Gemcitabine

Based on NIAGARA Phase III trial results which showed a 32% reduction in the risk of recurrence and a 25% reduction in the risk of death vs. neoadjuvant chemotherapy alone LONDON, UK I March 31, 2025 I AstraZeneca’s Imfinzi (durvalumab) in combination with gemcitabine and cisplatin as neoadjuvant treatment, followed by Imfinzi as adjuvant monotherapyafter radical cystectomy (surgery to remove the bladder) has been approved in the US for the treatment of adult patients with muscle-invasive bladder cancer (MIBC). The approval was granted by the Food and Drug Administration (FDA) after securing Priority Review and was based on results from the NIAGARA Phase III trial which were presented during a Presidential Symposium at the 2024 European Society for Medical Oncology (ESMO) Congress and simultaneously published in The New England Journal of Medicine . In 2024, over 20,000 people in the US were treated for MIBC. 1 Bladder cancer is considered muscle-invasive when there is evidence of the tumour invading the muscle wall of the bladder but no distant metastases. 2 This represents a curative-intent setting, where the current standard of care is neoadjuvant chemotherapy and radical cystectomy. 3 However, even after surgery, patients experience high rates of disease recurrence and have a poor prognosis. 3 Matthew ND. Galsky, Lillian and Howard Stratton Professor of Medicine, Director of Genitourinary Medical Oncology, The Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai, New York, and NIAGARA investigator and steering committee member, said: “This approval for the durvalumab-based perioperative regimen is a major breakthrough for people with muscle-invasive bladder cancer, nearly half of whom see their cancer return despite chemotherapy and surgery with curative-intent. This durvalumab regimen significantly extended patients’ lives in the NIAGARA trial and has the potential to transform care.” Dave Fredrickson, Executive Vice President, Oncology Haematology Business Unit, AstraZeneca, said: “Today’s approval for Imfinzi represents a paradigm shift, bringing the first perioperative immunotherapy to patients in the US with muscle-invasive bladder cancer and addressing a significant need for better treatment options. The NIAGARA trial showed more than 80 per cent of patients were still alive at two years, underscoring the potential of this innovative perioperative regimen to become a new standard of care in this setting.” Meri-Margaret Deoudes, CEO of the Bladder Cancer Advocacy Network, said: “More than 20,000 people in the US were treated for muscle-invasive bladder cancer last year and there is a significant need for new treatment options that improve patient outcomes. The approval of the durvalumab perioperative regimen is welcome news, transforming how clinicians will tackle this disease in future and offering new hope to patients and their loved ones.” In the trial, patients were treated with four cycles of Imfinzi in combination with neoadjuvant chemotherapy before radical cystectomy followed by eight cycles of Imfinzi monotherapy, or neoadjuvant chemotherapy before radical cystectomy. In a planned interim analysis, the Imfinzi -basedperioperative regimen demonstrated a 32% reduction in the risk of disease progression, recurrence, not undergoing surgery, or death versus the comparator arm (based on event-free survival [EFS] hazard ratio [HR] of 0.68; 95% confidence interval [CI] 0.56-0.82; p<0.0001). Estimated median EFS was not yet reached for the Imfinzi arm versus 46.1 months for the comparator arm. An estimated 67.8% of patients treated with the regimen were event free at two years compared to 59.8% in the comparator arm. Results from the key secondary endpoint of overall survival (OS) showed that the Imfinzi -based perioperative regimen reduced the risk of death by 25% versus neoadjuvant chemotherapy with radical cystectomy (based on OS HR of 0.75; 95% CI 0.59-0.93; p=0.0106). Median survival was not yet reached for either arm. An estimated 82.2% of patients treated with the regimen were alive at two years compared to 75.2% in the comparator arm. Imfinzi was generally well tolerated, and no new safety signals were observed in the neoadjuvant and adjuvant settings. Further, adding Imfinzi to neoadjuvant chemotherapy was consistent with the known profile for this combination and did not compromise patients’ ability to complete surgery compared to neoadjuvant chemotherapy alone. Immune-mediated adverse events (imAEs) were consistent with the known profile of Imfinzi , manageable and mostly low-grade. In February 2025, perioperative treatment with durvalumab ( Imfinzi ), neoadjuvant cisplatin-based chemotherapy and cystectomy was added to the NCCN Clinical Practical Guidelines in Oncology (NCCN Guidelines ® ) as a NCCN Category 1 Recommended regimen for patients with MIBC based on the data from NIAGARA. 4 Imfinzi is also approved in Brazil in this setting based on the NIAGARA results. Regulatory applications are currently under review in the EU, Japan and several other countries. Notes Muscle-invasive bladder cancer Bladder cancer is the 9th most common cancer in the world, with more than 614,000 patients diagnosed each year. 5 The most common type of bladder cancer is urothelial carcinoma, which begins in the urothelial cells of the urinary tract. 6 In MIBC, approximately 50% of patients who undergo bladder removal surgery experience disease recurrence. 3 Treatment options that prevent disease recurrence after surgery are critically needed in this curative-intent setting. NIAGARA NIAGARA is a randomised, open-label, multi-centre, global Phase III trial evaluating perioperative Imfinzi as treatment for patients with MIBC before and after radical cystectomy. In the trial, 1,063 patients were randomised to receive Imfinzi plus neoadjuvant chemotherapy prior to cystectomy followed by Imfinzi, or neoadjuvant chemotherapy alone prior to cystectomy with no further treatment after surgery. NIAGARA is the largest global Phase III trial in this setting. The trial is being conducted at 192 centres across 22 countries including in North America, South America, Europe, Australia and Asia. Its dual primary endpoints are EFS and pathologic complete response (pCR) at the time of cystectomy. Key secondary endpoints are OS and safety. Imfinzi Imfinzi (durvalumab) is a human monoclonal antibody that binds to the PD-L1 protein and blocks the interaction of PD-L1 with the PD-1 and CD80 proteins, countering the tumour’s immune-evading tactics and releasing the inhibition of immune responses. In addition to the indication in bladder cancer, Imfinzi is the global standard of care based on OS in the curative-intent setting of unresectable, Stage III non-small cell lung cancer (NSCLC) in patients whose disease has not progressed after chemoradiotherapy (CRT). Additionally, Imfinzi is approved as a perioperative treatment in combination with neoadjuvant chemotherapy in resectable NSCLC, and in combination with a short course of Imjudo (tremelimumab) and chemotherapy for the treatment of metastatic NSCLC. Imfinzi is also approved for limited-stage small cell lung cancer (SCLC) in patients whose disease has not progressed following concurrent platinum-based CRT; and in combination with chemotherapy (etoposide and either carboplatin or cisplatin) for the treatment of extensive-stage SCLC. In addition to its indications in lung cancers, Imfinzi is approved in combination with chemotherapy (gemcitabine plus cisplatin) in locally advanced or metastatic biliary tract cancer and in combination with Imjudo in unresectable hepatocellular carcinoma (HCC). Imfinzi is also approved as a monotherapy in unresectable HCC in Japan and the EU. In March 2025, perioperative Imfinzi added to standard-of-care chemotherapy met the primary endpoint of event-free survival in the MATTERHORN Phase III trial in resectable gastric and gastroesophageal junction cancers. Imfinzi in combination with chemotherapy followed by Imfinzi monotherapy is approved as a 1 st -line treatment for primary advanced or recurrent endometrial cancer (mismatch repair deficient disease only in US and EU). Imfinzi in combination with chemotherapy followed by Lynparza (olaparib) and Imfinzi is approved for patients with mismatch repair proficient advanced or recurrent endometrial cancer in EU and Japan. Since the first approval in May 2017, more than 374,000 patients have been treated with Imfinzi . As part of a broad development programme, Imfinzi is being tested as a single treatment and in combinations with other anti-cancer treatments for patients with SCLC, NSCLC, bladder cancer, breast cancer, several gastrointestinal and gynaecologic cancers, and other solid tumours. AstraZeneca in immuno-oncology (IO) AstraZeneca is a pioneer in introducing the concept of immunotherapy into dedicated clinical areas of high unmet medical need. The Company has a comprehensive and diverse IO portfolio and pipeline anchored in immunotherapies designed to overcome evasion of the anti-tumour immune response and stimulate the body’s immune system to attack tumours. AstraZeneca strives to redefine cancer care and help transform outcomes for patients with Imfinzi as a monotherapy and in combination with Imjudo as well as other novel immunotherapies and modalities. The Company is also investigating next-generation immunotherapies like bispecific antibodies and therapeutics that harness different aspects of immunity to target cancer, including cell therapy and T-cell engagers. AstraZeneca is pursuing an innovative clinical strategy to bring IO-based therapies that deliver long-term survival to new settings across a wide range of cancer types. The Company is focused on exploring novel combination approaches to help prevent treatment resistance and drive longer immune responses. With an extensive clinical programme, the Company also champions the use of IO treatment in earlier disease stages, where there is the greatest potential for cure. AstraZeneca in oncology AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients. The Company’s focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyse changes in the practice of medicine and transform the patient experience. AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death. AstraZeneca AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca’s innovative medicines are sold in more than 125 countries and used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on social media @AstraZeneca . References SOURCE: AstraZeneca

March 27, 2025 TIVDAK® is the first and only antibody-drug conjugate (ADC) approved for patients with advanced or recurrent cervical cancer in Japan Approval is based on results from the global Phase 3 innovaTV 301 trial, in which TIVDAK demonstrated superior overall survival compared to chemotherapy Rising cervical cancer incidence and mortality rates in Japan signify need for new treatment options Genmab A/S (Nasdaq: GMAB) today announced that the Japan Ministry of Health, Labour and Welfare has approved TIVDAK® (tisotumab vedotin) for the treatment of advanced or recurrent cervical cancer that has progressed on or after cancer chemotherapy. TIVDAK is the first and only ADC to be approved for people living with cervical cancer in Japan. In recent years, cervical cancer incidence and mortality rates have increased in Japan, particularly among women under age 50.i,ii,iii Moreover, patients with recurrent or metastatic cervical cancer whose disease has progressed after first-line therapy have limited treatment options. “Patients with advanced or recurrent cervical cancer, in general, have a poor prognosis. The advent of new treatment options, especially for second-line or later treatment, is much needed,” said Aikou Okamoto, M.D., Ph.D., Chief Professor, Department of Obstetrics and Gynecology at The Jikei University School of Medicine. “Cervical cancer treatment has advanced in recent years, but it is very meaningful that the approval of tisotumab vedotin as an ADC has increased the number of treatment options with a new mechanism of action that is expected to prolong overall survival. This is good news for patients and healthcare professionals.” The approval is based on data from the randomized, open-label, global Phase 3 innovaTV 301 clinical trial that evaluated the efficacy and safety of TIVDAK compared to chemotherapy in patients with advanced or recurrent cervical cancer who were previously treated with chemotherapy. The trial included 502 patients, 101 of which were Japanese. The trial met its primary endpoint of overall survival (OS), demonstrating a 30% reduction in risk of death (HR: 0.70 [95% CI: 0.54-0.89], two-sided p=0.0038) compared to chemotherapy. Median OS was 11.5 months [95% CI: 9.8-14.9] among patients treated with TIVDAK compared to 9.5 months [95% CI: 7.9-10.7] for patients who received chemotherapy. Secondary endpoints of progression-free survival (PFS) and confirmed objective response rate (ORR) were also met. Adverse drug reactions occurred in 219 (87.6%) of 250 patients (including 50 Japanese patients) treated with TIVDAK. The most common (≥20%) adverse reactions included conjunctivitis (n=76; 30.4%), nausea (n=73; 29.2%), peripheral sensory neuropathy (n=67; 26.8%), alopecia (n=61; 24.4%), and epistaxis (n=57; 22.8%), at the data cutoff date of July 24, 2023. “As a company, we understand the urgent need for patients with advanced cervical cancer whose disease has progressed,” said Judith Klimovsky, M.D., Executive Vice President and Chief Development Officer of Genmab. “This approval marks an important step forward in transforming the treatment paradigm in Japan, ultimately bringing new hope and possibility to patients and their loved ones.” The innovaTV 301 trial (NCT04697628) is a global, 1:1 randomized, open-label Phase 3 trial evaluating tisotumab vedotin versus investigator’s choice of single agent chemotherapy (topotecan, vinorelbine, gemcitabine, irinotecan or pemetrexed) in 502 patients with recurrent or metastatic cervical cancer who received one or two prior systemic regimens in the recurrent or metastatic setting. Patients with recurrent or metastatic cervical cancer with squamous cell, adenocarcinoma or adenosquamous histology, and disease progression during or after treatment with chemotherapy doublet +/- bevacizumab and an anti-PD-(L)1 agent (if eligible) are included. The primary endpoint was overall survival. The main secondary outcomes were progression-free survival and objective response rate. The study was conducted by Seagen, which was acquired by Pfizer in December 2023, in collaboration with Genmab, European Network of Gynaecological Oncological Trial Groups (ENGOT, study number ENGOT cx-12) and the Gynecologic Oncology Group (GOG) Foundation (study number GOG 3057), as well as other global gynecological oncology cooperative groups. For more information about the Phase 3 innovaTV 301 clinical trial and other clinical trials with tisotumab vedotin, please visit www.clinicaltrials.gov. Tisotumab vedotin (approved under the brand name TIVDAK® in the U.S. and Japan) 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 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 also mediates antibody-dependent cellular phagocytosis and antibody-dependent cellular cytotoxicity. Tisotumab vedotin is co-developed and co-commercialized globally by Genmab and Pfizer, under an agreement in which the companies share costs and profits. With respect to the commercialization of tisotumab vedotin in previously treated recurrent or metastatic cervical cancer, Genmab leads commercialization in Japan and all other regions globally, outside the United States and China. In these regions, Pfizer partners with Genmab and Zai Lab, respectively, on commercialization. Genmab 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 more than 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. i Cancer Statistics Cervix, National Cancer Center, Cancer Information Service, ganjoho.jp/reg_stat/statistics/stat/cancer/17_cervix_uteri.html#anchor1. Accessed 14 Feb. 2025. ii Trends in Cancer Incidence and Mortality Rates, World Health Organization, gco.iarc.fr/overtime/en. Accessed 14 Feb. 2025. iii For Correct Understanding of Cervical Cancer and HPV Vaccine, Japan Society of Obstetrics and Gynecology, www.jsog.or.jp/citizen/5765/. Accessed 14 Feb. 2025. The content above comes from the network. if any infringement, please contact us to modify.