Irinotecan Hydrochloride

On April 8, 2025, the Food and Drug Administration approved nivolumab (Opdivo, Bristol Myers Squibb Company) with ipilimumab (Yervoy, Bristol Myers Squibb Company) for adult and pediatric patients 12 years of age and older with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer (CRC). The FDA also converted the accelerated approval to regular approval for single agent nivolumab for adult and pediatric patients 12 years of age and older with MSI-H or dMMR metastatic CRC, that has progressed following fluoropyrimidine, oxaliplatin, and irinotecan.Full prescribing information for Opdivo and Yervoy will be posted on Drugs@FDA.Efficacy and SafetyEfficacy of nivolumab with ipilimumab was evaluated in CHECKMATE-8HW (NCT04008030), a randomized, three-arm, open-label trial in immunotherapy-naïve patients with unresectable or metastatic CRC with known MSI-H or dMMR status. Patients were randomized to receive one of the following treatments:nivolumab 240 mg every 3 weeks and ipilimumab 1 mg/kg every 3 weeks for a maximum of 4 doses, then nivolumab 480 mg every 4 weeks,nivolumab 240 mg every 2 weeks for 6 doses, then nivolumab 480 mg every 4 weeks, orinvestigator’s choice chemotherapy:The major efficacy outcome measure was progression-free survival (PFS) assessed by blinded independent central review (BICR) per RECIST v1.1 in patients with centrally confirmed MSI-H/dMMR status in the following pre-specified settings:First-line setting: nivolumab + ipilimumab versus chemotherapy,All lines: nivolumab + ipilimumab versus nivolumab alone.The analysis of nivolumab + ipilimumab versus chemotherapy in the first line setting was conducted in 255 patients with centrally confirmed MSI-H/dMMR status of 303 patients based on local testing. Median PFS was not reached (NR) (95% CI: 38.4, not estimable [NE]) in the nivolumab + ipilimumab arm and 5.8 months (95% CI: 4.4, 7.8) in the chemotherapy arm (Hazard ratio 0.21 [95% CI: 0.14, 0.32] p-value <0.0001). Comparative results of ORR and OS between arms were not available at the time of the interim PFS analysis due to statistical testing strategy.The analysis of nivolumab + ipilimumab versus nivolumab (all lines) was conducted in 582 patients with centrally confirmed MSI-H/dMMR status of 707 patients based on local testing. Median PFS was NR (95% CI: 53.8, NE) in the nivolumab + ipilimumab arm and 39.3 months (95% CI: 22.1, NE) in the nivolumab arm (Hazard ratio 0.62 [95% CI: 0.48, 0.81] p-value 0.0003). ORR was 71% (95% CI: 65, 76) in the nivolumab + ipilimumab arm and 58% (95% CI: 52, 63) in the nivolumab arm (p-value 0.0011). The comparative results of OS between arms were not available at the interim PFS analysis due to statistical testing strategy.The most common adverse reactions reported in ≥20% of patients treated with nivolumab with ipilimumab were fatigue, diarrhea, pruritus, abdominal pain, musculoskeletal pain, and nausea. The most common adverse reactions reported in ≥20% of patients treated with nivolumab as a single agent were fatigue, diarrhea, abdominal pain, pruritis, and musculoskeletal pain.See the prescribing information for the recommended doses of nivolumab and ipilimumab.Expedited ProgramsThis review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, FDA collaborated with the Brazilian Health Regulatory Agency (ANVISA), the Israel Ministry of Health (IMoH), and Health Canada (HC). The application reviews are ongoing at the other regulatory agencies.This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. The FDA approved this application 10 weeks ahead of the FDA goal date.This application was granted priority review, breakthrough designation, and orphan drug designation. FDA expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.Follow the Oncology Center of Excellence on X: @FDAOncology.

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.