On January 10, 2024 Focal Medical, Inc., ("Focal") a privately held biopharmaceutical company developing a targeted therapeutic system to treat inoperable tumors and to deliver genomic medicines, reported U.S. Food and Drug Administration (FDA) clearance of an Investigational New Drug (IND) application to initiate a Phase 1b clinical trial of ACT-IOP-003, the Company’s first targeted therapeutic product (Press release, Focal Medical, JAN 10, 2024, View Source [SID1234639197]). The trial will evaluate the safety and tolerability of targeted delivery of gemcitabine to locally advanced nonresectable (LANR) pancreatic tumors. The clinical trial is expected to start mid-2024.

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"Pancreatic cancer is a devastating disease with a very poor prognosis," said Dr. William Daunch, Chief Technology Officer of Focal. "Once a locally advanced tumor is not resectable, treatment options are limited and these patients experience a significantly reduced survival outlook compared to resectable cases. Our thesis, which we have demonstrated in animal models of pancreatic cancer, is that localized delivery of high concentrations of gemcitabine via our implantable iontophoretic device can reduce tumor volume to a point where surgical removal may be possible, while also minimizing systemic exposure and associated toxicity. If successful, we may offer the opportunity of extended survival for the significant number of pancreatic cancer patients presenting with nonresectable disease."

Pancreatic adenocarcinoma, which represents more than 90 percent of pancreatic cancer diagnoses, is an especially challenging disease to treat. According to The American Cancer Society, the incidence of pancreatic cancer in the U.S. is more than 62,000 cases annually and it represents the third leading cause of cancer death. Patients whose tumors are resectable have the best chance for cure and, for these patients, surgical resection with or without neoadjuvant chemotherapy, is the standard of care. Treatment options for locally advanced nonresectable tumors comprise a variety of systemic chemotherapy regimens, which are rarely curative unless there is dramatic response to chemotherapy that allows the tumor to be resected.

The multi-center, open label, modified dose escalation phase 1b clinical trial will assess the safety, tolerability, and clinical activity of the implantable ACT-IOP-003 targeted therapeutic product delivering gemcitabine directly into the pancreas to treat LANR pancreatic cancer. Eligible patients would be enrolled into one of two cohorts, receiving treatment either once or twice weekly over 8 weeks (approximately 5 patients per cohort). Up to 12 patients may be enrolled in the study which is expected to start mid-2024.

"Clinicians who treat pancreatic cancer need new and more powerful tools in their armamentarium to address this terrible disease," commented Jen Jen Yeh, M.D., Focal Medical Co-founder and Non-executive Director, and Professor and Vice Chair of Research, Department of Surgery and Director of the Pancreatic Cancer Center of Excellence at the Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill. "The novel approach that the Focal Medical system employs to drive gemcitabine directly and selectively into the pancreas may offer new hope for patients."

Michael Aldridge, CEO of Focal added, "The FDA’s clearance of Focal’s IND for ACT-IOP-003 for pancreatic cancer is an important achievement for the Company. We remain focused on our important mission to provide hope for patients suffering with this devastating disease."

On January 10, 2024 Novocure (NASDAQ: NVCR) reported that the final patient has been enrolled in the global phase 3 TRIDENT clinical trial evaluating the safety and efficacy of initiating Optune Gio (formerly known as Optune) concurrent with radiation therapy and temozolomide (TMZ) for the treatment of adult patients with newly diagnosed glioblastoma (GBM) (Press release, NovoCure, JAN 10, 2024, View Source [SID1234639196]).

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"TTFields therapy has played a critical role in the treatment of newly diagnosed glioblastoma for nearly a decade, and the TRIDENT trial represents the potential evolution of this treatment paradigm by introducing TTFields earlier, at the same time as radiation therapy and temozolomide," said Asaf Danziger, Novocure’s Chief Executive Officer. "Preclinical research has shown that the application of TTFields together with radiation therapy leads to a more pronounced cytotoxic effect in glioma cell lines as compared to TTFields after administration of radiation therapy. The TRIDENT study could unlock our ability to reach patients earlier in their treatment journey, further extending patient survival. We remain committed to exploring opportunities to further extend the survival horizon for patients diagnosed with glioblastoma."

Optune Gio is currently approved for use together with maintenance TMZ for the treatment of newly diagnosed GBM following maximal debulking surgery and the completion of radiation therapy.

The TRIDENT clinical trial is a randomized, open-label study designed to enroll 950 adult patients with newly diagnosed GBM. Following maximal debulking surgery, patients enrolled in TRIDENT were randomized to receive either TTFields therapy, concomitant with TMZ and radiation therapy, or TMZ and radiation therapy for six weeks. Following the initial six-week period, all patients receive the current standard of care – TTFields therapy together with maintenance TMZ for a period of 24 months or until a second disease progression is experienced. TRIDENT began enrolling patients in December 2020 and is the largest trial Novocure has conducted to date.

Final data from the TRIDENT trial is anticipated in 2026. The trial’s primary endpoint is overall survival. Secondary endpoints are progression-free survival, one-year and two-year survival rate, overall radiological response, next progression-free survival, progression-free survival at six and 12 months, severity and frequency of adverse events, pathological changes in resected GBM tumors following study treatments, quality of life, dependence of overall survival on TTFields dose at the tumor, and neurological assessment using the NANO scale.

About Optune Gio

Optune Gio delivers Tumor Treating Fields (TTFields) therapy to the region of the tumor. Optune Gio, previously known as Optune, is a noninvasive, antimitotic cancer treatment for glioblastoma (GBM).

TTFields therapy uses electric fields to physically disrupt cell division. TTFields therapy does not stimulate or heat tissue and targets dividing cancer cells of a specific size. TTFields therapy takes advantage of the special characteristics and geometrical shape of dividing cells, which make them susceptible to the effects of the alternating electric fields. TTFields therapy causes minimal damage to healthy cells. Mild to moderate skin irritation is the most common side effect reported. TTFields therapy is approved in certain countries for the treatment of adults with glioblastoma, malignant pleural mesothelioma and pleural mesothelioma, some of the most difficult cancer types to treat.

Important Safety Information

Contraindications

Do not use Optune Gio in patients with an active implanted medical device, a skull defect (such as, missing bone with no replacement), or bullet fragments. Use of Optune Gio together with implanted electronic devices has not been tested and may theoretically lead to malfunctioning of the implanted device. Use of Optune Gio together with skull defects or bullet fragments has not been tested and may possibly lead to tissue damage or render Optune Gio ineffective.

Do not use Optune Gio in patients that are known to be sensitive to conductive hydrogels. In this case, skin contact with the gel used with Optune Gio may commonly cause increased redness and itching, and rarely may even lead to severe allergic reactions such as shock and respiratory failure.

Warnings and Precautions

Do not prescribe Optune Gio for patients that are pregnant, you think might be pregnant or are trying to get pregnant, as the safety and effectiveness of Optune Gio in these populations have not been established.

The most common (≥10%) adverse events involving Optune Gio in combination with temozolomide were thrombocytopenia, nausea, constipation, vomiting, fatigue, medical device site reaction, headache, convulsions, and depression.

The most common (≥10%) adverse events seen with Optune Gio monotherapy were medical device site reaction and headache.

The following adverse reactions were considered related to Optune Gio when used as monotherapy: medical device site reaction, headache, malaise, muscle twitching, fall and skin ulcer.

Use of Optune Gio in patients with an inactive implanted medical device in the brain has not been studied for safety and effectiveness, and use of Optune Gio in these patients could lead to tissue damage or lower the chance of Optune Gio being effective.

If the patient has an underlying serious skin condition on the scalp, evaluate whether this may prevent or temporarily interfere with Optune Gio treatment.

On January 10, 2024 Dxcover Limited, a clinical-stage diagnostics company pioneering multi-omic spectral analysis (MOSA) for early detection of multiple cancers, reported that it is initiating three pivotal clinical trials measuring efficacy of the company’s liquid biopsy technology for the detection of brain, colorectal and lung cancer (Press release, Dxcover, JAN 10, 2024, View Source [SID1234639195]).

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The company has launched its EMBRACE study, a 2,200-patient trial focused on the early detection of brain cancer. Dxcover Brain Cancer is a qualitative in vitro diagnostic (IVD) test analyzing blood serum by infrared spectroscopy to detect the signals indicative of brain cancer. This highly sensitive test is to help determine the necessary treatment of patients presenting vague symptoms in primary care environments. The results of the test would prioritize individuals who require a confirmatory brain scan, potentially enabling earlier detection to save lives and reduce healthcare costs. The Dxcover Brain Cancer test has been developed over four years with clinical support from NHS Lothian. This pivotal study is partially funded by a €2.5m grant from the European Innovation Council.

The CREATE2 trial will be conducted to evaluate diagnostic accuracy for colorectal cancer and high-risk adenoma in patients undergoing a colonoscopy. The study will have two recruitment pathways, one in the US and one in the UK, each with 700 patients. The US cohort will be assessed in the average risk population 45-84 who are intending to undergo a screening colonoscopy, while the UK cohort will be assessed post-referral at colonoscopy. CREATE2 aims to validate the previous CREATE study which showed Dxcover’s ability to achieve accurate detection of pre-cancerous lesions and stage 1 colorectal cancer, detection at these stages will enable a positive impact on patients’ lives.

The SPIRALS trial is focused on the management of indeterminant pulmonary nodules by scanning for nodules in the size range between 0.8 – 3.0 mm range. At this size range the nodules are small, however 80% have an intermediate risk score where next steps are unclear resulting in unnecessary surgery and missed cancer diagnoses. Dxcover will be analyzing more than 1,800 samples in order to provide a rapid, cost-effective tool that can help patients receive the correct next steps in their journey.

"Each cancer follows a unique development path, and these are important trials to assess brain, colorectal and lung cancer separately to zero in on the distinct triggers of each disease and, based on the results, identify the most effective treatment for each patient," said Professor Matthew Baker, Founder and CEO, Dxcover. "As the medical community gathers this week in San Francisco for what is always one of the most significant gatherings in the healthcare industry, I’m looking forward to meeting with like-minded partners whose mission is to eradicate the devastating effects of cancers. At Dxcover, we are firm believers that the key to improving patient outcomes lies in the early detection of cancer, expanding intervention and treatment options. Not only does this have the potential to enhance the efficacy of medical intervention, but also contributes to prolonging and promoting healthier lives."

The Dxcover Cancer Liquid Biopsy test uses Fourier transform infrared (FTIR) spectroscopy and machine learning algorithms to build a classifier of the resultant spectral profiles to detect cancer and can be fine-tuned to maximize either sensitivity or specificity depending on the requirements of specific disease pathway.

On January 10, 2024 Debiopharm, an independent biopharmaceutical company headquartered in Switzerland, and ThinkingNodeLife.ai (TNL), a trailblazer in AI Digital Cells Lab in USA, reported a collaborative partnership aimed at advancing the development of a cutting-edge cancer drug (Press release, Debiopharm, JAN 10, 2024, View Source [SID1234639194]). This strategic alliance leverages the unique capabilities of TNL’s AI Digital Cells Lab platform and Debiopharm’s deep pharmaceutical expertise to bring cancer drugs into new frontiers of innovation.

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Key Highlights of the Partnership: 1) Expanding Indications: The partnership will harness TNL’s AI Digital Cells Lab platform to explore additional indications for one of Debiopharm’s cancer drugs. 2) Drugs’ Combination Identification: Utilizing TNL’s AI digital knockdowns, it will identify valuable combinations with other drugs in development, enhancing the therapeutic potential of Debiopharm’s cancer drug. 3) Mechanism of Action Validation: TNL’s mechanistic digital cell clones will be instrumental in validating the mechanism of action of Debiopharm’s cancer drug, ensuring a deep understanding of its efficacy. 4) Drugs’ Comparison: TNL’s digital cell clones will provide comparative analysis, allowing Debiopharm to assess its cancer drug against other existing cancer treatments. 5) Biomarker Discovery: TNL partnership will focus on identifying valuable predictive biomarkers.

"We’re intrigued to discover what this collaboration with ThinkingNodeLife.ai will bring to the advancement of our oncology drug programs. Integrating AI-powered solutions into our research processes, such as TNL’s AI-Enabled Digital Cells Lab platform, aligns with our aim to adopt smarter practices in our R&D, in order to broaden drug application to more cancer types and speed up the time it takes to bring new drugs to patients," explained Bertrand Ducrey, CEO of Debiopharm.

"We are excited to start this strategic partnership with Debiopharm, a highly esteemed and innovative Swiss pharmaceutical company. We are confident that the synergy between TNL’s unique Digital Cell Clones Lab platform and Debiopharm’s profound expertise in drug R&D will show the transformative potential of AI-enabled Digital Labs from disease-target discovery to the optimization of clinical trials. As we look forward to an exhilarating 2024, we believe this partnership will pave the way for significant advancements in the field of drug R&D for the benefit of the patients," explained Khai Pham, CEO of ThinkingNodeLife.ai

On January 10, 2024 According to preclinical research published online today in Cell, one of the world’s premier scientific journals, researchers with City of Hope, one of the largest cancer treatment and research organizations in the United States, reported that a type of immune cell in the human body known to be important for allergy and other immune responses can also attack cancer (Press release, City of Hope, JAN 10, 2024, View Source [SID1234639193]).

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Furthermore, these cells, called human type 2 innate lymphoid cells (ILC2s), can be expanded outside of the body and applied in larger numbers to overpower a tumor’s defenses and eliminate malignant cells in mouse models with cancer.

"The City of Hope team has identified human ILC2 cells as a new member of the cell family capable of directly killing all types of cancers, including blood cancers and solid tumors," said Jianhua Yu, Ph.D., a professor in the Department of Hematology & Hematopoietic Cell Transplantation at City of Hope and the study’s senior author. "In the future, these cells could be manufactured, preserved by freezing, and then administered to patients. Unlike T cell-based therapies, such as CAR T cells, which necessitate using the patient’s own cells due to their specific characteristics, ILC2s might be sourced from healthy donors, presenting a distinct potential therapeutic approach as an allogeneic and ‘off-the-shelf’ product."

In previous research focused on mouse cells, ILC2s had not consistently shown promise when tested for their cancer-killing abilities.

However in the highly translational labs at City of Hope, researchers prioritized the examination of human cells and found that human ILC2s do not work the same as mouse ILC2s.

"Typically, mice are reliable models for predicting human immunity, so it was a real surprise in the field to find that human ILC2s function as direct cancer killers while their mouse counterparts do not," said Michael Caligiuri, M.D., who is a co-senior author of the study and also a City of Hope professor in the Department of Hematology & Hematopoietic Cell Transplantation. "It is remarkable that something has evolved so distinctly in going from mouse to human."

Finding a New Function

To test human ILC2s, Yu and the team first isolated the cells from a blood sample. Then, they developed a novel platform, which in four weeks can expand ILC2s 2000-fold from those harvested in the body. They next injected these ex-vivo expanded ILC2s into mice engrafted with human acute myeloid leukemia (AML) or solid tumors, including pancreatic cancer, lung cancer, and glioblastoma. The results showed that this ILC2 population could kill these tumors via a previously unknown cancer-killing mechanism.

"One convincing and direct piece of evidence appeared when we placed one ILC2 and one tumor cell directly together and found that the tumor cell died, but the ILC2 cell survived," explained Yu. "This proves that the ILC2s directly killed the cancer cell in that absence of any other cell."

Yu noted that the ILC2s do not need to come from the cancer patient’s own cells, meaning that there may be the possibility of harvesting and freezing ILC2s from healthy donors for ILC2 treatment options in the future.

Investigating Killer Cells

Yu and Caligiuri have been investigating a different type of cancer killer called natural killer cells, or NK cells, for decades. In fact, Yu is founding director of the Natural Killer Cell Biology Research Program at City of Hope, a national leader in the field.

Yu and Caligiuri said ILC2s now represent a new member of the cytotoxic immune effector cell family, alongside NK cells and CD8+ T cells, which help the body fight against cancer. They are excited to see how researchers might be able to harness the collective power of these different killer cells to better fight other diseases as well.

Next Steps

Yu and Caligiuri caution that because they are still in the early days of understanding ILC2s’ cancer-killing functions, many questions remain. However, they plan to continue to work with their collaborators to understand and learn more about human ILC2s now that they know the cells are killers.

"We aim to really expand the applications of these findings, potentially beyond cancer treatments," Yu said, noting that ILC2s may even work against viruses, such as COVID-19. "Additionally, we are working towards translating our discovery into tangible clinical benefits."

The team has already jumped at least one hurdle in getting ILC2s to clinical trials, which is having enough of the product to test. ILC2s are rare in the body, Caligiuri said. The team has a platform to grow them quickly.

"You have to be able to expand these cells for human clinical trials and one of the exciting things is that we are on the right track," Caligiuri said. "At City of Hope, we have the advantage of access to our good manufacturing practices-compliant facilities that can manufacture cells for us and speed discoveries into clinical trials."

The study team also included lead authors Zhenlong Li, Rui Ma, and Hejun Tang from the Yu and Caligiuri labs, as well as David Artis, Ph.D., the Michael Kors Professor of Immunology and director of the Jill Roberts Institute for Inflammatory Bowel Disease Research at Weill Cornell Medicine. The work was supported by grants from the National Institutes of Health and The Leukemia & Lymphoma Society.