A Window of Opportunity Trial Evaluating the Oral TGF-beta Receptor I Inhibitor Vactosertib in Patients Undergoing Standard of Care Chemoradiotherapy for Locally Advanced Esophageal Adenocarcinoma

This interventional clinical trial aims to find ways of improving treatments for individuals with esophageal cancer. Laboratory-based studies show that using medicines that affect a protein called TGF-beta (TGFβ) can kill esophageal cancer cells in individuals who have localized esophageal adenocarcinoma and are being considered for standard-of-care chemoradiation prior to surgery. Participants of this study will take a pill called vactosertib for two weeks before starting standard of care chemoradiation. At the end of the two weeks of taking vactosertib, participants will have a Positron Emission Tomography Computer Assisted Tomography (PET CT) scan and undergo an endoscopy with a biopsy to determine if the vactosertib is working. After chemoradiation, participants will take vactosertib again for four weeks and then be considered for surgery.

Start Date01 Jan 2025

Sponsor / Collaborator

The Case Comprehensive Cancer Center

NCT05588648

/ RecruitingPhase 1/2

A Phase I/II, Open-label, Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of Vactosertib as a Single Agent in Adolescents and Adults With Recurrent, Refractory or Progressive Osteosarcoma

MP-VAC-209 is a Phase I/II, open label, single arm, multi-center study to assess safety, tolerability, and antitumor activity of vactosertib as a single agent in adolescents and adults with recurrent, refractory, or progressive osteosarcoma. Vactosertib is given orally, twice a day, to people 14 years of age and older who meet the criteria for study enrollment.

Start Date31 Mar 2023

Sponsor / Collaborator

MedPacto, Inc.

KCT0007745

/ Not yet recruitingPhase 2IIT

A phase II multicenter study to assess the antitumor activity of vactosertib in combination with pembrolizumab in acral and mucosal melanoma patients progressed from prior immune check point inhibitor)

Start Date03 Oct 2022

Sponsor / Collaborator

Yonsei University Severance Hospital

100 Clinical Results associated with Vactosertib

100 Translational Medicine associated with Vactosertib

100 Patents (Medical) associated with Vactosertib

Literatures (Medical) associated with Vactosertib

01 Jan 2025·BIOMEDICAL CHROMATOGRAPHY

Quantification of Vactosertib an Inhibitor of TGFBR1 by LC–MS/MS in Rat Plasma and Its Pharmacokinetic Profiling

Article

Author: Konidala, Sathish Kumar ; Boggavarapu, Rajesh Kumar ; Chimakurthy, Jithendra

ABSTRACT:

Vactosertib, an inhibitor of transforming growth factor β‐receptor type‐1 (TGFBR1) effective in preventing tumor cell proliferation, is approved for treating various cancers by FDA. The literature revealed that no LC–MS/MS method was reported for the quantification of vactosertib. To develop a validated LC–MS/MS method for the quantification of vactosertib in rat plasma, vactosertib and cabozantinib (internal standard [IS]) were detected using Waters LC–MS/MS system in MRM positive ionization mode, with a mixture of 0.2% formic acid and acetonitrile (70:30, v/v) on an Agilent XDB C18 (50 × 2.1 mm, 5 μm) column at a flow rate of 0.8 mL/min. The method was validated in accordance with M10 bioanalytical method validation USFDA guidelines and applied for the determination of pharmacokinetic parameters in rat plasma. The analytes were detected at m/z 400.23 → 289.19 and m/z 502.13 → 323.07 for vactosertib, and IS, respectively. The method demonstrated a sensitivity of 1.0 ng/mL, linearity ranging from 1.0 to 1000.0 ng/mL, an r2 of 0.999, accuracy ranged between 91.60% and 100.70%, and the drug was found to be stable across all freeze–thaw cycles. The results indicated that the method was selective, accurate, and validated for quantification of vactosertib in biological fluids and pharmacokinetic profiling of vactosertib.

01 Dec 2024·JOURNAL OF CONTROLLED RELEASE

Surface-engineered mesenchymal stem cell for refractory asthma therapy: Reversing airway remodeling

Article

Author: Zhao, Yu-Chen ; Han, Meng-Meng ; Jeong, Jee-Heon ; Wang, Guang-Ji ; Wang, Jing ; Tang, Ling ; Jiang, Hu-Lin ; He, Xing-Yue ; Xing, Lei ; Wang, Yi ; Wei, Ning ; Zhou, Fang

In the development of asthma, subepithelial fibrosis and vascular proliferation cause airway remodeling and narrowing, leading to disease deterioration and respiratory failure. In the clinic, the treatment of asthma was aimed at reducing the frequency of acute asthma attacks through inhaled corticosteroids (ICSs). However, ICSs cannot prevent the progression into refractory asthma due to the formation of airway remodeling mainly by subepithelial fibrosis and angiogenesis surrounding the tracheal lumen. Herein, we constructed surface-engineered mesenchymal stem cells (MSCs/PVLA) via the bioconjugation of MSCs and reactive oxygen species-responsive polymeric micelles loaded with vactosertib (VST) and linifanib (LFN) for treating refractory asthma through reversing airway remodeling. MSCs/PVLA migrated to the tracheal lumen due to the inflammation tropism of MSCs, and subsequently released VST and LFN could inhibit the formation of airway remodeling by preventing subepithelial fibrosis and angiogenesis. Meanwhile, MSCs reduced inflammatory cell infiltration and cytokine secretion to regulate the pathological microenvironment. Our results suggested that MSCs/PVLA could serve as a promising candidate to prevent disease exacerbations and treat refractory asthma.

01 Oct 2024·Tissue barriers

The interplay between the epithelial permeability barrier, cell migration and mitochondrial metabolism of growth factors and their inhibitors in a human endometrial carcinoma cell line

Article

Author: Okada, Tadahi ; Yamazaki, Yuya ; Shimada, Hiroshi ; Sugiyama, Tomoki ; Kura, Arisa ; Kohno, Takayuki ; Konno, Takumi ; Ohsaki, Yuki ; Kikuchi, Shin ; Matsuura, Motoki ; Saito, Tsuyoshi ; Saito, Kimihito ; Kojima, Takashi

It is known that there are abnormalities of tight junction functions, cell migration and mitochondrial metabolism in human endometriosis and endometrial carcinoma. In this study, we investigated the effects of growth factors and their inhibitors on the epithelial permeability barrier, cell migration and mitochondrial metabolism in 2D and 2.5D cultures of human endometrioid endometrial carcinoma Sawano cells. We also investigated the changes of bicellular and tricellular tight junction molecules and ciliogenesis induced by these inhibitors. The growth factors TGF-β and EGF affected the epithelial permeability barrier, cell migration and expression of bicellular and tricellular tight junction molecules in 2D and 2.5D cultures of Sawano cells. EW-7197 (a TGF-β receptor inhibitor), AG1478 (an EGFR inhibitor) and SP600125 (a JNK inhibitor) affected the epithelial permeability barrier, cell migration and mitochondrial metabolism and prevented the changes induced by TGF-β and EGF in 2D and 2.5D cultures. EW-7197 and AG1478 induced ciliogenesis in 2.5D cultures. In conclusion, TGF-β and EGF promoted the malignancy of endometrial cancer via interplay among the epithelial permeability barrier, cell migration and mitochondrial metabolism. EW-7197 and AG1478 may be useful as novel therapeutic treatments options for endometrial cancer.

News (Medical) associated with Vactosertib

28 Nov 2023

·www.prnewswire.com

Navigating the Evolving Market Dynamics of Bone Sarcoma: A Comprehensive Analysis of Osteosarcoma, Ewing Sarcoma, and Chondrosarcoma | DelveInsight

Each individual's risk of being diagnosed with primary bone sarcoma and their chances of recovery following diagnosis are influenced by a range of unique factors. In 2023, it is anticipated that 4K individuals of all ages in the United States will be diagnosed with primary bone sarcoma, including 2K males and 1.8K females. In 2020, approximately 400 cases were reported among those aged 15 to 19. LAS VEGAS, Nov. 28, 2023 /PRNewswire/ -- Bone sarcoma is a rare and aggressive form of cancer that originates in the bone tissue. It poses significant challenges during its treatment due to several factors. Firstly, its rarity often leads to delayed diagnosis, as symptoms can mimic other common conditions. Additionally, bone sarcoma typically affects children and young adults, making the emotional toll of the disease particularly challenging. Treatment often involves a combination of surgery, chemotherapy, and radiation therapy, which can be physically demanding and cause severe side effects. Moreover, because bone sarcoma tends to occur in the extremities, treatment may require complex and lengthy surgical procedures, potentially affecting mobility and quality of life. Furthermore, the risk of recurrence remains a constant concern, necessitating long-term monitoring and follow-up care. Despite these challenges, ongoing research and advancements in medical technology offer hope for improved outcomes and a better quality of life for those battling bone sarcoma. DelveInsight has recently released a series of epidemiology-based market reports focusing on benign bone sarcoma including Osteosarcoma Market Report, Ewing Sarcoma Market Report, and Chondrosarcoma Market Report. These reports include a comprehensive understanding of current treatment practices, historical and forecasted patient pool, emerging drugs, market share of individual therapies, and historical and forecasted market size from 2019 to 2032 segmented into 7MM [the United States, the EU-4 (Italy, Spain, France, and Germany), the United Kingdom, and Japan]. Additionally, the reports feature exhaustive analysis of prominent companies working with their emerging candidates in different stages of clinical development. Let's deep dive into the assessment of these bone sarcoma markets individually. Osteosarcoma Market Osteosarcoma is a rare bone tumor affecting having an annual incidence of 3.4 cases per million. It is the most prevalent form of bone cancer, primarily developed in the osteoblast cells of bones, with a predilection for long bones near the knee joint. However, it can also manifest in other locations, including the upper leg, lower leg, upper arm, and virtually any bone in the body, including those in the pelvis, shoulder, and skull. It has the potential to invade adjacent tissues, such as tendons and muscles, and can metastasize to distant organs or other bones via the bloodstream. As per DelveInsight analysts, the total incident population of osteosarcoma in the 7MM was ~2K in 2022. The estimates show the highest incident cases of osteosarcoma in the United States with ~1K cases in 2022, and it is expected to increase by 2032. Osteosarcoma is commonly treated through a combination of chemotherapy, surgery, and radiation therapy. Despite some recent developments, limited progress has been achieved since the late 1980s when chemotherapy was added to surgical treatment, leading to improved survival rates. Radiation therapy impacts both normal and cancerous cells, causing various effects. Chemotherapeutic drugs like cisplatin, doxorubicin, ifosfamide, and high-dose methotrexate with leucovorin calcium rescue (HDMTX) are widely used. Additionally, a few FDA-approved products, such as FUSILEV and KHAPZORY, are available for osteosarcoma treatment. As per DelveInsight analysis, the osteosarcoma market size is expected to increase at a significant CAGR by 2032. This growth would be fuelled by the increase in the patient pool and the expected entry of emerging therapies. Osteosarcoma Pipeline Therapies and Companies Lenvatinib: Eisai Naxitamab: Y-mAbs Therapeutics BAY80-6946: Bayer Vactosertib: MedPacto For a comprehensive view of the osteosarcoma market, check out the Osteosarcoma Market Assessment Ewing Sarcoma Market Ewing Sarcoma, a malignant tumor, typically initiates its growth within the bones, with a higher incidence among children and young adults, often manifesting during adolescence. Although it can originate in any bone, it predominantly affects the long bones, such as the thigh bone, shin bone, and upper arm bone. The pelvis bones are also frequently involved. In some cases, the tumor may originate in muscle and soft tissues. Common symptoms include bone stiffness, pain, swelling, or tenderness, along with tissue surrounding the affected bone. As per the assessment done by DelveInsight, the total incident cases of Ewing sarcoma in the 7MM comprised approximately 1.2K cases in 2022 and are projected to increase during the forecasted period. The management of Ewing sarcoma typically adopts a comprehensive approach, which may encompass surgery, chemotherapy, and radiation therapy. The National Comprehensive Cancer Network (NCCN) offers specific chemotherapy regimens for localized and metastatic Ewing sarcoma. For first-line treatment, NCCN suggests VDC/IE (vincristine, doxorubicin, and cyclophosphamide alternating with ifosfamide and etoposide), VAIA (vincristine, doxorubicin, ifosfamide, and dactinomycin), and VIDE (vincristine, ifosfamide, doxorubicin, and etoposide) for both initial presentations and as primary therapy for metastatic disease. In the second-line setting, NCCN recommends options like Cyclophosphamide and topotecan, Irinotecan + temozolomide ± Vincristine, Ifosfamide, carboplatin, etoposide, and Lurbinectedin. As per the latest Ewing Sarcoma Market Report, the total Ewing sarcoma market size in the 7MM is approximately USD 26 million in 2022 and is projected to increase during the forecast period (2023–2032). The expected introduction of upcoming therapies and the deepened integration of early patient screening, medication management in secondary care, and diverse clinical setups, ongoing research into optimal implementation approaches, and a surge in public awareness will ultimately pave the way for the advancement of efficient treatment choices. Ewing Sarcoma Pipeline Therapies and Companies SECLIDEMSTAT (SP-2577): Salarius Pharmaceuticals ZEPZELCA (LURBINECTEDIN): Jazz Pharmaceuticals and PharmaMar VERZENIO (ABEMACICLIB): Eli Lilly IBRANCE (PALBOCICLIB): Pfizer MECBOTAMAB VEDOTIN (BA3011): Bioatla IOPOFOSINE I 131 (CLR 131): Cellectar Biosciences TP-1287: Sumitomo Pharma Oncology NBRX-109: Inhibrx Explore in-depth for a comprehensive understanding of the Ewing Sarcoma Clinical Trials Chondrosarcoma Market Chondrosarcoma comprises a group of bone tumors originating from cells that overproduce cartilage. Among these tumors, conventional chondrosarcoma is the most frequent type and is generally associated with slow growth. Conversely, rarer subtypes like dedifferentiated chondrosarcoma, myxoid chondrosarcoma, clear cell chondrosarcoma, and mesenchymal chondrosarcoma tend to exhibit a more aggressive growth pattern and have the potential to spread to distant body parts. DelveInsight estimated that the total incident cases of chondrosarcoma in the 7MM comprised approximately 2K cases in 2022 and are projected to increase during the forecasted period. The management approach for chondrosarcoma is contingent upon factors like tumor type, grade, and location, with the grading system serving as the most reliable indicator of clinical prognosis. It is firmly established that surgical intervention remains the gold standard and sole effective treatment for chondrosarcoma, as alternative modalities such as radiotherapy and chemotherapy exhibit limited responsiveness and resistance. Surgical options encompass curettage, radical resection, and amputation, each necessitating comprehensive clinical judgment and contingent upon variables such as lesion size, location, and malignant characteristics. Anticipated advancements in upcoming therapies and increased integration of early patient screening and medication within secondary care and other clinical settings, along with ongoing research to determine the best implementation methods, are expected to contribute to the development of more effective treatment options. However, chondrosarcoma, being an orphan disease, presents challenges in conducting clinical trials. Limited outcome data for locally advanced or metastatic patients underscore the need for new treatment approaches. Phase I trials, due to their small number of chondrosarcoma patients at varying dose levels, make it difficult to draw definitive conclusions. Nevertheless, some Phase II trials have yielded promising results, warranting further investigation. Encouraging retrospective studies could help augment the currently limited data. Urgent efforts to boost research studies on this orphan disease are imperative. As per DelveInsight analysis, the total market size of chondrosarcoma in the 7MM is approximately USD 9 million in 2022 and is projected to increase at a massive CAGR of 24.8% due to increasing awareness of the disease and the launch of the emerging therapy. Chondrosarcoma Pipeline Therapies and Companies INBRX-109: Inhibrx To access a complete analysis of the chondrosarcoma market, visit Chondrosarcoma Market Assessment Trending Oncology Reports Non-Small Cell Lung Cancer Market Non-Small Cell Lung Cancer Market Insights, Epidemiology, and Market Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key NSCLC companies, including EMD Serono, Merck, Cellular Biomedicine Group, Inc., Celgene, CellSight Technologies, Inc., BeyondSpring Pharmaceuticals Inc., J Ints Bio, Forward Pharmaceuticals Co., Ltd., AstraZeneca, Bristol-Myers Squibb, Teligene US, Rain Oncology Inc, ReHeva Biosciences, Inc., Amgen, Novartis, RedCloud Bio, Parexel, Vitrac Therapeutics, LLC, Mythic Therapeutics, Instil Bio, Mirati Therapeutics Inc., Daiichi Sankyo, Inc., AstraZeneca, Precision Biologics, Inc, Promontory Therapeutics Inc., Palobiofarma SL, Regeneron Pharmaceuticals, Revolution Medicines, Inc., Cullinan Oncology, LLC, Iovance Biotherapeutics, Inc., Innate Pharma, among others. Non-Hodgkin Lymphoma Market Non-Hodgkin Lymphoma Market Insights, Epidemiology, and Market Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key NHL companies, including GAbbVie, Genmab, Novartis, Angiocrine Bioscience, Autolus, Zentera Therapeutics, Jiangsu Hengrui Medicine, among others. Oncolytic Virus Cancer Therapies Market Oncolytic Virus Cancer Therapies Market Insights, Epidemiology, and Market Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key oncolytic virus cancer therapies companies, including Targovax, Replimune, Genelux Corporation, Candel Therapeutics, DNAtrix, SillaJen, Treovir, Lokon Pharma AB, Istari Oncology, CG Oncology, Amgen, Daiichi Sankyo, among others. Multiple Myeloma Market Multiple Myeloma Market Insights, Epidemiology, and Market Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key multiple myeloma companies, including Johnson & Johnson (Janssen), Pfizer, AbbVie and Roche (Genentech), Regeneron Pharmaceuticals, Bristol-Myers Squibb, Celgene, Roche (Genentech), Arcellx, Novartis, Regeneron Pharmaceuticals, BeiGene, CARsgen Therapeutics, Cartesian Therapeutics, C4 Therapeutics, Heidelberg Pharma, Bristol-Myers Squibb, RAPA Therapeutics, AbbVie (TeneoOne), Takeda, among others. Oncology Conference Coverage Services DelveInsight's Oncology Conference Coverage Services deliver a comprehensive examination of conference outcomes from a range of prominent events, such as ASCO, ESMO, ASH, AACR, ASTRO, SOHO, SITC, European CAR T-cell Meeting, and IASLC 2023. This in-depth analysis equips businesses with the insights they need for effective competitive intelligence and forecasting market trends, aiding in the development of future strategies. About DelveInsight DelveInsight is a leading healthcare-focused market research and consulting firm that provides clients with high-quality market intelligence and analysis to support informed business decisions. With a team of experienced industry experts and a deep understanding of the life sciences and healthcare sectors, we offer customized research solutions and insights to clients across the globe. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . Contact Us Shruti Thakur [email protected] +1(919)321-6187 Logo: SOURCE DelveInsight Business Research, LLP

Phase 2Clinical ResultRadiation TherapyASCO

31 Oct 2023

·www.prnewswire.com

CHIMERIC THERAPEUTICS ANNOUNCES FDA CLEARANCE OF IND APPLICATION FOR CHM 2101, A NOVEL CDH17 CAR T CELL THERAPY FOR ADVANCED GASTROINTESTINAL CANCERS

FDA IND Clearance for CHM 2101, a novel 3rd generation CDH17 CAR T cell therapy Anticipated to be the first CDH17 CAR T cell therapy to enter the clinic Phase 1A clinical trial to initiate patient enrolment in 2024 Phase 1A clinical trial will enroll patients with advanced Colorectal Cancer, Gastric Cancer and Neuroendocrine Tumours SYDNEY, Oct. 31, 2023 /PRNewswire/ -- Chimeric Therapeutics (ASX:CHM, "Chimeric" or the "Company"), an Australian leader in cell therapy, announced today that the U.S. Food and Drug Administration (FDA) has cleared the Investigational New Drug (IND) application of CHM 2101, Chimeric's first in class CDH17 CAR T cell therapy for gastrointestinal cancers. The company plans to investigate CHM 2101 in a multi center, open label Phase 1A/B clinical trial for patients with advanced Colorectal Cancer, Gastric Cancer and Neuroendocrine Tumours. CHM 2101 is a 3rd generation, novel CDH17 CAR T cell therapy that targets CDH17, a cancer target associated with poor prognosis and metastasis in the most common gastrointestinal tumors including Colorectal Cancer, Gastric Cancer and Neuroendocrine Tumours. The clinical program for CHM 2101 builds upon the preclinical studies published in the preeminent scientific journal, Nature Cancer in March 2022 by leading immunotherapy scientist Xianxin Hua, MD, PhD, and his team at the Abramson Family Cancer Research Institute at the University of Pennsylvania. These experiments demonstrated that CHM 2101 was able to eradicate established tumours in seven cancer models with no toxicity to normal tissues. "It is exciting to see the advancement from discovery of the CDH17 target and CAR T therapy in preclinical studies to the initiation of clinical trials in patients with GI-cancers and neuroendocrine tumors," said Xianxin Hua, MD, PhD, Professor of Cancer Biology in Penn's Perelman School of Medicine, an investigator at the Abramson Family Cancer Research Institute and a Harrington Scholar Innovator. "This is a critical step forward in developing an entirely new CAR T therapy for GI-cancers and neuroendocrine tumors, providing new hopes for the cancer patients who are refractory to the existing therapies." With the FDA IND clearance Chimeric will now begin the initiation of a phase 1 /2 multi-site clinical trial in patients with advanced Colorectal Cancer, Gastric Cancer and Neuroendocrine Tumours. The study is planned to begin patient enrollment in 2024. (ClinicalTrials.gov ID: NCT06055439) "I am really excited about the planned Phase 1 clinical trial of CHM 2101 and the opportunity to bring a potentially transformative new investigational agent to cancer patients who need them most," said Michael R. Bishop, MD, Professor of Medicine and Director, The David and Etta Jonas Center for Cellular Therapy, University of Chicago. ABOUT CHIMERIC THERAPEUTICS Chimeric Therapeutics, a clinical stage cell therapy company and an Australian leader in cell therapy, is focused on bringing the promise of cell therapy to life for more patients with cancer. We believe that cellular therapies have the promise to cure cancer, not just delay disease progression. To bring that promise to life for more patients, Chimeric's world class team of cell therapy pioneers and experts is focused on the discovery, development, and commercialization of the most innovative and promising cell therapies. Chimeric currently has a diversified portfolio that includes first in class autologous CAR T cell therapies and best in class allogeneic NK cell therapies. Chimeric assets are being developed across multiple different disease areas in oncology with 3 current clinical programs and plans to open additional clinical programs in 2023. CHM 1101 (CLTX CAR T) is a novel and promising CAR T therapy developed for the treatment of patients with solid tumours. CHM 1101 is currently being studied in a phase 1B clinical trial in recurrent / progressive glioblastoma. Initial positive data from the investigator-initiated phase 1A trial has been presented on patients treated in the first two dose levels of the trial. CHM 2101 (CDH17 CAR T) is a first-in-class, 3rd generation CDH17 CAR T invented at the world-renowned cell therapy centre, the University of Pennsylvania. Preclinical evidence for CHM 2101 was published in March 2022 in Nature Cancer demonstrating complete eradication of tumors in 7 types of cancer. CHM 2101 (CDH17 CAR T) is currently in preclinical development with a planned phase 1A clinical trial in gastrointestinal and neuroendocrine tumours. CHM 0201 (CORE-NK platform) is a potentially best-in-class, clinically validated NK cell platform. Data from the complete phase 1A clinical trial was published in March 2022, demonstrating safety and efficacy in blood cancers and solid tumours. Based on the promising activity signal demonstrated in that trial, an additional Phase1B clinical trial investigating CHM 0201 in combination with IL2 and Vactosertib is now underway. From the CHM 0201 platform, Chimeric has initiated development of new next generation NK and CAR NK assets. Authorised on behalf of the Chimeric Therapeutics board of directors by Chairman Paul Hopper. CONTACT Investors Jennifer Chow Chief Executive Officer and Managing Director Chimeric Therapeutics T: + 1 9087238387 E: [email protected] Paul Hopper Executive Chairman Chimeric Therapeutics T: + 61 406 671 515 E: [email protected] W: Media Matthew Wright NWR Communications P: +61 451 896 420 E: [email protected] SOURCE Chimeric Therapeutics

Phase 1Cell TherapyINDImmunotherapy

05 Jun 2023

·www.globenewswire.com

Chimeric Announces Launch of New Phase 1B Glioblastoma Clinical Trial

New CHM 1101 (CLXT CAR T) multi-center clinical trial activated at Sarah Cannon Research Institute (SCRI) in Austin, Texas Enrolment now open to patients with recurrent and/or progressive glioblastoma multiforme (GBM), the most common and most deadly primary brain cancer Chimeric Therapeutics (ASX:CHM, “Chimeric” or the “Company”), the only clinical stage cell therapy company on the ASX, is pleased to announce activation of a Phase 1B clinical trial in patients with recurrent and/ or progressive glioblastoma multiforme (GBM) to assess the safety and efficacy of CHM 1101, the company’s first in class CLTX CAR T cell therapy. (ClinicalTrials.gov Identifier: NCT05627323) The trial is now open for enrollment at the Sarah Cannon Transplant & Cellular Therapy Program at St. David’s South Austin Medical Center in Austin, Texas. “We are very excited to be activating the first site in our CHM 1101 Phase 1B clinical trial as it marks a new chapter in the development of CHM 1101,” said Jennifer Chow, CEO and Managing Director of Chimeric Therapeutics. “This multi-center trial will enable us to more rapidly advance the development of CHM 1101 with recruitment across multiple clinical trial sites and also prepare us to accelerate the next phase of development if supported by the clinical results.” This Phase 1B trial, being conducted under a US IND, is a two-part clinical trial designed to determine a recommended Phase 2 dose and administration schedule. Part A of the trial will enroll 3-6 patients at the highest dose tested in the ongoing clinical trial at City of Hope Cancer Centre. In late 2023, Chimeric will assess the clinical safety and activity from the CHM 1101 clinical program. Based on a favorable review of the results of that assessment, Part B of the trial, a dose expansion cohort, will be opened to enroll 12 to 26 additional patients. Upon successful completion of the Part B dose expansion cohort, the Company intends to design and initiate a registration trial, in collaboration with global regulatory feedback. “We’re very pleased to be building upon the City of Hope investigator-initiated trial and advancing CHM 1101 to a multi-center clinical trial. GBM continues to represent an important unmet medical need and the early clinical results from the City of Hope trial provide support that CHM 1101 may improve outcomes for GBM patients,” said Jason B Litten MD, Chief Medical Officer, Chimeric Therapeutics. CHM 1101 demonstrated safety with ~70% disease stability in the initial two dose cohorts in the City of Hope Phase 1A investigator-initiated clinical trial. Additional details on the CHM Phase 1B trial design and objectives were presented on June 3 at the American Society of Clinical Oncology (ASCO) annual meeting as part of the Central Nervous System Tumors section as abstract TPS2086/Poster 440a, “Phase 1B multicenter study to evaluate CHM 1101 in patients with recurrent or progressive glioblastoma”. About CHM 1101: CHM 1101 (CLTX CAR T) is a first-in-class CAR T therapy that has the potential to address the high unmet medical need of patients with recurrent or progressive glioblastoma. Research to develop the intellectual property covering this CAR T cell therapy took place at City of Hope. CHM 1101 cells uniquely utilize chlorotoxin (CLTX), a peptide component of scorpion venom, as the tumour-targeting component of the chimeric antigen receptor (CAR). CHM 1101 CAR T cells have been shown in preclinical models to bind more broadly and specifically to GBM cells than other targeting domains like EGFR, HER-2 or IL-13. In preclinical models, CHM 1101 cells also demonstrated potent antitumor activity against glioblastoma while not exhibiting any off-tumor recognition of normal human cells and tissues, indicating a potentially optimal safety and efficacy profile. CHM 1101 is currently being studied in a Phase 1B clinical trial in recurrent / progressive glioblastoma. Initial positive data from the investigator-initiated Phase 1A trial has been presented on patients treated in the first two dose levels of the trial. ABOUT CHIMERIC THERAPEUTICS Chimeric Therapeutics, a clinical stage cell therapy company and an Australian leader in cell therapy, is focused on bringing the promise of cell therapy to life for more patients with cancer. We believe that cellular therapies have the promise to cure cancer, not just delay disease progression. To bring that promise to life for more patients, Chimeric’s world-class team of cell therapy pioneers and experts is focused on the discovery, development, and commercialization of the most innovative and promising cell therapies. Chimeric currently has a diversified portfolio that includes first-in-class autologous CAR T cell therapies and best-in-class allogeneic NK cell therapies. Chimeric assets are being developed across multiple different disease areas in oncology with 3 current clinical programs and plans to open additional clinical programs in 2023. CHM 1101 (CLTX CAR T) is a novel and promising CAR T therapy developed for the treatment of patients with solid tumours. CHM 1101 is currently being studied in a Phase 1B clinical trial in recurrent / progressive glioblastoma. Initial positive data from the investigator-initiated Phase 1A trial has been presented on patients treated in the first two dose levels of the trial. CHM 2101 (CDH17 CAR T) is a first-in-class, 3rd generation CDH17 CAR T invented at the world-renowned cell therapy centre, the University of Pennsylvania. Preclinical evidence for CHM 2101 was published in March 2022 in Nature Cancer demonstrating complete eradication of tumors in 7 types of cancer. CHM 2101 (CDH17 CAR T) is currently in preclinical development with a planned Phase 1A clinical trial in gastrointestinal and neuroendocrine tumours. CHM 0201 (CORE-NK platform) is a potentially best-in-class, clinically validated NK cell platform. Data from the complete Phase 1A clinical trial was published in March 2022, demonstrating safety and efficacy in blood cancers and solid tumours. Based on the promising activity signal demonstrated in that trial, an additional Phase 1B clinical trial investigating CHM 0201 in combination with IL2 and Vactosertib is now underway. From the CHM 0201 platform, Chimeric has initiated development of new next generation NK and CAR NK assets. 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Cell TherapyASCOImmunotherapy

100 Deals associated with Vactosertib

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KEGG	Wiki	ATC	Drug Bank
-	-	-	DB15310

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Osteosarcoma	Phase 2	US	MedPacto, Inc.	31 Mar 2023
Osteosarcoma	Phase 2	KR	MedPacto, Inc.	31 Mar 2023
Multiple Myeloma	Phase 2	US	MedPacto, Inc.	30 Jan 2022
Non-Small Cell Lung Cancer	Phase 2	KR	Merck & Co., Inc.	30 Jan 2022
Non-Small Cell Lung Cancer	Phase 2	KR	AstraZeneca PLC	30 Jan 2022
Aggressive Fibromatosis	Phase 2	KR	MedPacto, Inc.	01 Jun 2021
PD-L1 positive Non-Small Cell Lung Cancer	Phase 2	KR	MedPacto, Inc.	17 Dec 2020
Metastatic Pancreatic Cancer	Phase 2	KR	Samsung Medical Center	17 Jun 2019
Metastatic Pancreatic Ductal Adenocarcinoma	Phase 2	KR	Samsung Medical Center	17 Jun 2019
Pancreatic Cancer	Phase 2	KR	Samsung Bioepis Co., Ltd.	19 Apr 2019

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


605 (SITC2024)	Phase 1/2	PD-L1 positive Non-Small Cell Lung Cancer Second line PD-L1-positive	60	Vactosertib 200 mg	qwazlwfsqi(gkfcfowuel) = 6.7% pmshqkwuhi (knxjejtrss ) View more	Positive	05 Nov 2024
605 (SITC2024)	Phase 1/2		60	Durvalumab 1500 mg		Positive	05 Nov 2024
ASH2023	Phase 1	Relapse multiple myeloma	-	Vactosertib	syxojswncb(pptcvlfktk) = kxzmmyklsw wsmcupyemg (uxuqcgares )	-	11 Dec 2023
NCT03724851 (ESMO2023) Manual	Phase 1/2	Metastatic Microsatellite Stable Colorectal Carcinoma Microsatellite Stable (MSS)	105	Vactosertib+pembrolizumab	twzmbsubcv(mzpfqlsyln) = jvpcylcith eylnougzfj (rlmhkhmgzg, 7.5 - 21.4) View more	Positive	22 Oct 2023
SOHO2023	Not Applicable	Multiple Myeloma	-	Vactosertib	mgmwvejqrk(zrugylrmbx) = Vactosertib + POM was well tolerated at all doses and had a manageable adverse event profile wvagcvtqyd (enmacheckp )	-	01 Sep 2023
NCT03666832 (ASCO2022) Manual	Phase 1	Metastatic Pancreatic Cancer Second line	16	FOLFOX+vactosertib	rkflfmnwdt(hkcaixapgg) = wrjldtdvic psuqpefphm (ikgvgurepb ) View more	Positive	02 Jun 2022
NCT03724851 (MP-VAC-204, SITC2021)	Phase 1/2	Metastatic Colorectal Carcinoma TIL \| TGF-Î² \| PD-L1-positive ... View more	-	Vactosertib in combination with pembrolizumab	ewtzvuiwzo(vlhyqcmzcz) = swmdupatmm ppmxhcbtjx (zeshyizjfk ) View more	Positive	10 Nov 2021
NCT03143985 (ASCO 12021 \| ASCO 22021) Manual	Phase 1	Relapse multiple myeloma Third line	15	pomalidomide+vactosertib	jxfzjexhkr(zfadhqopgg) = grade II fatigue and pain in one pt, one episode of grade III renal failure that ~ ok less than 7 days ~ get back ~ baseline on another patient, sinus bradycardia that reversed ~ sinus rythem and an Afib that was rate controlled with beta blocerk hpbbxlegwp (wdkyydytqd )	Positive	28 May 2021
NCT03724851 (ASCO 12021 \| ASCO 22021) Manual	Phase 1/2	Metastatic Microsatellite Stable Colorectal Carcinoma Microsatellite Stable (MSS)	33	vactosertib+pembrolizumab	ditbnavram(fpixxlrmhk) = wulupjzwxo kcwebmhoyg (iwqnqsstmg ) View more	Positive	28 May 2021
NCT03732274 (phase 1b/2a study, SITC2020)	Phase 1/2	PD-L1 positive Non-Small Cell Lung Cancer PD-L1 positive	26	Vactosertib 200 mg	pqzfnliiwp(khalcuafmy) = Grade 4 TRAE qkaurnlgvl (axpuullyxw ) View more	Positive	09 Nov 2020
NCT03732274 (phase 1b/2a study, SITC2020)	Phase 1/2	PD-L1 positive Non-Small Cell Lung Cancer PD-L1 positive	26	Durvalumab 1500 mg		Positive	09 Nov 2020
NCT03698825 (ESMO2020) Manual	Phase 1	Metastatic gastric adenocarcinoma Second line	12	paclitaxel+vactosertib	ctjftfskmi(aqmahcxxid) = vactosertib 300mg BID and weekly paclitaxel nqiilkanlg (ymxnnxhasj ) View more	Positive	17 Sep 2020
NCT03698825 (ESMO2020) Manual	Phase 1	Metastatic gastric adenocarcinoma Second line	12	paclitaxel+vactosertib		Positive	17 Sep 2020

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