treated with PROVENGE (35.2 months vs. 20.7 months; p<0.0001).
Three-year survival rates were significantly higher in men who received PROVENGE in any line of treatment compared to men who never received treatment with PROVENGE (48% vs. 28%; p<0.0001).
More than 150 variations of mCRPC treatment sequences were identified in the analysis, underscoring the importance of developing a structured approach to managing mCRPC patients.
Further statistical analysis of these treatment cohorts is underway.
"These findings underscore the importance of using complementary MOAs to maximize patient survival outcomes, and highlights the critical role immunotherapy plays in the mCRPC treatment regimen," said Bruce A. Brown, M.D., chief medical officer at Dendreon. "These real-world data contribute to a growing body of evidence that PROVENGE continues to deliver on its promise of helping men with advanced prostate cancer live longer."

Additional findings on the use of immunotherapy in earlier stage prostate cancer and the potential impact of the treatment on cell death were presented today in poster sessions at the 2020 ASCO (Free ASCO Whitepaper) GU Cancers Symposium:

A comparison of sipuleucel-T (sip-T) product parameters from two phase III studies: ProVent in active surveillance prostate cancer and IMPACT in metastatic castrate-resistant prostate cancer (mCRPC) (abstract #321, Poster Session A, 11:30 a.m. PST)
This study compared the final product parameters (CD54 upregulation, CD54+ cell count and total nucleated cell [TNC] count) in 313 men on active surveillance (AS) enrolled in the ongoing Phase 3 ProVent clinical trial and 341 men with mCRPC treated with sip-T in the randomized, pivotal Phase 3 IMPACT trial. Results showed that men enrolled in ProVent yielded higher apheresis TNC and CD54+ cell counts than men in IMPACT, possibly a reflection of a healthier immune system in patients in the ProVent trial. Additionally, final product CD54+ cell counts, CD54 upregulation and TNC cell counts were statistically higher in men enrolled in ProVent than in men enrolled in IMPACT.

The association of humoral antigen spread (AgS) with cytotoxic T lymphocyte (CTL) activity after sipuleucel-T (sip-T) treatment in two phase II clinical studies: STAMP and STRIDE (abstract #112, Poster Session A, 11:30 a.m. PST)
One mechanism of action of cancer immunotherapy is to induce an immune response to specific antigen-bearing tumor cells. The resultant destruction of the tumor cells by the immune system’s T cells leads to the release of additional tumor-associated antigens. These secondary antigens prime subsequent immune responses – a process called antigen spread. This immunological phenomena was previously shown to correlate with survival benefit in the IMPACT study. Sip-T has been shown in clinical trials to induce lytic T cell responses against the immunizing antigen (PA2024) and/or the target antigen (prostatic acid phosphatase or PAP), with responses correlating with overall survival. In this analysis, researchers demonstrated that antigen spread observed after sipuleucel-T treatment correlated with observed lytic T cell responses, concluding that treatment with sip-T in men with mCRPC appears to invoke the tumor immunity cycle, in which tumor cell death releases secondary antigens resulting in antigen spread.

About PROVENGE (sipuleucel-T)

PROVENGE is the only FDA-approved immunotherapy made from a patient’s own immune cells for the treatment of prostate cancer. More than 30,000 men have been prescribed PROVENGE, and it has been clinically proven to extend life for certain men in advanced stages of the disease.

INDICATION

PROVENGE is an autologous cellular immunotherapy indicated for the treatment of asymptomatic or minimally symptomatic metastatic castrate-resistant (hormone-refractory) prostate cancer.

IMPORTANT SAFETY INFORMATION

Acute Infusion Reactions: Acute infusion reactions (reported within 1 day of infusion) may occur and include nausea, vomiting, fatigue, fever, rigor or chills, respiratory events (dyspnea, hypoxia, and bronchospasm), syncope, hypotension, hypertension, and tachycardia.

Thromboembolic Events: Thromboembolic events, including deep venous thrombosis and pulmonary embolism, can occur following infusion of PROVENGE. The clinical significance and causal relationship are uncertain. Most patients had multiple risk factors for these events. PROVENGE should be used with caution in patients with risk factors for thromboembolic events.

Vascular Disorders: Cerebrovascular events (hemorrhagic/ischemic strokes and transient ischemic attacks) and cardiovascular disorders (myocardial infarctions) have been reported following infusion of PROVENGE. The clinical significance and causal relationship are uncertain. Most patients had multiple risk factors for these events.

Handling Precautions: PROVENGE is not tested for transmissible infectious diseases.

Concomitant Chemotherapy or Immunosuppressive Therapy: Chemotherapy or immunosuppressive agents (such as systemic corticosteroids) given concurrently with the leukapheresis procedure or PROVENGE has not been studied. Concurrent use of immune-suppressive agents may alter the efficacy and/or safety of PROVENGE.

Adverse Reactions: The most common adverse reactions reported in clinical trials (≥ 15% of patients receiving PROVENGE) were chills, fatigue, fever, back pain, nausea, joint ache, and headache.

Riptide Bioscience Announces Discovery of Novel Immune Checkpoint

On February 13, 2020 Riptide Bioscience, Inc., reported the publication in Science Translational Medicine of a seminal article establishing a novel immune checkpoint, potentially useful in the treatment of both cancer and fibrosis (Press release, Riptide Bioscience, FEB 13, 2020, View Source [SID1234554312]).

"We’re now engaging with larger pharmaceutical companies to move this important program into clinic. I see a real opportunity, similar in many ways to the discovery of the first checkpoint inhibitors, to make a major impact on clinical practice."

The article is entitled "Mannose receptor (CD206) activation in tumor-associated macrophages enhances adaptive and immune antitumor immune responses." (View Source). Riptide originated the development program and collaborated with Tuskegee University’s Cancer Research Center and the National Institutes of Health under separate research agreements. First author, Dr. Jesse Jaynes, Professor of Integrative Biosciences at Tuskegee, was joined by 42 co-authors from the National Cancer Institute, the National Center for Advancing Translational Sciences, and Tuskegee in this publication.

The article documents extensive research to evaluate the efficacy and confirm the mechanism of Riptide drug candidate RP-182. RP-182 is the first of several engineered peptides emerging from a years-long effort to enhance the activity of naturally occurring host defense peptides (HDPs) with immunomodulatory properties.

HDPs have the capacity to directly kill invasive microbes by forming pores in their membranes. However, certain HDPs also activate the immune system to fight the invaders – an activity which Riptide scientists discovered could be turned against "non-self" cancer cells.

Jaynes commented, "We did an extensive search for the cellular target of these peptides. Surprisingly it turned out to be CD206, the canonical biomarker for M2-polarized tumor-associated macrophages (TAMs). That made these small proteins really promising as potential drugs, since CD206 is many times more highly expressed on M2 macrophages than on any other somatic cell type."

TAMs are the most common immune cells in the tumor microenvironment, often outnumbering cancer cells themselves in solid tumors. TAMs produce a tumor-promoting tissue environment. Riptide scientists demonstrated that engaging a specific set of amino acids in a particular domain of CD206, returned the macrophage population from M2-dominant to M1-dominant, restoring a tumor-inhibiting microenvironment.

Jaynes’ colleague, Dr. Clayton Yates, Director of Tuskegee’s Cancer Research Center, added, "CD206 is a perfect narrow target for an exquisitely specific therapy. Our team was the first to show that this receptor could serve as a ‘toggle switch’ between macrophage phenotypes. We think it’s accurate to consider it a novel immune checkpoint – a completely natural mechanism that can have a profound effect on tumor etiology, without significant toxicity."

Yates continued, "We demonstrated that both in vitro and in vivo, the RP class of peptides are able to repolarize the macrophage population, and that once repolarized, the macrophages return to phagocytic activity and begin consuming cancer cells. They also send downstream signals to the T-cell, NK-cell and B-cell populations to attack the tumor."

Riptide President Dr. George Martin commented, "The results in animal models of organ cancers have been spectacular. RP-182, administered in combination with gemcitabine, produced the best results ever shown in NCI’s KRAS-p16 pancreatic cancer model. Also, with its distinctive mechanism, it has been shown to powerfully complement both chemotherapy and checkpoint inhibitor immunotherapy."

Dr. Martin continued, "Riptide has built very solid intellectual property around this program, and following the promising early work with RP-182, has developed two other peptide candidates with even better efficacy and excellent pharmacokinetics. These have demonstrated striking results in preclinical models of colon, breast, prostate, and skin cancers."

Riptide Executive Vice President Dr. Henry Lopez added, "Also, since M2 macrophages are important in the progress of certain fibroses, including scleroderma and IPF, we anticipated – and have recently confirmed – potent efficacy in animal models of those diseases."

Dr. Martin concluded, "We’re now engaging with larger pharmaceutical companies to move this important program into clinic. I see a real opportunity, similar in many ways to the discovery of the first checkpoint inhibitors, to make a major impact on clinical practice."

Riptide Bioscience, Inc., with laboratories in Vallejo, California, maintains an intensive program of research into peptide-based therapeutics

SOPHiA GENETICS Appoints Chief Medical Officer to Accelerate the Execution of Medical Strategy

On February 13, 2020 SOPHiA GENETICS, leader in Data-Driven Medicine, reported the appointment of Philippe Menu, MD-PhD, MBA, as Chief Medical Officer (Press release, Sophia Genetics, FEB 13, 2020, View Source [SID1234554311]).

Dr. Philippe Menu brings a unique blend of medical expertise across multiple areas including clinical medicine, fundamental research in molecular biology, and management consulting. He spent the last eight years at McKinsey & Company where he co-led the McKinsey Cancer Center and served dozens of clients in the biopharma sector. Dr. Menu advised global pharmaceutical companies, mid-size players and biotech alike across the entire value chain, with a major focus on innovative therapies and diagnostics in oncology and rare diseases.

"The potential linked to new-generation health data is limitless and it is our goal to continue expanding the scope of new clinical applications for our community of more than 1,000 hospitals across 82 countries," affirmed Jurgi Camblong, CEO and Co-founder of SOPHiA GENETICS. "Philippe’s background and track record across different sectors of life sciences, including biopharma, will help the execution of new clinical-grade applications. In turn, this will allow the longitudinal monitoring of patients through multi-modal data approaches and the optimization of drug development."

"It is a privilege to be joining SOPHiA GENETICS as Chief Medical Officer," said Dr. Menu. "I am incredibly inspired by what the SOPHiA team has already achieved by analyzing half a million patients’ genomic profiles across the world through its unique and growing global network of hospital partners. Looking ahead, I am most impressed by the full potential to positively impact patients’ lives that still lies ahead of us through the application of SOPHiA’s multi-modal data approach. SOPHiA is uniquely positioned to help deliver transformative progress for patients around the world: we can help discover new biomarkers to develop new therapies, match the right treatment to the right patients in clinical trials as well as in routine clinical care, and follow patients longitudinally through a multi-omics approach to help predict who will most benefit from which therapies and why. I look forward to working closely with our hospital, biopharma and other healthcare ecosystem partners to help accelerate the adoption of Data-Driven Medicine."

Genetron Health Announces NMPA Approval of its 8-gene Lung Cancer Assay and NGS Platform GENETRON S2000

On February 13, 2020 Genetron Holdings Limited ("Genetron Health"), a China-based precision oncology company that covers full-cycle cancer care, reported that the National Medical Products Administration (NMPA) has approved its 8-gene Lung Cancer Assay and high-throughput NGS platform GENETRON S2000 to empower comprehensive panel genomic testing for more patients (Press release, Genetron Health Technologies, FEB 13, 2020, View Source [SID1234554310]).

The 8-gene Lung Cancer Assay is the first lung cancer clinical testing assay based on Genetron One-Step Seq Method approved by NMPA, offering fast and easy-to-use testing procedures, that is suitable for independent operation within hospitals. With the Genetron One-Step Seq technology, the library construction process is finished in one step of reaction, minimizing manual operation to one mixture of reagents with DNA/cDNA. The chance of contamination in the process is minimal with the "sample in library out" workflow. The assay is compatible with both the Genetron S5 sequencing platform and the Genetron Chef System. The 8-gene Lung Cancer Assay covers EGFR, ALK, ROS1, BRAF, KRAS, HER2, MET, PIK3CA, and 7 genes of them are recommended biomarkers by the 2018 NCCN guideline for Non-Small Cell Lung Cancer (NSCLC) patients.

GENETRON S2000 enables comprehensive genomic testing for high-throughput clinical testing centers such as large hospitals and regional medical testing centers. GENETRON S2000 adopts an innovative Flow Cell system that provides two types of Flow Cells to support various sequencing modes, and an optimized optical and biochemical system which enables the whole sequencing process to complete within a short period of time, offering a simplified and streamlined sequencing experience with a highly-automated process and friendly operating system. The data output could range from 55G to 1440G. With the approved platform, Genetron Health is developing testing solutions covering multi-application scenarios.

Based on patented technologies including the One-Step Seq Method, Genetron Health has developed seven NMPA approved clinical molecular testing equipment or assays on NGS, digital PCR and qPCR platforms, and has now realized full-range sequencing capabilities with the medium-throughput NGS system Genetron S5, featuring 8-gene Lung Cancer Assay, and the high-throughput NGS platform GENETRON S2000, featuring 825-gene Testing Assay.

GeneCentric Therapeutics to Present New Analyses of Molecular Characterization and Prediction of Treatment Response in Patients with Muscle Invasive Bladder Cancer (MIBC)

On February 13, 2020 GeneCentric Therapeutics reported it will present two posters during the ASCO (Free ASCO Whitepaper) GU Cancers Symposium to be held in San Francisco, California, February 13-15, 2020 (Press release, GeneCentric Therapeutics, FEB 13, 2020, View Source [SID1234554309]). The data are derived from GeneCentric’s expertise in the identification of RNA-based Predictive Response Signatures and through collaborations with researchers at leading institutions and pharmaceutical companies. First to be presented is a real-world pooled analysis of patients with metastatic, muscle invasive bladder cancer (MIBC), derived from the ongoing collaboration with researchers at the University of North Carolina at Chapel Hill Lineberger Comprehensive Cancer Center and Janssen Research & Development, LLC. The predictive value of fibroblast growth factor (FGFR) alterations on the treatment outcome of MIBC patients treated with immune checkpoint blockade (Anti-PD-L1/Anti-PD-1) was evaluated in the current analysis.

"With the recent targeted therapy advances for patients with MIBC, including FGFR inhibition, it is essential that new molecular diagnostic tools ensure the right treatments are delivered to the right patients to maximize clinical outcomes," said Dr. Mike Milburn, President and CEO of GeneCentric Therapeutics. "We look forward to our continued collaborations with key academic and pharmaceutical collaborators to achieve this goal."

In another presentation, GeneCentric and their strategic laboratory services provider, OmniSeq, will provide initial results from an ongoing collaboration on molecular characterization of advanced MIBC samples where a new, low-input targeted RNAseq approach requiring 1/20th of the RNA normally required for next-generation sequencing and gene-expression analysis was demonstrated.

"We are excited to see the further evolution of targeted RNAseq strategies where cancer patients with limited tumor specimens may have the opportunity to still benefit from the recent advances with RNA-based molecular characterization," said Jeffrey Conroy, Chief Scientific Officer of OmniSeq.

Copies of both presentations will be available following the meeting at View Source

Details of the presentations are as follows:

Title: "Predictive value of fibroblast growth factor receptor (FGFR) alterations on anti-PD-(L)1 treatment outcomes in patients (Pts) with advanced urothelial cancer (UC): Pooled analysis of real-world data."
Abstract Number: 493
Date: February 14, 2020
Time: 12:15 to 1:45 PM and 5:15 to 6:15 PM
First Author: William Kim, MD, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill

Title: "Molecular characterization of advanced muscle invasive bladder cancer (MIBC): Comparison of low-input targeted RNA sequencing (RNAseq) strategies."
Abstract Number: 564
Date: February 14, 2020
Time: 12:15 to 1:45 PM and 5:15 to 6:15 PM
First Author: Yoichiro Shibata, PhD, Senior Bioinformatics Scientist, GeneCentric Therapeutics