Designation Granted for Potential First-Line Treatment of Patients with Advanced Unresectable Hepatocellular Carcinoma Not Amenable to Locoregional Treatment
?Merck (NYSE: MRK), known as MSD outside the United States and Canada, and Eisai today announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation for KEYTRUDA, Merck?s anti-PD-1 therapy, in combination with LENVIMA, the orally available kinase inhibitor discovered by Eisai, for the potential first-line treatment of patients with advanced unresectable hepatocellular carcinoma (HCC) not amenable to locoregional treatment. This is the third Breakthrough Therapy designation for the KEYTRUDA plus LENVIMA combination and is based on updated interim results from the Phase 1b trial KEYNOTE-524/Study 116. An earlier interim analysis was presented at the American Association for Cancer Research (AACR) Annual Meeting 2019. The first two Breakthrough Therapy designations for the combination were in advanced and/or metastatic renal cell carcinoma and advanced and/or metastatic non-microsatellite instability-high (MSI-H)/proficient mismatch repair (pMMR) endometrial carcinoma, received in January 2018 and July 2018, respectively. The combination of KEYTRUDA plus LENVIMA is investigational. The efficacy and safety of this combination has not been established. The KEYTRUDA plus LENVIMA combination is not approved in any cancer types today.
?As part of our ongoing collaboration with Eisai, we are committed to evaluating the potential of KEYTRUDA plus LENVIMA across a number of different types of cancer,? said Dr. Jonathan Cheng, Vice President, Oncology Clinical Research, Merck Research Laboratories. ?With this Breakthrough Therapy designation from the FDA, we look forward to working with Eisai to potentially build upon our existing indications for this difficult-to-treat cancer, so that we can help patients through a combination approach.? ?We are excited that the FDA has recognized the potential of KEYTRUDA plus LENVIMA in combination in advanced unresectable hepatocellular carcinoma not amenable to locoregional treatment with this Breakthrough Therapy designation,? said Dr. Takashi Owa, Vice President, Chief Medicine Creation and Chief Discovery Officer, Oncology Business Group at Eisai. ?We are dedicated to working together with Merck to potentially bring another important option to patients.? The Breakthrough Therapy designation is intended to expedite development and review of medicines for serious or life-threatening conditions and to qualify for this designation, preliminary clinical evidence must demonstrate that the therapy may provide substantial improvement over currently available therapy on at least one clinically significant endpoint. About KEYNOTE-524/Study 116 KEYNOTE-524/Study 116 is a multi-center, open-label, single-arm Phase 1b study evaluating the safety and efficacy of the combination of KEYTRUDA (200 mg intravenously every three weeks) and LENVIMA (12 mg/day for patients weighing 60 kg or more, and 8 mg/day for patients weighing less than 60 kg) in patients with unresectable HCC, Barcelona Clinic Liver Cancer (BCLC) stage B (not eligible for transarterial chemoembolization [TACE]) or C, Child-Pugh class A, and ECOG performance status (PS) of 0 or 1. The primary endpoints are tolerability and safety, and the secondary endpoints include overall survival (OS), objective response rate (ORR), progression-free survival (PFS) and time to progression (TTP) using modified Response Evaluation Criteria In Solid Tumors (mRECIST) criteria. Tumor assessments of complete response (CR) or partial response (PR) were confirmed at least four weeks (or longer) after initial response. The first part of the trial evaluated tolerability by assessing dose-limiting toxicities (DLTs) during the first cycle of treatment in patients for whom no other appropriate therapy was available. After tolerability was confirmed, additional patients with no prior systemic therapy for unresectable HCC were enrolled in the expansion part of the trial, which is evaluating ORR and duration of response as measured by mRECIST and Response Evaluation Criteria In Solid Tumors (RECIST 1.1) based on independent imaging review (IIR). About Hepatocellular Carcinoma The prevalence and mortality rate of liver cancer have been rising steadily over the past decade. In 2019, it is estimated there will be more than 42,000 new liver cancer cases diagnosed in the U.S. (including intrahepatic bile duct cancer). Additionally, it is estimated there will be nearly 32,000 deaths from liver cancer in the U.S. Liver cancer ? which is often diagnosed at an advanced stage ? has one of the highest mortality rates of solid cancers, with a five-year survival rate of about 18%. Hepatocellular carcinoma is the most common type of liver cancer, accounting for approximately 90% of these cases. The stage of disease at diagnosis largely determines the treatment approach, with potentially curative options, like resection or transplantation, only available for early-stage HCC. Unresectable HCC, a type of liver cancer that cannot be removed by surgery, has a worse prognosis, with a median survival of less than one year. Unfortunately, approximately 70% of patients are diagnosed too late to be eligible for resection, ablation or transplantation, and there have been limited treatment options available for patients with unresectable disease. About KEYTRUDA??(pembrolizumab) Injection, 100 mg 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 1,000 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. KEYTRUDA??(pembrolizumab) Indications and Dosing Melanoma KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma. The recommended dose of KEYTRUDA in patients with unresectable or metastatic melanoma is 200 mg administered as an intravenous infusion over 30 minutes every three weeks until disease progression or unacceptable toxicity. KEYTRUDA is indicated for the adjuvant treatment of patients with melanoma with involvement of lymph node(s) following complete resection. The recommended dose of KEYTRUDA for the adjuvant treatment of adult patients with melanoma is 200 mg administered as an intravenous infusion over 30 minutes every three weeks until disease recurrence, unacceptable toxicity, or for up to 12 months in patients without disease recurrence. 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 stage III where patients are not candidates for surgical resection or definitive chemoradiation, or metastatic. 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. In NSCLC, the recommended dose of KEYTRUDA is 200 mg administered as an intravenous infusion over 30 minutes every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression. When administering KEYTRUDA in combination with chemotherapy, KEYTRUDA should be administered prior to chemotherapy when given on the same day. See also the Prescribing Information for the chemotherapy agents administered in combination with KEYTRUDA, as appropriate. Small Cell Lung Cancer KEYTRUDA is indicated for the treatment of patients with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy and at least one other prior line of therapy. 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 confirmatory trials. In SCLC, the recommended dose of KEYTRUDA is 200 mg administered as an intravenous infusion over 30 minutes every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression. Head and Neck 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 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. In HNSCC, the recommended dose of KEYTRUDA is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression. When administering KEYTRUDA in combination with chemotherapy, administer KEYTRUDA prior to chemotherapy when given on the same day. Refer to the Prescribing Information for the chemotherapy agents administered in combination with KEYTRUDA for recommended dosing information, as appropriate. Classical Hodgkin Lymphoma KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory classical Hodgkin lymphoma (cHL), or who have relapsed after 3 or more prior lines of therapy. 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. In adults with cHL, KEYTRUDA 200 mg is administered as an intravenous infusion over 30 minutes every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression. In pediatric patients with cHL, KEYTRUDA is administered as an intravenous infusion over 30 minutes at a dose of 2 mg/kg (up to a maximum of 200 mg) every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression. 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. 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 confirmatory trials. KEYTRUDA is not recommended for the treatment of patients with PMBCL who require urgent cytoreductive therapy. In adults with PMBCL, KEYTRUDA 200 mg is administered as an intravenous infusion over 30 minutes every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression. In pediatric patients with PMBCL, KEYTRUDA is administered as an intravenous infusion over 30 minutes at a dose of 2 mg/kg (up to a maximum of 200 mg) every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression. Urothelial Carcinoma KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 [ CPS =10] as determined by an FDA-approved test, or in patients who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status. This indication is approved under accelerated approval based on tumor 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. KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. In locally advanced or metastatic urothelial carcinoma, KEYTRUDA 200 mg is administered as an intravenous infusion over 30 minutes every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression. Microsatellite Instability-High (MSI-H) 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 that have progressed following prior treatment and who have no satisfactory alternative treatment options, or
- colorectal cancer that has progressed following treatment with fluoropyrimidine, oxaliplatin, and irinotecan.
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