Data Demonstrate Efficacy and Safety of KEYTRUDA 400 mg Every Six Weeks (Q6W) Comparable to Approved 200 mg Every Three Weeks (Q3W) Regimen
Resubmitted Supplemental Biologics License Applications (sBLAs) for KEYTRUDA Q6W Dosing Under Review with US FDA Across All Approved Adult Indications
KENILWORTH, NJ, USA I April 27, 2020 I Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced the presentation of interim data from Cohort B of KEYNOTE-555, a Phase 1 trial evaluating a 400 mg every six-week (Q6W) dosing regimen for KEYTRUDA, Merck’s anti-PD-1 therapy, in patients with metastatic melanoma. Results of the study – which represent the first clinical outcomes evaluating Q6W dosing for KEYTRUDA – demonstrated efficacy and safety comparable to findings from previous melanoma trials evaluating KEYTRUDA monotherapy. Interim data showed an overall response rate (ORR) of 38.6% (n=17/44) (95% CI, 24.4-54.5) in patients who received KEYTRUDA 400 mg Q6W, the primary endpoint of the study.
As previously announced, Merck resubmitted supplemental Biologics License Applications (sBLAs) to the U.S. Food and Drug Administration (FDA) to update the dosing frequency for KEYTRUDA to include a 400 mg Q6W option across all approved adult indications. The results of KEYNOTE-555 supported the resubmission. In the EU, 400 mg Q6W dosing for KEYTRUDA monotherapy was approved by the European Commission in March 2019.
“We remain committed to improving cancer care, which includes the ability to offer greater flexibility in administering KEYTRUDA,” said Dr. Scot Ebbinghaus, vice president, clinical research, Merck Research Laboratories. “These data, coupled with extensive model-based assessments, provide strong evidence for a six-week dosing regimen for KEYTRUDA.”
Results from KEYNOTE-555 Cohort B will be presented tomorrow in an online plenary session at the American Association for Cancer Research (AACR) Virtual Annual Meeting I (Abstract #CT042).
Additional Data from KEYNOTE-555 Cohort B (Abstract #CT042)
KEYNOTE-555 (ClinicalTrials.gov, NCT03665597) is a Phase 1 open-label trial evaluating the relative bioavailability of subcutaneous injection versus intravenous infusion in patients with unresectable stage III or IV melanoma. The primary endpoint is ORR; secondary endpoints include pharmacokinetic (PK) exposures, progression-free survival (PFS) and safety. In Cohort B, 100 patients were assigned to receive KEYTRUDA 400 mg Q6W. An analysis was conducted in the first 44 patients who had sufficient follow-up to evaluate for efficacy. The ORR was 38.6% (n=17/44) (95% CI, 24.4-54.5) in patients treated with the KEYTRUDA 400 mg Q6W regimen, with a complete response rate of 9.1% (n=4/44) and partial response rate of 29.5% (n=13/44). Efficacy findings were comparable to findings observed in previous melanoma trials evaluating KEYTRUDA monotherapy. Additionally, PK exposures for KEYTRUDA 400 mg Q6W were within clinical experience with other tested dosing regimens. Trough concentrations at 400 mg Q6W were comparable to the KEYTRUDA 200 mg and 2 mg/kg every three week (Q3W) regimens and peak concentrations were lower than the KEYTRUDA 10 mg/kg every two week (Q2W) regimen.
The safety profile of KEYTRUDA 400 mg Q6W was consistent with the safety profile of KEYTRUDA 200 mg Q3W, which has been demonstrated in more than 12 tumor types. Any grade all-cause adverse events occurred in 97.7% (n=43/44) of patients. Grade 3-4 all-cause adverse events occurred in 25.0% (n=11/44) of patients. Treatment-related adverse events (TRAEs) occurred in 68.2% (n=30/44) of patients. Grade 3-4 TRAEs occurred in 2.3% (n=1/44) of patients. There were no treatment-related deaths.
About Melanoma
Melanoma, the most serious form of skin cancer, is characterized by the uncontrolled growth of pigment-producing cells. The incidence of melanoma has been increasing over the past few decades – approximately 288,000 new cases were diagnosed worldwide in 2018. In the U.S., melanoma is one of the most common types of cancer diagnosed and is responsible for the vast majority of skin cancer deaths. In 2020, more than 100,000 people are expected to be diagnosed and an estimated 7,000 people are expected to die of the disease in the U.S. alone.
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 1,200 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
Melanoma
KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.
KEYTRUDA is indicated for the adjuvant treatment of patients with melanoma with involvement of lymph node(s) 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 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.
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 1 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.
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 head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy.
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.
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 treatment of patients with PMBCL who require urgent cytoreductive therapy.
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 [combined positive score (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 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.
KEYTRUDA 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 (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.
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 MSI-H central nervous system cancers have not been established.
Gastric Cancer
KEYTRUDA is indicated for the treatment of patients with recurrent locally advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test, with disease progression on or after two or more prior lines of therapy including fluoropyrimidine- and platinum-containing chemotherapy and if appropriate, HER2/neu-targeted 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.
Esophageal Cancer
KEYTRUDA is indicated for the treatment of patients with recurrent locally advanced or metastatic squamous cell carcinoma of the esophagus whose tumors express PD-L1 (CPS ≥10) as determined by an FDA-approved test, with disease progression after one or more prior lines of systemic therapy.
Cervical Cancer
KEYTRUDA 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. 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
KEYTRUDA is indicated 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.
Merkel Cell Carcinoma
KEYTRUDA is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC). 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.
Renal Cell Carcinoma
KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of patients with advanced renal cell carcinoma (RCC).
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 Merck
For more than 125 years, Merck, 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 in pursuit of our mission to save and improve lives. We demonstrate our commitment to patients and population health by increasing access to health care through far-reaching policies, programs and partnerships. Today, Merck continues to be at the forefront of research to prevent and treat diseases that threaten people and animals – including cancer, infectious diseases such as HIV and Ebola, and emerging animal diseases – as we aspire to be the premier research-intensive biopharmaceutical company in the world. For more information, visit www.merck.com and connect with us on Twitter, Facebook, Instagram, YouTube and LinkedIn.
SOURCE: Merck