Policy & Regulation
FDA Grants Priority Review to Merck's Supplemental Biologics License Application for Keytruda (pembrolizumab) for the First-Line Treatment of Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (HNSCC)
11 February 2019 - - The US Food and Drug Administration has accepted a new supplemental Biologics License Application for Keytruda, US-based biopharmaceutical company Merck's (NYSE: MRK) anti-PD-1 therapy, as monotherapy or in combination with platinum and 5-fluorouracil chemotherapy for the first-line treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), the company said.

This sBLA is based in part on data from the pivotal Phase 3 KEYNOTE-048 trial where Keytruda demonstrated a significant improvement in overall survival compared with the standard of care, as monotherapy in patients whose tumors expressed PD-L1 with CPS≥20 and CPS≥1 and in combination with chemotherapy in the total patient population. These data were presented at the European Society for Medical Oncology 2018 Congress.

The FDA has granted Priority Review to this sBLA and set a Prescription Drug User Fee Act (PDUFA), or target action, date of June 10, 2019.

KEYNOTE-048 also serves as the confirmatory trial for KEYNOTE-012, a Phase 1b study which supported the previous accelerated approval for Keytruda as monotherapy for the treatment of patients with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy.

Merck currently has the largest immuno-oncology clinical development program in HNSCC and is continuing to advance multiple registration-enabling studies investigating Keytruda as monotherapy and in combination with other cancer treatments--including KEYNOTE-412, KEYNOTE-689 and KEYNOTE-122.

KEYNOTE-048, a randomised, open-label Phase 3 trial (ClinicalTrials.gov, NCT02358031), evaluated Keytruda monotherapy or Keytruda combination, compared with the EXTREME regimen, as first-line treatment in 882 patients with recurrent or metastatic HSNCC.

The dual primary endpoints were OS and PFS. The secondary endpoints were PFS (at 6 months and 12 months), objective response rate and time to deterioration in Quality of Life Global Health Status/Quality of Life Scales of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire and Safety.

Duration of response was evaluated as part of a pre-specified exploratory analysis.

The primary and secondary endpoints, as well as exploratory DOR analysis, were evaluated in patients whose tumors expressed PD-L1 with CPS ≥20 and CPS ≥1, and in the total population, regardless of PD-L1 expression, based on a fixed sequential testing strategy.

At the time of the analysis, the median follow-up was 11.7 months for KEYTRUDA monotherapy, 13.0 months for Keytruda combination and 10.7 months for the EXTREME regimen, respectively.

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.

The leading modifiable risk factors for head and neck cancer include tobacco and heavy alcohol use, and other risk factors include infection with certain types of HPV, also called human papillomaviruses.

In the US, it is estimated that there will be more than 65,000 new cases of head and neck cancer diagnosed in 2019.

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 humanised 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 900 trials studying Keytruda across a range 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 is indicated for the treatment of patients with unresectable or metastatic melanoma at a fixed dose of 200 mg every three weeks until disease progression or unacceptable toxicity.

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 nab-paclitaxel, 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 metastatic NSCLC whose tumors have high PD-L1 expression [tumor proportion score ≥50%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.

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 metastatic NSCLC, Keytruda is administered at a fixed dose of 200 mg 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.
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