Last update 29 Jun 2024

Temozolomide

Last update 29 Jun 2024

Overview

R&D Status

Clinical Result

Translational Medicine

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

3,4-dihydro-3-methyl-4-oxoimidazo(5,1-d)-1,2,3,5-tetrazine-8-carboxamide, 3,4-dihydro-3-methyl-4-oxoimidazo(5,1-d)-as-tetrazine-8-carboxamide, 3-methyl-4-oxo-3,4-dihydroimidazo(5,1-d)(1,2,3,5)tetrazine-8-carboxamide

+ [24]

Target

DNA

Mechanism

DNA inhibitors(DNA inhibitors), DNA alkylating agents

Therapeutic Areas

NeoplasmsNervous System DiseasesSkin and Musculoskeletal Diseases+ [6]

Active Indication

Ewing SarcomaMalignant glioma of brainGlioblastoma+ [26]

Inactive Indication

Acute myeloid leukaemia with 11q23 abnormalityAcute Myeloid LeukemiaAdrenal Gland Pheochromocytoma+ [106]

Originator Organization

Merck Sharp & Dohme Corp.

Active Organization

United Therapeutics Corp.

Jiangsu Tasly Diyi Pharmaceutical Co., Ltd.

National Cancer Institute

+ [20]

Inactive Organization

Bayer AG

The American College of Radiology

Radiation Therapy Oncology Group

+ [41]

Drug Highest PhaseApproved

First Approval Date

EU (26 Jan 1999),

AstrocytomaGlioblastoma MultiformeGlioma

RegulationAccelerated Approval (US), Orphan Drug (US), Orphan Drug (EU), Priority Review (CN)

Structure

Molecular FormulaC6H6N6O2

InChIKeyBPEGJWRSRHCHSN-UHFFFAOYSA-N

CAS Registry85622-93-1

998

Clinical Trials associated with Temozolomide

NCT04199026 / Not yet recruitingEarly Phase 1IIT

Pilot Trial of an Implantable Microdevice for In Vivo Drug Sensitivity Testing in Patients With Sarcomas

This early phase I trial studies the side effects of implanting and removing a microdevice in patients with sarcomas that have spread to other places in the body (metastatic) or have come back (recurrent). Microdevices are rice-sized devices that are implanted into tumor tissue and are loaded with 10 different drugs that are delivered at very small doses, or "microdoses," which may only affect a very small, local area inside the tumor. The purpose of this study is to determine which drugs delivered in the microdevice affect tumor tissue in patients with sarcomas.

Start Date31 Jan 2025

Sponsor / Collaborator

The University of Texas MD Anderson Cancer Center

[+1]

NCT06218524 / Not yet recruitingPhase 2IIT

Clinical Study for Evaluating the Effectiveness of Haloperidol and Temozolomide Synergism on Adult Recurrence Glioblastoma

The study of investigators indicated that TMZ can up-regulate dopamine D2 receptor (DRD2) expression, and mediates Ferroptosis inhibition and chemoresistance of GBM. The clinical data also proved that the DRD2 expression in recurrent GBM is significantly higher than that in primary GBM. Moreover, the DRD2 antagonist haloperidol can attenuate the above function of DRD2, and increase the sensitivity of GBM to the TMZ by inducing fatal autophagy and ferroptosis. In xenograft mice, the combined usage of haloperidol and Temozolomide (TMZ) can significantly inhibit tumor growth and increase overall survival. The investigators' findings have been published in Clinical cancer research. Haloperidol known as a butylbenzene antipsychotic drug, has been widely used in several kinds of mental illnesses, such as depression, schizophrenia, and Bipolar disorder. And the safe dosage of the haloperidol is clear so far. So in this study, the investigators will recruit the patients who suffered from recurrent GBM, and evaluate the effectiveness of single TMZ chemotherapy or combined with haloperidol.

Start Date01 Dec 2024

Sponsor / Collaborator

Southern Medical University

NCT06428045 / Not yet recruitingPhase 1IIT

Synergistic Treatment With Antiretrovirals and Laser Interstitial Thermal thErapy (STARLITE) for Unresectable High-Grade Gliomas: A Phase 1 Study

The purpose of this study is to determine whether newly diagnosed high-grade glioma(s) that cannot be removed surgically change as a result of the study treatment; and to identify and evaluate the potential side effects (good and bad) of the study treatment in patients with newly diagnosed high-grade glioma(s) that cannot be removed surgically.

Start Date31 Aug 2024

Sponsor / Collaborator

University of Miami

[+1]

100 Clinical Results associated with Temozolomide

100 Translational Medicine associated with Temozolomide

100 Patents (Medical) associated with Temozolomide

10,372

Literatures (Medical) associated with Temozolomide

05 Jul 2106·Oncotarget

NOTCH blockade combined with radiation therapy and temozolomide prolongs survival of orthotopic glioblastoma

Article

Author: Theys, Jan ; Vooijs, Marc ; Groot, Arjan J. ; Granton, Patrick V. ; Prickaerts, Jos ; Chalmers, Anthony J. ; Barbeau, Lydie M.O. ; Iglesias, Venus Sosa ; Habets, Roger ; King, Henry ; van Hoof, Stefan J. ; Short, Susan C. ; Verhaegen, Frank ; Eekers, Daniëlle B.P. ; Yahyanejad, Sanaz

Glioblastoma multiforme (GBM) is the most common malignant brain tumor in adults. The current standard of care includes surgery followed by radiotherapy (RT) and chemotherapy with temozolomide (TMZ). Treatment often fails due to the radiation resistance and intrinsic or acquired TMZ resistance of a small percentage of cells with stem cell-like behavior (CSC). The NOTCH signaling pathway is expressed and active in human glioblastoma and NOTCH inhibitors attenuate tumor growth in vivo in xenograft models. Here we show using an image guided micro-CT and precision radiotherapy platform that a combination of the clinically approved NOTCH/γ-secretase inhibitor (GSI) RO4929097 with standard of care (TMZ + RT) reduces tumor growth and prolongs survival compared to dual combinations. We show that GSI in combination with RT and TMZ attenuates proliferation, decreases 3D spheroid growth and results into a marked reduction in clonogenic survival in primary and established glioma cell lines. We found that the glioma stem cell marker CD133, SOX2 and Nestin were reduced following combination treatments and NOTCH inhibitors albeit in a different manner. These findings indicate that NOTCH inhibition combined with standard of care treatment has an anti-glioma stem cell effect which provides an improved survival benefit for GBM and encourages further translational and clinical studies.

01 Dec 2024·Molecular biology reports

Tumor-derived extracellular vesicles: how they mediate glioma immunosuppression

Review

Author: Feng, Xinli ; Zhang, Zhenchang ; Su, Gang ; Wu, Qionghui ; Ma, Tianfei ; Shen, Minghui

Gliomas, the most common malignant brain tumor, present a grim prognosis despite available treatments such as surgical resection, temozolomide (TMZ) therapy, and radiation therapy. This is due to their aggressive growth, high level of immunosuppression, and the blood-brain barrier (BBB), which obstruct the effective exchange of therapeutic drugs. Gliomas can significantly affect differentiation and function of immune cells by releasing extracellular vesicles (EVs), resulting in a systemic immunosuppressive state and a highly immunosuppressive microenvironment. In the tumor immune microenvironment (TIME), the primary immune cells are regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), and tumor-associated macrophages (TAMs). In particular, glioma-associated TAMs are chiefly composed of monocyte-derived macrophages and brain-resident microglia. These cells partially exhibit characteristics of a pro-tumorigenic, anti-inflammatory M2-type. Glioma-derived EVs can hijack TAMs to differentiate into tumor-supporting phenotypes or directly affect the maturation of peripheral blood monocytes (PBMCs) and promote the activation of MDSCs. In addition, EVs impair the ability of dendritic cells (DCs) to process antigens, subsequently hindering the activation of lymphocytes. EVs also impact the proliferation, differentiation, and activation of lymphocytes. This is primarily evident in the overall reduction of CD4 + helper T cells and CD8 + T cells, coupled with a relative increase in Tregs, which possess immunosuppressive characteristics. This study investigates thoroughly how tumor-derived EVs impair the function of immune cells and enhance immunosuppression in gliomas, shedding light on their potential implications for immunotherapy strategies in glioma treatment.

01 May 2024·Genes & diseases

Transcriptomic analysis identifies the neuropeptide cortistatin (CORT) as an inhibitor of temozolomide (TMZ) resistance by suppressing the NF-κB-MGMT signaling axis in human glioma

Article

Author: Tian, Jie ; Chen, Longyi ; Wang, Qi ; Tang, Jian ; Jia, Ping ; Peng, Bo ; Liu, Ping ; He, Zongze ; Feng, Jie ; Liao, Yiwei

Glioma is a common tumor originating in the brain that has a high mortality rate. Temozolomide (TMZ) is the first-line treatment for high-grade gliomas. However, a large proportion of gliomas are resistant to TMZ, posing a great challenge to their treatment. In the study, the specific functions and mechanism(s) by which cortistatin (CORT) regulates TMZ resistance and glioma progression were evaluated. The decreased expression of CORT was detected in glioma tissues, and highly expressed CORT was associated with a better survival rate in patients with glioma. CORT overexpression notably decreased the capacity of glioma cells to proliferate and migrate in vitro and to form tumors in vivo. CORT overexpression also markedly suppressed the viability and enhanced the apoptosis of TMZ-resistant U251 cells by regulating MGMT, p21, and Puma expression. Importantly, CORT overexpression reduced the resistance of gliomas to TMZ in vivo. CORT expression was negatively correlated with MGMT expression in both glioma tissues and cells, and it was found that CORT inhibited NF-κB pathway activation in glioma cells, thereby inhibiting MGMT expression. In conclusion, CORT regulates glioma cell growth, migration, apoptosis, and TMZ resistance by weakening the activity of NF-κB/p65 and thereby regulating MGMT expression. The CORT/NF-κB/MGMT axis might be regarded as a molecular mechanism contributing to the resistance of glioma to TMZ. Our data also suggest that CORT regulates the viability and metastatic potential of glioma cells, independent of its effects on TMZ resistance, providing evidence of novel therapeutic targets for glioma that should be evaluated in further studies.

235

News (Medical) associated with Temozolomide

18 Jun 2024

·www.biospace.com

Erasca Initiates SEACRAFT-2 Pivotal Phase 3 Trial Evaluating Naporafenib Plus Trametinib in Patients with NRAS-Mutant Melanoma

Naporafenib is a potential first-in-class and best-in-class pan-RAF inhibitor for multiple RAS/MAPK pathway-driven tumors and has been dosed in over 500 patients to date Favorable mOS and mPFS demonstrated in pooled analysis of Phase 1b and Phase 2 trials in NRASm melanoma Randomized Stage 1 readout for naporafenib plus trametinib vs. trametinib monotherapy expected in 2025 SAN DIEGO, June 18, 2024 (GLOBE NEWSWIRE) -- Erasca, Inc. (Nasdaq: ERAS), a clinical-stage precision oncology company singularly focused on discovering, developing, and commercializing therapies for patients with RAS/MAPK pathway-driven cancers, today announced the initiation of the global SEACRAFT-2 Phase 3 trial evaluating the pan-RAF inhibitor naporafenib in combination with the MEK inhibitor trametinib (MEKINIST®) in patients with NRAS-mutant (NRASm) melanoma. Naporafenib is a potential first-in-class and best-in-class pan-RAF inhibitor that has been dosed in over 500 patients to date and is being developed to treat multiple types of RAS/MAPK pathway-driven tumors. “NRASm melanoma is an aggressive disease with no approved targeted therapies, underscoring the high unmet need for these patients. We are pleased to announce the initiation of our SEACRAFT-2 pivotal Phase 3 trial, which has a two-stage design. Importantly, Stage 1 is expected to provide a randomized data readout of naporafenib plus trametinib against single agent trametinib in 2025 and will inform the randomized Phase 2 dose (RP2D) for the combination,” said Shannon R. Morris, M.D., Ph.D., Erasca’s chief medical officer. “Stage 2, which incorporates feedback from the United States Food and Drug Administration (FDA) and European health authorities, is designed for regulatory approval and will compare the combination against physician’s choice of chemotherapy or a single agent MEK inhibitor using dual primary endpoints of progression free survival (PFS) and overall survival (OS).” A pooled analysis of the Phase 1b and Phase 2 trials of patients with NRASm melanoma dosed with naporafenib in combination with trametinib showed a median OS (mOS) of 13.0 and 14.1 months and a median PFS (mPFS) of 5.1 and 4.9 months at two doses of the combination, respectively. The pooled dataset at each dose compares favorably relative to historical benchmarks. About SEACRAFT-2 SEACRAFT-2 is a randomized, pivotal Phase 3 trial evaluating the clinical efficacy of naporafenib in combination with trametinib (MEKINIST®) compared to physician’s choice of therapy (dacarbazine, temozolomide, or trametinib monotherapy) in the post-immunotherapy setting in patients with NRAS-mutant metastatic melanoma. A randomized Stage 1 readout for naporafenib plus trametinib compared to trametinib alone is expected in 2025. About Naporafenib Naporafenib (formerly LXH254) is a potent and selective pan-RAF inhibitor, with a potential first-in-class and best-in-class profile. Naporafenib has been dosed in over 500 patients to date, whereby safety, tolerability, pharmacokinetics, and pharmacodynamics have been established in both monotherapy and select combinations. Clinical proof-of-concept (PoC) has been established for the combination with trametinib for patients with NRAS-mutant (NRASm) melanoma, which includes NRAS Q61X melanoma, and preliminary clinical PoC has been established for the combination with trametinib for patients with RAS Q61X in non-small cell lung cancer (NSCLC). Erasca plans to focus initially on advancing and securing regulatory approval for naporafenib plus trametinib in NRASm melanoma as part of the SEACRAFT-2 pivotal Phase 3 trial and in RAS Q61X solid tumors as part of the ongoing SEACRAFT-1 Phase 1b trial, respectively. Erasca is also exploring additional combinations of naporafenib with other proprietary therapeutic agents in our pipeline. Naporafenib has received Fast Track Designation from the United States Food and Drug Administration (FDA) for patients with advanced NRASm melanoma. About Erasca At Erasca, our name is our mission: To erase cancer. We are a clinical-stage precision oncology company singularly focused on discovering, developing, and commercializing therapies for patients with RAS/MAPK pathway-driven cancers. Our company was co-founded by leading pioneers in precision oncology and RAS targeting to create novel therapies and combination regimens designed to comprehensively shut down the RAS/MAPK pathway for the treatment of cancer. We have assembled one of the deepest RAS/MAPK pathway-focused pipeline in the industry. We believe our team’s capabilities and experience, further guided by our scientific advisory board which includes the world’s leading experts in the RAS/MAPK pathway, uniquely position us to achieve our bold mission of erasing cancer. Cautionary Note Regarding Forward-Looking Statements Erasca cautions you that statements contained in this press release regarding matters that are not historical facts are forward-looking statements. The forward-looking statements are based on our current beliefs and expectations and include, but are not limited to: our expectations regarding the potential therapeutic benefits of our product candidates, including naporafenib; the planned advancement of our development pipeline, including the anticipated timing of the Stage 1 data readout for the SEACRAFT-2 trial, and other upcoming development milestones. Actual results may differ from those set forth in this press release due to the risks and uncertainties inherent in our business, including, without limitation: our approach to the discovery and development of product candidates based on our singular focus on shutting down the RAS/MAPK pathway, a novel and unproven approach; the analysis of pooled Phase 1 and Phase 2 naporafenib plus trametinib data covers two clinical trials with different designs and inclusion criteria, which cannot be directly compared, and therefore may not be a reliable indicator of mOS data; due to differences between trial designs and subject characteristics, comparing data across different trials may not be a reliable indicator of data; results from preclinical studies or early clinical trials, including the clinical trial results discussed in this press release, not necessarily being predictive of future results; unfavorable results from preclinical studies or clinical trials; we have not completed any clinical trials of naporafenib and are reliant on data generated by Novartis in prior clinical trials conducted by it; our planned SEACRAFT trials may not support the registration of naporafenib; later developments with the FDA or EU health authorities may be inconsistent with the feedback received to date regarding our development plans and trial designs; our assumptions around which programs may have a higher probability of success may not be accurate, and we may expend our limited resources to pursue a particular product candidate and/or indication and fail to capitalize on product candidates or indications with greater development or commercial potential; potential delays in the commencement, enrollment, and completion of clinical trials and preclinical studies; our dependence on third parties in connection with manufacturing, research, and preclinical and clinical testing; unexpected adverse side effects or inadequate efficacy of our product candidates that may limit their development, regulatory approval, and/or commercialization, or may result in recalls or product liability claims; the inability to realize any benefits from our current licenses, collaborations, acquisitions, and collaborations, and any future licenses, acquisitions, or collaborations, and our ability to fulfill our obligations under such arrangements; our ability to obtain and maintain intellectual property protection for our product candidates; regulatory developments in the United States and foreign countries; Fast Track Designation may not lead to a faster development or regulatory review or approval process, and does not increase the likelihood that our product candidates will receive marketing approval; our ability to fund our operating plans with our current cash, cash equivalents, and marketable securities; and other risks described in our prior filings with the Securities and Exchange Commission (SEC), including under the heading “Risk Factors” in our annual report on Form 10-K for the year ended December 31, 2023, and any subsequent filings with the SEC. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof, and we undertake no obligation to update such statements to reflect events that occur or circumstances that exist after the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement, which is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. MEKINIST® is a registered trademark owned by or licensed to Novartis AG, its subsidiaries, or affiliates. Contact: Joyce Allaire LifeSci Advisors, LLC jallaire@lifesciadvisors.com Source: Erasca, Inc.

Phase 1Phase 3Clinical ResultFast TrackPhase 2

11 Jun 2024

·www.prnewswire.com

Last patient in: Laminar Pharmaceuticals S.A. completes recruitment for CLINGLIO, the phase 2b/3 Clinical Trial of idroxioleic acid (LAM561) in combination with RT and TMZ for adults with newly diagnosed glioblastoma

140 patients have been recruited at sites in Spain, Italy, France and United Kingdom. The open readout of the trial is expected by late 2024. Laminar aims to submit regulatory filings or conditional marketing authorization by early 2025. PALMA DE MALLORCA, Spain, June 11, 2024 /PRNewswire/ -- Laminar Pharmaceuticals S.A., a clinical-stage biotechnological company developing novel therapies to treat diverse pathologies with unmet clinical needs, is pleased to announce the recruitment of patients for the CLINGLIO (NCT04250922) study has been closed after 140 adult patients have been successfully enrolled. The CLINGLIO study is a multinational, phase 2b/3, randomized, placebo-controlled, double-blind clinical trial evaluating idroxioleic acid in combination with Standard of Care (combined tumour resection and chemoradiotherapy) for the treatment of newly diagnosed glioblastoma patients. The CLINGLIO trial, funded by a European Commission Grant (H2020) is being carried out in 21 hospitals in Spain, Italy, France, and United Kingdom. The investigational study drug, idroxioleic acid (LAM561, sodium; 2-OHOA) is a synthetic fatty acid with a novel therapeutic approach, administrated orally to treat this devastating type of cancer. "We are pleased to announce that the pivotal phase 2b/3 trial recruitment is completed, as this means that the results and outcome of the trial will be soon available," said Adrian McNicholl, Chief of Clinical Operations at Laminar Pharmaceuticals. The trial is expected to reach the trigger event for interim analysis in July 2024, which would provide an unblinded readout the last quarter of this year. "If idroxioleic acid is able to show compelling evidence demonstrating significant progression free survival benefit with overall survival, it could imply the first addition to the Standard of Care for glioblastoma patients since the approval of Temozolomide in 2005, 19 years ago." These unblinded results will be submitted for EMA evaluation for Conditional Marketing Authorization in early 2025, and the trial will continue until final analysis of survival in 2026. Pablo Escribá, CEO of Laminar Pharmaceuticals, said: "The completion of the recruitment is a huge milestone in our clinical trial and in the development of this potential new therapy for glioblastoma patients. We are excited about the possibility of offering a new treatment available for this fatal disease, which has some of the clearer unmet needs across the oncology field". The CLINGLIO trial, which was initiated in December 2019, has enrolled 140 participants across 4 countries in Europe. Those patients were randomized 1:1 versus placebo. Idroxioleic acid or placebo is added to Standard of Care, and continued for as long as the tumour does not progress. Idroxioleic acid has shown a favorable safety profile in pre-clinical and clinical trials so far. Additionally, no safety concerns were raised by an Independent Data Monitoring Committee (IDMC) who recommended "continue without modifications" after unblinded reviews of the available safety and efficacy data. The trial will continue until the final analysis of overall survival. The CLINGLIO trial is considered pivotal in that results showing significant clinical benefit could be sufficient for a request for conditional marketing authorization in the EU late this year; and potential full marketing authorization in 2026, for which enabling pre-submission interactions with the EMA have been initiated. About Laminar Pharmaceuticals S.A. Laminar Pharmaceuticals S.A. (Laminar) is a Spanish biotechnological company created in 2006, committed to translational health research, for the rational design and development of drugs to treat oncological and other pathologies in the form of synthetic fatty acids considered "First-in-class Health Solutions" and based on a novel technology, the Melitherapy (MLT or Membrane Lipid Therapy). Laminar controls all the processes, from the rational design of the molecules to the clinical trials that lead up to the launch of a new drug, with constant investment in R&D and high-quality standards. It is currently headquartered in Mallorca (Spain) with a subsidiary in Massachusetts (USA). About Glioblastoma Glioblastoma is the most common primary malignant brain tumour and accounts for nearly 50 percent of all gliomas and approximately 25 percent of all primary brain and CNS malignant tumours. The incidence of GBM in Europe is currently above 25,000 new cases each year, rising to over 100,000 cases per year worldwide. The prognosis for Glioblastoma patients is very poor, with a median survival time of about 14.5 months despite optimum chemo-radiation treatment. About 15% of patients survive two years after diagnosis and ca. 4% survive for five or more years. In this scenario, there is a desperate need for novel treatment alternatives that provide safe and more efficacious clinical outcomes. About idroxioleic acid Idroxioleic acid (LAM561; 2-hydroxyoleic acid (2-OHOA)) is a synthetic derivative of oleic acid and Laminar's most advanced R&D product, which is taken orally. This drug alters the composition of the plasma membrane in cancer cells, reducing the activity of membrane-associated signaling proteins that are known to promote tumour growth and affecting tumours in the brain. LAM561 is in the process of completing its last clinical development phase in adults and has shown promising preliminary clinical activity in the treatment of aggressive high-grade glioblastoma. SOURCE Laminar Pharmaceuticals, S.A.

Drug ApprovalClinical Study

11 Jun 2024

·www.globenewswire.com

TRACON Announces Publication in Clinical Cancer Research of Phase 2 Clinical Data for TRC102, a DNA Damage Repair Inhibitor, in Recurrent Glioblastoma Patients

Publication Highlights Activity of the Combination of TRC102 and Temodar (Temozolomide) in Patients who Progressed Following Initial Treatment with Surgical Resection, Temodar and External Beam Radiotherapy Consistent with the TRC102 Mechanism of Action, Extended Survival was Demonstrated in Patients with Activation of DNA Damage Response Pathways Prior to TRC102 Treatment SAN DIEGO, June 11, 2024 (GLOBE NEWSWIRE) -- TRACON Pharmaceuticals (NASDAQ: TCON), a clinical stage biopharmaceutical company utilizing a cost-efficient, CRO-independent Product Development Platform (PDP) to advance its pipeline of novel targeted cancer therapeutics and to partner with other life science companies, today announced the publication of Phase 2 clinical data of its DNA damage repair inhibitor drug candidate, TRC102, in patients with glioblastoma in Clinical Cancer Research. The article, entitled, “Evaluating the Base Excision Repair Inhibitor TRC102 and Temozolomide for patients with Recurrent Glioblastoma in the Phase 2 Adult Brain Tumor Consortium Trial BERT,” highlights the activity of TRC102 given in combination with Temodar chemotherapy in patients with recurrent glioblastoma: https://pubmed-ncbi-nlm-nih-gov.libproxy1.nus.edu.sg/38836759/ TRC102 was evaluated in a Phase 2 trial in combination with Temodar in 19 patients with progressive or recurrent glioblastoma following surgical resection, Temodar and external beam radiotherapy. Extended survival was observed in two patients (progression-free survival ≥ 17 months and overall survival > 32 months), both of whom demonstrated significantly enriched signatures of DNA damage response (DDR), chromosomal instability, and cellular proliferation by RNA sequencing prior to initiating treatment with Temodar and TRC102. The study was completed by the Adult Brain Tumor Consortium and led by Manmeet Alhuwalia, MD while he was Chair of Neuro-Oncology at Cleveland Clinic prior to his appointment as Chief of Medical Oncology, Chief Scientific Officer, and Deputy Director of the Miami Cancer Institute. The authors concluded the study findings confirm the safety and feasibility of TRC102 given with Temodar for recurrent glioblastoma patients and warrant further evaluation of combination therapy in biomarker-enriched trials enrolling glioblastoma patients with baseline hyperactivated DDR pathways. “We believe that the data generated to date provides a strong rationale for studying TRC102 in combination with Temodar and radiotherapy in newly diagnosed patients with malignant glioma,” said James Freddo, M.D., Chief Medical Officer of TRACON. “The Clinical Cancer Research publication supports prior data published in Cancer Cell (https://pubmed-ncbi-nlm-nih-gov.libproxy1.nus.edu.sg/33217343) that patients whose cancers demonstrate activation of DDR pathways may be particularly sensitive to the pharmacologic effects of TRC102.” Based on a 100% response rate (including a 20% complete response rate) in a Phase 1 clinical trial combining TRC102 with pemetrexed, cisplatin and radiation therapy in 15 patients with stage III non-squamous non-small cell lung cancer (https://pubmed-ncbi-nlm-nih-gov.libproxy1.nus.edu.sg/34740922), TRC102 is currently being studied in a randomized Phase 2 clinical trial in combination with chemotherapy (pemetrexed, cisplatin or carboplatin) and radiation therapy for stage III non-squamous non-small cell lung cancer (NCT05198830: https://clinicaltrials.gov/study/NCT05198830?intr=TRC102&rank=6). This trial is sponsored by the National Cancer Institute (NCI) through a Cooperative Research and Development Agreement (CRADA). Determination of the primary endpoint of progression free survival is expected in 2025. TRACON and the NCI have a longstanding history of partnership to develop TRC102, whereby the NCI has funded six Phase 1 or Phase 2 trials through the CRADA. About TRC102 TRC102 (methoxyamine) is a novel, clinical-stage small molecule inhibitor of the DNA base excision repair pathway, which is a pathway that causes resistance to alkylating and antimetabolite chemotherapeutics. TRC102 is currently being studied in multiple randomized Phase 2 clinical trial entitled Testing the Addition of an Anti-Cancer Drug, TRC102, to the Usual Chemotherapy Treatment (Pemetrexed, Cisplatin or Carboplatin) During Radiation Therapy for Stage III Non-Squamous Non-Small Cell Lung Cancer (NCT05198830) that is sponsored by the NCI through a CRADA. TRC102 was granted orphan drug designation by the US FDA for the treatment of malignant glioma in 2020. For more information about the clinical trials, please visit TRACON’s website at www.traconpharma.com/clinical-trials. About Malignant Glioma and Glioblastoma Glioblastoma (GBM) is a rapidly growing malignant glioma that develops from glial cells (astrocytes and oligodendrocytes) that support the health of the nerve cells within the brain. GBM is the most invasive type of glial tumors, rapidly growing and commonly invading into nearby brain tissue. The National Cancer Institute estimates that approximately 22,850 adults are diagnosed with brain and other nervous system cancers annually in the U.S. and approximately 15,320 of these diagnoses will result in death. GBM has an incidence of two to three per 100,000 adults per year in the U.S., and accounts for 52 percent of all primary brain tumors. About TRACON TRACON utilizes a cost-efficient, CRO-independent, product development platform to advance its pipeline of novel targeted cancer therapeutics and to partner with other life science companies. TRACON believes it can serve as a solution for companies without clinical capabilities who wish to become CRO-independent. To learn more about TRACON, visit TRACON’s website at www.traconpharma.com. Forward-Looking Statements Statements made in this press release regarding matters that are not historical facts are “forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward‐looking statements. Such statements include, but are not limited to, statements regarding TRACON’s and the NCI’s plans to further develop product candidates, expectations regarding clinical trials, development and regulatory plans, the potential benefits of TRC102, the potential for TRC102 to become a treatment option for patients with the glioblastoma or lung cancer, market estimates regarding annual diagnoses of brain and other nervous system cancer, and TRACON’s business development strategy and goals. Risks that could cause actual results to differ from those expressed in these forward‐looking statements include: risks associated with TRACON’s ability to remain listed on a national securities exchange, risks associated with clinical development and regulatory approval of pharmaceutical product candidates, including the results of clinical trials involving TRC102 and whether the results of earlier studies or trials will be consistent with or otherwise achieved in later trials; risks relating to TRACON’s ability to continue as a going concern; risks relating to other therapies that are being developed and compete with TRACON’s product candidates; whether TRACON or others will be able to complete or initiate clinical trials on TRACON’s expected timelines, if at all, including due to risks associated with macroeconomic and geopolitical events; potential changes in regulatory requirements in the United States and foreign countries; TRACON’s reliance on third parties for the development of its product candidates, including the conduct of its clinical trials and manufacture of its product candidates; whether TRACON will be able to obtain additional financing on favorable terms or at all; and other risks described in TRACON’s filings with the Securities and Exchange Commission under the heading “Risk Factors”. All forward‐looking statements contained in this press release speak only as of the date on which they were made and are based on management’s assumptions and estimates as of such date. TRACON undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made except as required by law. Company Contact:Investor Contact:Charles TheuerBrian RitchieChief Executive OfficerLifeSci Advisors LLC(858) 550-0780(212) 915-2578ctheuer@traconpharma.combritchie@lifesciadvisors.com

Phase 2Phase 1Orphan DrugRadiation TherapyClinical Result

100 Deals associated with Temozolomide

External Link

KEGG	Wiki	ATC	Drug Bank
D06067	Temozolomide	L01AX03	DB00853

R&D Status

Approved

10 top approved records.

to view more data

Indication	Country/Location	Organization	Date
Ewing Sarcoma	JP	MSD KK	21 Feb 2019
Malignant glioma of brain	EU	Teva Pharmaceuticals Europe BV	28 Jan 2010
Malignant glioma of brain	IS	Teva Pharmaceuticals Europe BV	28 Jan 2010
Malignant glioma of brain	LI	Teva Pharmaceuticals Europe BV	28 Jan 2010
Malignant glioma of brain	NO	Teva Pharmaceuticals Europe BV	28 Jan 2010
Glioblastoma	CN	Jiangsu Tasly Diyi Pharmaceutical Co., Ltd.	30 Apr 2004
Astrocytoma	EU	Merck Sharp & Dohme BV	26 Jan 1999
Astrocytoma	IS	Merck Sharp & Dohme BV	26 Jan 1999
Astrocytoma	LI	Merck Sharp & Dohme BV	26 Jan 1999
Astrocytoma	NO	Merck Sharp & Dohme BV	26 Jan 1999
Glioblastoma Multiforme	EU	Merck Sharp & Dohme BV	26 Jan 1999
Glioblastoma Multiforme	IS	Merck Sharp & Dohme BV	26 Jan 1999
Glioblastoma Multiforme	LI	Merck Sharp & Dohme BV	26 Jan 1999
Glioblastoma Multiforme	NO	Merck Sharp & Dohme BV	26 Jan 1999
Glioma	EU	Merck Sharp & Dohme BV	26 Jan 1999
Glioma	IS	Merck Sharp & Dohme BV	26 Jan 1999
Glioma	LI	Merck Sharp & Dohme BV	26 Jan 1999
Glioma	NO	Merck Sharp & Dohme BV	26 Jan 1999

Developing

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Recurrent Glioblastoma	Phase 3	-	Merck Sharp & Dohme Corp.	02 Mar 2005
Brain metastases	Phase 3	US	National Cancer Institute	06 Oct 2004
Brain metastases	Phase 3	US	Radiation Therapy Oncology Group	06 Oct 2004
Brain metastases	Phase 3	CA	Radiation Therapy Oncology Group	06 Oct 2004
Brain metastases	Phase 3	CA	National Cancer Institute	06 Oct 2004
metastatic non-small cell lung cancer	Phase 3	US	Radiation Therapy Oncology Group	06 Oct 2004
metastatic non-small cell lung cancer	Phase 3	US	National Cancer Institute	06 Oct 2004
metastatic non-small cell lung cancer	Phase 3	CA	National Cancer Institute	06 Oct 2004
metastatic non-small cell lung cancer	Phase 3	CA	Radiation Therapy Oncology Group	06 Oct 2004
Recurrent Non-Small Cell Lung Cancer	Phase 3	US	Radiation Therapy Oncology Group	06 Oct 2004

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ASCO2024	Not Applicable	Refractory Melanoma	10	Cisplatin-Vinblastine-Temozolomide (CVT) regimen	lormpsbtgg(rwtltarwfm) = asaxkstafy krnwuqnwcd (xjiriwnaiz ) View more	Positive	24 May 2024
ASCO2024	Not Applicable	-	-	Procarbazine, CCNU, and Vincristine (PCV) + Radiotherapy	wcxtjxqqdx(brazcofhvp) = devhdmzxzt bvqkvbjiqa (uijlhtzcnt, 61 - 85) View more	-	24 May 2024
				Temozolomide (TMZ) + Radiotherapy	wcxtjxqqdx(brazcofhvp) = sogwclnaxx bvqkvbjiqa (uijlhtzcnt, 49 - 73) View more
ASCO2024	Not Applicable	Primary Central Nervous System Lymphoma	-	Orelabrutinib	qjtagttrtc(djxijhgcgz) = Only 1 (10%) pts experienced ≥grade 3 AEs—acute kidney injury ujipnfrrgv (dzrlhqxajw ) View more	-	24 May 2024
				Rituximab
ChiCTR2000039485 (EHA2024)	Phase 4	Primary Central Nervous System Lymphoma First line	32	Zanubrutinib+Lenalidomide+Rituximab+Temozolomide+Methotrexate (RLZT+MTX)	yjfcrclapo(dzeudlmubm) = wyevnrckbs uesdeqsazs (ewrcputfbj ) View more	-	14 May 2024
				Rituximab+Temozolomide+Methotrexate (RLZT)	yjfcrclapo(dzeudlmubm) = cgzajdvebn uesdeqsazs (ewrcputfbj ) View more
NCT03405792 (2-THE-TOP, CTgov)	Phase 2	Glioblastoma	40	Optune System+Temozolomide (TMZ)+pembrolizumab (Optune System Combined With Temozolomide (TMZ) + Pembrolizumab)	vjzamgnadd(mbtlofbpyw) = tcxgmnzhmo albtgszosk (sffaabrwvo, psyqrkdirz - kembohntpd) View more	-	15 Apr 2024
				Optune System+Temozolomide (TMZ) (Historical Control)	vjzamgnadd(mbtlofbpyw) = spcofglelo albtgszosk (sffaabrwvo, euexkohwaj - ruvicsnldb)
NCT04122911 (TENEC-TRIAL, Pubmed)	Phase 2	Advanced Neuroendocrine Carcinoma Second line Ki67 index	38	Temozolomide 75 mg/m2/day	ydnyeqkish(ofucjulakd) = axnspszifc xvpysbdduz (ofpggnoijm ) View more	Positive	13 Apr 2024
NCT03927222 (I-ATTAC, CTgov)	Phase 2	Glioblastoma	6	Human CMV pp65-LAMP mRNA-pulsed autologous DCs containing GM CSF+Temozolomide	yrrxsbqzju(qsuvadntkf) = wbvxklxxjq qikdscjhoq (mdftgebpac, jztmynmpko - fqzeqctsen) View more	-	08 Apr 2024
NCT04560166 (CTgov)	Phase 2	Neuroblastoma recurrent	2	Temozolomide	ercreajnqx(qcoofenhzj) = cpydrjntrj uuaqnyjyyn (sqhooolirm, ejiijxnbbz - airozoqwat) View more	-	18 Mar 2024
IRCT20160706028815N3 (ESMO_SRC2024) Manual	Phase 3	High grade glioma Adjuvant	100	temozolomide (6 cycles)	zqcwmaprvi(hosiuwuspd) = qfmwxbdmcd yqwpnsdpae (qdopddywtx ) View more	Negative	15 Mar 2024
				temozolomide (12 cycles)	zqcwmaprvi(hosiuwuspd) = nsesncozcq yqwpnsdpae (qdopddywtx ) View more
NCT02331498 (PAZOGLIO, ESMO_TAT2024) Manual	Phase 1/2	Glioblastoma Multiforme First line	20	Pazopanib+temozolomide	qerixukupm(jkcwijobsw) = ebuwedzzqi puefzelyth (mskktvxdns, 52 - 96) View more	Positive	26 Feb 2024

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