Mesothelioma, Malignant

Exploratory subgroup analysis from INNOVATE-3 finds that pegylated liposomal doxorubicin (PLD) -naïve patients randomized to receive TTFields therapy and paclitaxel had a median overall survival of 16.0 months compared to 11.7 months in PLD-naïve patients treated with paclitaxel alone ROOT, Switzerland--(BUSINESS WIRE)-- Novocure (NASDAQ: NVCR) today announced a late breaking abstract which reviews the results of an exploratory subgroup analysis of the phase 3 ENGOT-ov50 / GOG-3029 / INNOVATE-3 (INNOVATE-3) clinical trial has been selected for presentation at the “Best Oral Session – Late Breaking Abstracts” on Sunday, March 10, 2024 at the European Society on Gynaecological Oncology (ESGO) 2024 Congress in Barcelona. The randomized, phase 3 INNOVATE-3 clinical trial evaluated the use of Tumor Treating Fields (TTFields) therapy together with paclitaxel in platinum-resistant ovarian cancer (PROC) in patients with a maximum of five total prior lines of systemic therapy. While the INNOVATE-3 study did not meet its primary endpoint of overall survival in the intent-to-treat population, an exploratory analysis of a subgroup from the trial concluded that PLD-naïve patients treated with TTFields therapy and paclitaxel saw a significant improvement in overall survival compared to PLD-naïve patients treated with paclitaxel alone. Of the 558 total patients enrolled in the INNOVATE-3 clinical trial, 201 patients (36%) were PLD-naïve. Overall survival in PLD-naïve patients randomized to receive TTFields therapy and paclitaxel was 16.0 months (n=113), compared to 11.7 months in PLD-naïve patients randomized to receive paclitaxel alone (n=88). In the PLD-naïve subgroup, baseline demographics were similar across both cohorts. Novocure is further exploring the effect of doxorubicin on tumor tissue alteration and the potential consequences for TTFields dose. The findings from this post-hoc analysis may help explain the potential survival benefit observed in INNOVATE-3 patients who received only one prior line of therapy, as previously reported. TTFields therapy was well-tolerated, and no additive systemic toxicity or safety signals were observed. “We are extremely pleased to share these data with our colleagues at ESGO and humbled by the selection for a best oral presentation session,” said primary investigator Professor Ignace Vergote, MD, PhD, Professor at the Catholic University of Leuven, Belgium. “There is an immense clinical need for safe, effective and less toxic therapies for PROC patients and I look forward to continued exploration of TTFields therapy in gynecological cancers.” “The presentation of these data is an exciting achievement for the INNOVATE-3 investigators, as well as the Novocure team, reflecting exceptional work, collaboration and dedication,” said Nicolas Leupin, MD, PhD, Novocure’s Chief Medical Officer. “I would like to thank our collaborators, ENGOT and The GOG Foundation, for their partnership designing and conducting the INNOVATE-3 trial. These findings provide valuable new insights, and we are eager to continue exploring the capabilities of TTFields therapy in the treatment of solid tumors.” The exploratory analysis from the INNOVATE-3 data will be presented on Sunday, March 10, 2024 at 11:50 a.m. UTC+1 by Professor Vergote, and has been selected for inclusion in the “Best Oral Session – Late Breaking Abstracts” as part of the European Society on Gynaecological Oncology (ESGO) annual congress. About ENGOT-ov50 / GOG-3029 / INNOVATE-3 The ENGOT-ov50 / GOG-3029 / INNOVATE-3 clinical trial was designed to evaluate the safety and effectiveness of TTFields together with paclitaxel in patients with platinum-resistant ovarian cancer and a maximum of five total prior lines of systemic therapy. The primary endpoint of INNOVATE-3 was overall survival. Secondary endpoints include progression-free survival, objective response rate, severity and frequency of adverse events, time to undisputable deterioration in health-related quality of life or death, and quality of life. Enrollment in the trial closed in October 2021 with 558 patients enrolled, beginning the minimum 18-month follow-up period. In 2023, Novocure announced the trial did not meet its primary endpoint. Together with investigators, the company will continue to analyze the data from the INNOVATE-3 trial. The European Network for Gynaecological Oncological Trial groups ("ENGOT") and The GOG Foundation, Inc. ("GOG"), third-party clinical trial networks, collaborated with Novocure on the trial. Both ENGOT and GOG were involved in the development and facilitation of the trial at leading cancer centers in Europe and the United States. About Ovarian Cancer In the U.S., ovarian cancer ranks fifth in cancer deaths among women, with approximately 24,000 women diagnosed each year. Ovarian cancer incidence increases with age, and the median age at time of diagnosis is 63 years old. Physicians use different combinations of surgery and pharmacological therapies to treat ovarian cancer, depending on the stage of the disease. Surgery is usually used in early stages of the disease and is usually combined with chemotherapy, including paclitaxel and platinum-based chemotherapy. Unfortunately, the majority of patients are diagnosed at an advanced stage when the cancer has spread outside of the ovaries to include regional tissue involvement and/or metastases. Platinum-based chemotherapy remains part of the standard of care in advanced ovarian cancer, but most patients with advanced ovarian cancer will have tumor progression or, more commonly, recurrence. Almost all patients with recurrent disease ultimately develop platinum resistance, and the prognosis for this population remains poor. About Tumor Treating Fields Therapy Tumor Treating Fields (TTFields) are electric fields that exert physical forces to kill cancer cells via a variety of mechanisms. TTFields do not significantly affect healthy cells because they have different properties (including division rate, morphology, and electrical properties) than cancer cells. The multiple, distinct mechanisms of TTFields therapy work together to selectively target and kill cancer cells. Due to its multimechanistic actions, TTFields therapy can be added to cancer treatment modalities in approved indications and demonstrates enhanced effects across solid tumor types when used with chemotherapy, radiotherapy, immune checkpoint inhibition, or PARP inhibition in preclinical models. TTFields therapy provides clinical versatility that has the potential to help address treatment challenges across a range of solid tumors. To learn more about Tumor Treating Fields therapy and its multifaceted effect on cancer cells, visit tumortreatingfields.com. About Novocure Novocure is a global oncology company working to extend survival in some of the most aggressive forms of cancer through the development and commercialization of its innovative therapy, Tumor Treating Fields. Novocure’s commercialized products are approved in certain countries for the treatment of adult patients with glioblastoma, malignant pleural mesothelioma and pleural mesothelioma. Novocure has ongoing or completed clinical studies investigating Tumor Treating Fields in brain metastases, gastric cancer, glioblastoma, liver cancer, non-small cell lung cancer, pancreatic cancer and ovarian cancer. Headquartered in Root, Switzerland and with a growing global footprint, Novocure has regional operating centers in Portsmouth, New Hampshire and Tokyo, as well as a research center in Haifa, Israel. For additional information about the company, please visit Novocure.com and follow @Novocure on LinkedIn and Twitter. About ENGOT and BGOG ( and ) The European Network of Gynaecological Oncology Trial groups (ENGOT) is a platform that guarantees that the European spirit and culture is incorporated into the medical progress in gynaecological oncology, and that all European patients and countries can participate in an active way in clinical research and progress. The ultimate goal is to bring the best treatment to gynecological cancer patients through the best science and enabling every patient in every European country to access a clinical trial. The Belgium and Luxembourg Gynaecological Oncology Group (BGOG) is one of the founding study groups of ENGOT. About The GOG Foundation, Inc. (GOG-F) ( ) The GOG Foundation, Inc. is a not-for-profit organization with the purpose of promoting excellence in the quality and integrity of clinical and translational scientific research in the field of gynecologic malignancies. The GOG Foundation is committed to maintaining the highest standards in clinical trials development, execution, analysis, and distribution of results. The GOG Foundation is the only clinical trialist group in the United States that focuses its research on patients with pelvic malignancies, such as cancer of the ovary (including surface peritoneal malignancies), uterus (including endometrium, soft tissue sarcoma, and gestational trophoblastic neoplasia), cervix, and vulva. The GOG Foundation is multi-disciplinary in its approach to clinical trials, and includes gynecologic oncologists, medical oncologists, pathologists, radiation oncologists, oncology nurses, biostatisticians (including those with expertise in bioinformatics), basic scientists, quality of life experts, data managers, and administrative personnel. About GOG Partners Program Supported by industry, GOG Partners is structured to work directly with pharmaceutical organizations and operate clinical trials outside the National Cancer Institute (NCI) framework. The GOG Partners Program shares the same mission of the GOG Foundation dedicated to transforming the care in Gynecologic Oncology. By providing an alternative venue for patient accrual and site infrastructure support, GOG Partners has helped provide additional trials and opportunities for patients outside the national gynecologic clinical trials network. Forward-Looking Statements In addition to historical facts or statements of current condition, this press release may contain forward-looking statements. Forward-looking statements provide Novocure’s current expectations or forecasts of future events. These may include statements regarding anticipated scientific progress on its research programs, clinical study progress, development of potential products, interpretation of clinical results, prospects for regulatory approval, manufacturing development and capabilities, market prospects for its products, coverage, collections from third-party payers and other statements regarding matters that are not historical facts. You may identify some of these forward-looking statements by the use of words in the statements such as “could” “anticipate,” “estimate,” “expect,” “project,” “intend,” “plan,” “believe” or other words and terms of similar meaning. Novocure’s performance and financial results could differ materially from those reflected in these forward-looking statements due to general financial, economic, environmental, regulatory and political conditions and other more specific risks and uncertainties facing Novocure such as those set forth in its Annual Report on Form 10-K filed on February 22, 2024, and subsequent filings with the U.S. Securities and Exchange Commission. Given these risks and uncertainties, any or all of these forward-looking statements may prove to be incorrect. Therefore, you should not rely on any such factors or forward-looking statements. Furthermore, Novocure does not intend to update publicly any forward-looking statement, except as required by law. Any forward-looking statements herein speak only as of the date hereof. The Private Securities Litigation Reform Act of 1995 permits this discussion. View source version on businesswire.com: Contacts Investors: Ingrid Goldberg investorinfo@novocure.com media@novocure.com 610-723-7427 Source: Novocure View this news release online at:

With the 18-month minimum follow-up of the patients in the INITIUM trial, the trial did not meet the primary endpoint of prolonging progression-free survival (PFS). Median PFS was not reached in either arm. Evaluation of secondary endpoints did not show a difference in overall survival and objective response rate between the treatment and control arms UV1 maintained its positive safety profile with similar safety and tolerability as observed in the control arm Ultimovacs remains confident in the potential of the UV1 vaccine and its promise in specific therapeutic combinations and indications Upcoming data from the FOCUS Phase II trial and overall survival updates from the NIPU Phase II trial will be the next important data points for the further assessment of UV1 Cash preservation initiatives will be implemented to ensure that the available financial resources will sustain the company into 2025, enabling the achievement of upcoming key inflection points. March 7 2024: Ultimovacs ASA ("Ultimovacs") (OSE ULTI), a clinical-stage biotechnology leader in novel immunotherapeutic cancer vaccines, today announced topline results from the Phase II clinical trial, INITIUM (NCT04382664), evaluating the company’s therapeutic cancer vaccine candidate UV1 as first-line treatment in unresectable or metastatic malignant melanoma. The study’s primary endpoint was to investigate progression-free survival (PFS) in the experimental arm (UV1 plus treatment with checkpoint inhibitors (CPIs) ipilimumab and nivolumab) as compared to the control arm (ipilimumab and nivolumab alone). Secondary endpoints included overall survival (OS), objective response rate (ORR) as well as duration of response (DOR) and safety. Topline data demonstrated that the combined treatment of UV1 with ipilimumab and nivolumab showed similar clinical benefits as treatment with ipilimumab and nivolumab alone, meaning the primary and secondary endpoints of the study were not met. With the 18-month minimum follow-up of the patients in the trial, the median PFS was not reached in either arm, and the Hazard Ratio (HR) between the arms for PFS was 0.95. Evaluation of secondary endpoints did not show a difference in overall survival and objective response rate between the arms. UV1 maintained a positive safety and tolerability profile. Ultimovacs will further analyze the full data set while continuing to advance its ongoing Phase II trials for UV1. “Ultimovacs had set a very high bar for UV1 by comparing it to the ipilimumab and nivolumab combination, currently considered the most effective treatment for this patient population. Nevertheless, we are disappointed that UV1 did not add further clinical benefit for these late-stage melanoma patients in the INITIUM trial. Looking forward, our first objective is to complete the analysis of the full data set in depth to gain further insights on UV1’s effects,” said Jens Bjørheim, Chief Medical Officer, Ultimovacs. “We wish to thank the patients for their trust and the investigators for their collaboration with us.” “We have seen signals in previous trials that UV1 has the ability to show positive effects in cancer patients. We remain committed to UV1, and we look forward to thoroughly examining the INITIUM data, receiving the FOCUS data, and updated NIPU survival data over the next several months. Our objective is to define the best path forward for our development strategy for UV1,” said Carlos de Sousa, Chief Executive Officer, Ultimovacs. Ultimovacs is evaluating the universal cancer vaccine UV1 in a broad clinical development program across various cancer indications with different biology and disease stages, in combination with different checkpoint inhibitors. The topline data from INITIUM is the second readout among the five randomized trials in the UV1 Phase II clinical program. In October 2023, the UV1 Phase II trial NIPU in malignant mesothelioma reported a clinically meaningful overall survival benefit in the patients receiving UV1 vaccination on top of ipilimumab and nivolumab compared to ipilimumab and nivolumab alone, with no added toxicities. Per protocol, the overall survival results were statistically significant. In addition to the studies in malignant melanoma and malignant mesothelioma, Phase II studies are ongoing in patients with head and neck cancer (FOCUS), ovarian cancer (DOVACC), and non-small cell lung cancer (LUNGVAC). The data from the FOCUS trial is expected in the third quarter of 2024. The Company will host a webcast presentation and discussion of the results from the INITIUM study on Thursday, March 7 2024 at 08:00 (CET). Link to the webcast here: https://channel.royalcast.com/landingpage/hegnarmedia/20240307_2/ Ultimovacs is a clinical-stage biotechnology leader in novel immunotherapeutic cancer vaccines with broad applicability. Ultimovacs’ lead cancer vaccine candidate UV1 is directed against human telomerase (hTERT) an antigen which is present in 85-90% of cancers in all stages of tumor growth. A broad clinical program, with Phase II trials in five cancer indications enrolling more than 670 patients, aims to demonstrate UV1’s impact in combination with other immunotherapies in multiple cancer types expressing telomerase and where patients have unmet medical needs. UV1 is universal, off-the-shelf and easy to use, and is a patented technology owned by Ultimovacs. In addition, Ultimovacs holds all rights of the proprietary TET technology platform for any possible future use of formulations in various solid tumor indications. The Company is listed on Euronext Oslo Stock Exchange (ULTI.OL). INITIUM is an Ultimovacs-sponsored randomized, comparative, multicenter Phase II trial in which the universal cancer vaccine UV1 will be evaluated in combination with the checkpoint inhibitors ipilimumab and nivolumab for first-line treatment of patients with unresectable or metastatic malignant melanoma. The first patient received treatment in the INITIUM trial in June 2020, and the last patient was enrolled in July 2022. The study is being conducted at 39 hospitals across the U.S., U.K., Belgium, and Norway. The initial study design called for enrollment of 154 patients. Two additional patients were enrolled bringing the total number of patients in the study to 156. The immunotherapeutic cancer vaccine UV1 is investigated in combination with checkpoint inhibitors in patients with various cancer indications with diverse tumor biology. The diversity of the UV1 Phase II program places Ultimovacs in a favorable position to capture the cancer vaccine’s potential broad applicability when combined with checkpoint inhibitors: INITIUM: Evaluating UV1 in combination with ipilimumab and nivolumab as first-line treatment for patients with malignant melanoma. Enrollment of 156 patients completed in July 2022. Sponsored by Ultimovacs. NIPU: Evaluating UV1 in combination with ipilimumab and nivolumab as second-line treatment for patients with malignant pleural mesothelioma. Enrollment of 118 patients completed in January 2023. Data presented at the ESMO Congress in October 2023, showed that UV1 as add-on to ipilimumab and nivolumab, demonstrated a statistically significant and clinically meaningful improvement of overall survival versus ipilimumab and nivolumab alone. 31% of the patients receiving UV1 vaccine experienced an objective response, compared to 16% in the control arm. The investigator-initiated study is led by Oslo University Hospital and supported by Bristol-Myers Squibb and Ultimovacs. FOCUS: Evaluating UV1 in combination with pembrolizumab as first-line treatment for patients with head and neck cancer. Enrollment of 75 patients completed in August 2023, expected readout Q3 2024. The investigator-initiated study is led by Halle University in Germany, supported by Ultimovacs. DOVACC: Evaluating UV1 in combination with olaparib and durvalumab as maintenance therapy in non-BRCA mutated patients with advanced ovarian cancer. 75 of 184 patients enrolled as of Q4 2023 reporting, expected readout H1 2025. The investigator-initiated study is led by NSGO-CTU and supported by ENGOT, AstraZeneca, and Ultimovacs. LUNGVAC: Evaluating UV1 combined with cemiplimab as first-line treatment of non-small cell lung cancer patients. 23 of 138 patients enrolled as of Q4 2023 reporting, expected readout H2 2025. The investigator-initiated study is led by Vestre Viken (Drammen Hospital) and supported by Ultimovacs. UV1 is a universal cancer vaccine designed to induce a specific T-cell response against telomerase. UV1 consists of long, synthetic peptides representing a sequence in the reverse transcriptase subunit of telomerase (hTERT), shown to induce CD4+ T-cells. These CD4+ T-cells have the potential to provide inflammatory signals, and T-cell support is believed to be critical for triggering a strong anti-tumor immune response. Following intradermal injection, antigen-presenting cells (APCs) in the skin are exposed to the vaccine peptides. These APCs will process the peptides and present vaccine epitopes on Human Leukocyte Antigen (HLA) molecules to naïve T-cells in the lymph nodes. Activated vaccine-specific T-cells will then enter the circulation and search for cells displaying their cognate antigen in the context of HLA molecules. The UV1 peptides contain several epitopes, shown to be non-restrictive in terms of (HLA) alleles for presentation. It is, therefore not required to perform HLA pre-screening of patients, which potentially enables broad population utilization of the vaccine. UV1 is administered over three months as eight intradermal injections together with the immune-modulator GM-CSF. The content above comes from the network. if any infringement, please contact us to modify.

Clinical-stage CAR-T company is actively recruiting patients to evaluate SynKIR™-110, a new treatment candidate for ovarian cancer, mesothelioma, and cholangiocarcinoma PHILADELPHIA, March 7, 2024 /PRNewswire/ -- Verismo Therapeutics, a clinical-stage CAR-T company developing the novel KIR-CAR platform technology, today announced that it has activated a second clinical site for its STAR-101 Phase 1 clinical trial at The University of Texas MD Anderson Cancer Center. STAR-101 is a multi-center clinical trial designed to evaluate Verismo Therapeutic's lead candidate, SynKIR™-110, for the treatment of mesothelin-overexpressing ovarian cancer, malignant pleural mesothelioma, and cholangiocarcinoma. "This milestone marks the steady progress towards our goal of bringing SynKIR™-110 to as many patients as possible," said Dr. Bryan Kim, Co-Founder and CEO of Verismo Therapeutics. "We are grateful for the opportunity to work with Dr. Mehmet Altan at MD Anderson to bring us closer to that goal." Verismo achieved clearance from the FDA to initiate this multi-center clinical trial for SynKIR™-110 and has partnered with the Hospital of the University of Pennsylvania as the first clinical site. Verismo has previously announced that SynKIR™-110 received Orphan Drug Designation and Fast Track Designation for the treatment of mesothelin-expressing mesotheliomas. For more information about the STAR-101 clinical trial, please visit ClinicalTrials.gov NCT05568680. About the KIR-CAR Platform The KIR-CAR platform is a dual-chain CAR T cell therapy and has been shown in preclinical animal models to be capable of maintaining antitumor T cell activity even in challenging solid tumor environments. DAP12 acts as a novel costimulatory molecule for T cells using additional T cell stimulating pathways, further sustaining chimeric receptor expression and improving KIR-CAR T cell functional persistence. This continued T cell function and persistence can lead to ongoing regression of solid tumors in preclinical models, including those resistant to traditional CAR T cell therapies. The KIR-CAR platform is being investigated in combination with many additional emerging technologies, such as in vivo gene engineering, advanced cell manufacturing and reprogramming, combinational therapies, and even allogeneic cellular therapies to potentially provide the next-generation multimodal targeted immunotherapy for patients in need. About Verismo Therapeutics Verismo Therapeutics is a pioneer in dual-chain KIR-CAR technology, with its first asset SynKIR™-110 under investigation in a first-in-human clinical trial. Verismo is the only company developing the KIR-CAR platform, a modified NK-like receptor designed to improve persistence and efficacy against aggressive solid tumors. The KIR-CAR platform technology was developed specifically for advanced solid tumors, an area of high unmet medical need. For more information, visit: CONTACT: Raymond Luke, raymond.luke@verismotherapeutics.com