KENILWORTH, N.J.–(BUSINESS WIRE) November 9, 2018 –Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced that the U.S. Food and Drug Administration (FDA) has approved Keytruda, Merck’s anti-PD-1 therapy, for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. 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.
“Hepatocellular carcinoma is the most common type of liver cancer in adults, and while we have seen recent therapeutic advancements, there are still limited treatment options for advanced recurrent disease,” said Dr. Andrew X. Zhu, lead investigator and director of liver cancer research at Massachusetts General Hospital and professor of medicine at Harvard Medical School. “Today’s approval of Keytruda is important, as it provides a new treatment option for patients with hepatocellular carcinoma who have been previously treated with sorafenib.”
Immune-mediated adverse reactions, which may be severe or fatal, can occur with Keytruda, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, severe skin reactions, solid organ transplant rejection, and complications of allogeneic hematopoietic stem cell transplantation (HSCT). Based on the severity of the adverse reaction, Keytruda should be withheld or discontinued and corticosteroids administered if appropriate. Keytruda can also cause severe or life-threatening infusion-related reactions. Based on its mechanism of action, Keytruda can cause fetal harm when administered to a pregnant woman. For more information, see “Selected Important Safety Information” below.
“The approval of Keytruda for advanced hepatocellular carcinoma marks the second FDA approval for hepatocellular carcinoma in Merck’s oncology portfolio this year, underscoring our commitment to help bring forward new treatment options for cancers that have historically been very challenging to treat,” said Dr. Scot Ebbinghaus, vice president, clinical research, Merck Research Laboratories. “We look forward to continuing to advance research for hepatocellular carcinoma across our portfolio with the goal to help even more patients affected by this type of cancer.”
Data Supporting the Approval
The approval was based on data from KEYNOTE-224, a single-arm, open-label, multicenter trial evaluating Keytruda in 104 patients with HCC who had disease progression on or after sorafenib or were intolerant to sorafenib. Additional eligibility included having measurable disease and Child-Pugh class A liver impairment. Patients with active and inactive hepatitis B virus (HBV) as well as patients with past or ongoing hepatitis C virus (HCV) infection were eligible for the trial. Patients with active autoimmune disease, greater than one etiology of hepatitis, a medical condition that required immunosuppression, or clinical evidence of ascites by physical exam were ineligible for the trial.
Patients received Keytruda 200 mg every three weeks until unacceptable toxicity or confirmed disease progression. Patients without disease progression were treated for up to 24 months. Assessment of tumor status was performed every nine weeks. The major efficacy outcome measures were objective response rate (ORR) and duration of response according to RECIST v1.1, modified to follow a maximum of 10 target lesions and a maximum of five target lesions per organ, as assessed by blinded independent central review (BICR).
Among the 104 patients treated, the baseline characteristics were: median age 68 years (67% age 65 or older); 83 percent were male; 81 percent were White; 14 percent were Asian; ECOG PS of 0 (61%) or 1 (39%); Child Pugh class and score were A5 (72%), A6 (22%), B7 (5%), and B8 (1%); 21 percent were HBV seropositive and 25% HCV seropositive. Nine patients (9%) were seropositive for both HBV and HCV. Sixty-four percent of patients had extrahepatic disease, 17 percent had vascular invasion, and 9 percent had both, and 38 percent had alfa-fetoprotein (AFP) levels greater than 400 ug/mL. All patients received prior sorafenib; reasons for discontinuation were intolerance in 20 percent of patients.
In KEYNOTE-224, the ORR was 17 percent (95% CI, 11-26), with a complete response rate of 1 percent and a partial response rate of 16 percent. Among the responding patients (n=18), 89 percent experienced a DOR for six months or longer and 56 percent experienced a DOR for 12 months or longer.
Among the 104 patients in KEYNOTE-224, the median duration of exposure to Keytruda was 4.2 months (range, 1 day to 1.5 years). Adverse reactions occurring in patients with HCC were generally similar to those in patients with melanoma or non-small cell lung cancer, with the exception of increased incidences of ascites (8% Grades 3-4) and immune-mediated hepatitis (2.9%). Laboratory abnormalities (Grades 3-4) that occurred at a higher incidence were elevated AST (20%), ALT (9%), and hyperbilirubinemia (10%).
About Keytruda (pembrolizumab) Injection, 100mg
Keytruda is an anti-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 850 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.
Merck’s Focus on Cancer
Our goal is to translate breakthrough science into innovative oncology medicines to help people with cancer worldwide. At Merck, the potential to bring new hope to people with cancer drives our purpose and supporting accessibility to our cancer medicines is our commitment. As part of our focus on cancer, Merck is committed to exploring the potential of immuno-oncology with one of the largest development programs in the industry across more than 30 tumor types. We also continue to strengthen our portfolio through strategic acquisitions and are prioritizing the development of several promising oncology candidates with the potential to improve the treatment of advanced cancers. For more information about our oncology clinical trials, visit www.merck.com/clinicaltrials.
About the Merck Access Program for Keytruda
At Merck, we are committed to supporting accessibility to our cancer medicines. Merck provides multiple programs to help ensure that appropriate patients who are prescribed Keytruda have access to our anti-PD-1 therapy. The Merck Access Program provides reimbursement support for patients receiving Keytruda, including information to help with out-of-pocket costs and co-pay assistance for eligible patients. Merck also offers free product through our patient assistance program to eligible patients, primarily the uninsured, who, without our assistance, could not afford their medicine. More information is available by calling 855-257-3932 or visiting www.merckaccessprogram-keytruda.com.
About Merck’s Patient Support Program for Keytruda
Merck is committed to helping provide patients and their caregivers support throughout their treatment with Keytruda. The KEY+YOU Patient Support Program provides a range of resources and services. For further information and to sign up, patients and physicians may call 85-KEYTRUDA (855-398-7832) or visit www.keytruda.com.
For more than a century, Merck, a leading global biopharmaceutical company known as MSD outside of the United States and Canada, has been inventing for life, bringing forward medicines and vaccines for many of the world’s most challenging diseases. Through our prescription medicines, vaccines, biologic therapies and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to health care through far-reaching policies, programs and partnerships. Today, Merck continues to be at the forefront of research to advance the prevention and treatment of diseases that threaten people and communities around the world – including cancer, cardio-metabolic diseases, emerging animal diseases, Alzheimer’s disease and infectious diseases including HIV and Ebola. For more information, visit www.merck.com and connect with us on Twitter, Facebook, Instagram, YouTube and LinkedIn.
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Posted: November 2018
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- FDA Approves Expanded Label for Merck’s Keytruda (pembrolizumab) in Patients with Metastatic Nonsquamous NSCLC with No EGFR or ALK Genomic Tumor Aberrations – August 21, 2018
- FDA Approves Keytruda (pembrolizumab) for Treatment of Refractory or Relapsed Primary Mediastinal Large B-Cell Lymphoma (PMBCL) – June 13, 2018
- FDA Approves Keytruda (pembrolizumab) for Previously Treated Patients with Recurrent or Metastatic Cervical Cancer Whose Tumors Express PD-L1 – June 12, 2018
- FDA Approves Merck’s Keytruda (pembrolizumab) for Previously Treated Patients with Recurrent Locally Advanced or Metastatic Gastric or Gastroesophageal Junction Cancer Whose Tumors Express PD-L1 – September 22, 2017
- FDA Approves Keytruda (pembrolizumab) as First Cancer Treatment for any Solid Tumor with a Specific Genetic Feature – May 23, 2017
- FDA Approves Merck’s Keytruda (pembrolizumab) for Certain Patients with Locally Advanced or Metastatic Urothelial Carcinoma – May 18, 2017
- FDA Approves Merck’s Keytruda (pembrolizumab) as First-Line Combination Therapy for Patients with Metastatic Nonsquamous Non-Small Cell Lung Cancer (NSCLC), Irrespective of PD-L1 Expression – May 10, 2017
- FDA Approves Merck’s Keytruda (pembrolizumab) for Classical Hodgkin Lymphoma (cHL) – March 15, 2017
- FDA Approves Merck’s Keytruda (pembrolizumab) for First-Line Treatment of Certain Patients with Metastatic Non-Small Cell Lung Cancer – October 24, 2016
- FDA Approves Merck’s Keytruda (pembrolizumab) for Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma – August 5, 2016
- FDA Approves Expanded Indication for Keytruda (pembrolizumab) for the Treatment of Patients with Advanced Melanoma – December 18, 2015
- FDA Approves Keytruda (pembrolizumab) for Advanced Non-Small Cell Lung Cancer – October 2, 2015
- FDA Approves Keytruda (pembrolizumab) for Advanced Melanoma – September 4, 2014
- Merck to Present New Data in Five Tumor Types from Studies Evaluating Pembrolizumab – September 2, 2014
- Merck’s Investigational Anti-PD-1 Antibody, Pembrolizumab, Under Regulatory Review in Europe for Advanced Melanoma – June 30, 2014
Keytruda (pembrolizumab) FDA Approval History