Hypothyroidism

KEYNOTE-689 marks the first positive trial in more than two decades for patients with resected locally advanced head and neck squamous cell carcinoma (LA-HNSCC) Results to be presented at American Association for Cancer Research (AACR) Annual Meeting 2025 during a Plenary Session and included in official meeting press program RAHWAY, NJ, USA I April 27, 2025 I Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced results from the Phase 3 KEYNOTE-689 trial evaluating KEYTRUDA ® (pembrolizumab), Merck’s anti-PD-1 therapy, as a perioperative treatment regimen for patients with stage III or IVA, resected, locally advanced head and neck squamous cell carcinoma (LA-HNSCC). Results at the first interim analysis of the trial showed KEYTRUDA significantly improved event-free survival (EFS) as part of a perioperative treatment regimen with adjuvant standard of care (SOC) radiotherapy with or without cisplatin compared to adjuvant standard of care (SOC) radiotherapy with or without cisplatin alone in patients with resectable LA-HNSCC. These data are being presented for the first time today during a Plenary Session at the American Association for Cancer Research (AACR) Annual Meeting 2025 (Abstract #CT001) and were selected for the AACR press program. After a median follow-up of 38.3 months (range, 9.0-66.5), treatment with KEYTRUDA before surgery (neoadjuvant), then continued in combination with standard of care radiotherapy (with or without cisplatin) after surgery followed by KEYTRUDA alone (adjuvant), reduced the risk of EFS events by 34% (HR=0.66 [95% CI, 0.49-0.88]; p=.0022) in the combined positive score (CPS) ≥10 population, by 30% (HR=0.70 [95% CI, 0.55-0.89; p=.0014) in the CPS ≥1 population and by 27% (HR=0.73 [95% CI 0.58-0.92]; p=.0041) in the intent-to-treat (ITT) population, compared to adjuvant radiotherapy (with or without cisplatin) alone in the ITT population. Among the CPS ≥10 population, median EFS was 59.7 months in the KEYTRUDA plus SOC group (95% CI, 41.1-not reached) versus 26.9 months (95% CI, 18.3-51.5) in the SOC group. Among the CPS ≥1 population, median EFS was 59.7 months (95% CI, 37.9-not reached) in the KEYTRUDA plus SOC group versus 29.6 months (95% CI, 19.5-41.9) in the SOC group. In the ITT population, median EFS was 51.8 months (95% CI, 37.5-not reached) in the KEYTRUDA plus SOC group versus 30.4 months (95% CI, 21.8-50.1) in the SOC group. The safety profile of KEYTRUDA was consistent with that observed in previously reported studies; no new safety signals were identified. “As the first positive trial in over two decades for patients with resectable, locally advanced head and neck squamous cell carcinoma, the presentation of these landmark results marks an important moment for these patients and those who care for them,” said Dr. Ravindra Uppaluri, the study’s co-principal investigator, director of Head and Neck Surgical Oncology, Brigham and Women’s Hospital and Dana-Farber Cancer Institute. “KEYNOTE-689 represents a meaningful development with a potential to provide an option that helps certain patients with LA-HNSCC reduce the risk of recurrence and disease progression earlier in their treatment journey.” “The addition of immunotherapy using KEYTRUDA to standard of care surgery and adjuvant (chemo)radiotherapy resulted in a significant reduction in the risk of event-free survival events by 27%, compared with standard of care therapy alone,” said study co-principal investigator Dr. Douglas Adkins, Professor, Division of Oncology, Washington University School of Medicine in St. Louis. “These results are notable as they mark the first time an anti-PD-1 therapy has demonstrated a statistically significant and clinically meaningful improvement in event-free survival in the neoadjuvant and adjuvant setting in earlier stages of head and neck squamous cell carcinoma.” The study also showed a statistically significant improvement in major pathological response (mPR) rate, a key secondary endpoint, in patients with CPS ≥10 (difference in mPR rates: 13.7% [95% CI, 9.7-18.7]; p<0.00001), CPS ≥1 (9.8% [95% CI, 7.0-13.3]; p<0.00001) and in the ITT population (9.3% [95% CI, 6.7–12.8, P<.00001), compared to adjuvant radiotherapy alone. A trend toward improvement in overall survival (OS), another key secondary endpoint, was observed in patients with CPS ≥10 (HR=0.72 [95% CI, 0.52-0.98])at the time of this interim analysis for the KEYTRUDA plus standard of care regimen versus standard of care alone. The OS results did not reach statistical significance at the time of this interim analysis. Due to the statistical testing hierarchy, formal testing was not performed in the CPS ≥1 and ITT populations. OS will be evaluated at the next interim analysis. “As the 12 th positive pivotal trial for a KEYTRUDA-based regimen in earlier-stage cancers, the results from KEYNOTE-689 are a testament to our commitment to address an unmet need in this important area of research,” said Dr. Marjorie Green, senior vice president and head of oncology, global clinical development, Merck Research Laboratories. “These compelling results illustrate the potential of this regimen to change the landscape of care for certain patients facing this challenging disease. We are working with the FDA and other global authorities to bring this new option to patients as quickly as possible.” A supplemental Biologics License Application (sBLA) for KEYTRUDA based on data from KEYNOTE-689 is under priority review with the U.S. Food and Drug Administration (FDA), with a Prescription Drug User Fee Act (PDUFA), or target action, date of June 23, 2025. KEYTRUDA is currently approved as monotherapy and in combination regimens for appropriate patients with metastatic or unresectable, recurrent HNSCC in the U.S., Europe, China, Japan and other countries around the world. For more information, please see the “Selected KEYTRUDA ® (pembrolizumab) Indications in the U.S.” section below. Study design and additional data from KEYNOTE-689 KEYNOTE-689 is a randomized, active-controlled, open-label Phase 3 trial (ClinicalTrials.gov, NCT03765918 ) evaluating KEYTRUDA as neoadjuvant treatment and KEYTRUDA in combination with standard of care radiotherapy (with or without cisplatin) as adjuvant treatment in treatment-naïve patients with newly diagnosed, stage III or IVA resectable, locally advanced head and neck squamous cell carcinoma (LA-HNSCC). Efficacy outcomes are classified by programmed cell death ligand 1 (PD-L1) combined positive score (CPS) status. The primary endpoint is EFS, which is defined as the time from randomization to the first occurrence of radiographic disease progression; local or distant progression or recurrence; or death due to any cause. The secondary endpoints include OS, mPR, pathological complete response and safety. The study enrolled 714 patients who were randomized 1:1 to receive: The safety profile of KEYTRUDA was consistent with that observed in previously reported studies. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 44.6% of patients receiving KEYTRUDA plus standard of care radiotherapy versus 42.9% of patients receiving standard of care radiotherapy alone. TRAEs led to death in 1.1% of patients receiving the KEYTRUDA regimen (n=4) and 0.3% of patients receiving standard of care radiotherapy (n=1). No new safety concerns were identified. Immune-mediated adverse events (AEs) of any grade occurred in 43.2% of patients receiving the KEYTRUDA regimen, most commonly hypothyroidism (24.7%). About head and neck cancer Head and neck cancer describes a number of different tumors that develop in or around the throat, larynx, nose, sinuses and mouth. Most head and neck cancers are squamous cell carcinomas that begin in the flat, squamous cells that make up the thin surface layer of the structures in the head and neck. Locally advanced head and neck squamous cell carcinoma (LA-HNSCC) is cancer that has grown outside the original location, but has not yet spread to distant parts of the body. There are several factors that greatly increase the risk of developing head and neck cancer, including tobacco and alcohol use and human papillomavirus (HPV). It is estimated there were more than 947,200 new cases of head and neck cancer diagnosed and over 482,400 deaths from the disease in 2022 globally. In the U.S., it is estimated there will be approximately 72,680 new cases of head and neck cancer diagnosed and more than 16,680 deaths from the disease in 2025. About Merck’s early-stage cancer clinical program Finding cancer at an earlier stage may give patients a greater chance of long-term survival. Many cancers are considered most treatable and potentially curable in their earliest stage of disease. Building on the strong understanding of the role of KEYTRUDA in later-stage cancers, Merck is evaluating our portfolio of medicines and pipeline candidates in earlier disease states, with more than 30 ongoing registrational studies across multiple types of cancer. About KEYTRUDA ® (pembrolizumab) injection, 100 mg KEYTRUDA is an anti-programmed death receptor-1 (PD-1) therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD- L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells. Merck has the industry’s largest immuno-oncology clinical research program. There are currently more than 1,600 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient’s likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers. Selected KEYTRUDA ® (pembrolizumab) Indications in the U.S. Head and Neck Squamous Cell Cancer KEYTRUDA, in combination with platinum and fluorouracil (FU), is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent head and neck squamous cell carcinoma (HNSCC). KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 [Combined Positive Score (CPS) ≥1] as determined by an FDA-approved test. KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy. Melanoma KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma. KEYTRUDA is indicated for the adjuvant treatment of adult and pediatric (12 years and older) patients with Stage IIB, IIC, or III melanoma following complete resection. Non-Small Cell Lung Cancer KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations. KEYTRUDA, in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, is indicated for the first-line treatment of patients with metastatic squamous NSCLC. KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with NSCLC expressing PD-L1 [Tumor Proportion Score (TPS) ≥1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and is: KEYTRUDA, as a single agent, is indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA. KEYTRUDA is indicated for the treatment of patients with resectable (tumors ≥4 cm or node positive) NSCLC in combination with platinum-containing chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery. KEYTRUDA, as a single agent, is indicated as adjuvant treatment following resection and platinum-based chemotherapy for adult patients with Stage IB (T2a ≥4 cm), II, or IIIA NSCLC. Malignant Pleural Mesothelioma KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of adult patients with unresectable advanced or metastatic malignant pleural mesothelioma (MPM). Classical Hodgkin Lymphoma KEYTRUDA is indicated for the treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma (cHL). KEYTRUDA is indicated for the treatment of pediatric patients with refractory cHL, or cHL that has relapsed after 2 or more lines of therapy. Primary Mediastinal Large B-Cell Lymphoma KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after 2 or more prior lines of therapy. KEYTRUDA is not recommended for treatment of patients with PMBCL who require urgent cytoreductive therapy. Urothelial Cancer KEYTRUDA, in combination with enfortumab vedotin, is indicated for the treatment of adult patients with locally advanced or metastatic urothelial cancer. KEYTRUDA, as a single agent, is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma: KEYTRUDA, as a single agent, is indicated for the treatment of patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy. Microsatellite Instability-High or Mismatch Repair Deficient Cancer KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options. Microsatellite Instability-High or Mismatch Repair Deficient Colorectal Cancer KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic MSI-H or dMMR colorectal cancer (CRC) as determined by an FDA-approved test. Gastric Cancer KEYTRUDA, in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval of this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. KEYTRUDA, in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma. Esophageal Cancer KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic esophageal or gastroesophageal junction (GEJ) (tumors with epicenter 1 to 5 centimeters above the GEJ) carcinoma that is not amenable to surgical resection or definitive chemoradiation either: Cervical Cancer KEYTRUDA, in combination with chemoradiotherapy (CRT), is indicated for the treatment of patients with FIGO 2014 Stage III-IVA cervical cancer. KEYTRUDA, in combination with chemotherapy, with or without bevacizumab, is indicated for the treatment of patients with persistent, recurrent, or metastatic cervical cancer whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test. KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test. Hepatocellular Carcinoma KEYTRUDA is indicated for the treatment of patients with hepatocellular carcinoma (HCC) secondary to hepatitis B who have received prior systemic therapy other than a PD-1/PD-L1-containing regimen. Biliary Tract Cancer KEYTRUDA, in combination with gemcitabine and cisplatin, is indicated for the treatment of patients with locally advanced unresectable or metastatic biliary tract cancer (BTC). Merkel Cell Carcinoma KEYTRUDA is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC). Renal Cell Carcinoma KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC). KEYTRUDA is indicated for the adjuvant treatment of patients with RCC at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions. Endometrial Carcinoma KEYTRUDA, in combination with carboplatin and paclitaxel, followed by KEYTRUDA as a single agent, is indicated for the treatment of adult patients with primary advanced or recurrent endometrial carcinoma. KEYTRUDA, as a single agent, is indicated for the treatment of adult patients with advanced endometrial carcinoma that is MSI-H or dMMR, as determined by an FDA-approved test, who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation. Tumor Mutational Burden-High Cancer KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) [≥10 mutations/megabase (mut/Mb)] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with TMB-H central nervous system cancers have not been established. Cutaneous Squamous Cell Carcinoma KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cutaneous squamous cell carcinoma (cSCC) or locally advanced cSCC that is not curable by surgery or radiation. Triple-Negative Breast Cancer KEYTRUDA is indicated for the treatment of patients with high-risk early-stage triple-negative breast cancer (TNBC) in combination with chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery. KEYTRUDA, in combination with chemotherapy, is indicated for the treatment of patients with locally recurrent unresectable or metastatic TNBC whose tumors express PD-L1 (CPS ≥10) as determined by an FDA-approved test. Merck’s focus on cancer Every day, we follow the science as we work to discover innovations that can help patients, no matter what stage of cancer they have. As a leading oncology company, we are pursuing research where scientific opportunity and medical need converge, underpinned by our diverse pipeline of more than 25 novel mechanisms. With one of the largest clinical development programs across more than 30 tumor types, we strive to advance breakthrough science that will shape the future of oncology. By addressing barriers to clinical trial participation, screening and treatment, we work with urgency to reduce disparities and help ensure patients have access to high-quality cancer care. Our unwavering commitment is what will bring us closer to our goal of bringing life to more patients with cancer. For more information, visit http://www.merck.com/research/oncology . About Merck At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit www.merck.com and connect with us on X (formerly Twitter) , Facebook , Instagram , YouTube and LinkedIn . SOURCE: Merck

On April 23, 2025, the Food and Drug Administration approved penpulimab-kcqx (Akeso Biopharma Co., Ltd.) with cisplatin or carboplatin and gemcitabine for the first-line treatment of adults with recurrent or metastatic non-keratinizing nasopharyngeal carcinoma (NPC). FDA also approved penpulimab-kcqx as a single agent for adults with metastatic non-keratinizing NPC with disease progression on or after platinum-based chemotherapy and at least one other prior line of therapy.Full prescribing information for penpulimab-kcqx will be posted on Drugs@FDA.Efficacy and SafetyEfficacy of penpulimab-kcqx with cisplatin or carboplatin and gemcitabine was evaluated in Study AK105-304 (NCT04974398), a randomized, double-blind, multi-center trial in 291 patients with recurrent or metastatic NPC who had not received previous systemic chemotherapy for recurrent or metastatic disease. Patients were randomized (1:1) to receive either penpulimab-kcqx with cisplatin or carboplatin and gemcitabine, followed by penpulimab-kcqx, or placebo with cisplatin or carboplatin and gemcitabine, followed by placebo. Chemotherapy regimens are described in the full prescribing information.The primary efficacy outcome measure was progression-free survival (PFS), as assessed by a Blinded Independent Review Committee according to RECIST v1.1. Overall survival (OS) was a key secondary endpoint. Median PFS was 9.6 months (95% CI: 7.1, 12.5) in the penpulimab-kcqx arm and 7.0 months (95% CI: 6.9, 7.3) in the placebo arm (hazard ratio [HR] 0.45 [95% CI: 0.33, 0.62], two-sided p-value <0.0001), with 31% and 11% of patients alive and progression-free after 12 months of follow-up in the penpulimab-kcqx and placebo arms, respectively. While OS results were immature, with 70% of pre-specified deaths for the final analysis reported, no detrimental trend was observed.Efficacy of single-agent penpulimab-kcqx was evaluated in Study AK105-202 (NCT03866967), an open-label, multicenter, single-arm trial conducted in a single country. The trial included a total of 125 patients with unresectable or metastatic non-keratinizing NPC who had disease progression after platinum-based chemotherapy and at least one other line of therapy. Patients received penpulimab-kcqx until disease progression or unacceptable toxicity, for a maximum of 24 months.The major efficacy outcome measures were objective response rate (ORR) and duration of response (DOR) according to RECIST v1.1 as assessed by an Independent Radiology Review Committee. The ORR was 28% (95% CI: 20, 37) and median DOR was not reached (95% CI: 9.2, not estimable).Immune-mediated adverse reactions occurred with penpulimab-kcqx including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis with renal dysfunction, and skin adverse reactions. The most common adverse reactions (≥20%) for penpulimab-kcqx with cisplatin or carboplatin and gemcitabine were nausea, vomiting, hypothyroidism, constipation, decreased appetite, decreased weight, cough, COVID-19 infection, fatigue, rash, and pyrexia. The most common adverse reactions (≥20%) for single-agent penpulimab-kcqx were hypothyroidism and musculoskeletal pain. Fatal adverse reactions occurred in 1% of patients, including a case each of pneumonitis, septic shock, colitis, and hepatitis.The recommended penpulimab-kcqx dose with cisplatin or carboplatin and gemcitabine is 200 mg every three weeks until disease progression or unacceptable toxicity, for a maximum of 24 months. The recommended single-agent penpulimab-kcqx dose for previously treated NPC is 200 mg every two weeks until disease progression or unacceptable toxicity, for a maximum of 24 months.Expedited ProgramsThis review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.This application was granted fast track designation, 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.

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