High Grade Sarcoma

HIGHLIGHTS Data from preclinical studies in ovarian cancer presented at premier international conference in Boston, USA. Results indicate that Amplia's proprietary FAK inhibitor narmafotinib (AMP945) performs better than standard-of-care in models of chemotherapy-resistant high-grade serous ovarian cancer Data from these studies support clinical study of narmafotinib in ovarian cancer – with plans now commencing with leading international cancer specialists MELBOURNE, Australia, Oct. 9, 2023 /PRNewswire/ -- Amplia Therapeutics Limited (ASX: ATX), ("Amplia" or the "Company") is pleased to announce that a poster, detailing a series of preclinical studies in ovarian cancer models, was presented at the American Association for Cancer Research (AACR) Special Conference In Cancer Research: Ovarian Cancer meeting, held in Boston, USA over the weekend. The poster describes research with narmafotinib (AMP945) conducted by the company's collaborators at the University of California, San Diego (UCSD), and was presented by lead researcher Prof Dwayne Stupack. The data presented clearly demonstrates that narmafotinib is active in mouse models of chemotherapy-resistant ovarian cancer with improved tumour growth inhibition activity and tolerability compared to a PARP inhibitor (niraparib), the current standard-of-care agent for this chemotherapy-resistant patient population. Moreover, narmafotinib showed promising activity in a model where niraparib therapy is ineffective. These results build on previous research by Prof. Stupack and his collaborators showing that activity of the FAK enzyme is upregulated in chemotherapy-resistant ovarian cancer and that FAK inhibition resensitises the cancer to standard-of-care chemotherapy and immunotherapy as well. Lead researcher Prof Dwayne Stupack stated: "PARP inhibitors are now widely used in the treatment of high-grade serous ovarian cancer (HGSOC) and work well in a subset of patients with what's known as homologous recombinant deficient (HRD) HGSOC – at least until drug resistance occurs. We have shown in our preclinical models that narmafotinib (AMP945) has better activity across the non-HRD disease, and importantly works in PARP inhibitor-resistant disease as well. Moreover, it appears to be very well tolerated, which is important for a drug that will be taken daily." A copy of the presentation, entitled 'Maintenance therapy inhibition of ptk2 [FAK] yields decreased disease in preclinical models of HRP/HRD models of recurrent HGSOC' is available on the Company's website here. Amplia CEO and MD, Dr Chris Burns commented: "The research results presented today by Prof. Stupack are extremely exciting and clearly demonstrate that our best-in-class FAK inhibitor narmafotinib has significant potential in the treatment of ovarian cancer. Given that over 1000 women in Australia die each year of this disease, there is a clear need for better treatment, and plans are now underway to work with local and international ovarian cancer specialists to initiate a clinical trial of narmafotinib in ovarian cancer patients. "The clinical potential of FAK inhibition in ovarian cancer was demonstrated earlier this year with the first-generation FAK inhibitor defactinib showing promising activity in patients with low-grade serous ovarian cancer. Our preclinical results in models of high-grade disease, which represents over 90% of all ovarian cancer patients, further underscore the potential role of FAK inhibitors in treatment of this disease." This ASX announcement was approved and authorised for release by the Board. About Amplia Therapeutics Limited Amplia Therapeutics Limited is an Australian pharmaceutical company advancing a pipeline of Focal Adhesion Kinase (FAK) inhibitors for cancer and fibrosis. FAK is an increasingly important target in the field of cancer and Amplia has a particular development focus in fibrotic cancers such as pancreatic cancer. FAK also plays a significant role in a number of chronic diseases, such as idiopathic pulmonary fibrosis (IPF). For more information visit and follow Amplia on Twitter (@ampliatx), Threads (@ampliatx) and LinkedIn. SOURCE Amplia Therapeutics

Findings presented at the 2023 World Conference on Lung Cancer show that VGT-309 improves surgeons’ ability to see tumors in real time during minimally invasive and robotic procedures MINNEAPOLIS--(BUSINESS WIRE)-- Vergent Bioscience, a clinical-stage biotechnology company developing tumor-targeted imaging agents, and its wholly owned subsidiary Vergent Bioscience Australia Pty Ltd, announced that new data presented at the IASLC 2023 World Conference on Lung Cancer (#WCLC23) suggest the company’s tumor-targeted fluorescent imaging agent is active and can safely be used to detect tumor tissue in the lung with high accuracy. Findings from the Phase 2 surgical study evaluating VGT-309 suggest the investigational agent could improve surgeons’ ability to see difficult-to-find and previously undetected tumors in real time to help optimize patient outcomes. “The widespread adoption of minimally invasive lung cancer surgery, coupled with increasing numbers of small tumors being detected, have made it much more challenging for surgeons to see all tumor tissue during surgery,” said Gavin M. Wright, Ph.D., associate professor and director of Surgical Oncology, St. Vincent’s Hospital, Melbourne, Australia. “The findings from our study confirm that VGT-309 could enhance the success of minimally invasive surgery by improving tumor visualization and reducing the potential for cancer to be left behind.” The Phase 2 study evaluated the safety and efficacy of VGT-309 in 27 individuals with suspected or proven cancer in the lung who were eligible for surgery. Each patient in the study received a VGT-309 infusion on the day prior to or day of surgery. Following an attempt to identify each tumor using standard surgical techniques, researchers used a commercially available near-infrared (NIR) endoscope to assess the lung for the presence of any additional tumor tissue, which was then confirmed by pathology. The study findings presented today at the WCLC23 provide compelling evidence that VGT-309 has a high affinity for malignant tissue in the lung, increasing the potential that surgeons can identify all tumor tissue during surgery. Of the 27 participants, 23 had confirmed cancer, one had typical carcinoid, and three had non-neoplastic processes. The following tumor types were visualized intraoperatively with VGT-309 and NIR imaging: non-small cell lung cancer (adenocarcinoma and squamous cell carcinoma), metastatic carcinoma with breast origin, and high-grade sarcoma of epithelioid morphology. In two patients, VGT-309 identified tumor tissue in lymph nodes that was pathologically confirmed to be cancer, resulting in upstaging that could potentially impact patient treatment and outcomes. VGT-309 appeared to be safe and well tolerated across all dose levels studied, with no infusion reactions and only one patient experiencing a serious adverse event - a transient elevated liver-function test that resolved without intervention. “This study provides encouraging results demonstrating the clinical performance of VGT-309, including the breadth of tumors the agent can help surgeons visualize and its corresponding potential to enhance outcomes from minimally invasive surgery,” said John Santini, Ph.D., president and chief executive officer at Vergent Bioscience. “We look forward to expanding on these results in future studies including our upcoming multi-center Phase 2 clinical trial.” About VGT-309 VGT-309 is a tumor-targeted imaging agent designed to enable a complete product solution for optimal tumor visualization during open, MIS, and robotic-assisted surgical procedures. VGT-309 is delivered to patients by a short infusion several hours before surgery. Invented in Professor Matt Bogyo’s Lab at Stanford University School of Medicine, the molecule binds tightly (i.e., covalently) to cathepsins, a family of proteases that are overexpressed across a broad range of solid tumors. This approach provides distinct clinical advantages and positions VGT-309 as an ideal tumor-imaging agent. VGT-309’s imaging component is the near infrared (NIR) dye indocyanine green (ICG), which is compatible with all commercially available NIR intraoperative imaging systems that support MIS technologies and is the preferred dye to minimize confounding background autofluorescence. About Vergent Bioscience Vergent Bioscience is a clinical-stage biotechnology company that is helping surgeons realize the full potential of minimally invasive and robotic surgery by significantly improving the visibility of tumors. Vergent’s lead compound, VGT-309, is a tumor-targeted fluorescent imaging agent designed to enable surgeons to see difficult-to-find or previously undetected tumors in real-time during surgery, ensuring all tumor tissue is removed. The company is first evaluating VGT-309 for cancer in the lung, with the potential to expand its application to a wide range of solid tumors. Vergent Bioscience is a privately held company based in Minneapolis, Minn. Vergent Bioscience Australia Pty Ltd is a wholly owned subsidiary of Vergent Bioscience. For more information, visit vergentbio.com.

April 4, 2023 -- Results from a clinical trial conducted by researchers at the National Institutes of Health (NIH) show that people with low-grade lymphomatoid granulomatosis who are treated with interferon alfa-2b, a type of immunotherapy, can live for decades after diagnosis. Lymphomatoid granulomatosis is a rare precancerous condition triggered by Epstein-Barr virus infection. Left untreated, the disease can progress to a high-grade form, which has a poorer prognosis and can quickly turn into an aggressive and fatal B-cell lymphoma. In the phase 2 trial, led by researchers in the Center for Cancer Research at the National Cancer Institute (NCI), part of NIH, patients treated with interferon alfa-2b lived for a median of about 20 years. By contrast, past studies reported a median survival of less than two years for people with lymphomatoid granulomatosis. The findings suggest that immunotherapy can prevent the progression of low-grade disease to high-grade disease. The results were published March 31, 2023, in Lancet Haematology . “We have shown in this rare disorder that using a novel immunotherapy-based approach for low-grade disease is effective and improves survival compared with historical treatments such as chemotherapy and corticosteroids,” said Christopher J. Melani, M.D., of NCI’s Center for Cancer Research, who co-led the study. “I think the results of this study represent a significant contribution to determining the standard-of-care treatment for this rare disease.” Lymphomatoid granulomatosis causes an overproduction of white blood cells known as B lymphocytes. Patients typically have lesions in the lungs, central nervous system, skin, liver, and kidneys. Symptoms can include cough, shortness of breath, fever, weight loss, and fatigue. Chemotherapy is currently the standard treatment for people with high-grade disease, but there is no standard treatment for low-grade disease. “Although lymphomatoid granulomatosis is uncommon, the effects of high-grade disease can be debilitating,” said Jeffrey Cohen, M.D., chief of the Laboratory of Infectious Diseases at the National Institute of Allergy and Infectious Diseases and a co-leader of the study. “We need better ways to prevent the disease from progressing to this more severe state, such as interferon alfa-2b.” NIH researchers have been studying lymphomatoid granulomatosis since the 1980s. In the early 1990s, Wyndham Wilson, M.D., Ph.D., also of NCI’s Center for Cancer Research, hypothesized that low-grade disease results from a defective immune response to the Epstein-Barr virus and could therefore be treated with immunotherapy, whereas high-grade disease requires chemotherapy to curb uncontrolled cell growth. He and his colleagues treated four people with low-grade lymphomatoid granulomatosis with interferon alfa-2b over a 5-year period, and the treatment eradicated all signs of the disease in three of those patients, known as a complete remission. That study laid the foundation for the phase 2 trial of interferon alfa-2b in lymphomatoid granulomatosis, which has taken 30 years to complete because of the rarity of the disease and the challenges of recruiting enough patients for the study. “This really illustrates the unique ability of NIH to do a study like this that nobody else could do and no one else ever has done for this particular disease,” said Dr. Wilson, who co-led the study. The trial included 67 people with lymphomatoid granulomatosis, 37 with low-grade disease and 30 with high-grade disease. In all cases, the participants had not yet been treated for the disease or their disease had not responded to or had returned after other treatments. During their initial treatment, most of the patients with low-grade disease received subcutaneous injections of interferon alfa-2b three times a week in increasing doses for about one year. Most of the patients with high-grade disease were given six cycles of intravenous chemotherapy every three weeks. Both groups improved, with the disease disappearing in 27 of 44 patients (61%) treated with interferon alfa-2b, and 8 of 17 patients (47%) treated with chemotherapy. After their initial treatment, some patients subsequently received the other therapy, called crossover treatment. Patients with low-grade disease that worsened after immunotherapy were given chemotherapy, whereas patients with high-grade disease that came back after chemotherapy were given interferon alfa-2b. Previous work showed that after high-grade disease is eliminated with chemotherapy, low-grade disease can re-emerge. The crossover treatments were also effective, with the disease disappearing in 4 of 8 patients (50%) treated with interferon alfa-2b after chemotherapy and 7 of 15 patients (47%) treated with chemotherapy after interferon alfa-2b. Median overall survival was 20.6 years for patients treated initially with interferon alfa-2b and 19.8 years for patients who crossed over to receive interferon alfa-2b. Median overall survival was 12.1 years for patients treated initially with chemotherapy and not reached for those who crossed over to receive chemotherapy. The most common side effect of interferon alfa-2b treatment was low white blood cell count, and the most common side effects with chemotherapy were low white blood cell count and infection. Serious side effects occurred in only a quarter of the patients treated with interferon alfa-2b, compared with nearly two-thirds of patients treated with chemotherapy. Many newer immunotherapies, such as nivolumab, could potentially be used to treat low-grade lymphomatoid granulomatosis and other Epstein-Barr virus–associated disorders and may have fewer side effects. “The trial of interferon alfa-2b established that immunotherapy improves survival in patients with low-grade lymphomatoid granulomatosis,” Dr. Melani said. “Now we can look into more novel immunotherapies that are easier to tolerate to see if they can improve on the efficacy of our current treatment.” The study was funded by the intramural research programs of NCI and the National Institute of Allergy and Infectious Diseases. About the National Cancer Institute (NCI): NCI leads the National Cancer Program and NIH’s efforts to dramatically reduce the prevalence of cancer and improve the lives of people with cancer. NCI supports a wide range of cancer research and training extramurally through grants and contracts. NCI’s intramural research program conducts innovative, transdisciplinary basic, translational, clinical, and epidemiological research on the causes of cancer, avenues for prevention, risk prediction, early detection, and treatment, including research at the NIH Clinical Center—the world’s largest research hospital. Learn more about the intramural research done in NCI’s Center for Cancer Research. For more information about cancer, please visit the NCI website at cancer.gov or call NCI’s contact center at 1-800-4-CANCER (1-800-422-6237). About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov . NIH…Turning Discovery Into Health ® Source: NIH Posted: April 2023