On September 14, 2021 Bayer reported A post-hoc analysis of the Phase III ARAMIS trial presented at the 2021 AUA Annual Meeting assessing NUBEQA (darolutamide) in men with non-metastatic castration-resistant prostate cancer (nmCRPC) reinforces the established clinical profile.1,2 NUBEQA is indicated in the U.S. for the treatment of men with nmCRPC (Press release, Bayer, SEP 14, 2021, View Source [SID1234587689]).

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Research presented at the meeting found that NUBEQA plus androgen deprivation therapy (ADT) prolonged time to first prostate cancer-related invasive procedures, an exploratory endpoint (HR=0.416; 95% CI, 0.279-0.620), and was associated with a reduction in locally invasive procedures versus ADT alone (4.7% versus 9.6%). In a post-hoc analysis, NUBEQA plus ADT also delayed the time to deterioration in quality of life (QoL) in two of the six subscales of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-PR25): urinary symptoms (25.8 versus 14.8 months; HR=0.64; 95% CI, 0.54-0.76) and bowel symptoms (18.4 versus 11.5 months; HR=0.78; 95% CI, 0.66-0.92) versus ADT alone.1

In the Phase III ARAMIS trial primary analysis, serious adverse reactions in ≥ 1% of patients who received NUBEQA included urinary retention, pneumonia, and hematuria.

"Local symptoms from the prostate and surrounding tissues can be very detrimental to patients’ QoL. The occurrence of local symptoms and invasive procedures is very important in initial nmCRPC treatment discussions between patients and physicians," said Neal Shore, MD, FACS, Medical Director, CPI, Carolina Urologic Research Center. "The results on QoL and invasive procedures reinforce NUBEQA’s value in nmCRPC."

Data from the Phase III ARAMIS Trial

Previously published results in 1,509 patients from the Phase III ARAMIS trial demonstrated a highly significant improvement in the primary efficacy endpoint of metastasis-free survival (MFS), with a median of 40.4 months (n=955) with NUBEQA plus ADT, compared to 18.4 months (n=554) for placebo plus ADT (p<0.001). MFS is defined as the time from randomization to the time of first evidence of blinded independent central review (BICR)-confirmed distant metastasis or death from any cause within 33 weeks after the last evaluable scan, whichever occurred first.2

The six subscales of the EORTC-QLQ-PR25 are: urinary symptoms, bowel symptoms, hormone treatment-related symptoms, incontinence aid use, sexual activity and sexual functioning.

The proven tolerability of NUBEQA was supported by the three adverse reactions occurring more frequently in the NUBEQA arm (≥2% over placebo): fatigue (16% versus 11%), pain in extremity (6% versus 3%) and rash (3% versus 1%). NUBEQA was not studied in women and there is a warning and precaution for embryo-fetal toxicity.2

About NUBEQA (darolutamide)2

NUBEQA is an androgen receptor inhibitor (ARi) with a distinct chemical structure that competitively inhibits androgen binding, AR nuclear translocation, and AR-mediated transcription.2 A Phase III study in metastatic hormone-sensitive prostate cancer (ARASENS) is ongoing. Information about this trial can be found at www.clinicaltrials.gov.

INDICATION FOR NUBEQA (darolutamide)

NUBEQA (darolutamide) is an androgen receptor inhibitor indicated for the treatment of patients with non-metastatic castration-resistant prostate cancer.

IMPORTANT SAFETY INFORMATION FOR NUBEQA (darolutamide)

Embryo-Fetal Toxicity: Safety and efficacy of NUBEQA have not been established in females. NUBEQA can cause fetal harm and loss of pregnancy. Advise males with female partners of reproductive potential to use effective contraception during treatment with NUBEQA and for 1 week after the last dose.

Adverse Reactions

Serious adverse reactions occurred in 25% of patients receiving NUBEQA and in 20% of patients receiving placebo. Serious adverse reactions in ≥1 % of patients who received NUBEQA were urinary retention, pneumonia, and hematuria. Overall, 3.9% of patients receiving NUBEQA and 3.2% of patients receiving placebo died from adverse reactions, which included death (0.4%), cardiac failure (0.3%), cardiac arrest (0.2%), general physical health deterioration (0.2%), and pulmonary embolism (0.2%) for NUBEQA.

Adverse reactions occurring more frequently in the NUBEQA arm (≥2% over placebo) were fatigue (16% vs 11%), pain in extremity (6% vs 3%) and rash (3% vs 1%).

Clinically significant adverse reactions occurring in ≥2% of patients treated with NUBEQA included ischemic heart disease (4.0% vs 3.4% on placebo) and heart failure (2.1% vs 0.9% on placebo).

Drug Interactions

Effect of Other Drugs on NUBEQA – Combined P-gp and strong or moderate CYP3A4 inducers decrease NUBEQA exposure, which may decrease NUBEQA activity. Avoid concomitant use.

Combined P-gp and strong CYP3A4 inhibitors increase NUBEQA exposure, which may increase the risk of NUBEQA adverse reactions. Monitor more frequently and modify NUBEQA dose as needed.

Effects of NUBEQA on Other Drugs – NUBEQA inhibits breast cancer resistance protein (BCRP) transporter. Concomitant use increases exposure (AUC) and maximal concentration of BCRP substrates, which may increase the risk of BCRP substrate-related toxicities. Avoid concomitant use where possible. If used together, monitor more frequently for adverse reactions, and consider dose reduction of the BCRP substrate.

NUBEQA inhibits OATP1B1 and OATP1B3 transporters. Concomitant use may increase plasma concentrations of OATP1B1 or OATP1B3 substrates. Monitor more frequently for adverse reactions and consider dose reduction of these substrates.

Review the prescribing information of drugs that are BCRP, OATP1B1, and OATP1B3 substrates when used concomitantly with NUBEQA.

For important risk and use information about NUBEQA, please see the accompanying full Prescribing Information.

About Prostate Cancer

Prostate cancer is the second most commonly diagnosed malignancy in men worldwide.3 In 2020, about 192,000 men in the U.S. were diagnosed with prostate cancer and an estimated 33,000 have died from the disease.4 Prostate cancer is the fifth leading cause of death from cancer in men.3 Prostate cancer results from the abnormal proliferation of cells within the prostate gland, which is part of a man’s reproductive system.5 It mainly affects men over the age of 50, and the risk increases with age.6

Treatment options range from surgery to radiation treatment to therapy using hormone-receptor antagonists, i.e., substances that stop the formation of testosterone or prevent its effect at the target location.7 However, in nearly all cases, the cancer eventually becomes resistant to conventional hormone therapy.8

Castration-resistant prostate cancer (CRPC) is an advanced form of the disease where the cancer keeps progressing even when the amount of testosterone is reduced to very low levels in the body. The field of treatment options for castration-resistant patients is evolving rapidly for CRPC patients who have prostate cancer that has not spread to other parts of the body with rising prostate-specific antigen (PSA) levels despite a castrate testosterone level, which is called non-metastatic castration-resistant prostate cancer, or nmCRPC.9,10 About one-third of men with nmCRPC go on to develop metastases within two years.11 In men with progressive nmCRPC, a short PSA doubling time is correlated with shortened time to first metastasis and death.10

About Oncology at Bayer

Bayer is committed to delivering science for a better life by advancing a portfolio of innovative treatments. The oncology franchise at Bayer includes six marketed products and several other assets in various stages of clinical development. Together, these products reflect the company’s approach to research, which prioritizes targets and pathways with the potential to impact the way that cancer is treated.

On September 14, 2021 Immunicom, Inc., a clinical-stage biotechnology company pioneering "subtractive" advanced cancer therapies, reported that promising preliminary data from trials investigating Immunopheresis therapy for metastatic, refractory, solid tumor cancer patients who previously failed multiple lines of therapy (Press release, Immunicom, SEP 14, 2021, View Source [SID1234587688]). The results presented by Immunicom’s Chief Medical Officer, Dr. Robert Segal, at the JCA-AACR Precision Cancer Medicine International Conference virtual joint conference established that Immunopheresis therapy administered to end-stage cancer patients was generally well-tolerated and has the potential for treating refractory malignancies.

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Immunicom’s ongoing clinical trials are in the most difficult to treat, late-stage cancer patients. Immunicom’s novel Immunopheresis therapy uses its proprietary subtractive LW-02 column to selectively remove immune-suppressive cytokines produced by cancer tumors.

"Standard cancer treatments are surgery, radiation or those that typically require the infusion of drugs, antibodies or proteins into the patient. Although chemotherapy and the available immunotherapy drugs can be effective, introducing these foreign substances into the body frequently leads to toxic side-effects, often severe enough to require that the dose be reduced or the therapy be discontinued entirely," said Immunicom’s Chief Medical Officer, Dr. Robert Segal. "At Immunicom, we have developed a novel approach to treat cancer by safely removing specific cytokines to boost the immune system to potentially fight cancer cells. The Immunopheresis therapy is an extracorporeal treatment and is thereby designed to be safer and with less risk of typical side-effects seen with standard chemotherapy and immunotherapy treatment regimens."

Dr. Segal’s presentation focused on results from over 1,100 Immunopheresis procedures conducted in 40 end-stage cancer patients from ongoing clinical trials, demonstrating the viability of this technology as a new treatment strategy. The multinational clinical trials are evaluating the LW-02 column for treating multiple cancers, including triple negative breast cancer (TNBC), non-small cell lung cancer (NSCLC), metastatic melanoma, and renal cell carcinoma. The LW-02 column is being investigated both as a monotherapy and in combination with low-dose chemotherapy or the well-known immunotherapy checkpoint inhibitors Opdivo (Bristol-Myers Squibb) and Tecentriq (Roche). These trials are being conducted in collaboration with world-renowned research organizations and thought leaders including:

Poland – at Jagiellonian University of Krakow Hospital, under the direction of Principal Investigator, Professor Piotr Wysocki, MD, PhD;

Israel – at Sheba Medical Center’s Ella Lemelbaum Institute for Immuno-Oncology (Tel Aviv), under the direction of Dr. Ronnie Shapira, MD and Prof. Gal Markel, MD, PhD; and

Turkey – at Acıbadem Altunizade Hospital (Istanbul), a member of the Acıbadem/IHH Healthcare Group, under the direction of Principal Investigator, Prof. Dr. Gokhan Demir, MD, PhD.

Subtractive Therapy – Immunopheresis and the LW-02 Column

Immunicom’s innovative Immunopheresis approach uses the LW-02 column to extract specific immune-suppressive cytokines produced by cancer tumors. Selective removal of these targeted cytokines is intended to neutralize cancer’s ability to block a patient’s natural immune defense mechanisms which are significantly compromised in late-stage, metastatic disease and thereby "re-energizes the immune system to aggressively fight cancer." Immunopheresis is a "subtractive therapy," in contrast to drugs that are "additive." Subtractive therapy is meant to avoid the side effects, toxicity and negative impact on a patient’s quality of life typical of other cancer treatments.

Based on Immunicom’s clinical program, the LW-02 column could be used either in combination with other therapies or as a stand-alone treatment. The LW-02 Immunopheresis column has already received Breakthrough Device Designation for stage IV metastatic cancers from the U.S. Food and Drug Administration (FDA) and European regulatory clearance (CE Mark certification) for use in adults with advanced, refractory TNBC. Immunicom has obtained ISO 13485 certification for its manufacturing and related quality systems.

For an overview of how Immunopheresis breakthrough technology works, watch Immunicom’s How it Works video.

Immunopheresis and the LW-02 column is considered an investigational therapy by the U.S. FDA and other regulatory authorities. The clinical efficacy of the LW-02 column has not yet been demonstrated. Clinical investigations evaluating the clinical efficacy of the LW-02 column for TNBC are ongoing.

To view Dr. Segal’s presentation for the JCA-AACR Precision Cancer Medicine International Conference please see the conference website.

On September 14, 2021 bioAffinity Technologies, a privately held biotech company advancing innovative cancer diagnostics, reported that Precision Pathology Services, a CAP/CLIA-certified anatomic and clinical pathology laboratory, has fully validated the clinical performance of CyPath Lung, a non-invasive flow cytometric test for early-stage lung cancer (Press release, BioAffinity Technologies, SEP 14, 2021, View Source [SID1234587687]). Precision Pathology licensed bioAffinity’s intellectual property for development of CyPath Lung as a laboratory developed test (LDT).

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"Physician reports can be generated immediately after flow cytometry acquires sample data. Looking beyond lung cancer, we believe our automated platform can be successfully applied to cancer diagnostic tests for several other cancers, which will improve overall survival rates for patients through early diagnosis and treatment."

"We are confident that the validations we have completed and the systems we have implemented will enable high scalability of the CyPath Lung flow cytometry test," said Roby Joyce, MD, President of Precision Pathology. "We will be adding this test to our menu of services in the coming months. This is a very exciting time for us. Lung cancer is the leading cancer killer. Our test for early detection of this dreaded disease can help many people live longer and healthier lives."

Validation of CyPath Lung was conducted in accordance with College of American Pathologists (CAP) guidelines and Clinical Laboratory Improvement Amendments (CLIA) regulations. The CAP/CLIA validation establishes and validates the performance of CyPath Lung, including accuracy, precision, reproducibility and analytical specificity, that are necessary for commercialization. After Precision Pathology adds CyPath Lung to its menu of tests, physicians will be able to order the test for their patients at high risk for lung cancer who receive a positive screening result or are otherwise suspected of having the disease.

"Precision Pathology rightfully enjoys an excellent reputation for quick turnaround times while providing accurate pathology diagnoses. The company is known for its exceptionally responsive and helpful service to the physicians and patients it serves," bioAffinity President and CEO Maria Zannes said. "Dr. Joyce and his team will bring the same very high quality to the commercialization of CyPath Lung. CyPath Lung is in excellent hands."

CyPath Lung is a flow cytometric test to aid in the diagnosis of lung cancer. Patients collect sputum samples non-invasively at home, a particular benefit during the COVID-19 pandemic. The sample is shipped overnight to the laboratory for processing. Sample data is acquired by flow cytometry, a technique that can count, sort and profile individual cells with remarkable speed. Using an automated analysis with pre-set parameters, CyPath Lung profiles the lung environment, including the presence of cancer-associated cells. Data acquisition and physician reports can be generated in minutes.

bioAffinity Technologies recently completed a test validation trial of CyPath Lung evaluating sputum from people at high risk for lung cancer, including patients with the disease and others who were cancer-free. The trial resulted in 92% sensitivity and 87% specificity in high-risk patients who had nodules smaller than 20 mm.

The U.S. Preventive Services Task Force recommends that smokers and former smokers at high risk for lung cancer undergo annual screening by low dose computed tomography (LDCT). Screening by LDCT has been proven to detect lung cancer at earlier stages when it can be more successfully treated. The National Lung Cancer Screening Trial (NLCST) of more than 53,000 participants resulted in a 20% decrease in lung cancer-specific mortality when LDCT screening was performed in high-risk patients. However, screening by LDCT had a low 3.8% positive predictive value (PPV) which raises the risk of unnecessary, invasive and costly procedures for those who test positive. In the NLCST, for every 100 people who received a positive LDCT, less than four of those individuals actually had lung cancer.

"CyPath Lung can assist physicians in determining next steps after a patient presents with a positive LDCT result, particularly in many cases where the lung nodule is considered indeterminate. In our test validation trial, bioAffinity successfully tested the automated analysis program used by CyPath Lung and found it to be fast and very robust in predicting who has cancer and who was at high risk but did not have lung cancer," Zannes said. "Physician reports can be generated immediately after flow cytometry acquires sample data. Looking beyond lung cancer, we believe our automated platform can be successfully applied to cancer diagnostic tests for several other cancers, which will improve overall survival rates for patients through early diagnosis and treatment."

On September 14, 2021 TumorGen Inc., a biotechnology company, and PhenoVista Biosciences LLC, a specialized contract research organization, reported that they are partnering to characterize metastatic cancer cell clusters (MCCCs) (Press release, TumorGen, SEP 14, 2021, View Source [SID1234587686]). By revealing the traits that govern MCCCs, they hope to identify potential therapeutic targets and catalyze efforts to develop much-needed anti-metastatic drugs.

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"The analytical imaging power PhenoVista can bring to our MCCC capture technology is essential," said TumorGen Founder, President and CEO, Jeffrey K. Allen, Ph.D. "Working directly with PhenoVista will help leverage our MCCC capture capabilities to identify unseen drug targets. With this data, TumorGen will be well-positioned to begin commercialization efforts and establish partnerships with biopharmaceutical companies focused on emerging anti-metastatic therapeutics."

TumorGen will use its microfluidic platform to capture MCCCs from patient blood. PhenoVista will apply its specialized cell analysis technologies to illuminate how these clusters hold together and avoid the body’s immune response. Revealing these inter-cellular signals will change how we understand metastasis, leading to new therapies.

"Characterizing MCCCs with our high-content imaging technology could reveal the critical inter-cellular communication within the cluster that makes it so deadly," said James Evans, Ph.D., PhenoVista Biosciences CEO. "Illuminating the complex interactions between cancer cells and immune cells, such as macrophages, and neutrophils, will reveal how MCCCs evade immune surveillance and form new tumors."

Metastasis (the spread of malignant cells throughout the body) causes over 90% of cancer deaths. Scientists have known MCCCs drive this spread but have lacked easy methods to investigate these critically important cell clusters. Also significant is that MCCCs contain both cancer and immune cells, thus providing the opportunity to develop cutting-edge therapies based on immuno-oncology which can inhibit metastasis.

"Understanding MCCC cell status, including whether immune cells are tumor suppressive or tumor supportive, is critically important," said Darren Finlay, Ph.D., Director of Tumor Analysis at Sanford Burnham Prebys Medical Discovery Institute, an NCI-Designated Cancer Center. Finlay is co-investigator on TumorGen’s recent SBIR grant from the National Cancer Institute. "These findings could provide huge insights to leverage the immune system to develop first-in-class, anti-metastatic drugs."

On September 14, 2021 Cleveland Diagnostics, Inc., a commercial stage biotechnology company developing next-generation diagnostic tests for the early detection of cancers, reported that Eric Klein, MD, Chairman of the Glickman Urological & Kidney Institute at Cleveland Clinic, delivered two presentations at the annual meeting of the American Urological Association regarding the company’s prostate cancer test, IsoPSA (Press release, Cleveland Diagnostics, SEP 14, 2021, View Source [SID1234587685]).

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In the first presentation, entitled "IsoPSA: Clinical Performance of a Single Parameter, Structure Based Test for High Grade Prostate Cancer in a Large, Multicenter, Prospective Validation Trial", Dr. Klein provided data used to validate the diagnostic accuracy of the novel, structure-based IsoPSA assay to improve early detection strategies for prostate cancer vs. standard of care PSA and % free PSA tests. In the prospective, multicenter study of 1,093 men IsoPSA showed an AUC of 0.790 for the detection of high grade cancer (Gleason grade group 2 or higher) (vs. 0.674 for PSA and 0.727 for % free PSA). IsoPSA had a sensitivity of 90% for high-grade prostate cancer, and specificity of 47% (compared to 21% for PSA and 14% for % free PSA). Data were consistent and reliable across patients who were biopsy naïve and who had a prior negative biopsy, and IsoPSA maintained its statistical accuracy across a wide range of elevated PSA values (from 4ng/mL to 100ng/mL).

In the second presentation, entitled "IsoPSA Reduces Provider Recommendations for Biopsy and MRI in Men with Total PSA ≥ 4ng/mL: A Real-World Observational Clinical Utility Study", Dr. Klein reported that 38 providers practicing in a variety of clinical settings evaluating 900 patients for prostate cancer substantially altered their behavior and patient management decisions following IsoPSA testing. Provider recommendations for biopsy and MRI were modified post-IsoPSA in 66% of cases in this prospective study, and concordance between IsoPSA results and biopsy recommendations was very high. Overall, IsoPSA test results reduced provider biopsy recommendations by 55% and MRI recommendations by 9%. In twenty cases, biopsies that were recommended after, but not before, IsoPSA testing, led to the detection of additional prostate cancers that would have been missed had it not been for IsoPSA testing.

"The data from these two studies demonstrate that IsoPSA is not only effective at detecting high-grade prostate cancer, but also holds promise to change the diagnostic paradigm, which could result in both improved patient outcomes and reduced costs to the healthcare system," said Eric Klein, MD.

"The real world implications of these findings are important and considerable," added Arnon Chait, PhD, CEO of Cleveland Diagnostics, Inc. "Using IsoPSA, we believe that providers save lives, and save the healthcare system considerable money while doing so. Reducing the number of unnecessary biopsies, increasing biopsy yield, and distinguishing high grade disease risk from low grade or benign disease with an effective blood test will be critical to savings lives, costs, and significantly improve overall patient care."

The 2021 American Urological Association annual meeting was held virtually this year from September 10-13, 2021. More information can be found at www.aua2021.org.