Tisotumab Vedotin-tftv

Pictured: FDA sign outside its office in Washington, DC/iStock, JHVEPhoto AbbVie and Genmab’s bispecific antibody Epkinly (epcoritamab) can now be used to treat patients with relapsed or refractory follicular lymphoma, based on an FDA approval on Wednesday. Epkinly is now the “first and only” T-cell-engaging bispecific antibody for the subcutaneous treatment of relapsed or refractory follicular lymphoma, according to the companies. The label expansion was approved under the FDA’s accelerated pathway, and its continued approval will depend on the validation of its clinical benefit in a confirmatory Phase III trial. Mariana Cota Stirner, therapeutic area head for hematology at AbbVie, in a statement said that with the label expansion Epkinly now “offers a new treatment option for relapsed or refractory follicular lymphoma, particularly following failure of other therapies.” Given its deep and durable response rates and convenient dosing, Epkinly “has the potential to be a core therapy in the treatment of multiple B-cell malignancies,” Stirner said. Epkinly is an IgG1-bispecific antibody that targets the CD3 protein—found on T cells—and the CD20 antigen, which is typically expressed by B cells. This dual-targeting mechanism of action enables Epkinly to bring the cytotoxic T cells close to the malignant B cells and mount an anti-cancer response. The bispecific antibody was first developed by Genmab using its proprietary DuoBody platform. In June 2020, AbbVie paid Genmab $750 million upfront and pledged up to $3.15 billion in milestones to jointly develop and commercialize the therapy. The partners won their first FDA approval in May 2023, allowing the use of Epkinly in relapsed or refractory diffuse large B-cell lymphoma. Wednesday’s label expansion was backed by data from the Phase I/II EPCORE NHL-1 trial, which included 127 adult follicular lymphoma patients who had undergone a median of three prior lines of therapy. The majority of the patients also had double refractory disease. Results from the trial showed that Epkinly achieved an objective response rate of 82%, including a 60% complete response rate and a 22% partial response rate. After a median follow-up of 14.8 months, more than half of responders remained responsive to Epkinly. EPCORE NHL-1 did not reach the median duration of response. For AbbVie, Epkinly’s label expansion could help soothe the FDA’s rejection of its Parkinson’s disease therapy ABBV-95 earlier this week, citing issues with a third-party manufacturer. At the same time, the regulator found no issues with the candidate’s safety or efficacy, nor did it identify problems with the administration device. Meanwhile, Wednesday’s approval continued Genmab’s regulatory winning streak which includes an April 2024 full FDA approval for its Pfizer-partnered antibody-drug conjugate Tivdak (tisotumab vedotin-tftv) in recurrent or metastatic cervical cancer. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

Media Release COPENHAGEN, Denmark; June 3, 2024 Results from innovaTV207 evaluating tisotumab vedotin, showing 32.5% confirmed objective response rate in patients with recurrent or metastatic HNSCC, presented in a rapid oral session at 2024 ASCO® Annual MeetingHNSCC is the sixth most common cancer worldwide, with incidence rates expected to increase 30% by 2030i Genmab A/S (Nasdaq: GMAB) announced today that data from the Phase 2 innovaTV 207 trial (NCT03485209) Part C (n=40), investigating tisotumab vedotin, an antibody-drug conjugate directed to tissue factor, demonstrated encouraging antitumor activity as a monotherapy in patients with head and neck squamous cell carcinoma (HNSCC) who experienced disease progression on or after first-line therapy. The study showed 32.5% of patients achieved a confirmed objective response rate (cORR), one patient experienced a complete response (CR) and 12 achieved a partial response (PR). These results were presented in a rapid oral session today at the 2024 ASCO Annual Meeting, being held in Chicago, Illinois, May 31 – June 4, 2024. In the HNSCC cohort of innovaTV 207 Part C (n=40), median duration of response (DOR) was 5.6 months and median time-to-response (TTR) was 1.4 months. All patients were required to have received a platinum-based regimen in the recurrent or metastatic setting or have persistent disease following platinum-based chemoradiation and a checkpoint inhibitor (CPI), if eligible. The study also showed that among patients with no more than one or two lines of therapy in the recurrent or metastatic setting (n=25), 40% had achieved a cORR at the time of data cut-off. “Most patients with recurrent or metastatic head and neck squamous cell carcinoma experience disease progression despite the use of platinum-based therapy and immunotherapy, and treatment options are limited,” said Dr. Judith Klimovsky, Executive Vice President and Chief Development Officer of Genmab, “These updated results underscore the importance of our ongoing work with our partner to advance the clinical development program for tisotumab vedotin and investigate potential treatment options for pretreated patients living with unmet needs.” The safety findings were consistent with previous tisotumab vedotin trials, and no new safety signals were observed. Grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 67.5% of patients, and the most common were peripheral neuropathy events (40%). Adverse events of special interest (of any grade) were prespecified for ocular, peripheral neuropathy, and bleeding events, and occurred in 52.5%, 47.5%, and 40% patients, respectively. As of December 2023, 40 patients with recurrent or metastatic HNSCC were treated with tisotumab vedotin monotherapy (1.7 mg/kg intravenously, once every two weeks). In this cohort, 32 (80%) received prior platinum-based therapy, 19 (47.5%) received at least two prior lines of systemic therapy (median: 2; range: 1-3), 40 (100%) received prior CPI, 23 (57.5%) received prior taxane, and 27 (67.5%) received prior cetuximab. The primary sites at diagnosis were oropharynx (n=16), larynx (n=13), and oral cavity (n=9). About the innovaTV 207 TrialThe innovaTV 207 trial (NCT03485209) is an open-label, global, Phase 2, multicohort, multicenter study evaluating tisotumab vedotin monotherapy or in combination for advanced solid tumors. In Part C, patients with recurrent or metastatic HNSCC received tisotumab vedotin monotherapy (1.7 mg/kg IV once every two weeks). All patients were required to have received a platinum-based regimen, either in the recurrent/metastatic setting, or to have persistent disease following platinum-based chemoradiation and a checkpoint inhibitor, if eligible. The primary endpoint of the trial is confirmed objective response rate (cORR) per RECIST 1.1 per investigator, defined as the proportion of patients who achieve a confirmed complete or partial response. Selected secondary endpoints include duration of response (DOR), time-to-response (TTR), and safety. For more information about the phase 2 innovaTV 207 clinical trial of tisotumab vedotin, please visit www.clinicaltrials.gov. About Tisotumab VedotinTisotumab vedotin is an antibody-drug conjugate (ADC) composed of Genmab’s human monoclonal antibody directed to tissue factor (TF) and Pfizer’s ADC technology that utilizes a protease-cleavable linker that covalently attaches the microtubule-disrupting agent monomethyl auristatin E (MMAE) to the antibody. Nonclinical data suggest that the anticancer activity of tisotumab vedotin-tftv is due to the binding of the ADC to TF-expressing cancer cells, followed by internalization of the ADC-TF complex, and release of MMAE via proteolytic cleavage. MMAE disrupts the microtubule network of actively dividing cells, leading to cell cycle arrest and apoptotic cell death. In vitro, tisotumab vedotin-tftv also mediates antibody-dependent cellular phagocytosis and antibody-dependent cellular cytotoxicity. Tisotumab vedotin (TIVDAK®) has received full approval by the U.S. FDA for the treatment of adult patients with recurrent or metastatic cervical cancer (r/mCC) with disease progression on or after chemotherapy. Tisotumab vedotin in HNSCC is not approved in any country, including the U.S. and the EU. The safety and efficacy of tisotumab vedotin has not been established for these investigational uses. Virtual mid- to late-stage pipeline update at ASCO 2024On Monday, June 3, at 9:00 AM CDT (10:00 AM EDT/4:00 PM CEST), Genmab will host a review of data presented at ASCO from its mid- to late-stage pipeline. The event will be virtual and webcast live. Details, including the webcast link and registration will be available on www.genmab.com. This meeting is not an official program of the ASCO Annual Meeting. About GenmabGenmab is an international biotechnology company with a core purpose of guiding its unstoppable team to strive toward improving the lives of patients with innovative and differentiated antibody therapeutics. For 25 years, its passionate, innovative and collaborative team has invented next-generation antibody technology platforms and leveraged translational, quantitative and data sciences, resulting in a proprietary pipeline including bispecific T-cell engagers, antibody-drug conjugates, next-generation immune checkpoint modulators and effector function-enhanced antibodies. By 2030, Genmab’s vision is to transform the lives of people with cancer and other serious diseases with knock-your-socks-off (KYSO®) antibody medicines.    Established in 1999, Genmab is headquartered in Copenhagen, Denmark, with international presence across North America, Europe and Asia Pacific. For more information, please visit Genmab.com and follow us on LinkedIn and X. About the Pfizer and Genmab Collaboration Tisotumab vedotin is co-owned by Genmab and Pfizer, under an agreement in which the companies share costs and profits for the product on a 50:50 basis. Contact: David Freundel, Senior Director, Global Communications & Corporate AffairsT: +1 609 430 2481; E: dafr@genmab.com Andrew Carlsen, Vice President, Head of Investor RelationsT: +45 3377 9558; E: acn@genmab.com This Media Release contains forward looking statements. The words “believe,” “expect,” “anticipate,” “intend” and “plan” and similar expressions identify forward looking statements. Actual results or performance may differ materially from any future results or performance expressed or implied by such statements. The important factors that could cause our actual results or performance to differ materially include, among others, risks associated with pre-clinical and clinical development of products, uncertainties related to the outcome and conduct of clinical trials including unforeseen safety issues, uncertainties related to product manufacturing, the lack of market acceptance of our products, our inability to manage growth, the competitive environment in relation to our business area and markets, our inability to attract and retain suitably qualified personnel, the unenforceability or lack of protection of our patents and proprietary rights, our relationships with affiliated entities, changes and developments in technology which may render our products or technologies obsolete, and other factors. For a further discussion of these risks, please refer to the risk management sections in Genmab’s most recent financial reports, which are available on www.genmab.com and the risk factors included in Genmab’s most recent Annual Report on Form 20-F and other filings with the U.S. Securities and Exchange Commission (SEC), which are available at www.sec.gov. Genmab does not undertake any obligation to update or revise forward looking statements in this Media Release nor to confirm such statements to reflect subsequent events or circumstances after the date made or in relation to actual results, unless required by law. Genmab A/S and/or its subsidiaries own the following trademarks: Genmab®; the Y-shaped Genmab logo®; Genmab in combination with the Y-shaped Genmab logo®; HuMax®; DuoBody®; HexaBody®; DuoHexaBody®, HexElect® and KYSO™. Tivdak® is a trademark of Pfizer Inc. i Johnson, Daniel E., et al. “Head and Neck Squamous Cell Carcinoma.” Nature Reviews Disease Primers, Nature Publishing Group, 26 Nov. 2020, https://www.nature.com/articles/s41572-020-00224-3#Fig2. Media Release no. 10CVR no. 2102 3884LEI Code 529900MTJPDPE4MHJ122 Genmab A/SCarl Jacobsens Vej 302500 ValbyDenmark Attachment 030624_MRi10_TV207 ASCO HNSCC GLOBAL