A Pilot Study of Epcoritamab With Dose Adjusted Etoposide, Cyclophosphamide, Vincristine, Doxorubicin, Prednisone and Rituximab (EPOCH-R) for Upfront Treatment of Aggressive B-Cell Non-Hodgkin Lymphomas

This phase II trial tests the safety, best dose, and effectiveness of epcoritamab when given with etoposide, cyclophosphamide, vincristine, doxorubicin, prednisone and rituximab (EPOCH-R) for the treatment of patients with aggressive B-cell non-Hodgkin lymphoma. Epcoritamab is a bispecific antibody that can bind to two different antigens at the same time. Epcoritamab binds to CD3, a T-cell surface antigen, and CD20 (a tumor-associated antigen that is expressed on B-cells during most stages of B-cell development and is often overexpressed in B-cell cancers) and may interfere with the ability of cancer cells to grow and spread. Etoposide is in a class of medications known as podophyllotoxin derivatives. It blocks a certain enzyme needed for cell division and DNA repair and may kill cancer cells. Cyclophosphamide is in a class of medications called alkylating agents. It works by damaging the cell's DNA and may kill cancer cells. It may also lower the body's immune response. Vincristine is in a class of medications called vinca alkaloids. It works by stopping cancer cells from growing and dividing and may kill them. Doxorubicin is in a class of medications called anthracyclines. Doxorubicin damages the cell's DNA and may kill cancer cells. It also blocks a certain enzyme needed for cell division and DNA repair. Prednisone is in a class of medications called corticosteroids. It is used to reduce inflammation and lower the body's immune response to help lessen the side effects of chemotherapy drugs. Rituximab is a monoclonal antibody. It binds to a protein called CD20, which is found on B cells (a type of white blood cell) and some types of cancer cells. The EPOCH-R is administrated as the standard of care treatment. This may help the immune system kill cancer cells. Giving epcoritamab with EPOCH-R may be safe, tolerable, and effective in treating patients with aggressive B-cell non-Hodgkin lymphoma.

Start Date01 Jan 2026

Sponsor / Collaborator

University of Washington

[+1]

NCT05403723

/ SuspendedPhase 1IIT

A Phase 1b Trial of Adaptive Stereotactic Body Radiotherapy in Combination With Durvalumab (MEDI4736), Platinum, and Etoposide in Extensive Stage Small Cell Lung Cancer

This is trial studying the safety of adaptive stereotactic body radiotherapy (SBRT) combined with durvalumab immunotherapy, platinum chemotherapy, and etoposide chemotherapy in platinum refractory extensive stage small cell lung cancer (SCLC).

Start Date31 Dec 2025

Sponsor / Collaborator

University of Maryland Baltimore

[+1]

NCT07141771

/ Not yet recruitingPhase 1/2IIT

An Umbrella Study of Recurrent, Extensive Stage Small Cell Lung Cancer Based on Molecular Typing

Small-cell lung cancer (SCLC) has a high degree of malignancy and extremely poor prognosis, slow progress in the treatment of ES-SCLC, and a more ideal posterior therapy needs to be explored. This is an I / II, phase umbrella study to explore afterline treatment options following progression of frontline platinum-containing therapy for small cell lung cancer.
This study includes 2 parts:
Part 1 will enroll patients with end of first-line platinum-containing therapy and progression interval of less than 180 days or more of second-line therapy (no first-line relapse time required).
Part 2 will enroll patients with end of first-line platinum-containing therapy greater than 180 days.
Based on the optimal selection of patients with recurrent broad-stage small cell lung cancer with different molecular and clinical characteristics, we further explored different treatment modes suitable for different populations through umbrella cohort studies.

Start Date31 Dec 2025

Sponsor / Collaborator

Cancer Hospital Chinese Academy of Medical Sciences

100 Clinical Results associated with Etoposide

100 Translational Medicine associated with Etoposide

100 Patents (Medical) associated with Etoposide

32,292

Literatures (Medical) associated with Etoposide

31 Dec 2025·NMC case report journal

A Primary Spinal Intramedullary Mixed Germ Cell Tumor: A Case Report and Literature Review

Article

Author: SHIMAUCHI-OHTAKI, Hiroya ; HIRATO, Junko ; HORIGUCHI, Keishi ; HONDA, Fumiaki ; NAKATA, Satoshi ; YOKOO, Hideaki ; GOTO, Yuta ; OYA, Soichi ; TOMOMASA, Ran ; NAKAMURA, Shunsuke

Central nervous system germ cell tumors are rare and account for 2% to 3% of all central nervous system tumors in Japan. Here, we report an extremely rare case of a primary spinal intramedullary mixed germ cell tumor. A 33-year-old man presented with a chief report of dysuria and numbness in the right lower extremity. Magnetic resonance imaging revealed a mass lesion on the left side of the intramedullary spinal cord at the Th10-11 vertebral body level with hyperintensity on T2-weighted images, isointensity on T1-weighted images, and uniform contrast in gadolinium. Cerebrospinal fluid examination revealed a few atypical cells. Although tumor removal using the posterior median sulcus approach was attempted, only a biopsy was performed because intraoperative rapid pathology suggested a possible diagnosis of germinoma. Permanent pathology revealed a mixed germ cell tumor (mainly comprising a germinoma with a yolk sac tumor). Postoperatively, cerebrospinal irradiation and 8 courses of the carboplatin and etoposide regimen were administered. No recurrence or new lesions were observed on magnetic resonance imaging at 94 months postoperatively. Our extensive literature search found only 4 cases of a mixed germ cell tumor of primary intramedullary origin in the spinal cord. Most spinal germ cell tumors described in the literature are either germinomas or mature teratomas; however, mixed germ cell tumors can also occur, albeit infrequently. Although additional cases need to be accumulated, our case suggests that yolk sac elements in spinal mixed germ cell tumors might not be directly associated with poor life expectancy.

31 Dec 2025·Hematology

The effectiveness of etoposide-containing chemotherapy regimens in the initial treatment of Hemophagocytic Syndrome in pregnancy

Article

Author: Wang, Jie ; Hu, Hongli ; Wei, Na ; Wang, Jingshi ; Wang, Zhao ; Wu, Lin

OBJECTIVE:

To summarize the clinical characteristics, treatment outcomes, and prognosis of pregnant patients with hemophagocytic lymphohistiocytosis (HLH), and to evaluate the efficacy of chemotherapy regimens containing etoposide (VP16) in these patients and their impact on survival outcomes.

METHODS:

A retrospective analysis was performed on 41 pregnant HLH patients admitted to our hospital between April 2015 and March 2024, focusing on clinical features, treatment strategies, and prognostic factors.

RESULTS:

Among the 41 cases, 29 developed HLH during pregnancy and 12 postpartum. Etiologies included malignancy-related HLH (5 cases), Epstein-Barr virus (EBV)-related HLH (5 cases), rheumatologic disease-related HLH (2 cases), and pregnancy-related HLH (29 cases, defined as no comorbid HLH-related etiologies except pregnancy). In pregnancy-related HLH patients presenting during gestation, the 2-week overall response rate (ORR) was significantly higher in those receiving VP16-containing induction chemotherapy compared to glucocorticoids-only induction therapy (P = 0.011). Multivariate analysis identified the interval from symptom onset to VP16 initiation as an independent prognostic factor for pregnancy-related HLH (P = 0.025). Survival analysis revealed improved survival in patients who received VP16 within 7 weeks of onset versus those treated after 7 weeks (P = 0.044).

DISCUSSION AND CONCLUSION:

HLH in pregnancy progresses rapidly. Early administration of VP16-containing chemotherapy significantly improves ORR and survival outcomes, particularly in pregnancy-related HLH.

31 Dec 2025·JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY

Synthesis, in vitro and in silico studies of a novel chrysin-ferrocene Schiff base with potent anticancer activity via G1 arrest, caspase-dependent apoptosis and inhibition of topoisomerase II

Article

Author: Break, Mohammed Khaled Bin ; Alkahtani, Hamad M. ; Ansari, Siddique Akber ; Alshammari, Maali D. ; Katamesh, Ahmed A. ; Albadari, Najah

A novel chrysin-ferrocene Schiff base (CFSB) was synthesised as a potential anticancer agent. CFSB demonstrated high cytotoxicity against cancer cells with HepG2 (liver) being the most susceptible (IC₅₀ = 3.11 µM). The compound was less toxic towards normal MRC5 cells and exhibited ∼5-fold selectivity towards most cancer cells. CFSB caused G1-phase arrest, induced caspase-dependent apoptosis by increasing Bax/Bcl2 ratio and reduced metastasis by decreasing MMP9 in HepG2. Furthermore, CFSB was inactive against CDK2, EGFR, TrkA and VEGFR, but it strongly inhibited topoisomerase II (IC₅₀ = 20 µM) with potency comparable to etoposide (IC₅₀ = 15 µM), while weak inhibition was observed against tubulin (IC₅₀ = 76 µM). DFT calculations revealed that CFSB had desirable reactivity, while docking indicated high binding affinity with topoisomerase II. Molecular dynamics and MM-GBSA analyses showed that CFSB-topoisomerase II complex was stable with favourable binding energies, while in silico ADMET studies showed drug-like properties for CFSB.

301

News (Medical) associated with Etoposide

16 Sep 2025

·www.globenewswire.com

ORYZON Strengthens Patent Portfolio for Iadademstat and Vafidemstat with New Decisions to Grant

In Australia and EuropeMADRID and CAMBRIDGE, Mass., Sept. 16, 2025 (GLOBE NEWSWIRE) -- Oryzon Genomics, S.A. (ISIN Code: ES0167733015, ORY), a clinical-stage biopharmaceutical company and a European leader in epigenetics, today announced that it continues to expand its patent portfolio for iadademstat and vafidemstat, Oryzon’s clinical-stage LSD1 inhibitors for oncology and central nervous system (CNS) disorders, following new Decisions to Grant from the Australian and European patent offices. The Australian Patent Office has issued a Decision to Grant for Oryzon’s patent application AU2020249493, titled “Combinations of iadademstat for cancer therapy”. The allowed claims cover combinations of iadademstat with PD1 or PD-L1 inhibitors for the treatment of cancer, including small cell lung cancer (SCLC). A Decision to Grant is an official communication from a national patent office indicating that a patent application has met all requirements for issuance as a patent. Once formally granted, this Australian patent will remain in force until at least 2040, not including any potential patent term extensions. A corresponding patent has also been granted in Russia, and applications are pending in Europe, the United States, Japan, China, and other countries. Iadademstat is currently being evaluated in combination with PD-L1 inhibitors (atezolizumab or durvalumab) in first line SCLC patients with extensive disease in a Phase I/II trial conducted and sponsored by the U.S. National Cancer Institute (NCI) under a Cooperative Research and Development Agreement (CRADA) with Oryzon. More than 30 sites across the U.S. participate in the trial, including leading institutions such as Memorial Sloan Kettering Cancer Center, Johns Hopkins, City of Hope, Yale University and the University of Chicago, among others. Oryzon has also received a Decision to Grant from the European Patent Office for its patent application EP24205125.8, titled “Vafidemstat for treating behavior alterations”. The allowed claims cover the use of vafidemstat for the treatment of aggressiveness and social withdrawal associated with CNS diseases. Among the allowed claims, there are claims specifically aimed at the treatment of aggressiveness associated with Borderline Personality Disorder (BPD), Autism Spectrum Disorder (ASD), Alzheimer’s disease and other conditions, as well as claims directed to treating social withdrawal associated with diseases such as schizophrenia or ASD. Once formally granted, this European patent will remain in force until at least 2038, not including any potential patent term extensions. Additional patents in this family have already been granted or allowed in Europe, Australia, Canada, Hong Kong, Israel, South Korea, Malaysia, the Philippines, and Russia, with applications pending in other countries. Vafidemstat is in advanced clinical development for the treatment of aggression in psychiatric disorders, with an upcoming Phase III trial in aggression in BPD (protocol submitted), and a Phase II trial in aggression in ASD patients under preparation. In addition, a Phase II trial is ongoing in schizophrenia, with a focus on negative symptoms. One of the most prominent negative symptoms of schizophrenia is social withdrawal. “These new patent grants strengthen Oryzon’s global IP position by protecting key therapeutic indications under clinical development for iadademstat and vafidemstat, thereby extending the commercial life for both compounds”, said Neus Virgili, Oryzon’s Chief IP Officer. About OryzonFounded in 2000 in Barcelona, Spain, Oryzon (ISIN Code: ES0167733015) is a clinical stage biopharmaceutical company and the European leader in epigenetics, with a strong focus on personalized medicine in CNS disorders and oncology. Oryzon’s team is composed of highly qualified professionals from the pharma industry located in Barcelona, Boston, and San Diego. Oryzon has an advanced clinical portfolio with two LSD1 inhibitors, vafidemstat in CNS (Phase III-ready) and iadademstat in oncology (Phase II). The company has other pipeline assets directed against other epigenetic targets like HDAC-6 where a clinical candidate, ORY-4001, has been nominated for its possible development in CMT and ALS. In addition, Oryzon has a strong platform for biomarker identification and target validation for a variety of malignant and neurological diseases. For more information, visit www.oryzon.com About IadademstatIadademstat (ORY-1001) is a small oral molecule, which acts as a highly selective inhibitor of the epigenetic enzyme LSD1 and has a powerful differentiating effect in hematologic cancers (see Maes et al., Cancer Cell 2018 Mar 12; 33 (3): 495-511.e12.doi: 10.1016 / j.ccell.2018.02.002.). A FiM Phase I/IIa clinical trial with iadademstat in R/R AML patients demonstrated the safety and good tolerability of the drug and preliminary signs of antileukemic activity, including a CRi (see Salamero et al, J Clin Oncol, 2020, 38(36): 4260-4273. doi: 10.1200/JCO.19.03250). Iadademstat has shown encouraging safety and strong clinical activity in combination with azacitidine in a Phase IIa trial in elder 1L AML patients (ALICE trial) (see Salamero et al., ASH 2022 oral presentation & The Lancet Haematology, 2024, 11(7):e487-e498). Iadademstat is currently being evaluated in combination with gilteritinib in the ongoing Phase Ib FRIDA trial in patients with relapsed/refractory AML with FLT3 mutations, and in combination with azacitidine and venetoclax in 1L AML in an investigator-initiated study led by OHSU and in a trial sponsored by the U.S. National Cancer Institute (NCI) under the Cooperative Research and Development Agreement (CRADA) signed between Oryzon and the NCI to collaborate on further clinical development of iadademstat in different types of hematologic and solid cancers. Beyond hematological cancers, the inhibition of LSD1 has been proposed as a valid therapeutic approach in some solid tumors such as small cell lung cancer (SCLC), neuroendocrine tumors (NET), medulloblastoma and others. In a Phase IIa trial in combination with platinum/etoposide in second line ED-SCLC patients (CLEPSIDRA trial), preliminary activity and safety results have been reported (see Navarro et al., ESMO 2018 poster). Iadademstat is in a Phase I/II randomized trial in 1L ED-SCLC in combination with ICI sponsored by NCI and led by the Memorial Sloan Kettering Cancer Center. Oryzon is further expanding the clinical development of iadademstat in oncology through additional CRADA and investigator-initiated studies. In addition, Oryzon is expanding iadademstat’s clinical development into non-oncological hematology indications, with trials in sickle cell disease (CTA approved) and essential thrombocythemia (trial in preparation). Iadademstat has orphan drug designation for SCLC in the US and for AML in the US and EU. About Vafidemstat Vafidemstat (ORY-2001) is an oral, CNS-optimized LSD1 inhibitor. The molecule acts on several levels: it reduces cognitive impairment, including memory loss and neuroinflammation, and at the same time has neuroprotective effects. In animal studies vafidemstat not only restores memory but reduces the exacerbated aggressiveness of SAMP8 mice, a model for accelerated aging and Alzheimer’s disease (AD), to normal levels and also reduces social avoidance and enhances sociability in murine models. In addition, vafidemstat exhibits fast, strong, and durable efficacy in several preclinical models of multiple sclerosis (MS). Oryzon has performed two Phase IIa clinical trials in aggressiveness in patients with different psychiatric disorders (REIMAGINE, see Ferrer et al, Psychiatry & Clin Neurosci, 2025, doi.org/10.1111/pcn.13800) and in aggressive/agitated patients with moderate or severe AD (REIMAGINE-AD), with positive clinical results reported in both. Additional finalized Phase IIa clinical trials with vafidemstat include the ETHERAL trial in patients with Mild to Moderate AD, where a significant reduction of the inflammatory biomarker YKL40 was observed after 6 and 12 months of treatment, and the pilot, small-scale SATEEN trial in Relapse-Remitting and Secondary Progressive MS, where anti-inflammatory activity was also observed. Vafidemstat has also been tested in a Phase II in severe Covid-19 patients (ESCAPE) assessing the capability of the drug to prevent ARDS, one of the most severe complications of the viral infection, where it showed significant anti-inflammatory effects in severe Covid-19 patients. Following completion of the global, randomized, double blind Phase IIb PORTICO trial in Borderline Personality Disorder (BPD), with final data presented at ECNP-2024, vafidemstat is advancing as a Phase III-ready asset for agitation/aggression in BPD (PhIII protocol submitted). Vafidemstat is also being investigated in a double-blind, randomized, placebo-controlled Phase IIb trial in negative symptoms of schizophrenia (EVOLUTION trial, recruitment ongoing). The company is also deploying a CNS precision medicine approach with vafidemstat in genetically defined patient subpopulations of certain CNS disorders, as well as in neurodevelopmental syndromes, and is preparing a clinical trial in aggression in autistic conditions like Phelan-McDermid syndrome. FORWARD-LOOKING STATEMENTS This communication contains, or may contain, forward-looking information and statements about Oryzon, including financial projections and estimates and their underlying assumptions, statements regarding plans, objectives, and expectations with respect to future operations, capital expenditures, synergies, products and services, and statements regarding future performance. Forward-looking statements are statements that are not historical facts and are generally identified by the words “expects,” “anticipates,” “believes,” “intends,” “estimates” and similar expressions. Although Oryzon believes that the expectations reflected in such forward-looking statements are reasonable, investors and holders of Oryzon shares are cautioned that forward-looking information and statements are subject to various risks and uncertainties, many of which are difficult to predict and generally beyond the control of Oryzon that could cause actual results and developments to differ materially from those expressed in, or implied or projected by, the forward-looking information and statements. These risks and uncertainties include those discussed or identified in the documents sent by Oryzon to the Spanish Comisión Nacional del Mercado de Valores (CNMV), which are accessible to the public. Forward-looking statements are not guarantees of future performance and have not been reviewed by the auditors of Oryzon. You are cautioned not to place undue reliance on the forward-looking statements, which speak only as of the date they were made. All subsequent oral or written forward-looking statements attributable to Oryzon or any of its members, directors, officers, employees, or any persons acting on its behalf are expressly qualified in their entirety by the cautionary statement above. All forward-looking statements included herein are based on information available to Oryzon on the date hereof. Except as required by applicable law, Oryzon does not undertake any obligation to publicly update or revise any forward‐looking statements, whether as a result of new information, future events, or otherwise. This document does not constitute an offer or invitation to purchase or subscribe shares in accordance with the provisions of Regulation (EU) 2017/1129 of the European Parliament and of the Council of 14 June 2017, and/or the restated text of the Securities Market Law, approved by Law 6/2023 of 17 March, and its implementing regulations. Nothing in this document constitutes investment advice. In addition, this document does not constitute an offer of purchase, sale or exchange, nor a request for an offer of purchase, sale or exchange of securities, nor a request for any vote or approval in any jurisdiction. The shares of Oryzon Genomics, S.A. may not be offered or sold in the United States of America except pursuant to an effective registration statement under the Securities Act of 1933 or pursuant to a valid exemption from registration. SpainOryzonIR & Media, Europe & USPatricia Cobo/Mario CorderaEmili TorrellSandya von der WeidAtreviaChief BD OfficerLifeSci Advisors, LLC+34 91 564 07 25 +34 673 33 97 65+34 93 515 1313+41 78 680 05 38pcobo@atrevia.com mcordera@atrevia.cometorrell@oryzon.comsvonderweid@lifesciadvisors.com

Phase 2Orphan DrugClinical ResultPhase 1

11 Sep 2025

·www.globenewswire.com

First Disclosure of Global Interim Phase 2 Data for BioNTech and Bristol Myers Squibb PD-L1xVEGF-A Bispecific Antibody Pumitamig (BNT327/BMS986545) in Patients with Extensive-Stage Small Cell Lung Cancer Shows Encouraging Antitumor Activity

PD-L1xVEGF-A bispecific antibody pumitamig (BNT327/BMS986545) plus chemotherapy continues to show encouraging antitumor activity in patients with extensive-stage small cell lung cancer (”ES-SCLC”), expanding evidence for its potential to set a new standard of care in first-line ES-SCLC and beyond Global interim Phase 2 data showed a 76.3% confirmed objective response rate (cORR), 100% disease control rate (DCR), a median progression free survival (mPFS) of 6.8 months and a manageable safety profile Data confirm dose selection for the ongoing global pivotal Phase 3 ROSETTA LUNG-01 trial September 8, 2025 – BioNTech SE (Nasdaq: BNTX, “BioNTech”) and Bristol Myers Squibb Company (NYSE: BMY, “BMS”) today presented interim data from a global randomized Phase 2 trial (NCT06449209) evaluating pumitamig (also known as BNT327 or BMS986545), an investigational bispecific antibody targeting PD-L1 x VEGF-A, plus chemotherapy in patients with extensive-stage small cell lung cancer (“ES-SCLC”). The data, which are consistent with data presented at the European Lung Cancer Congress (“ELCC”) 2025 from a Phase 2 trial conducted in China (NCT05844150), showed encouraging anti-tumor responses with a positive trend in the secondary endpoint progression free survival. Pumitamig plus chemotherapy demonstrated a manageable safety profile with no new safety signals and a low discontinuation rate. The data are being presented today as a late-breaker oral presentation at the IASLC 2025 World Conference on Lung Cancer (“WCLC”) hosted by the International Association for the Study of Lung Cancer in Barcelona. “Small cell lung cancer is the most aggressive type of lung cancer with rapid growth, a poor prognosis and 5-year relative survival rate of just 5% in advanced stages.1,2,3 While approximately 60-70% of patients initially respond to current standard of care treatments, most progress within months after treatment signifying an urgent need for new treatment options which improve outcomes,” said John V. Heymach, M.D., Lead Investigator and Chair of Thoracic/Head and Neck Medical Oncology at The University of Texas MD Anderson Cancer Center. “The response rate and early progression free survival we are seeing in this interim analysis are encouraging and merit further investigation in a larger trial to validate pumitamig’s potential to offer patients more durable anti-tumor responses relative to current standard of care.” The interim analysis included 43 patients with untreated extensive-stage small cell lung cancer (Cohort 1) who received pumitamig in combination with standard of care chemotherapy in two dose levels. At the August 7, 2025 data cut-off, among 38 efficacy-evaluable patients, the confirmed overall response rate was 76.3% (85.0% at 20 mg/kg [dose level 1] and 66.7% at 30 mg/kg [dose level 2]) and the disease control rate (DCR) was 100%. The mean best percentage change in tumor size showed a tumor shrinkage of 56.7% with 89.5% of patients achieving early tumor shrinkage. Median progression-free survival (mPFS) was 6.8 months (6.3 months at 20 mg/kg and 7.0 months at 30 mg/kg), with mOS not being mature at the time of the analysis. Pumitamig plus chemotherapy showed a manageable safety profile, with no new safety signals beyond those typically described for chemotherapy agents and anti-PD-(L)1 and anti-VEGF monotherapies, and a discontinuation rate of 14%. Out of 43 patients, pumitamig-related treatment-emergent adverse events of Grade ≥3 were reported in 1 patient at dose level 1 and five patients at dose level 2. “Every innovation we pursue starts with the needs of patients. These interim data for pumitamig presented today show encouraging signals for our science-driven approach to address two fundamental drivers of small cell lung cancer in one single molecule,” said Prof. Özlem Türeci, M.D., Co-Founder and Chief Medical Officer at BioNTech. “Our ultimate goal is to translate science into meaningful survival benefits for many patients by overcoming some of the biggest treatment challenges, not only in small cell lung cancer but also across other difficult-to-treat solid tumors. These interim data for pumitamig represent an important step in the right direction.” “Today’s data add to the growing body of evidence indicating the potential of pumitamig to improve outcomes across a wide range of solid tumors,” said Bryan Campbell, Senior Vice President, Head of Program Leadership, Hematology, Oncology, Cell Therapy at Bristol Myers Squibb. “These are the first-ever data in a global population in advanced small cell lung cancer for a PD-(L)1 x VEGF bispecific antibody, supporting a possible new standard of care for patients with extensive-stage small cell lung cancer. We look forward to continuing to jointly advance research and development of pumitamig as a potential new treatment option with meaningful clinical benefit for patients in need.” A global randomized Phase 3 trial, ROSETTA-LUNG-01 (NCT06712355), evaluating pumitamig plus chemotherapy versus atezolizumab plus chemotherapy as a first-line treatment in patients with untreated ES-SCLC is ongoing. The pivotal trial is enrolling patients at clinical trial sites in the United States, the United Kingdom, Türkiye, China, the Republic of Korea, and Australia with additional sites planned to open globally. Pumitamig received Orphan Drug designation from the U.S. Food and Drug Administration (“FDA”) for the treatment of patients with small cell lung cancer in 2025. The full abstract is available on the WCLC website. Click here for further information on BioNTech’s pipeline assets. The global randomized, open-label, parallel group Phase 2 clinical trial (BNT327-01; NCT06449209) evaluated pumitamig (BNT327/BMS986545) in patients with untreated extended-stage small-cell lung cancer (ES-SCLC) (Cohort 1) or small-cell lung cancer (SCLC) who progressed on first- or second-line treatment (Cohort 2 and Cohort 3). In Cohort 1, patients received pumitamig in two dose levels + chemotherapy (etoposide+carboplatin) for four cycles, followed by pumitamig maintenance for up to 2 years or until disease progression or unacceptable toxicity to identify an optimized dose for future clinical investigation. Cohort 2 and Cohort 3 explored the combination of two dose levels of pumitamig plus paclitaxel, or topotecan in the second- or third-line setting. The co-primary endpoints of the trial were per RECIST 1.1 objective response rate (ORR), change in tumor size and early tumor shrinkage, and safety per NCI CTCAE v5.0. Secondary endpoints include duration of response (DoR), disease control rate (DCR), progression free survival (PFS) and overall survival (OS). Small cell lung cancer (SCLC) accounts for 15% of all lung cancer cases, with an estimated 250,000 new cases globally per year.1 It is the most aggressive type of lung cancer often spreading early to other parts of the body and developing resistance mechanisms which makes it more challenging to treat.1,2 Platinum-based chemotherapy combined with etoposide chemotherapy has been the standard first-line treatment for decades. While the addition of immune checkpoint inhibitors to chemotherapy has shown improved survival outcomes for patients with advanced or extensive-stage disease, most patients progress within months after treatment, and the prognosis remains poor. The 5-year survival rate for patients with extensive-stage SCLC is only 5%, emphasizing the need for new treatment options that extend progression-free survival.2, 3 Pumitamig is a novel investigational bispecific antibody, jointly developed by BioNTech and BMS, combining two complementary, validated mechanisms in oncology into one single molecule. Pumitamig combines PD-L1 checkpoint inhibition aimed at restoring T cells’ ability to recognize and destroy tumor cells with the neutralization of VEGF-A. The blocking of VEGF-A is aimed at reversing the tumor’s immuno-suppressive effect in its microenvironment and cutting off the blood and oxygen supply that feeds tumor cells (anti-angiogenesis effect), with the intention of preventing the tumor from growing and proliferating. Pumitamig may be differentiated via its mechanism of action of targeting PD-L1 on tumor cells to localize anti-VEGF activity within the tumor microenvironment, aiming to enhance therapeutic precision and minimize systemic exposure. More than 1,200 patients have been treated with pumitamig in clinical trials to date. More than 20 clinical trials are currently ongoing or planned to evaluate pumitamig either as a monotherapy or in combination with other treatment modalities targeting different oncogenic pathways in more than 10 solid tumor indications. Multiple global trials are ongoing or planned to start in 2025, including three global clinical trials with registrational potential evaluating pumitamig plus chemotherapy compared to standard of care treatments in first-line small cell lung cancer (ROSETTA LUNG-01; NCT06712355), first-line non-small cell lung cancer (ROSETTA LUNG-02; NCT06712316) and first-line triple-negative breast cancer (ROSETTA BREAST-01). Additional trials are ongoing exploring novel treatment combinations of pumitamig, including combinations with BioNTech’s proprietary antibody-drug conjugate candidates (“ADCs”) or immunomodulator candidates. Biopharmaceutical New Technologies (BioNTech) is a global next generation immunotherapy company pioneering novel investigative therapies for cancer and other serious diseases. BioNTech exploits a wide array of computational discovery and therapeutic modalities with the intent of rapid development of novel biopharmaceuticals. Its diversified portfolio of oncology product candidates aiming to address the full continuum of cancer includes mRNA cancer immunotherapies, next-generation immunomodulators and targeted therapies such as antibody-drug conjugates (ADCs) and innovative chimeric antigen receptor (CAR) T cell therapies. Based on its deep expertise in mRNA development and in-house manufacturing capabilities, BioNTech and its collaborators are researching and developing multiple mRNA vaccine candidates for a range of infectious diseases alongside its diverse oncology pipeline. BioNTech has established a broad set of relationships with multiple global and specialized pharmaceutical collaborators, including Bristol Myers Squibb, Duality Biologics, Fosun Pharma, Genentech, a member of the Roche Group, Genevant, Genmab, MediLink, OncoC4, Pfizer and Regeneron. Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. 1 Rudin CM, Brambilla E, Faivre-Finn C, Sage J. Small-cell lung cancer. Nat Rev Dis Primers. 2021 Jan 14;7(1):3. doi: 10.1038/s41572-020-00235-0. PMID: 33446664; PMCID: PMC8177722. 2 Yılmaz, F., Yaşar, S., Tatar, Ö.D. et al. Prognostic value of the StAN score in elderly small cell lung cancer. Sci Rep 15, 23495 (2025). https://doi.org/10.1038/s41598-025-08115-x 3 Byers LA, Rudin CM. Cancer. 2014 Oct 21;121(5):664–672. The content above comes from the network. if any infringement, please contact us to modify.

Clinical ResultImmunotherapyVaccine

27 Aug 2025

·www.globenewswire.com

ORYZON Receives European Medicines Agency Approval to Initiate a Phase Ib Study of Iadademstat in Sickle Cell Disease

First iadademstat clinical trial in non-malignant hematological indications Aug. 25, 2025 -- Oryzon Genomics, S.A. (ISIN Code: ES0167733015, Ticker: ORY), a clinical-stage biopharmaceutical company and a European leader in epigenetics, today announced that the European Medicines Agency (EMA) has approved its Clinical Trial Application (CTA), the European equivalent to an IND, to initiate a Phase Ib trial of iadademstat in sickle cell disease (SCD). This will be the first clinical trial investigating iadademstat in a non-malignant hematological indication. The Phase Ib study, named RESTORE (REgulation of Sickling ThrOugh Reprogramming Epigenetics), will be conducted at multiple sites in Spain and aims to enroll 40 adult patients with SCD. The trial’s primary objectives will be to evaluate the safety and tolerability of iadademstat and to establish its Recommended Phase 2 dose (RP2D). Secondary objectives include assessing iadademstat’s activity to induce fetal hemoglobin (HbF), among others. SCD is a chronic, inherited blood disorder caused by a mutation in the β-globin gene, leading to the production of hemoglobin S (HbS) instead of the normal hemoglobin A. Under low oxygen conditions, HbS tends to polymerize, causing red blood cells to assume a sickle shape, becoming rigid and fragile. This results in microvascular occlusion, hemolysis, and chronic inflammation. The clinical manifestations of SCD include vaso-occlusion and hemolytic anemia, which lead to vaso-occlusive crises (VOCs), acute and progressive organ damage, reduced quality of life, and premature mortality. SCD is the most common inherited blood disorder in the United States and represents a significant unmet medical need, with limited therapeutic options currently available. Dr. Ana Limón, Senior Vice-president of Clinical Development and Medical Affairs at Oryzon said, “We are thrilled to be the only LSD1 inhibitor currently into clinical development for SCD. Targeting LSD1 presents a highly promising therapeutic approach for this disease, which affects approximately 7.7 million people worldwide as per 2025 estimates. Iadademstat has produced a significant increase in HbF levels in baboons, the only animal model with strong translational relevance to humans, after just a single dose. Increased HbF levels mitigate — and potentially reverse — the pathological phenotype of the disease, and increases in HbF have already been recognized by the FDA as a clinically meaningful endpoint for the treatment of SCD. The trial has been carefully designed to deliver a rapid and clear signal of biological activity.” According to multiple market research reports, the SCD treatment market is expected to grow substantially — from approximately USD 3 billion in 2025 to around USD 8 billion by 2032. While gene therapies that reinduce HbF have received FDA approval, their widespread use is constrained by technical complexity and very high costs, limiting access for much of the global patient population. Oxbryta, a once-approved oral therapy for SCD, reached annual sales of USD 328 million in a relatively short period of time, before being withdrawn from the market. This underscores both the strong commercial potential and the urgent unmet need for effective, scalable, and accessible treatments for SCD. Iadademstat is also under active investigation in multiple oncology clinical trials. These include the company-sponsored FRIDA trial in combination with gilteritinib in relapsed/refractory FLT3-mutated acute myeloid leukemia (AML), as well as several trials conducted under a Cooperative Research and Development Agreement (CRADA) in place with the U.S. National Cancer Institute or as investigator-initiated trials conducted by U.S. institutions, including two trials in combination with venetoclax and azacitidine in first-line AML, and a trial in combination with immune checkpoint inhibitors in small cell lung cancer. Founded in 2000 in Barcelona, Spain, Oryzon (ISIN Code: ES0167733015) is a clinical stage biopharmaceutical company and the European leader in epigenetics, with a strong focus on personalized medicine in CNS disorders and oncology. Oryzon’s team is composed of highly qualified professionals from the pharma industry located in Barcelona, Boston, and San Diego. Oryzon has an advanced clinical portfolio with two LSD1 inhibitors, vafidemstat in CNS (Phase III-ready) and iadademstat in oncology (Phase II). The company has other pipeline assets directed against other epigenetic targets like HDAC-6 where a clinical candidate, ORY-4001, has been nominated for its possible development in CMT and ALS. In addition, Oryzon has a strong platform for biomarker identification and target validation for a variety of malignant and neurological diseases. Iadademstat (ORY-1001) is a small oral molecule, which acts as a highly selective inhibitor of the epigenetic enzyme LSD1 and has a powerful differentiating effect in hematologic cancers (see Maes et al., Cancer Cell 2018 Mar 12; 33 (3): 495-511.e12.doi: 10.1016 / j.ccell.2018.02.002.). A FiM Phase I/IIa clinical trial with iadademstat in R/R AML patients demonstrated the safety and good tolerability of the drug and preliminary signs of antileukemic activity, including a CRi (see Salamero et al, J Clin Oncol, 2020, 38(36): 4260-4273. doi: 10.1200/JCO.19.03250). Iadademstat has shown encouraging safety and strong clinical activity in combination with azacitidine in a Phase IIa trial in elder 1L AML patients (ALICE trial) (see Salamero et al., ASH 2022 oral presentation & The Lancet Haematology, 2024, 11(7):e487-e498). Iadademstat is currently being evaluated in combination with gilteritinib in the ongoing Phase Ib FRIDA trial in patients with relapsed/refractory AML with FLT3 mutations, and in combination with azacitidine and venetoclax in 1L AML in an investigator-initiated study led by OHSU and in a trial sponsored by the U.S. National Cancer Institute (NCI) under the Cooperative Research and Development Agreement (CRADA) signed between Oryzon and the NCI to collaborate on further clinical development of iadademstat in different types of hematologic and solid cancers. Beyond hematological cancers, the inhibition of LSD1 has been proposed as a valid therapeutic approach in some solid tumors such as small cell lung cancer (SCLC), neuroendocrine tumors (NET), medulloblastoma and others. In a Phase IIa trial in combination with platinum/etoposide in second line ED-SCLC patients (CLEPSIDRA trial), preliminary activity and safety results have been reported (see Navarro et al., ESMO 2018 poster). Iadademstat is in a Phase I/II randomized trial in 1L ED-SCLC in combination with ICI sponsored by NCI and led by the Memorial Sloan Kettering Cancer Center. Oryzon is further expanding the clinical development of iadademstat in oncology through additional CRADA and investigator-initiated studies. In addition, Oryzon is expanding iadademstat’s clinical development into non-oncological hematology indications, with trials in sickle cell disease (CTA approved) and essential thrombocythemia (trial in preparation). Iadademstat has orphan drug designation for SCLC in the U.S. and for AML in the U.S. and EU. The content above comes from the network. if any infringement, please contact us to modify.

Orphan DrugGene TherapyClinical Result

100 Deals associated with Etoposide

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KEGG	Wiki	ATC	Drug Bank
D00125	Etoposide	L01CB01	DB00773

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Approved

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Indication	Country/Location	Organization	Date
Bladder Cancer	Japan	Clinigen Ltd.	30 Apr 1987
Leukemia	Japan	Clinigen Ltd.	30 Apr 1987
Lymphoma	Japan	Nippon Kayaku Co., Ltd.	31 Mar 1987
Ovarian Cancer	Japan	Nippon Kayaku Co., Ltd.	31 Mar 1987
Uterine Cervical Cancer	Japan	Nippon Kayaku Co., Ltd.	31 Mar 1987
Small Cell Lung Cancer	United States	Corden Pharma Latina SpA	10 Nov 1983
Testicular Neoplasms	United States	Corden Pharma Latina SpA	10 Nov 1983

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Indication	Highest Phase	Country/Location	Organization	Date
Platinum-Resistant Ovarian Carcinoma	Phase 3	China	Jiangsu Hengrui Pharmaceuticals Co., Ltd.	16 Aug 2019
Unknown Primary Neoplasms	Phase 3	United States	Pharmacia & Upjohn, Inc.	01 Sep 2003
Unknown Primary Neoplasms	Phase 3	United States	AstraZeneca PLC	01 Sep 2003
Unknown Primary Neoplasms	Phase 3	United States	Eli Lilly & Co.	01 Sep 2003
Extensive stage Small Cell Lung Cancer	Phase 3	United States	GSK Plc	01 Apr 2001
Extensive stage Small Cell Lung Cancer	Phase 3	China	GSK Plc	01 Apr 2001
Extensive stage Small Cell Lung Cancer	Phase 3	Austria	GSK Plc	01 Apr 2001
Extensive stage Small Cell Lung Cancer	Phase 3	Belgium	GSK Plc	01 Apr 2001
Extensive stage Small Cell Lung Cancer	Phase 3	Brazil	GSK Plc	01 Apr 2001
Extensive stage Small Cell Lung Cancer	Phase 3	Bulgaria	GSK Plc	01 Apr 2001

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04585893 (LCCC 1950, CTgov)	Phase 2	Multi-Centric Castleman's Disease	15	etoposide+rituximab (High-risk Patients)	mtzoqgtpgh = uxndwatkba biyiuigqdp (fosnlmaarm, ntbpxawmrm - pncahqcmth) View more	-	11 Sep 2025
NCT04585893 (LCCC 1950, CTgov)	Phase 2	Multi-Centric Castleman's Disease	15	rituximab (Low-risk Patients)	mtzoqgtpgh = iykmepvyve biyiuigqdp (fosnlmaarm, njgsokapcr - nqmjvnbpsg) View more	-	11 Sep 2025
NCT03517137 (COBRA \| EORTC-1537-COBRA, CTgov)	Phase 2	Hodgkin's Lymphoma \| Relapsing classical Hodgkin lymphoma	150	Radiation Therapy+Dacarbazine+Etoposide+Cyclophosphamide+Adriamycin+Vinblastine+Brentuximab Vedotin	dclcmfpvsx(clfnsiisur) = nzwhnoryqm vsvnjfnhcr (eozsqenmxz, ekmfxoxatr - vimrqrihxl) View more	-	11 Aug 2025
NCT02278796 (BEB-Trial \| BEB, CTgov)	Phase 2	Follicular Lymphoma \| Mantle-Cell Lymphoma \| Diffuse Large B-Cell Lymphoma	108	etoposide+bendamustine+melphalan+cytarabine (BeEAM)	msrhzlieed = kfimqcihgv edueyxdgpm (jcjbeztzau, unnorkcdoj - cgyqxbmfqh) View more	-	01 Aug 2025
NCT02278796 (BEB-Trial \| BEB, CTgov)	Phase 2		108	etoposide+carmustine+melphalan+cytarabine (BEAM)	msrhzlieed = onjninjbue edueyxdgpm (jcjbeztzau, ekzyoctqst - bpzmerhhdf) View more	-	01 Aug 2025
NCT00878254 (CTgov)	Phase 2	Mantle-Cell Lymphoma	25	Mesna+Etoposide+Cyclophosphamide+Leucovorin+G-CSF+Doxorubicin+ifosfamide+Methotrexate+Rituximab+Vincristine+Cytarabine	ienjyoukee(tznrtpkoai) = jmqsdapkdt exxatxetpp (saepsprllu, yvrbvurpzp - exzyncooiu) View more	-	23 Jul 2025
["HD21"] (Pubmed \| J Clin Oncol)	Phase 2	Classical Hodgkin's Lymphoma First line	83	Brentuximab vedotin + Etoposide + Cyclophosphamide + Doxorubicin + Dacarbazine + Dexamethasone (BrECADD) (PET2-negative)	gerobevczb(ikzodpypnd) = dumblowrhi fdfgyvwbxz (kqwqdphuwq, 84 - 98) View more	Positive	17 Jul 2025
["ENLEN-OC-001"] (Pubmed \| Oncologist)	Phase 2	Platinum-Resistant Ovarian Carcinoma	18	Envafolimab + Lenvatinib + Etoposide	yhzzijcyws(xzwzxczefg) = ysqacyobhg dcwitkcoxx (npdswsnzob, 21.5 - 69.2) View more	Positive	14 Jul 2025
NCT04530487 (CTgov)	Phase 2	Refractory Malignant Solid Neoplasm \| Relapsed Solid Neoplasm \| Neuroblastoma recurrent ... View more	1	ATG+cyclosporine+etoposide+mephalan+tacrolimus+MMF+thiotepa	jmgvtdlpag(cicujiniyu) = aakpbkfcha rnuozinjco (qjicsgnonr, mjwjylchst - idlrwfmoao) View more	-	29 Jun 2025
NCT03811002 (NRG-LU005, CTgov)	Phase 3	Small cell lung cancer limited stage	544	Intensity-Modulated Radiation Therapy+Etoposide+Carboplatin+cisplatin (Arm I (Chemotherapy, Radiation Therapy))	qwypfeplvj(uvfrghbekn) = lvwsbwocmd yjryvlrmcs (itjrupsnfs, aojmdrzfyo - vlmqlodjzz) View more	-	12 Jun 2025
NCT03811002 (NRG-LU005, CTgov)	Phase 3	Small cell lung cancer limited stage	544	Intensity-Modulated Radiation Therapy+Etoposide+Carboplatin+cisplatin+Atezolizumab (Arm II (Chemotherapy, Radiation Therapy, Atezolizumab))	qwypfeplvj(uvfrghbekn) = xmlxfgccbl yjryvlrmcs (itjrupsnfs, xevsvqrsac - lnzyffiqyf) View more	-	12 Jun 2025
NCT02262325 (CTgov)	Phase 2	Non-small cell lung cancer stage IIIA \| Non-small cell lung cancer stage IIIB \| Recurrent Non-Small Cell Lung Cancer ... View more	21	3-dimensional conformal radiation therapy+etoposide+cisplatin	iyjfwdertl = eeaksoqjus kuicvrbgpx (czrlipgwfm, yxvomijwjs - gzlfvysxlv) View more	-	12 Jun 2025
NCT00476190 (CTgov)	Phase 2	Adult Acute Lymphocytic Leukemia	112	Radiation Therapy+PEG-Asparaginase+Etoposide+doxorubicin+Hydrocortisone Sodium Succinate+6-MP+Methotrexate+Cytarabine+Methylprednisone+Cyclophosphamide+Imatinib+Dexamethasone+E. coli Asparaginase+Vincristine (Pre-amendment Cohort, 2500 IU/m2 q2 Weeks)	jpzlnqxrlh = krgctugbup dfviegyuuv (okxijypepk, pecvbxhrom - gnyiyzslcu) View more	-	12 Jun 2025
NCT00476190 (CTgov)	Phase 2	Adult Acute Lymphocytic Leukemia	112	Radiation Therapy+PEG-Asparaginase+Etoposide+Doxorubicin+Hydrocortisone Sodium Succinate+6-MP+Methotrexate+Cytarabine+Methylprednisone+Cyclophosphamide+Imatinib+Dexamethasone+E. coli Asparaginase+Vincristine (Post-amendment Cohort, 2000 IU/m2 q3 Weeks)	jpzlnqxrlh = azsceouuru dfviegyuuv (okxijypepk, rwgiqfkouz - cihsoveizo) View more	-	12 Jun 2025

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