PD-1抑制剂Keytruda(pembrolizumab) 治疗血癌总缓解率66％
Pharmacological Class:
Human programmed death receptor-1 (PD-1)-blocking antibody.
Active Ingredient(s):
Pembrolizumab 50mg; per vial; lyophilized powder for IV infusion after reconstitution; preservative-free.
Company
Merck & Co., Inc.
Indication(s):
Treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor.
Pharmacology:
Pembrolizumab is a humanized monoclonal antibody that binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2, releasing PD-1 pathway-mediated inhibition of the immune response, including the anti-tumor immune response.
Clinical Trials:
The efficacy of Keytruda was eva luated in a multicenter, open-label, randomized, dose-comparative, activity-estimating cohort of Trial 1. Key eligibility criteria were unresectable or metastatic melanoma with progression of disease; refractory to two or more doses of ipilimumab (3mg/kg or higher) and, if BRAF V600 mutation-positive, a BRAF or MEK inhibitor; and disease progression within 24 weeks following the last dose of ipilimumab. Patients were randomized to receive Keytruda 2mg/kg (n=89) or 10mg/kg (n=84) every 3 weeks until unacceptable toxicity or disease progression that was symptomatic, was rapidly progressive, required urgent intervention, occurred with a decline in performance status, or was confirmed at 4–6 weeks with repeat imaging. Tumor status was assessed every 12 weeks.
The major efficacy outcome measures were confirmed overall response rate (ORR) according to Response eva luation Criteria in Solid Tumors (RECIST 1.1) as assessed by blinded independent central review and duration of response.
The ORR was 24% (95% CI: 15, 34) in the 2mg/kg arm, consisting of 1 complete response and 20 partial responses. Among the 21 patients with an objective response, 3 (14%) had disease progression 2.8, 2.9, and 8.2 months after initial response. The remaining 18 patients (86%) had ongoing responses with durations ranging from 1.4–8.5+ months, which included 8 patients with ongoing responses of 6 months or longer.
There were objective responses in patients with and without BRAF V600 mutation-positive melanoma. Similar ORR results were observed in the 10mg/kg arm.
Legal Classification:
Rx
Adults:
Give as IV infusion over 30 minutes. 2mg/kg every 3 weeks until disease progression or unacceptable toxicity. Dose modifications: see full labeling. Administer corticosteroids for most Grade ≥2 related immune-mediated reactions.
Children:
Not established.
Warnings/Precautions:
Monitor for signs/symptoms of pneumonitis; withhold dose if Grade 2 pneumonitis; permanently discontinue if Grade 3 or 4 develops. Monitor for signs/symptoms of colitis; withhold dose if Grade 2 or 3 colitis; permanently discontinue if Grade 4 develops. Monitor for changes in liver function; withhold dose or discontinue based on severity of elevated liver enzymes. Monitor for hypophysitis; withhold dose if Grade 2 hypophysitis; withhold or discontinue if Grade 3; permanently discontinue if Grade 4 develops. Monitor for changes in renal function; withhold dose if Grade 2 nephritis; permanently discontinue if Grade 3 or 4 develops. Monitor thyroid function at treatment initiation, during, and as clinically indicated; withhold if Grade 3 hyperthyroidism; permanently discontinue if Grade 4 develops. Permanently discontinue if any severe or Grade 3 immune-mediated adverse reaction that recurs and for any life-threatening immune-mediated adverse reaction. Use highly effective contraception during treatment and for at least 4 months after the last dose. Pregnancy (Category D), nursing mothers: not recommended.
Adverse Reaction(s)
Fatigue, cough, nausea, pruritus, rash, decreased appetite, constipation, arthralgia, diarrhea, sepsis; renal failure, dyspnea, pneumonia, cellulitis.
How Supplied:
Single-use vial—1
LAST UPDATED:
1/13/2015
