FDA Approves Merck?s KEYTRUDA (pembrolizumab) for the Treatment of Adult and Pediatric Patients with Recurrent Locally Advanced or Metastatic Merkel Cell Carcinoma, a Rare Form of Skin Cancer
Accelerated Approval Based on Results of CITN-09/KEYNOTE-017, Where KEYTRUDA Monotherapy Demonstrated an Objective Response Rate of 56 percent
KENILWORTH, N.J.--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 adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC), based on the results of the Cancer Immunotherapy Trials Network (CITN)?s CITN-09/KEYNOTE-017 trial. In this Phase 2 trial of 50 patients with recurrent locally advanced or metastatic MCC who had not received prior systemic therapy for their advanced disease, KEYTRUDA monotherapy demonstrated an objective response rate of 56 percent (95% CI, 41-70), with a complete response rate of 24 percent (95% CI, 13-38) and a partial response rate of 32 percent (95% CI, 20-47). 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 CITN-09/KEYNOTE-017 trial demonstrates that first-line treatment with anti-PD1 therapy provides a meaningful advance for Merkel cell carcinoma patients who have historically had a poor long-term prognosis,? said Dr. Paul Nghiem, lead investigator, professor of dermatology at the University of Washington School of Medicine in Seattle and affiliate investigator at Fred Hutchinson Cancer Research Center. ?A few years ago, patients with Merkel cell carcinoma did not have treatment options beyond chemotherapy. As a practicing physician I am pleased that this approval provides another option for patients facing this rare and challenging disease.?
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.
?Merkel cell carcinoma is an aggressive and fast-growing form of skin cancer that has historically been challenging to treat,? said Dr. Scot Ebbinghaus, vice president, clinical research, Merck Research Laboratories. ?We thank the Cancer Immunotherapy Trials Network for initiating and conducting the trial, the National Cancer Institute for their sponsorship of the research that led to this approval, and the investigators who contributed to the findings. We also thank the patients who participated in the trial and are pleased to provide an important new therapeutic option for Merkel cell carcinoma patients.?
Data Supporting the Approval
The approval was based on data from CITN-09/KEYNOTE-017, a Phase 2, non-randomized, multicenter, open-label trial, initiated and conducted by the Cancer Immunotherapy Trials Network (CITN) based at the Fred Hutchinson Cancer Research Center and sponsored by the National Cancer Institute, evaluating KEYTRUDA in 50 patients with recurrent locally advanced or metastatic MCC who had not received prior systemic therapy for their advanced disease. Patients with active autoimmune disease or a medical condition that required immunosuppression were ineligible.
Patients received KEYTRUDA 2 mg/kg every three weeks until unacceptable toxicity or disease progression that was symptomatic, rapidly progressive, required urgent intervention, occurred with a decline in performance status, or was confirmed at least four weeks later with repeat imaging. Patients without disease progression were treated for up to 24 months. Assessment of tumor status was performed at 13 weeks followed by every nine weeks for the first year and every 12 weeks thereafter. The major efficacy outcome measures were objective response rate (ORR) and duration of response (DOR) as assessed by blinded independent central review per RECIST v1.1.
Among the 50 patients treated, the median age was 71 years (range, 46 to 91 years; 80% age 65 or older); 68 percent were male; 90 percent were White; and ECOG performance score was 0 (48%) and 1 (52%). Fourteen percent had stage IIIB disease, and 86 percent had stage IV. For patients with local or locoregional disease, 84 percent had prior surgery, and 70 percent had prior radiation therapy.
In CITN-09/KEYNOTE-017, the ORR was 56 percent (95% CI, 41-70), with a complete response rate of 24 percent (95% CI, 13-38) and a partial response rate of 32 percent (95% CI, 20-47). Among the responding patients, median DOR was not reached (range, 5.9 to 34.5+ months). Ninety-six percent of responding patients experienced a DOR for six months or longer, and 54 percent experienced a DOR for 12 months or longer.
Among the 50 patients with MCC enrolled in CITN-09/KEYNOTE-017, the median duration of exposure to KEYTRUDA was 6.6 months (range, 1 day to 23.6 months).
Adverse reactions occurring in patients with MCC were generally similar to those in patients with melanoma or NSCLC.
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.
KEYTRUDA? (pembrolizumab) Indications and Dosing
Melanoma
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.
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 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 non-small cell lung cancer (NSCLC) whose tumors have high PD-L1 expression [Tumor Proportion Score (TPS) =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.
Head and Neck Cancer
KEYTRUDA 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. 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 HNSCC, 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.
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 is administered at a fixed dose of 200 mg 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 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 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. In pediatric patients with PMBCL, KEYTRUDA is administered 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 [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 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 is administered at a fixed dose of 200 mg 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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