Irinotecan Hydrochloride

Orphelia said it will continue to make Kizfizo available to paediatric patients under certain programmes and clinical trials. Credit: Andrii Yalanskyi via Getty Images. Orphelia Pharma is exploring alternative regulatory pathways for Kizfizo (temozolomide) following a negative opinion from the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP). The latest decision follows another negative opinion for Orphelia’s marketing authorisation application (MAA) in November 2024. The CHMP determined that Kizfizo failed to demonstrate sufficient clinical benefit to establish a positive benefit-risk balance. The agency cited modest response rates and the lack of convincing evidence that Kizfizo offered significant advantages over existing therapies for relapsed/refractory neuroblastoma. In response to the initial negative opinion, Orphelia requested a re-examination of the decision in December 2024. However, after a re-evaluation on 27 February 2025, the CHMP upheld its initial stance, stating that the committee’s concerns were not resolved. The company shared this update in a press release today (12 March). Orphelia emphasised that it will continue to make Kizfizo available to paediatric patients under compassionate use or early access programmes as well as to patients participating in ongoing clinical trials. “Considering the important unmet medical need, we are currently exploring all available options to make Kizfizo available to the paediatric patients,” said Laurent Martin, chief pharmaceutical affairs officer at Orphelia Pharma in the 12 March announcement. Neuroblastoma is a type of cancer that forms in certain types of nerve tissue, mostly affecting children under the age of five. Neuroblastoma is the second most common solid tumour in children after brain tumours, according to the UK-based charity The Children & Young People’s Cancer Association (CCLG). Kizfizo was designed as a hybrid medicine similar to MSD’s chemotherapy agent Temodal but is formulated as a liquid for easier administration, as many babies and children cannot take oral tablets. Orphelia presented clinical data from studies enrolling 102 patients up to 21 years old. The Phase I TEMOkids (NCT04610736) and Ped-TMZ studies (NCT04467346) demonstrated safety, pharmacokinetics, and efficacy. The ongoing Phase I/II BEACON2 study is evaluating Kizfizo in combination with chemotherapies irinotecan or topotecan. Originally indicated exclusively for the treatment of glioblastoma in adults in the US, temozolomide has been used off label to treat neuroblastoma patients for years. The drug has been approved for treating glioblastoma in adults and children in Europe since 2010. Kizfizo was granted early access authorisation by the French authorities in March 2022 and has received orphan drug designation from the EMA and the US Food and Drug Administration (FDA). The only approved drug in Orphelia’s portfolio is Kigabeq (vigabatrin), its paediatric formulation of vigabatrin, which has an EU authorisation as a monotherapy for West syndrome and for use as a combination treatment for resistant partial epilepsy.

Approval based on results of Phase 3 CheckMate -9DW clinical trial demonstrating a statistically significant and clinically meaningful improvement in overall survival with Opdivo plus Yervoy compared to investigator’s choice of lenvatinib or sorafenib PRINCETON, NJ, USA I March 07, 2025 I Bristol Myers Squibb (NYSE: BMY) today announced that the European Commission (EC) has approved Opdivo ® (nivolumab) plus Yervoy ® (ipilimumab) for the first-line treatment of adult patients with unresectable or advanced hepatocellular carcinoma (HCC). “The European Commission’s approval for Opdivo plus Yervoy adds to the growing body of evidence demonstrating the value of dual immunotherapy and represents an important new treatment option that may extend survival for patients with hepatocellular carcinoma,” said Dana Walker, M.D., M.S.C.E., vice president, Opdivo global program lead, Bristol Myers Squibb. “This approval marks a critical milestone in our commitment to improving outcomes for patients with liver cancer. We look forward to bringing this new first-line treatment option to patients in the European Union.” The decision is based on results from the CheckMate -9DW study, which were presented at the 2024 American Society of Oncology (ASCO ® ) Annual Meeting , the 2024 European Society for Medical Oncology Congress and the 2025 ASCO Gastrointestinal Cancers Symposium. Results showed that dual immunotherapy treatment with Opdivo plus Yervoy led to a statistically significant and clinically meaningful improvement in overall survival (OS), the clinical trial’s primary endpoint. In the trial, 85% of patients in the comparator arm were treated with lenvatinib and 15% were treated with sorafenib. The median OS was 23.7 months (95% CI: 18.8–29.4) for Opdivo plus Yervoy compared to 20.6 months (95% CI: 17.5–22.5) with the investigator’s choice of lenvatinib or sorafenib (HR: 0.79 (0.65–0.96); p=0.018). The OS benefit was observed across clinically relevant patient subgroups. The trial also showed an overall response rate (ORR) of 36.1% (95% CI: 31-41.5) compared to 13.2% (95% CI: 9.8-17.3; P<0.0001) of patients treated with lenvatinib or sorafenib and a deeper response with Opdivo plus Yervoy . The safety profile for the combination of Opdivo plus Yervoy remained consistent with previously reported data and was manageable with established protocols, with no new safety signals identified. This approval by the EC for Opdivo plus Yervoy for the first-line treatment of adult patients with unresectable or advanced HCC is valid in all 27 member states of the European Union (EU), as well as Iceland, Liechtenstein and Norway. In addition to approval in HCC, Opdivo- based options are also approved for treatment of multiple tumor types in the EU. In August 2024, the U.S. FDA also accepted the Company’s supplemental Biologics License Application (sBLA) for Opdivo plus Yervoy as a potential first-line treatment option for adult patients with unresectable HCC and assigned a Prescription Drug User Fee Act (PDUFA) goal date of April 21, 2025. The combination of Opdivo plus Yervoy was granted accelerated approval as a second-line treatment for patients with advanced HCC by the U.S. FDA in 2020 based on results from the Phase 2 CheckMate -040 trial. Bristol Myers Squibb thanks the patients and investigators for their important contributions to the Phase 3 CheckMate -9DW clinical trial. About CheckMate -9DW CheckMate -9DW is a Phase 3 randomized, open-label clinical trial evaluating the combination of Opdivo plus Yervoy compared to investigator’s choice of lenvatinib or sorafenib monotherapy in adult patients with unresectable or advanced hepatocellular carcinoma who have not received prior systemic therapy. A total of 668 patients were randomized to receive Opdivo plus Yervoy ( Opdivo 1mg/kg plus Yervoy 3mg/kg Q3W for up to four doses, followed by Opdivo monotherapy 480mg Q4W) infusion, or single agent lenvatinib or sorafenib taken orally in the control arm. 85% of patients in the comparator arm were treated with lenvatinib and 15% were treated with sorafenib. The primary endpoint of the trial is overall survival (OS) and secondary endpoints include objective response rate (ORR) and time to symptom deterioration. The study was not designed to independently compare Opdivo plus Yervoy vs. lenvatinib or Opdivo plus Yervoy vs. sorafenib. About Hepatocellular Carcinoma Liver cancer is the third most frequent cause of cancer death worldwide. Hepatocellular carcinoma (HCC) is the most common type of liver cancer, accounting for 90% of global cases. HCC is often diagnosed at an advanced stage, where effective treatment options are limited and are usually associated with poor outcomes. Up to 70% of patients experience recurrence within five years, particularly those still considered to be at high risk after surgery or ablation. While most cases of HCC are caused by hepatitis B virus or hepatitis C virus infections, metabolic syndrome and nonalcoholic steatohepatitis are rising in prevalence and expected to contribute to increased rates of HCC. About Opdivo Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to uniquely harness the body’s own immune system to help restore anti-tumor immune response. By harnessing the body’s own immune system to fight cancer, Opdivo has become an important treatment option across multiple cancers. Opdivo ’s leading global development program is based on Bristol Myers Squibb’s scientific expertise in the field of Immuno-Oncology and includes a broad range of clinical trials across all phases, including Phase 3, in a variety of tumor types. To date, the Opdivo clinical development program has treated more than 35,000 patients. The Opdivo trials have contributed to gaining a deeper understanding of the potential role of biomarkers in patient care, particularly regarding how patients may benefit from Opdivo across the continuum of PD-L1 expression. In July 2014, Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world. Opdivo is currently approved in more than 65 countries, including the United States, the European Union, Japan and China. In October 2015, the Company’s Opdivo and Yervoy combination regimen was the first Immuno-Oncology combination to receive regulatory approval for the treatment of metastatic melanoma and is currently approved in more than 50 countries, including the United States and the European Union. About Yervoy Yervoy is a recombinant, human monoclonal antibody that binds to the cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4). CTLA-4 is a negative regulator of T-cell activity. Yervoy binds to CTLA-4 and blocks the interaction of CTLA-4 with its ligands, CD80/CD86. Blockade of CTLA-4 has been shown to augment T-cell activation and proliferation, including the activation and proliferation of tumor infiltrating T-effector cells. Inhibition of CTLA-4 signaling can also reduce T-regulatory cell function, which may contribute to a general increase in T-cell responsiveness, including the anti-tumor immune response. On March 25, 2011, the U.S. Food and Drug Administration (FDA) approved Yervoy 3 mg/kg monotherapy for patients with unresectable or metastatic melanoma. Yervoy is approved for unresectable or metastatic melanoma in more than 50 countries. There is a broad, ongoing development program in place for Yervoy spanning multiple tumor types. INDICATIONS OPDIVO® (nivolumab), as a single agent, is indicated for the treatment of adult and pediatric patients 12 years and older with unresectable or metastatic melanoma. OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of adult and pediatric patients 12 years and older with unresectable or metastatic melanoma. OPDIVO® is indicated for the adjuvant treatment of adult and pediatric patients 12 years and older with completely resected Stage IIB, Stage IIC, Stage III, or Stage IV melanoma. OPDIVO® (nivolumab), in combination with platinum-doublet chemotherapy, is indicated as neoadjuvant treatment of adult patients with resectable (tumors ≥4 cm or node positive) non-small cell lung cancer (NSCLC). OPDIVO® (nivolumab) in combination with platinum-doublet chemotherapy, is indicated for neoadjuvant treatment of adult patients with resectable (tumors ≥4 cm or node positive) non-small cell lung cancer (NSCLC) and no known epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements, followed by single-agent OPDIVO® as adjuvant treatment after surgery. OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 (≥1%) as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations. OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab) and 2 cycles of platinum-doublet chemotherapy, is indicated for the first-line treatment of adult patients with metastatic or recurrent non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations. OPDIVO® (nivolumab) is indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving OPDIVO. OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of adult patients with unresectable malignant pleural mesothelioma (MPM). OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of adult patients with intermediate or poor risk advanced renal cell carcinoma (RCC). OPDIVO® (nivolumab), in combination with cabozantinib, is indicated for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC). OPDIVO® (nivolumab) is indicated for the treatment of adult patients with advanced renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy. OPDIVO® (nivolumab) is indicated for the treatment of adult patients with classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and brentuximab vedotin or after 3 or more lines of systemic therapy that includes autologous HSCT. This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. OPDIVO® (nivolumab) is indicated for the treatment of adult patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) with disease progression on or after platinum-based therapy. OPDIVO® (nivolumab) is indicated for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. OPDIVO® (nivolumab), as a single agent, is indicated for the adjuvant treatment of adult patients with urothelial carcinoma (UC) who are at high risk of recurrence after undergoing radical resection of UC. OPDIVO® (nivolumab), in combination with cisplatin and gemcitabine, is indicated as first-line treatment for adult patients with unresectable or metastatic urothelial carcinoma. OPDIVO® (nivolumab), as a single agent, is indicated for the treatment of adult and pediatric (12 years and older) patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of adult and pediatric patients 12 years and older with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of adult patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. OPDIVO® (nivolumab) is indicated for the treatment of adult patients with unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC) after prior fluoropyrimidine- and platinum-based chemotherapy. OPDIVO® (nivolumab) is indicated for the adjuvant treatment of completely resected esophageal or gastroesophageal junction cancer with residual pathologic disease in adult patients who have received neoadjuvant chemoradiotherapy (CRT). OPDIVO® (nivolumab), in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adult patients with unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC). OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of adult patients with unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC). OPDIVO® (nivolumab), in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the treatment of adult patients with advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma. Please see U.S. Full Prescribing Information for OPDIVO and YERVOY . Clinical Trials and Patient Populations Checkmate 227-previously untreated metastatic non-small cell lung cancer, in combination with YERVOY; Checkmate 9LA–previously untreated recurrent or metastatic non-small cell lung cancer in combination with YERVOY and 2 cycles of platinum-doublet chemotherapy by histology; Checkmate 649–previously untreated advanced or metastatic gastric cancer, gastroesophageal junction and esophageal adenocarcinoma; Checkmate 577–adjuvant treatment of esophageal or gastroesophageal junction cancer; Checkmate 238–adjuvant treatment of patients with completely resected Stage III or Stage IV melanoma; Checkmate 76K–adjuvant treatment of patients 12 years of age and older with completely resected Stage IIB or Stage IIC melanoma; Checkmate 274–adjuvant treatment of urothelial carcinoma; Checkmate 275–previously treated advanced or metastatic urothelial carcinoma; Checkmate 142–MSI-H or dMMR metastatic colorectal cancer, as a single agent or in combination with YERVOY; Checkmate 142–MSI-H or dMMR metastatic colorectal cancer, as a single agent or in combination with YERVOY; Attraction-3–esophageal squamous cell carcinoma; Checkmate 648-previously untreated, unresectable advanced recurrent or metastatic esophageal squamous cell carcinoma in combination with chemotherapy; Checkmate 648-previously untreated, unresectable advanced recurrent or metastatic esophageal squamous cell carcinoma combination with YERVOY; Checkmate 040–hepatocellular carcinoma, in combination with YERVOY; Checkmate 743–previously untreated unresectable malignant pleural mesothelioma, in combination with YERVOY; Checkmate 037–previously treated metastatic melanoma; Checkmate 066–previously untreated metastatic melanoma; Checkmate 067–previously untreated metastatic melanoma, as a single agent or in combination with YERVOY; Checkmate 017–second-line treatment of metastatic squamous non-small cell lung cancer; Checkmate 057–second-line treatment of metastatic non-squamous non-small cell lung cancer; Checkmate 816–neoadjuvant non-small cell lung cancer, in combination with platinum-doublet chemotherapy; Checkmate 77T–Neoadjuvant treatment with platinum-doublet chemotherapy for non-small cell lung cancer followed by single-agent OPDIVO as adjuvant treatment after surgery; Checkmate 901–Adult patients with unresectable or metastatic urothelial carcinoma; Checkmate 141–recurrent or metastatic squamous cell carcinoma of the head and neck; Checkmate 025–previously treated renal cell carcinoma; Checkmate 214–previously untreated renal cell carcinoma, in combination with YERVOY; Checkmate 9ER–previously untreated renal cell carcinoma, in combination with cabozantinib; Checkmate 205/039–classical Hodgkin lymphoma. Bristol Myers Squibb: Creating a Better Future for People with Cancer Bristol Myers Squibb is inspired by a single vision — transforming patients’ lives through science. The goal of the company’s cancer research is to deliver medicines that offer each patient a better, healthier life and to make cure a possibility. Building on a legacy across a broad range of cancers that have changed survival expectations for many, Bristol Myers Squibb researchers are exploring new frontiers in personalized medicine and, through innovative digital platforms, are turning data into insights that sharpen their focus. Deep understanding of causal human biology, cutting-edge capabilities and differentiated research programs uniquely position the company to approach cancer from every angle. Cancer can have a relentless grasp on many parts of a patient’s life, and Bristol Myers Squibb is committed to taking actions to address all aspects of care, from diagnosis to survivorship. As a leader in cancer care, Bristol Myers Squibb is working to empower all people with cancer to have a better future. About the Bristol Myers Squibb and Ono Pharmaceutical Collaboration In 2011, through a collaboration agreement with Ono Pharmaceutical Co., Bristol Myers Squibb expanded its territorial rights to develop and commercialize Opdivo globally, except in Japan, South Korea and Taiwan, where Ono had retained all rights to the compound at the time. On July 23, 2014, Ono and Bristol Myers Squibb further expanded the companies’ strategic collaboration agreement to jointly develop and commercialize multiple immunotherapies – as single agents and combination regimens – for patients with cancer in Japan, South Korea and Taiwan. About Bristol Myers Squibb Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol Myers Squibb, visit us at BMS.com or follow us on LinkedIn , X , YouTube , Facebook and Instagram . SOURCE: Bristol Myers Squibb