FDA Approves Merck?s KEYTRUDA (pembrolizumab) as Monotherapy for Patients with Metastatic Small Cell Lung Cancer (SCLC) with Disease Progression on or After Platinum-Based Chemotherapy and at
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, as monotherapy 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 accelerated approval is 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. This marks the first indication for KEYTRUDA in SCLC.
?KEYTRUDA is already an established treatment option for non-small cell lung cancer, and today?s approval in small cell lung cancer demonstrates our commitment to bringing forward new treatment options for patients with advanced, difficult-to-treat cancers,? said Dr. Jonathan Cheng, vice president, oncology clinical research, Merck Research Laboratories. ?We look forward to continuing to advance important clinical research in small cell lung cancer.?
Immune-mediated adverse reactions, which may be severe or fatal, can occur with KEYTRUDA, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis and renal dysfunction, 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.
?Small cell lung cancer, which accounts for 10 to 15% of all lung cancers, is often diagnosed at an advanced stage where the prognosis is very poor and there have historically been limited treatment options,? said Dr. Patrick Ott, MD, PhD, clinical director, Center for Immuno-Oncology, Dana-Farber Cancer Institute. ?The approval of KEYTRUDA in small cell lung cancer provides an additional treatment option for patients based on the clinical response rates from KEYNOTE-158 and KEYNOTE-028.?
About KEYNOTE-158 and KEYNOTE-028
The approval was based on pooled data from KEYNOTE-158 (cohort G) and KEYNOTE-028 (cohort C1), two multicenter, multi-cohort, non-randomized, open-label trials evaluating KEYTRUDA in patients with SCLC who had disease progression on or after platinum-based chemotherapy and at least one other prior line of therapy. The trials excluded patients with autoimmune disease or a medical condition that required immunosuppression. Among the 83 patients enrolled in the trials and who were evaluated for efficacy, 64% received two prior lines of therapy and 36% received three or more lines of therapy; 60% received prior thoracic radiation therapy; 51% received prior radiation therapy to the brain.
Patients evaluated for efficacy received either KEYTRUDA 200 mg intravenously every three weeks (n=64) or 10 mg/kg intravenously every two weeks (n=19). Treatment with KEYTRUDA continued until documented disease progression, unacceptable toxicity or a maximum of 24 months. Patients with initial radiographic disease progression could receive additional doses of KEYTRUDA during confirmation of progression unless disease progression was symptomatic, was rapidly progressive, required urgent intervention or occurred with a decline in performance status. The major efficacy outcome measures were objective response rate (ORR) and duration of response (DOR) as assessed by BICR according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, modified to follow a maximum of 10 target lesions and a maximum of five target lesions per organ.
KEYTRUDA demonstrated an ORR of 19% (95% CI, 11-29), with a complete response rate of 2% and a partial response rate of 17%. Among the 16 responding patients, 94% had a DOR of six months or longer, 63% had a DOR of 12 months or longer and 56% had a DOR of 18 months or longer. Responses ranged from 4.1 to 35.8+ months.
Among the patients with SCLC enrolled in KEYNOTE-158 (cohort G) (n=107) and KEYNOTE-028 (cohort C1) (n=24) who were included in the safety analysis, the adverse reactions that occurred were similar to those occurring in patients with other solid tumors who received KEYTRUDA as a single agent.
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 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 benefiting 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.