Sorafenib Tosylate

On April 11, 2025, the Food and Drug Administration approved nivolumab (Opdivo, Bristol Myers Squibb Company) with ipilimumab (Yervoy, Bristol Myers Squibb Company) for the first-line treatment of adult patients with unresectable or metastatic hepatocellular carcinoma (HCC).Full prescribing information for Opdivo will be posted on Drugs@FDA.Efficacy and SafetyEfficacy was evaluated in CHECKMATE-9DW (NCT04039607), a randomized (1:1), open-label trial in 668 adults with unresectable or metastatic HCC. Patients had histologically confirmed HCC, Child Pugh Class A, ECOG performance status 0 or 1, and no prior systemic therapy for advanced disease. Patients were randomized to receive either nivolumab 1 mg/kg as an intravenous (IV) infusion with ipilimumab 3 mg/kg IV every 3 weeks for a maximum of 4 doses, followed by single agent nivolumab 480 mg IV every 4 weeks, or investigator’s choice of lenvatinib or sorafenib.The primary efficacy outcome measure was overall survival (OS) in all randomized patients. Overall response rate (ORR) based on RECIST 1.1 criteria, assessed by blinded independent central review, was an additional efficacy outcome measure. Median OS was 23.7 months (95% CI: 18.8, 29.4) in the nivolumab + ipilimumab arm and 20.6 months (95% CI: 17.5, 22.5) in the lenvatinib or sorafenib arm (Hazard Ratio 0.79 [95% CI: 0.65, 0.96] p-value <0.0180. ORR was 36.1% (95% CI: 31.0, 41.5) and 13.2% (95% CI: 9.8, 17.3) in the respective arms (p-value <0.0001).The most common adverse reactions (>20%) were rash, pruritus, fatigue, and diarrhea.The recommended nivolumab dose is 1 mg/kg with ipilimumab 3 mg/kg intravenously every three weeks for a maximum of four doses, followed by nivolumab 240 mg IV every 2 weeks or nivolumab 480 mg IV as a single agent every 4 weeks.This 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 Health Canada and Switzerland’s Swissmedic. The application reviews are ongoing at the other regulatory agencies.Expedited ProgramsThis review used the Real-Time Oncology Review (RTOR) pilot program, which streamlined data submission prior to the filing of the entire clinical application, and the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.This application was granted 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.

Based on the Phase 3 CheckMate-9DW trial, Opdivo plus Yervoy demonstrated a statistically significant overall survival benefit compared to investigator’s choice of lenvatinib or sorafenib 1 In the trial, 38% of patients were still alive at 3 years with this dual immunotherapy vs. 24% with the comparator arm 1 PRINCETON, N.J.--(BUSINESS WIRE)-- $BMY #BMS -- Bristol Myers Squibb (NYSE: BMY) today announced that the U.S. Food and Drug Administration (FDA) approved Opdivo ® (nivolumab) plus Yervoy ® (ipilimumab) as a first-line treatment for adult patients with unresectable or metastatic hepatocellular carcinoma (HCC), the most common primary liver cancer. 1,2 This approval is based on the results from the global Phase 3 randomized, open-label CheckMate-9DW trial evaluating the combination of Opdivo plus Yervoy compared to investigator’s choice of tyrosine kinase inhibitor monotherapy (lenvatinib or sorafenib) in patients with unresectable or metastatic HCC who have not received prior systemic therapy. 1 In the trial, Opdivo plus Yervoy demonstrated statistically significant overall survival (OS) and overall response rate (ORR) vs the comparator arm. 1 It is the only trial supporting an FDA approval to show superior results against this comparator arm. 1 “The CheckMate-9DW approval is an important advancement for patients, considering the incidence of liver cancer has tripled in the last four decades, yet prognosis for HCC patients remains poor,” said Aiwu Ruth He, MD, PhD, a CheckMate-9DW study investigator while at MedStar Georgetown University Hospital. 3,4 “The availability of a new first-line treatment option that demonstrated a deep response can offer adults with this form of liver cancer long-term overall survival and may help address an unmet need. 1,5,6 Given the strength of evidence from the trial, especially considering the selection and performance of a strong comparator arm, I believe that Opdivo plus Yervoy has the potential to become a standard of care for the first-line treatment of patients with unresectable or metastatic HCC.” 1 In the CheckMate-9DW trial, in which 85% of patients in the comparator arm were treated with lenvatinib and 15% were treated with sorafenib, mOS with Opdivo plus Yervoy (n=335) was 23.7 months (95% CI: 18.8-29.4) vs. 20.6 months (95% CI: 17.5-22.5) with lenvatinib or sorafenib (n=333; HR=0.79; 95% CI: 0.65-0.96 P =0.0180), reducing the risk of death by 21%. 1 Opdivo plus Yervoy showed an OS rate of 38% at three years vs. 24% with lenvatinib or sorafenib monotherapy. 1 The trial also showed a deeper response with Opdivo plus Yervoy, demonstrating an ORR of 36.1% (95% CI: 31-41.5) compared to 13.2% (95% CI: 9.8-17.3; P 20% of patients treated with Opdivo plus Yervoy were rash, pruritus, fatigue, and diarrhea. Fatal adverse reactions occurred in 12 (3.6%) patients who received Opdivo plus Yervoy ; these included 4 (1.2%) patients who died due to immune-mediated or autoimmune hepatitis and 4 (1.2%) patients who died of hepatic failure. 1 Permanent discontinuation due to an adverse reaction occurred in 27% of patients treated with Opdivo in combination with Yervoy . Adverse reactions leading to permanent discontinuation in >1% of patients included immune-mediated hepatitis (1.8%), diarrhea/colitis (1.8%), and hepatic failure (1.2%). 1 About Hepatocellular Carcinoma Hepatocellular carcinoma (HCC) is a type of primary liver cancer and is the most common form of liver cancer in adults. 2 Liver cancer is the sixth leading cause of cancer deaths in the United States. 8 HCC is often diagnosed at an advanced stage and is usually associated with poor prognosis with limited effective treatment options. 5,9,10 About 42,240 people in the United Stated will be diagnosed and about 30,090 people will die of liver cancer in 2025. 3 The incidence rates of liver cancer have tripled in the U.S. since 1980 and deaths have doubled since then. 3 HCC typically develops in patients with hepatitis virus infection or cirrhosis. 11 While most cases of HCC are caused by hepatitis B virus or hepatitis C virus infections, metabolic syndrome and metabolic dysfunction-associated steatohepatitis are rising in prevalence and expected to contribute to increased rates of HCC. 11 INDICATIONS OPDIVO ® (nivolumab), in combination with YERVOY ® (ipilimumab), is indicated for the first-line treatment of adult patients with unresectable or metastatic hepatocellular carcinoma (HCC). OPDIVO ® (nivolumab), in combination with YERVOY ® (ipilimumab), is indicated for the treatment of adult patients with unresectable or metastatic hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. IMPORTANT SAFETY INFORMATION Severe and Fatal Immune-Mediated Adverse Reactions Immune-mediated adverse reactions listed herein may not include all possible severe and fatal immune- mediated adverse reactions. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue. While immune-mediated adverse reactions usually manifest during treatment, they can also occur after discontinuation of OPDIVO or YERVOY. Early identification and management are essential to ensure safe use of OPDIVO or YERVOY and YERVOY. Monitor for signs and symptoms that may be clinical manifestations of underlying immune-mediated adverse reactions. Evaluate clinical chemistries including liver enzymes, creatinine, adrenocorticotropic hormone (ACTH) level, and thyroid function at baseline and periodically during treatment with OPDIVO and before each dose of YERVOY. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate. Withhold or permanently discontinue OPDIVO and YERVOY depending on severity (please see section 2 Dosage and Administration in the accompanying Full Prescribing Information). In general, if OPDIVO and YERVOY or YERVOY interruption or discontinuation is required, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroid therapy. Toxicity management guidelines for adverse reactions that do not necessarily require systemic steroids (e.g., endocrinopathies and dermatologic reactions) are discussed below. Immune-Mediated Pneumonitis OPDIVO and YERVOY can cause immune-mediated pneumonitis. The incidence of pneumonitis is higher in patients who have received prior thoracic radiation. In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, immune-mediated pneumonitis occurred in 7% (31/456) of patients, including Grade 4 (0.2%), Grade 3 (2.0%), and Grade 2 (4.4%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, immune-mediated pneumonitis occurred in 7% (31/456) of patients, including Grade 4 (0.2%), Grade 3 (2.0%), and Grade 2 (4.4%). Immune-Mediated Colitis OPDIVO and YERVOY can cause immune-mediated colitis, which may be fatal. A common symptom included in the definition of colitis was diarrhea. Cytomegalovirus (CMV) infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, immune-mediated colitis occurred in 25% (115/456) of patients, including Grade 4 (0.4%), Grade 3 (14%) and Grade 2 (8%). Immune-Mediated Hepatitis and Hepatotoxicity OPDIVO and YERVOY can cause immune-mediated hepatitis. In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, immune-mediated hepatitis occurred in 15% (70/456) of patients, including Grade 4 (2.4%), Grade 3 (11%), and Grade 2 (1.8%). Immune-Mediated Endocrinopathies OPDIVO and YERVOY can cause primary or secondary adrenal insufficiency, immune-mediated hypophysitis, immune-mediated thyroid disorders, and Type 1 diabetes mellitus, which can present with diabetic ketoacidosis. Withhold OPDIVO and YERVOY depending on severity (please see section 2 Dosage and Administration in the accompanying Full Prescribing Information). For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field defects. Hypophysitis can cause hypopituitarism; initiate hormone replacement as clinically indicated. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism; initiate hormone replacement or medical management as clinically indicated. Monitor patients for hyperglycemia or other signs and symptoms of diabetes; initiate treatment with insulin as clinically indicated. In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, adrenal insufficiency occurred in 8% (35/456), including Grade 4 (0.2%), Grade 3 (2.4%), and Grade 2 (4.2%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, hypophysitis occurred in 9% (42/456), including Grade 3 (2.4%) and Grade 2 (6%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, hyperthyroidism occurred in 9% (42/456) of patients, including Grade 3 (0.9%) and Grade 2 (4.2%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, hypothyroidism occurred in 20% (91/456) of patients, including Grade 3 (0.4%) and Grade 2 (11%). Immune-Mediated Nephritis with Renal Dysfunction OPDIVO and YERVOY can cause immune-mediated nephritis. Immune-Mediated Dermatologic Adverse Reactions OPDIVO can cause immune-mediated rash or dermatitis. Exfoliative dermatitis, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug rash with eosinophilia and systemic symptoms (DRESS) has occurred with PD-1/PD-L1 blocking antibodies. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate nonexfoliative rashes. YERVOY can cause immune-mediated rash or dermatitis, including bullous and exfoliative dermatitis, SJS, TEN, and DRESS. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-bullous/exfoliative rashes. Withhold or permanently discontinue OPDIVO and YERVOY depending on severity (please see section 2 Dosage and Administration in the accompanying Full Prescribing Information). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, immune-mediated rash occurred in 28% (127/456) of patients, including Grade 3 (4.8%) and Grade 2 (10%). Other Immune-Mediated Adverse Reactions The following clinically significant immune-mediated adverse reactions occurred at an incidence of 20%) in patients receiving OPDIVO with YERVOY (n=332) were rash (36%), pruritus (34%), fatigue (33%), and diarrhea (25%). In CheckMate-040, the most common adverse reactions (≥20%) in patients receiving OPDIVO with YERVOY (n=49) were rash (53%), pruritus (53%), musculoskeletal pain (41%), diarrhea (39%), cough (37%), decreased appetite (35%), fatigue (27%), pyrexia (27%), abdominal pain (22%), headache (22%), nausea (20%), dizziness (20%), hypothyroidism (20%), and weight decreased (20%). Please see U.S. Full Prescribing Information for OPDIVO and YERVOY . Clinical Trials and Patient Populations CheckMate-9DW – hepatocellular carcinoma, in combination with YERVOY; CheckMate-040 – hepatocellular carcinoma, in combination with YERVOY, after prior treatment with sorafenib. 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. Contacts Bristol Myers Squibb Media Inquiries: media@bms.com Investors: investor.relations@bms.com Read full story here