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FORE Biotherapeutics Announces Oral Presentation of Phase 1/2a Plixorafenib Data at the Society for Neuro-Oncology 2023 Annual Meeting

On November 10, 2023 FORE Biotherapeutics reported an oral presentation highlighting updated Phase 1/2a clinical data for plixorafenib (FORE8394; PLX8394), the company’s novel, investigational, small-molecule, next-generation, orally available selective inhibitor of BRAF alterations, will be given at the Society for Neuro-Oncology (SNO) 2023 Annual Meeting, taking place November 15-19, 2023, in Vancouver, Canada (Press release, Fore Biotherapeutics, NOV 10, 2023, View Source [SID1234637475]). The data being presented continue to demonstrate that plixorafenib has a favorable safety profile and results in durable responses in adults with primary central nervous system tumors with BRAF V600 alterations.

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Details for the SNO 2023 Oral Presentation:

Title: Efficacy of BRAF inhibitor plixorafenib (FORE8394) in recurrent, primary central nervous system tumors (PCNST)
Presenter: Macarena I. de la Fuente, MD, University of Miami, Sylvester Comprehensive Cancer Center
Abstract number: CTNI-76
Session: Clinical Trials – Non-immunologic
Presentation date and time: Friday, Nov 17, 2023, 3:55-4:05 p.m. PT

About Plixorafenib (FORE8394)

Plixorafenib is an investigational, novel, small-molecule, next-generation, orally available selective inhibitor of mutated BRAF. It was designed to target a wide range of BRAF mutations while sparing wild-type forms of RAF. Nonclinical studies and clinical trials have shown that its unique mechanism of action effectively inhibits not only the constitutively active BRAF V600 monomers targeted by first-generation BRAF inhibitors but also disrupts constitutively active dimeric non-V600 BRAF alterations (class 2 mutants, fusions, splice variants and others). Unlike first- and second-generation BRAF inhibitors, plixorafenib does not induce paradoxical activation of the MAPK pathway. This not only yields the potential for an improved safety profile, but also avoids the need to combine with a MEK inhibitor. As a "paradox breaker," plixorafenib could therefore yield improved safety and more durable efficacy than earlier generation BRAF inhibitors and have activity in settings of acquired resistance to current RAF inhibitors.

Plixorafenib is currently being evaluated in Phase 1/2a clinical trial in adults and children with advanced solid tumors (including brain and spinal cord tumors) with activating BRAF alterations. Interim clinical data presented at ESMO (Free ESMO Whitepaper) 2022, ASCO (Free ASCO Whitepaper) 2023, and SNO 2023 provide evidence of durable anti-tumor single-agent activity in patients with BRAF-mutated cancers.

Novocure Announces Presentations on Tumor Treating Fields Therapy, Including New Clinical Data and Real-World Evidence, at 2023 Society for Neuro-Oncology Annual Meeting

On November 10, 2023 Novocure (NASDAQ: NVCR) reported that research on Tumor Treating Fields (TTFields) therapy, including new data from the phase 2 2-THE-TOP trial and real-world evidence from patients diagnosed with glioblastoma (GBM) and other central nervous system tumors (CNS), will be presented at the 2023 Society for Neuro-Oncology (SNO) Annual Meeting from Nov. 16 to Nov. 19 in Vancouver, Canada (Press release, NovoCure, NOV 10, 2023, View Source [SID1234637474]).

Novocure’s presence at the SNO Annual Meeting will include medical booths, sponsored symposia and scientific presentations spanning preclinical, clinical and real-world outcomes research underscoring the safety and efficacy of TTFields therapy, as well as patient and healthcare provider satisfaction with the therapy.

"The SNO Annual Meeting is the largest annual conference focused on neuro-oncology and an ideal forum for sharing new data on the use of immunotherapy and TTFields therapy in the treatment of GBM as well as our largest real-world study to date and additional insights about the safety and efficacy of TTFields therapy," said Frank Leonard, President of Novocure’s U.S. CNS Cancers Franchise. "We are eager to engage with the neuro-oncology community as we strive to extend survival in some of the most aggressive forms of cancer."

Highlights include:

an oral presentation of data from the 2-THE-TOP trial, suggesting TTFields therapy had an enhanced effect with pembrolizumab in patients with newly diagnosed GBM. 2-THE-TOP is an investigator-sponsored phase 2 clinical trial of TTFields therapy plus pembrolizumab plus maintenance temozolomide.

an oral presentation of the final results of Novocure’s largest non-interventional real-world evidence study to date, the TTFields in Germany in Routine Clinical Care (TIGER) study in patients with newly diagnosed glioblastoma (GBM). A striking 82% of the 710 patients surveyed opted to use TTFields therapy and demonstrated sustained health-related quality of life, except for more itchy skin, consistent with results from the randomized, phase 3 EF-14 clinical study.
Novocure is also sponsoring an Independent Supported Session, titled Tumor Treating Fields vs. GBM —The Evidence and Experience, on Friday, Nov. 17, from 12:45-1:45 p.m. PST in Room 208-209, Vancouver Convention Centre.

A CME/Industry Sponsored Symposium, PeerView Live at SNO 2023, Shattering the Barriers to Glioblastoma Care: Revolutionary Advances With Innovative Technologies and Modern Systemic Approaches (in collaboration with the American Brain Tumor Association), will be held Thursday, Nov. 15 at 5:30-6:30 p.m. PST in Room 205-207, Vancouver Convention Centre.

The 2023 SNO Annual Meeting will also mark the debut of Novocure’s new Optune Gio brand. Optune, Novocure’s FDA-approved treatment for newly diagnosed and recurrent GBM, will be renamed Optune Gio on Nov. 15.

Presentations include:

Final efficacy and correlative analyses of 2-THE-TOP: A pilot study of TTFields (Optune) plus pembrolizumab plus maintenance temozolomide in patients with newly diagnosed glioblastoma (ndGBM). Presenter: David D. Tran. 8:06 p.m. PST on Friday, Nov. 17.
Treatment decision and quality of life of patients with newly diagnosed glioblastoma (ndGBM) receiving Tumor Treating Fields (TTFields) therapy in routine clinical care: First results of the TIGER study. Presenter: Martin Glas. 8:35 a.m. PST on Saturday, Nov. 18
Demographics, prescribing patterns, and satisfaction of healthcare professionals who prescribe Tumor Treating Fields (TTFields) therapy to patients with glioblastoma. Presenter: Elena Palmesino. 7:30 p.m. PST on Friday, Nov. 17.
Tumor Treating Fields (TTFields) therapy in glioblastoma (GBM): relationship between patient experience, global region, and age. Presenter: Eleni T. Batzianouli. 7:30 p.m. PST on Friday, Nov. 17.
Long-term global post-marketing surveillance data from pediatric, adult and elderly patients with central nervous system malignancies treated with Tumor Treating Fields (TTFields) therapy. Presenter: Maciej M. Mrugala. 7:30 p.m. PST on Friday, Nov. 17.
Real world experience with TTFields with emphasis on therapy compliance. Presenter: Claudius Jelgersma. 7:30 p.m. PST on Friday, Nov. 17.
Prolonged follow-up of an oligodendroglioma patient with history of Tumor Treating Fields (TTF) as post chemo-radiation maintenance therapy. Presenter: Xiao-Tang Kong. 7:30 p.m. PST on Friday, Nov. 17
Distant progression to the posterior fossa in supratentorial glioblastoma: A report of three cases during Tumor Treating Fields therapy. Presenter: Juri Kiyowaka. 7:30 p.m. PST on Friday, Nov. 17
Advanced MRI Biomarkers Predict Early Response to Tumor Treating Fields in Glioblastoma. Presenter: Kathleen Schmainda. 7:30 p.m. PST on Friday, Nov. 17
Investigating safety and efficacy of TTFields prior and concomitant to radiotherapy in newly diagnosed glioblastoma – first results of the PriCoTTF phase I/II trial. Presenter: Sied Kebir. 7:30 p.m. PST on Friday, Nov. 17
The pivotal METIS (EF-25) study of Tumor Treating Fields (TTFields) therapy for brain metastases from non-small cell lung cancer (NSCLC) following radiosurgery. Presenter: Minesh P. Mehta. 7:30 p.m. PST on Friday, Nov. 17
The pivotal TRIDENT study of Tumor Treating Fields (TTFields) therapy with chemoradiation, followed by maintenance TTFields therapy/temozolomide (TMZ), in newly diagnosed glioblastoma (ndGBM). Presenter: Wenyin Shi. 7:30 p.m. PST on Friday, Nov. 17
Adopting Tumor Treating Fields (TTFields) therapy for glioblastoma and other solid cancers: challenges and opportunities. Presenter: Leonardo Lustgarten. 7:30 p.m. PST on Friday, Nov. 17
Tumor Treating Fields: Real-World Survival and Quality of Life Outcomes on the XCELSIOR Platform. Presenter: Joshua Palmer. 7:30 p.m. PST on Friday, Nov. 17
Development of Tumor Treating Fields (TTFields) arrays for treatment of head tumors in mice models. Presenter: Moshe Giladi. 7:30 p.m. PST on Friday, Nov. 17
Molecular characterization of glioma tissue after TTFields treatment. Presenter: Christian Mawrin. 7:30 p.m. PST on Friday, Nov. 17
Dielectric properties of intracranial tumors – role of myelin content. Presenter: Martin A. Proescholdt. 7:30 p.m. PST on Friday, Nov. 17
About Tumor Treating Fields Therapy

Tumor Treating Fields (TTFields) are electric fields that exert physical forces to kill cancer cells via a variety of mechanisms. TTFields do not significantly affect healthy cells because they have different properties (including division rate, morphology, and electrical properties) than cancer cells. The multiple, distinct mechanisms of TTFields therapy work together to selectively target and kill cancer cells. Due to its multimechanistic actions, TTFields therapy can be added to cancer treatment modalities in approved indications and demonstrates enhanced effects across solid tumor types when used with chemotherapy, radiotherapy, immune checkpoint inhibition, or targeted therapies in preclinical models. TTFields therapy provides clinical versatility that has the potential to help address treatment challenges across a range of solid tumors. To learn more about Tumor Treating Fields therapy and its multifaceted effect on cancer cells, visit tumortreatingfields.com.

About Optune

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

TTFields therapy uses electric fields to 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. The therapy shows promise in multiple solid tumor types – including some of the most aggressive forms of cancer.

Rznomics Inc. Secures Fast Track Designation from the U.S. FDA for RZ-001

On November 10, 2023 Rznomics Inc., a South Korea based biopharmaceutical company specialized in the development of RNA-based gene therapeutics, reported that it has received Fast Track Designation from the U.S. Food and Drug Administration (FDA) for RZ-001, for the treatment of patients with Glioblastoma (GBM) (Press release, Rznomics, NOV 10, 2023, View Source [SID1234637473]).

Fast Track Designation is a process designed to facilitate the development and expedite the review of drugs to treat serious conditions and address unmet medical needs, thus enabling drugs to reach patients sooner. If relevant criteria are met, the drug with Fast Track Designation may also be eligible for Accelerated Approval and Priority Review.

GBM is known as the most malignant tumor in Central Nervous system with high mortality rate but lacks effective therapies. RZ-001, the RNA replacement enzyme-based cancer gene therapy for the treatment of GBM, targets and cleaves hTERT mRNA and replaces the mRNA with the therapeutic gene RNA. This induces anti-cancer activity and cytotoxic effect by trans-ligating an HSVtk-encoding sequence into the reprogrammed hTERT mRNA. RZ-001 has demonstrated very promising responses in preclinical studies in which an enhanced anti-cancer efficacy and a higher survival rate was observed.

"We are proud to receive Fast Track Designation from the FDA," said Dr. Seong-Wook Lee, Chief Executive Officer of Rznomics. "This designation signifies an important milestone in developing a safe and effective treatment for patients with GBM who are in need of new therapeutic options."

Rznomics received Phase I/IIa IND approval for RZ-001 from the FDA and the South Korean Ministry of Food and Drug Safety (MFDS) in Glioblastoma and the clinical trial will investigate the safety, tolerability, and efficacy of RZ-001 in patients with GBM. Subjects will be treated with RZ-001 according to the planned dose escalation design.

SeekIn Presents Retrospective and Prospective Validation Studies of SeekInCare Multi-omics Multi-cancer Early Detection test at the 20th ICGC Workshop and 7th ARGO Meeting in New York

On November 10, 2023 SeekIn Inc., a leader in blood-based pan-cancer early detection and monitoring technology, reported the validation studies consisting of one retrospective cohort and one prospective cohort that evaluate SeekInCare’s ability to detect cancer patients and predict the tissue of origin with one tube of blood (Press release, SeekIn, NOV 10, 2023, View Source [SID1234637472]). The results demonstrate the performance of SeekInCare with the consistent results among the two cohorts in ~2,400 cancer patients and non-cancer individuals. SeekInCare achieved overall 65.5% sensitivity at 97.9% specificity in the retrospective studies and 60.0% sensitivity at 96.1% specificity in the prospective cohort study, respectively, which is best-in-class in blood-based multi-cancer early detection (MCED). The findings were presented at the 20th ICGC Workshop and 7th ARGO Meeting in New York.

"Recent studies have demonstrated that blood-based multi-cancer early detection approaches may hold promise for identifying asymptomatic cancer patients from general population. However, most studies only exploit a single aspect of cancer hallmarks, which is challenging to achieve highly sensitive results because cancer is a heterogenous disease," said Mao Mao, MD, PhD, Founder and CEO of SeekIn. "For example, our OncoSeek test for multi-cancer early detection was designed with seven protein tumor markers. With the assistance of artificial intelligence (AI), the sensitivity of OncoSeek was 51.7% at 92.9% specificity. While OncoSeek significantly reduced false positive rates comparing with traditional methods, we believe sensitivity can be further improved when more omics data are included. And this is how SeekInCare was conceived."

SeekInCare was developed using proprietary AI- and big data-driven algorithm to distinguish cancer patients from non-cancer individuals by calculating cancer risk score (CRS) incorporating copy number aberrations (CNAs), fragment size (FS), end motifs and oncogenic viruses via shallow whole genome sequencing (sWGS) from cell-free DNA (cfDNA), and seven plasma tumor markers (PTMs), and to predict the possible affected tissue of origin (TOO) for those who have been detected with cancer signals in blood. SeekInCare’s performance was well-demonstrated by the overall 65.5% sensitivity at 97.9% specificity in the retrospective study and 60.0% sensitivity at 96.1% specificity in the prospective study. A critical attribute of a blood-based multi-cancer detection test is the ability to localize the TOO to direct the diagnostic workup. The overall accuracy of two most possible organs SeekInCare achieved was 85.4%, improved by 20.0% from OncoSeek.

"In addition to the performance improvement of SeekInCare in TOO prediction comparing with OncoSeek, significant improvements were also observed in major metrics such as sensitivity, specificity and accuracy. Unlike OncoSeek designed for low- and middle-income countries, SeekInCare enables us to provide a more sensitive and specific multi-cancer detection solution to the regions with purchasing power and high demands of advanced cancer screening," said Dr. Mao. "More importantly, comparing with the results of both retrospective and prospective studies from GRAIL and Exact Sciences, SeekInCare showed higher sensitivities with similar specificities."

The excellent consistency of validation results from both retrospective and prospective studies established SeekInCare’s clinical feasibility. With these achievements, SeekIn is planning for future investigation of SeekInCare’s clinical utility as a large-scale cancer screening test in average-risk populations.

RZNOMICS Inc. Announces Clinical Trial Collaboration and Supply Agreement to Evaluate RZ-001 in Combination with anti-PDL1 in liver cancer patients

On November 10, 2023 Rznomics Inc., a South Korea based biopharmaceutical company specialized in the development of RNA-based gene therapeutics, reported that it has entered into a clinical collaboration agreement with F. Hoffmann-La Roche Ltd (Roche) to study RZ-001, a gene therapy approach utilizing the company’s proprietary trans-splicing ribozyme-based RNA reprogramming and editing technology, in combination with Roche’s atezolizumab, in patients with hepatocellular carcinoma (HCC) (Press release, Rznomics, NOV 10, 2023, View Source [SID1234637471]). Under the terms of the agreement, Roche will provide atezolizumab to be used in combination with RZ-001 for the planned Phase 1b/2a study.

RZ-001, the RNA replacement enzyme based cancer gene therapy, targets and cleaves hTERT mRNA and replaces the mRNA with the therapeutic gene RNA. Specifically, RZ-001 induces anti-HCC activity by suppressing hTERT expression selectively in cancer cells, which express hTERT, and simultaneously inducing a cytotoxic effect by trans-ligating an HSVtk-encoding sequence into the reprogrammed hTERT mRNA. It also induces effective immune cell infiltration into treated tumors and reduces VEGF expression in the tumors, which leads to the anti-cancer efficacy and transformation of tumor microenvironment to be more responsive to immunotherapy.

RZ-001 has demonstrated therapeutic activity in preclinical studies and significant improvement in anti-cancer efficacy in a dose dependent manner in combination with atezolizumab. The clinical study will evaluate the safety and efficacy in liver cancer patients and it is anticipated that the combination of RZ-001 with atezolizumab may enhance response rate and anti-cancer efficacy that could benefit patients with HCC.

"We are excited to initiate collaboration with longstanding oncology leader, Roche, to further explore the potential benefits of combining checkpoint blockade with RZ-001," said Dr. Seong-Wook Lee, Chief Executive Officer of RZNOMICS. "We look forward to having this collaboration, evaluating combination therapy and continuing our mission to offer innovative therapies for patients in need."

About RZ-001

RZ-001 is the first Group I intron based trans-splicing ribozyme-based RNA reprogramming approach approved by the FDA for evaluation in patients. The treatment was developed utilizing Rznomics’ proprietary RNA reprogramming and editing technology and takes the form of an adenoviral vector that expresses an hTERT targeting trans-splicing ribozyme to treat hepatocellular carcinoma (HCC) patients. HCC is the most common type of primary liver cancer, accounting for 80 percent of cases worldwide.

Rznomics received Phase I/IIa IND approval for RZ-001 from the FDA and the South Korean Ministry of Food and Drug Safety (MFDS) in HCC and Glioblastoma as well.