Dataset Information

A Phase Ib Study of Pembrolizumab as Second-Line Therapy for Chinese Patients With Advanced or Metastatic Melanoma (KEYNOTE-151).

ABSTRACT: BACKGROUND:Pembrolizumab shows robust antitumor activity and favorable safety in metastatic melanoma. KEYNOTE-151 evaluated pembrolizumab in Chinese patients, who have more aggressive melanoma subtypes than other populations. METHODS:Chinese patients aged ?18years with advanced melanoma previously treated with one line of therapy received pembrolizumab 2 mg/kg every 3 weeks for 35 cycles or until confirmed disease progression, intolerable toxicity, or study withdrawal. Primary end points were objective response rate (ORR) per RECIST v1.1 by blinded independent central review and safety. Key secondary end points included duration of response (DOR) and progression-free survival (PFS) per RECIST v1.1 and overall survival (OS). RESULTS:Median age was 52 years (N=103); 37.9% had acral and 14.6% had mucosal melanoma. Median follow-up was 7.9months at data cutoff (December 27, 2017). ORR was 16.7% (95% CI, 10.0-25.3%) (1 complete, 16 partial responses). Disease control rate was 38.2%. ORR was 15.8% for acral, 13.3% for mucosal melanoma. Median DOR was 8.4months; 65.6% of patients had response duration ?6months. Median PFS was 2.8months (95% CI, 2.7-3.5months); 6-month rate was 20.4%. Median OS was 12.1months (95% CI, 9.6months-not reached); 6-month rate, 75.7%; 12-month rate, 50.6%. Treatment-related AEs (TRAEs) occurred in 87 (84.5%) patients; 9 (8.7%) experienced grade 3/4 TRAE and 2 (1.9%) discontinued because of TRAE; none died. Two deaths occurred that were unrelated to treatment. CONCLUSIONS:Pembrolizumab was well tolerated and provided clinically meaningful antitumor activity as second-line therapy in Chinese patients with advanced melanoma.

SUBMITTER: Si L

PROVIDER: S-EPMC6458446 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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A Phase Ib Study of Pembrolizumab as Second-Line Therapy for Chinese Patients With Advanced or Metastatic Melanoma (KEYNOTE-151).

Si Lu L Zhang Xiaoshi X Shu Yongqian Y Pan Hongming H Wu Di D Liu Jiwei J Lou Fang F Mao Lili L Wang Xuan X Wen Xizhi X Gu Yanhong Y Zhu Lingjun L Lan Shijie S Cai Xin X Diede Scott J SJ Zhou Yu Y Ge Jun J Li Jianfeng J Wu Haiyan H Guo Jun J

Translational oncology 20190410 6

<h4>Background</h4>Pembrolizumab shows robust antitumor activity and favorable safety in metastatic melanoma. KEYNOTE-151 evaluated pembrolizumab in Chinese patients, who have more aggressive melanoma subtypes than other populations.<h4>Methods</h4>Chinese patients aged ≥18years with advanced melanoma previously treated with one line of therapy received pembrolizumab 2 mg/kg every 3 weeks for 35 cycles or until confirmed disease progression, intolerable toxicity, or study withdrawal. Primary end ...[more]

PMID: 30981094

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Project description:Survival is generally poor for Chinese patients with advanced melanoma because of high rates of acral and mucosal melanoma and limited therapeutic options. The first analysis of the phase 1b KEYNOTE-151 study showed second-line pembrolizumab was well tolerated and had clinically meaningful antitumor activity in Chinese patients with advanced melanoma. Three-year follow-up is presented. Eligible patients were of Chinese descent and had unresectable stage III/IV melanoma that progressed after first-line therapy. Patients received pembrolizumab 2 mg/kg every 3 weeks for ≤35 cycles. Primary end points were safety and objective response rate (ORR). Secondary end points included duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Response was assessed per RECIST v1.1 by blinded independent central review. Subgroup analyses were conducted by melanoma subtype and BRAF and PD-L1 status (acral melanoma only). 103 patients were enrolled; median follow-up duration (time from first dose to data cutoff [July 13, 2020]) was 44.6 months (IQR, 39.1-46.2). Any-grade treatment-related adverse events (TRAEs) occurred in 85.4% of patients, and grade 3/4 TRAEs in 12.6%. No grade 5 TRAEs occurred. Three patients discontinued pembrolizumab because of TRAEs (immune-mediated hepatitis, pneumonia, and arthritis). Immune-mediated AEs and infusion reactions occurred in 34.0% (grade 3/4, 2.9%). ORR was 17.6% (95% CI, 10.8-26.4; 1 complete response/17 partial responses), and median DOR was 13.8 months (range, 2.7-37.4+). Median PFS was 2.8 months (95% CI, 2.7-3.5) and 36-month PFS rate was 5.0%. Median OS was 13.2 months (95% CI, 10.4-16.5) and 36-month OS rate was 22.3%. Median OS for patients with known melanoma subtype was 14.8 months for acral, 13.5 months for nonacral cutaneous, and 7.4 months for mucosal melanoma. Among the acral subgroup, median OS was 22.8 months for PD-L1-positive disease, 8.4 months for PD-L1-negative disease, 18.5 months for BRAF wild-type disease, and 5.8 months for BRAF-mutant disease. Over 3 years' follow-up, second-line pembrolizumab continued to show manageable safety, clinically meaningful antitumor activity, and durable responses in Chinese patients with advanced melanoma. Subgroup analysis suggested particular benefit in PD-L1-positive and BRAF wild-type acral melanoma, although small subgroup sizes preclude definitive conclusions.Clinical trial registrationhttps://clinicaltrials.gov, identifier NCT02821000.

Project description:IntroductionPembrolizumab plus chemotherapy significantly improved survival outcomes versus placebo plus chemotherapy in patients with previously untreated metastatic squamous NSCLC in the randomized, double-blind, phase 3 KEYNOTE-407 study. We present the results of Chinese patients enrolled in the KEYNOTE-407 global and China extension studies.MethodsPatients enrolled from mainland China in the KEYNOTE-407 global (NCT02775435) and China extension studies (NCT03875092) were randomized 1:1 to 35 cycles of pembrolizumab or placebo plus four cycles of carboplatin and paclitaxel or nab-paclitaxel. Dual primary end points were overall survival (OS) and progression-free survival (PFS) (based on the Response Evaluation Criteria in Solid Tumors version 1.1 by blinded independent central review).ResultsA total of 125 patients were randomized (pembrolizumab-chemotherapy, n = 65; placebo-chemotherapy, n = 60). As of September 30, 2020, median (range) study follow-up was 28.1 (25.1‒40.9) months. Pembrolizumab-chemotherapy improved OS (hazard ratio [HR] = 0.44, 95% confidence interval [CI]: 0.28-0.70) and PFS (HR = 0.35, 95% CI: 0.24-0.52) versus placebo-chemotherapy. Two-year OS and PFS rates for pembrolizumab-chemotherapy versus placebo-chemotherapy were 56.9% versus 31.7% and 24.2% versus 3.3%, respectively. Treatment-related grade 3 to 5 adverse events occurred in 81.5% and 81.7%, respectively. Relative to baseline, pembrolizumab-chemotherapy improved global health status/quality of life scores at week 18 versus placebo-chemotherapy (difference in least squares means = 7.6, 95% CI: 1.5-13.7) and prolonged time to deterioration in cough, chest pain, or dyspnea (HR = 0.50, 95% CI: 0.28-0.89).ConclusionsPembrolizumab-chemotherapy prolonged survival versus placebo-chemotherapy with manageable toxicity and preserved or improved health-related quality of life in Chinese patients with metastatic squamous NSCLC. These findings support pembrolizumab-chemotherapy as first-line therapy in this population.

Project description:BackgroundPatients with advanced urothelial carcinoma that progresses after platinum-based chemotherapy have a poor prognosis and limited treatment options.MethodsIn this open-label, international, phase 3 trial, we randomly assigned 542 patients with advanced urothelial cancer that recurred or progressed after platinum-based chemotherapy to receive pembrolizumab (a highly selective, humanized monoclonal IgG4κ isotype antibody against programmed death 1 [PD-1]) at a dose of 200 mg every 3 weeks or the investigator's choice of chemotherapy with paclitaxel, docetaxel, or vinflunine. The coprimary end points were overall survival and progression-free survival, which were assessed among all patients and among patients who had a tumor PD-1 ligand (PD-L1) combined positive score (the percentage of PD-L1-expressing tumor and infiltrating immune cells relative to the total number of tumor cells) of 10% or more.ResultsThe median overall survival in the total population was 10.3 months (95% confidence interval [CI], 8.0 to 11.8) in the pembrolizumab group, as compared with 7.4 months (95% CI, 6.1 to 8.3) in the chemotherapy group (hazard ratio for death, 0.73; 95% CI, 0.59 to 0.91; P=0.002). The median overall survival among patients who had a tumor PD-L1 combined positive score of 10% or more was 8.0 months (95% CI, 5.0 to 12.3) in the pembrolizumab group, as compared with 5.2 months (95% CI, 4.0 to 7.4) in the chemotherapy group (hazard ratio, 0.57; 95% CI, 0.37 to 0.88; P=0.005). There was no significant between-group difference in the duration of progression-free survival in the total population (hazard ratio for death or disease progression, 0.98; 95% CI, 0.81 to 1.19; P=0.42) or among patients who had a tumor PD-L1 combined positive score of 10% or more (hazard ratio, 0.89; 95% CI, 0.61 to 1.28; P=0.24). Fewer treatment-related adverse events of any grade were reported in the pembrolizumab group than in the chemotherapy group (60.9% vs. 90.2%); there were also fewer events of grade 3, 4, or 5 severity reported in the pembrolizumab group than in the chemotherapy group (15.0% vs. 49.4%).ConclusionsPembrolizumab was associated with significantly longer overall survival (by approximately 3 months) and with a lower rate of treatment-related adverse events than chemotherapy as second-line therapy for platinum-refractory advanced urothelial carcinoma. (Funded by Merck; KEYNOTE-045 ClinicalTrials.gov number, NCT02256436 .).

Project description:IntroductionKEYNOTE-240 investigated the efficacy and safety of pembrolizumab plus best supportive care (BSC) in sorafenib-treated patients with advanced hepatocellular carcinoma (HCC). Results for the subgroup of patients from Asia are described.MethodsAdults with advanced HCC previously treated with sorafenib were randomized 2:1 to pembrolizumab or placebo plus BSC. Here, the Asian subgroup comprised patients enrolled in Hong Kong, Japan, Korea, the Philippines, Taiwan, and Thailand. Primary endpoints were progression-free survival (PFS) per blinded central imaging review and overall survival (OS). Secondary endpoints included objective response rate (ORR) per blinded central imaging review, duration of response (DOR), and safety.ResultsThe Asian subgroup included 157 patients. As of January 2, 2019, the median follow-up in this subgroup was 13.8 months for pembrolizumab and 8.3 months for placebo. The median PFS was 2.8 months for pembrolizumab (95% confidence interval [CI] 2.6-4.1) versus 1.4 months (95% CI 1.4-2.4) for placebo (hazard ratio [HR] 0.48; 95% CI 0.32-0.70). The median OS was 13.8 months (95% CI 10.1-16.9) for pembrolizumab versus 8.3 months (95% CI 6.3-11.8) for placebo (HR 0.55; 95% CI 0.37-0.80). ORR was 20.6% (95% CI 13.4-29.5) for pembrolizumab versus 2.0% (95% CI 0.1-10.6) for placebo (difference: 18.5%; 95% CI 8.3-27.6). The median DOR was 8.6 and 2.8 months for pembrolizumab and placebo, respectively. Any grade treatment-related adverse events (TRAEs) occurred in 63 patients (58.9%) receiving pembrolizumab and 24 patients (48.0%) receiving placebo; 14 (13.1%) and 2 (4.0%) patients experienced grade 3-5 TRAEs, respectively. No treatment-related deaths occurred.ConclusionPembrolizumab demonstrated antitumor activity and was well tolerated in the Asian subgroup of KEYNOTE-240. A trend toward greater benefit with pembrolizumab in the Asian subgroup was observed compared with the overall cohort, supporting further evaluation of pembrolizumab treatment in this population.

Project description:BackgroundPembrolizumab demonstrated robust antitumor activity and safety in the phase Ib KEYNOTE-001 study (NCT01295827) of advanced melanoma. Five-year outcomes in all patients and treatment-naive patients are reported herein. Patients whose disease progressed following initial response and who received a second course of pembrolizumab were also analyzed.Patients and methodsPatients aged ≥18 years with previously treated or treatment-naive advanced/metastatic melanoma received pembrolizumab 2 mg/kg every 3 weeks, 10 mg/kg every 3 weeks, or 10 mg/kg every 2 weeks until disease progression, intolerable toxicity, or patient/investigator decision to withdraw. Kaplan-Meier estimates of overall survival (OS) and progression-free survival (PFS) were calculated. Objective response rate and PFS were based on immune-related response criteria by investigator assessment (data cut-off, September 1, 2017).ResultsKEYNOTE-001 enrolled 655 patients with melanoma; median follow-up was 55 months. Estimated 5-year OS was 34% in all patients and 41% in treatment-naive patients; median OS was 23.8 months (95% CI, 20.2-30.4) and 38.6 months (95% CI, 27.2-not reached), respectively. Estimated 5-year PFS rates were 21% in all patients and 29% in treatment-naive patients; median PFS was 8.3 months (95% CI, 5.8-11.1) and 16.9 months (95% CI, 9.3-35.5), respectively. Median response duration was not reached; 73% of all responses and 82% of treatment-naive responses were ongoing at data cut-off; the longest response was ongoing at 66 months. Four patients [all with prior response of complete response (CR)] whose disease progressed during observation subsequently received second-course pembrolizumab. One patient each achieved CR and partial response (after data cut-off). Treatment-related AEs (TRAEs) occurred in 86% of patients and resulted in study discontinuation in 7.8%; 17% experienced grade 3/4 TRAE.ConclusionsThis 5-year analysis of KEYNOTE-001 represents the longest follow-up for pembrolizumab to date and confirms the durable antitumor activity and tolerability of pembrolizumab in advanced melanoma.Clinical trial registryClinicalTrials.gov, NCT01295827.

Dataset Information

A Phase Ib Study of Pembrolizumab as Second-Line Therapy for Chinese Patients With Advanced or Metastatic Melanoma (KEYNOTE-151).

Publications

A Phase Ib Study of Pembrolizumab as Second-Line Therapy for Chinese Patients With Advanced or Metastatic Melanoma (KEYNOTE-151).

Similar Datasets

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