34 results match your criteria mirvetuximab soravtansine


Revisiting antibody-drug conjugates and their predictive biomarkers in platinum-resistant ovarian cancer.

Semin Cancer Biol 2021 Apr 1. Epub 2021 Apr 1.

Department of Medical Oncology, Mohammed VI University Hospital, Oujda, Morocco; Faculty of Medicine and Pharmacy, Mohammed Ist University, Oujda, Morocco.

Until to date, platinum derived drugs are still the backbone of treating ovarian cancer (OC). Most patients treated with platinum-based chemotherapy develop resistance during the course of their management. The treatment of platinum-resistant ovarian cancer (PROC) is challenging. Read More

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Phase III, randomized trial of mirvetuximab soravtansine versus chemotherapy in patients with platinum-resistant ovarian cancer: primary analysis of FORWARD I.

Ann Oncol 2021 Mar 2. Epub 2021 Mar 2.

Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, USA.

Background: Mirvetuximab soravtansine (MIRV) is an antibody-drug conjugate comprising a folate receptor alpha (FRα)-binding antibody, cleavable linker, and the maytansinoid DM4, a potent tubulin-targeting agent. The randomized, open-label, phase III study FORWARD I compared MIRV and investigator's choice chemotherapy in patients with platinum-resistant epithelial ovarian cancer (EOC).

Patients And Methods: Eligible patients with 1-3 prior lines of therapy and whose tumors were positive for FRα expression were randomly assigned, in a 2 : 1 ratio, to receive MIRV (6 mg/kg, adjusted ideal body weight) or chemotherapy (paclitaxel, pegylated liposomal doxorubicin, or topotecan). Read More

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A phase II study of Mirvetuximab Soravtansine in triple-negative breast cancer.

Invest New Drugs 2021 Apr 28;39(2):509-515. Epub 2020 Sep 28.

Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Dan L. Duncan Building CPB5.3542, 1515 Holcombe Blvd. Unit 1354, Houston, TX, 77030, USA.

Folate receptor alpha (FRα) has been reported to be expressed in up to 80% of triple-negative breast cancers (TNBC) with limited expression in normal tissues, making it a promising therapeutic target. Mirvetuximab soravtansine (mirvetuximab-s) is an antibody drug conjugate which has shown promise in the treatment of FRα-positive solid tumors in early phase clinical trials. Herein, are the results of the first prospective phase II trial evaluating mirvetuximab-s in metastatic TNBC. Read More

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Mirvetuximab Soravtansine Combination Yields Encouraging Response Rates in Ovarian Cancer.

Authors:
Matthew Fowler

Oncology (Williston Park) 2020 Jul;34(7):250

Mirvetuximab soravtansine in combination with bevacizumab (Avastin) to treat patients with platinum-agnostic ovarian cancer demonstrated a confirmed 64% overall response rate (ORR), regardless of platinum status, according to study results presented at the 2020 American Society of Clinical Oncology Virtual Scientific Program. Read More

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Novel antibody-drug conjugates: current and future roles in gynecologic oncology.

Curr Opin Obstet Gynecol 2021 Feb;33(1):26-33

Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut, USA.

Purpose Of Review: Antibody-drug conjugates (ADCs) represent a new class of drugs that combine a surface receptor-targeting antibody linked to a cytotoxic molecule. This review summarizes the current literature demonstrating their tremendous promise as therapeutic agents in the treatment of aggressive gynecologic malignancies.

Recent Findings: Several antigens have proven to be differentially overexpressed in a variety of gynecologic tumors when compared with normal surrounding tissue and serve as novel targets for ADC therapy. Read More

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February 2021

Antibody-drug conjugates for the treatment of ovarian cancer.

Expert Opin Biol Ther 2020 Jun 8:1-13. Epub 2020 Jun 8.

Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Ohio State University, Columbus, OH, USA.

Introduction: Ovarian cancer typically presents at an advanced stage and while initial chemotherapy response rates are favorable, a majority of patients experience recurrence with the subsequent development of chemoresistance. Recurrent, platinum-resistant disease is associated with a very poor prognosis as treatment in this setting is often limited by systemic toxicity. Antibody-drug conjugates (ADCs) are novel therapeutic agents designed to target antigens specific to ovarian tumor cells with direct delivery of cytotoxic agents to combat recurrent, platinum-resistant disease while limiting systemic toxicity. Read More

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Exploiting the folate receptor α in oncology.

Nat Rev Clin Oncol 2020 06 9;17(6):349-359. Epub 2020 Mar 9.

The Institute of Cancer Research, London, UK.

Folate receptor α (FRα) came into focus as an anticancer target many decades after the successful development of drugs targeting intracellular folate metabolism, such as methotrexate and pemetrexed. Binding to FRα is one of several methods by which folate is taken up by cells; however, this receptor is an attractive anticancer drug target owing to the overexpression of FRα in a range of solid tumours, including ovarian, lung and breast cancers. Furthermore, using FRα to better localize effective anticancer therapies to their target tumours using platforms such as antibody-drug conjugates, small-molecule drug conjugates, radioimmunoconjugates and, more recently, chimeric antigen receptor T cells could further improve the outcomes of patients with FRα-overexpressing cancers. Read More

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Phase Ib study of mirvetuximab soravtansine, a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC), in combination with bevacizumab in patients with platinum-resistant ovarian cancer.

Gynecol Oncol 2020 05 18;157(2):379-385. Epub 2020 Feb 18.

Stephenson Cancer Center at the University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States; Sarah Cannon Research Institute, Nashville, TN, United States. Electronic address:

Purpose: To evaluate the safety and clinical activity of mirvetuximab soravtansine, an antibody-drug conjugate comprising a humanized anti-folate receptor alpha (FRα) monoclonal antibody, cleavable linker, and the maytansinoid DM4, a potent tubulin-targeting agent, in combination with bevacizumab in patients with FRα-positive, platinum-resistant ovarian cancer.

Methods: Patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer were administered mirvetuximab soravtansine (6 mg/kg, adjusted ideal body weight) and bevacizumab (15 mg/kg) once every 3 weeks. Eligibility included FRα positivity by immunochemistry and prior bevacizumab exposure was permitted. Read More

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Novel therapeutics: response and resistance in ovarian cancer.

Authors:
Dmitriy Zamarin

Int J Gynecol Cancer 2019 08;29(Suppl 2):s16-s21

Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA

Here we review the latest pre-clinical and clinical developments for treatment of ovarian cancer, presented at the American Association of Cancer Research/Rivkin Center Ovarian Cancer Research Symposium held at the University of Washington in September 2018. Abstracts and presentations pertaining to the 'Novel Therapeutics' session were reviewed and are summarized here. The session featured a keynote presentation from Dr Ursula Matulonis, who summarized the current state of the art of treatment of ovarian cancer, including recent clinical trials incorporating the use of novel agents, including poly-ADP-ribose polymerase (PARP) inhibitors, other DNA-damaging agents, vascular endothelial growth factor receptor inhibitors, mirvetuximab soravtansine, and immune checkpoint blockade. Read More

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Folate Receptor α-Targeted Zr-M9346A Immuno-PET for Image-Guided Intervention with Mirvetuximab Soravtansine in Triple-Negative Breast Cancer.

Mol Pharm 2019 09 16;16(9):3996-4006. Epub 2019 Aug 16.

ImmunoGen, Inc. , Waltham , Massachusetts 02451 , United States.

Folate receptor α (FRα) is a well-studied tumor biomarker highly expressed in many epithelial tumors such as breast, ovarian, and lung cancers. Mirvetuximab soravtansine (IMGN853) is the antibody-drug conjugate of FRα-binding humanized monoclonal antibody M9346A and cytotoxic maytansinoid drug DM4. IMGN853 is currently being evaluated in multiple clinical trials, in which the immunohistochemical evaluation of an archival tumor or biopsy specimen is used for patient screening. Read More

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September 2019

Known and novel ocular toxicities of biologics, targeted agents, and traditional chemotherapeutics.

Graefes Arch Clin Exp Ophthalmol 2019 Aug 16;257(8):1771-1781. Epub 2019 May 16.

Department of Ophthalmology and Visual Science, Havener Eye Institute, The Ohio State University, Wexner Medical Center, 915 Olentangy River Rd, Ste 5000, Columbus, OH, 43212, USA.

Purpose: Increases in cancer with an aging population and the rapid development of new chemotherapeutics underscore the need for ophthalmologists to identify and manage potential ocular toxicities. This retrospective case series reports the ocular side effects of traditional and novel chemotherapeutic agents from a large center.

Methods: The medical records of 3537 adult patients 18 years and older who presented to an academic ophthalmology department on high-risk medications identified by ICD-9 search between January 2010 and February 2015 were reviewed. Read More

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Antibody-drug conjugates in gynecologic malignancies.

Gynecol Oncol 2019 06 28;153(3):694-702. Epub 2019 Mar 28.

Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA; Division of Gynecologic Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. Electronic address:

Antibody drug conjugates (ADCs) are an exciting class of oncologic therapeutics. ADCs have been FDA approved in hematologic malignancies and breast cancer and are a growing area of study in numerous solid malignancies. The desire for tumor-specific therapies with decreased systemic toxicity has driven over a decade of research into the design and optimization of ADCs, which are now in a third generation of development. Read More

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Highlights of the NCCN Oncology Research Program.

Authors:

J Natl Compr Canc Netw 2019 01;17(1):xxxvii

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January 2019

Clinical Trials of Novel Targeted Therapies in Ovarian Cancer: Moving Beyond Poly ADP Ribose Polymerase (PARP) Inhibitors.

Curr Pharm Biotechnol 2018 ;19(14):1114-1121

RD Center, Pacificbio Inc. Irvine, CA 92602, United States.

Background: Epithelial ovarian cancer (EOC) is one of the most common cancers in the female reproductive system and deadliest gynecological cancer in the United States. Standard treatments by surgery and platinum-based chemotherapy are not satisfied for the patients with high risk of relapse. Advances in molecular biology for EOC development have brought several targeted therapies to benefit recurrent patients. Read More

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Antibody-drug conjugates for ovarian cancer: current clinical development.

Curr Opin Obstet Gynecol 2019 02;31(1):18-23

Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, Duarte, California, USA.

Purpose Of Review: Antibody drug conjugates (ADC) are a novel class of cancer therapeutics, delivering cytotoxic therapy directly to cancer cells, and show promise in the management of platinum-resistant ovarian cancer. Herein we summarize the ADC landscape currently in clinical study.

Recent Findings: Mirvetuximab Soravtansine, IMGN853, is an ADC targeting the folate receptor alpha (FRα) and has demonstrated promising single agent activity and a favorable toxicity profile in FRα-positive, platinum-resistant, epithelial ovarian cancer (EOC). Read More

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February 2019

Antibodies to watch in 2019.

MAbs 2019 Feb/Mar;11(2):219-238. Epub 2018 Dec 22.

b The Antibody Society , Framingham , MA , USA.

For the past 10 years, the annual 'Antibodies to watch' articles have provided updates on key events in the late-stage development of antibody therapeutics, such as first regulatory review or approval, that occurred in the year before publication or were anticipated to occur during the year of publication. To commemorate the 10th anniversary of the article series and to celebrate the 2018 Nobel Prizes in Chemistry and in Physiology or Medicine, which were given for work that is highly relevant to antibody therapeutics research and development, we expanded the scope of the data presented to include an overview of all commercial clinical development of antibody therapeutics and approval success rates for this class of molecules. Our data indicate that: 1) antibody therapeutics are entering clinical study, and being approved, in record numbers; 2) the commercial pipeline is robust, with over 570 antibody therapeutics at various clinical phases, including 62 in late-stage clinical studies; and 3) Phase 1 to approval success rates are favorable, ranging from 17-25%, depending on the therapeutic area (cancer vs. Read More

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Review of Immune Therapies Targeting Ovarian Cancer.

Curr Treat Options Oncol 2018 11 14;19(12):74. Epub 2018 Nov 14.

Division of Gynecologic Oncology, Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland-Baltimore, 22 S. Greene Street S3AX31, Baltimore, MD, 21201, USA.

Opinion Statement: The rise of immunotherapy is the greatest advance in oncology to occur over the last several years, but applications in gynecologic malignancies lag behind other tumors. The term "immunotherapy" envelops monoclonal antibodies as receptor mediators, including immune checkpoint inhibitors (ICPI), cancer vaccines, and adoptive immunotherapies alone or in combination with other therapeutic approaches. The purpose of this review is to summarize the status of immunotherapy trials in ovarian cancer and to specifically highlight data published in the last 1-2 years. Read More

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November 2018

Evaluation of Prophylactic Corticosteroid Eye Drop Use in the Management of Corneal Abnormalities Induced by the Antibody-Drug Conjugate Mirvetuximab Soravtansine.

Clin Cancer Res 2019 03 9;25(6):1727-1736. Epub 2018 Nov 9.

University of Texas McGovern Medical School, Houston, Texas.

Purpose: Reversible, low-grade ocular adverse events (AE) are associated with administration of mirvetuximab soravtansine, a folate receptor alpha (FRα)-targeted antibody-drug conjugate undergoing phase III clinical evaluation in platinum-resistant ovarian cancer. This study investigated the underlying mechanisms of ocular toxicity and evaluated primary prophylactic use of corticosteroid eye drops in patients receiving mirvetuximab soravtansine.

Patients And Methods: Target expression in the human eye was determined by IHC. Read More

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Ocular Toxicity of Mirvetuximab.

Cornea 2019 Feb;38(2):229-232

Department of Ophthalmology, University Vita-Salute, IRCCS Ospedale San Raffaele, Milan, Italy.

Purpose: To report the clinical features and outcomes of corneal toxicity following mirvetuximab soravtansine therapy.

Methods: Five patients who were treated with mirvetuximab soravtansine were evaluated in our hospital for ocular symptoms during a period of 5 months between December 2017 and April 2018. A complete ophthalmologic examination, including anterior segment infrared reflectance (AS-IR) and anterior segment optical coherence tomography (AS-OCT), was performed. Read More

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February 2019

Potential Novel Therapy Targets in Neuroendocrine Carcinomas of the Breast.

Clin Breast Cancer 2019 04 5;19(2):131-136. Epub 2018 Sep 5.

Caris Life Sciences, Phoenix, AZ. Electronic address:

Introduction: Neuroendocrine carcinoma (NEC) of the breast is a rare, special type of breast cancer, reportedly constituting 2% to 5% of all breast cancers. Although breast NEC does not have a specific targeted therapy, several new targeted therapies based on specific biomarkers were recently investigated in the NEC of lung and in other types of breast carcinoma, which may provide guidance to their feasibility in breast NEC.

Materials And Methods: Twenty breast NECs were profiled for biomarkers of therapy including antibody-drug conjugates (DLL3, TROP-2, and FOLR1), histone deacetylase (H3K36Me3) inhibitors, tropomyosin receptor kinases (NTRK1/2/3 gene fusions) targeted inhibitors, alkylating agents (MGMT), and immune checkpoint inhibitors (PD-L1, TMB, and MSI) using immunohistochemistry and DNA/RNA next-generation sequencing assays. Read More

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Safety and activity findings from a phase 1b escalation study of mirvetuximab soravtansine, a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC), in combination with carboplatin in patients with platinum-sensitive ovarian cancer.

Gynecol Oncol 2018 10 6;151(1):46-52. Epub 2018 Aug 6.

Massachusetts General Hospital, Boston, MA, United States. Electronic address:

Purpose: To evaluate the safety profile and preliminary antitumor activity of mirvetuximab soravtansine when administered in combination with carboplatin to relapsed ovarian cancer patients.

Methods: Patients with recurrent, platinum-sensitive epithelial ovarian or fallopian tube cancer were enrolled. Eligibility included a minimum requirement of tumor FRα positivity (≥25% of cells with ≥2+ staining intensity). Read More

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October 2018

and Activity of IMGN853, an Antibody-Drug Conjugate Targeting Folate Receptor Alpha Linked to DM4, in Biologically Aggressive Endometrial Cancers.

Mol Cancer Ther 2018 05 13;17(5):1003-1011. Epub 2018 Feb 13.

Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, Connecticut.

Grade 3 endometrioid and uterine serous carcinomas (USC) account for the vast majority of endometrial cancer deaths. The purpose of this study was to determine folic acid receptor alpha (FRα) expression in these biologically aggressive (type II) endometrial cancers and evaluate FRα as a targetable receptor for IMGN853 (mirvetuximab soravtansine). The expression of FRα was evaluated by immunohistochemistry (IHC) and flow cytometry in 90 endometrioid and USC samples. Read More

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FORWARD I: a Phase III study of mirvetuximab soravtansine versus chemotherapy in platinum-resistant ovarian cancer.

Future Oncol 2018 Jul 9;14(17):1669-1678. Epub 2018 Feb 9.

Division of Hematology-Oncology, University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham, AL 35294, USA.

Mirvetuximab soravtansine, an antibody-drug conjugate that binds with high affinity to folate receptor-α to provide tumor-directed delivery of the potent microtubule-disrupting agent DM4, has emerged as a promising investigational agent for the treatment of ovarian cancer, particularly in the setting of platinum-resistant disease. Here we describe the rationale and design of FORWARD I (NCT02631876), the first randomized, multicenter Phase III study to compare the safety and efficacy of mirvetuximab soravtansine versus investigator's choice of chemotherapy in women with folate receptor-α-positive, platinum-resistant epithelial ovarian, primary peritoneal or fallopian tube cancer. Patients will be randomized in a 2:1 ratio. Read More

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Antibodies to watch in 2018.

MAbs 2018 Feb/Mar;10(2):183-203. Epub 2018 Jan 16.

b The Antibody Society , Framingham , MA , USA.

The pace of antibody therapeutics development accelerated in 2017, and this faster pace is projected to continue through 2018. Notably, the annual number of antibody therapeutics granted a first approval in either the European Union (EU) or United States (US) reached double-digits (total of 10) for the first time in 2017. The 10 antibodies granted approvals are: brodalumab, dupilumab, sarilumab, guselkumab, benralizumab, ocrelizumab, inotuzumab ozogamicin, avelumab, duvalumab, and emicizumab. Read More

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January 2019

New treatments in ovarian cancer.

Ann Oncol 2017 Nov;28(suppl_8):viii57-viii60

Hôpital Hôtel-Dieu, Centre des Cancers de la Femme et Recherche Clinique, AP-HP, Université Paris Descartes, Paris, France.

In targeting DNA repair pathways of the most genomic instable cancer, poly-(adenosine diphosphate [ADP])-ribose polymerase inhibitors (PARPi) have been demonstrated as the most effective drug since platinum in high grade serous or endometrioid ovarian cancer. Immunotherapy is strongly pushing the door of ovarian cancer and has the ambition to change the fate of this deadly disease when combined with chemotherapy, vascular endothelial growth factor inhibitor or PARPi. The activity of PARPi could also be improved by modulators of the cell cycle, which are required to give time enough for DNA repair. Read More

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November 2017

Antibody-Drug Conjugates for the Treatment of Solid Tumors: Clinical Experience and Latest Developments.

Target Oncol 2017 Dec;12(6):719-739

Massachusetts General Hospital Cancer Center, Harvard Medical School, Lawrence House 304, 10 North Grove St., Boston, MA, 02114, USA.

Antibody-drug conjugates (ADCs) are complex immunoconjugates designed to selectively deliver toxic small molecules preferentially to cancer cells. These immunoconjugates consist of a monoclonal antibody - directed to a tumor antigen - and a cytotoxic agent that is conjugated to the antibody via a molecular linker. Following the binding to a specific antigen on the surface of cancer cells, the conjugate is internalized and releases its cytotoxic payload to kill the malignant cell. Read More

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December 2017

A review of mirvetuximab soravtansine in the treatment of platinum-resistant ovarian cancer.

Future Oncol 2018 Jan 3;14(2):123-136. Epub 2017 Nov 3.

Gillette Center for Gynecologic Oncology, Massachusetts General Hospital, Boston, MA 02114, USA.

Resistance to platinum-based therapy poses a significant clinical challenge for the management of advanced ovarian cancer, a leading cause of cancer mortality among women. Mirvetuximab soravtansine is a novel antibody-drug conjugate that targets folate receptor-α, a validated molecular target for therapeutic intervention in this disease. Here, we examine mirvetuximab soravtansine's mechanism of action and pharmacology, and review its clinical evaluation in ovarian cancer to date. Read More

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January 2018

Characterization of folate receptor alpha (FRα) expression in archival tumor and biopsy samples from relapsed epithelial ovarian cancer patients: A phase I expansion study of the FRα-targeting antibody-drug conjugate mirvetuximab soravtansine.

Gynecol Oncol 2017 11 24;147(2):402-407. Epub 2017 Aug 24.

Massachusetts General Hospital, Boston, MA, United States. Electronic address:

Purpose: To characterize folate receptor alpha (FRα) expression in archival and fresh biopsy tumor samples from relapsed ovarian cancer patients.

Methods: Patients with ovarian tumors amenable to biopsy were eligible to enroll. Eligibility included a minimum requirement of FRα positivity in archival tumor samples (≥25% of cells with ≥2+ staining intensity). Read More

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November 2017

Development and Characterization of a Neutralizing Anti-idiotype Antibody Against Mirvetuximab for Analysis of Clinical Samples.

AAPS J 2017 07 22;19(4):1223-1234. Epub 2017 May 22.

BioAnalytical Sciences, ImmunoGen, Inc., 830 Winter Street, Waltham, Massachusetts, 02453, USA.

Antibody-drug-conjugates (ADCs) are an emerging class of biological therapeutics. Mirvetuximab soravtansine is a novel folate receptor alpha (FRα)-targeting ADC which represents a potential new treatment for patients with ovarian and other FRα-positive cancers. Since patient immune responses to biological therapeutics may negatively affect drug efficacy and patient safety, regulatory authorities require rigorous monitoring of patient samples. Read More

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Phase 1 dose-escalation study of mirvetuximab soravtansine (IMGN853), a folate receptor α-targeting antibody-drug conjugate, in patients with solid tumors.

Cancer 2017 Aug 25;123(16):3080-3087. Epub 2017 Apr 25.

Gillette Center for Gynecologic Oncology, Massachusetts General Hospital, Boston, Massachusetts.

Background: Mirvetuximab soravtansine (IMGN853) is an antibody-drug conjugate that selectively targets folate receptor α (FRα). In this phase 1 dose-escalation study, the authors investigated IMGN853 in patients with FRα-positive solid tumors.

Methods: Patients received IMGN853 on day 1 of a 21-day cycle (once every 3 weeks dosing), with cycles repeated until patients experienced dose-limiting toxicity or progression. Read More

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