المؤلفون: Gangadhar, Tara C, Hwu, Wen-Jen, Postow, Michael A, Hamid, Omid, Daud, Adil, Dronca, Roxana, Joseph, Richard, O’Day, Steven J, Hodi, FS, Pavlick, Anna C, Kluger, Harriet, Oxborough, Romina P, Yang, Aiming, Gazdoiu, Mihaela, Kush, Debra A, Ebbinghaus, Scot, Salama, April KS

المصدر: Journal of Immunotherapy. 40(9)

مصطلحات موضوعية: Clinical Research, Cancer, Clinical Trials and Supportive Activities, Adolescent, Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Humanized, Antineoplastic Agents, Clinical Trials as Topic, Drug Resistance, Neoplasm, Drug-Related Side Effects and Adverse Reactions, Exanthema, Fatigue, Female, Humans, Male, Melanoma, Middle Aged, Neoplasm Metastasis, Neoplasm Staging, Treatment Outcome, United States, Young Adult, expanded access program, immunotherapy, melanoma, PD-1, pembrolizumab, Immunology

الوصف: KEYNOTE-030 (ClinicalTrials.gov ID, NCT02083484) was a global expanded access program that allowed access to pembrolizumab, an antiprogrammed death 1 antibody, for patients with advanced melanoma before its regulatory approval. Patients with unresectable stage III/IV melanoma that progressed after standard-of-care therapy, including ipilimumab and, if BRAF mutant, a BRAF inhibitor, were eligible to receive pembrolizumab 2 mg/kg every 3 weeks. Response was assessed by immune-related response criteria by investigator review. Adverse events (AEs) were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. In the United States, 979 patients enrolled between April and September 2014. Of the 947 evaluable patients, 621 (65.6%) remained on treatment and transitioned to receive commercial pembrolizumab following approval by the Food and Drug Administration, whereas 326 (34.4%) discontinued, most commonly for disease progression (39.6%) or death (26.4%). Objective response rate was 14.5% (95% confidence interval, 12.2%-16.8%) in the treated population (n=947) and 22.1% (95% confidence interval, 18.8%-25.5%) in patients who had ≥1 response assessment reported (n=619). Twelve patients achieved complete response. One hundred eighty-one (19.1%) patients experienced ≥1 treatment-related AE, most commonly general disorders (8.0%), skin/subcutaneous tissue disorders (7.3%), and gastrointestinal disorders (6.4%); 29 (3.1%) patients experienced ≥1 grade 3/4 treatment-related AE. Immune-mediated AEs were also reported. There were no treatment-related deaths. The safety and efficacy observed in this expanded access program were consistent with those previously reported for similar populations and support the use of pembrolizumab for patients with advanced melanoma.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/60z5g7xzTest

المؤلفون: Gangadhar, Tara C, Hwu, Wen-Jen, Postow, Michael A, Hamid, Omid, Daud, Adil, Dronca, Roxana, Joseph, Richard, O'Day, Steven J, Hodi, FS, Pavlick, Anna C, Kluger, Harriet, Oxborough, Romina P, Yang, Aiming, Gazdoiu, Mihaela, Kush, Debra A, Ebbinghaus, Scot, Salama, April KS

المصدر: Journal of immunotherapy (Hagerstown, Md. : 1997). 40(9)

مصطلحات موضوعية: Humans, Melanoma, Neoplasm Metastasis, Exanthema, Fatigue, Antineoplastic Agents, Neoplasm Staging, Treatment Outcome, Drug Resistance, Neoplasm, Adolescent, Adult, Aged, Aged, 80 and over, Middle Aged, United States, Female, Male, Clinical Trials as Topic, Young Adult, Antibodies, Monoclonal, Humanized, Drug-Related Side Effects and Adverse Reactions, expanded access program, immunotherapy, melanoma, PD-1, pembrolizumab, Immunology

الوصف: KEYNOTE-030 (ClinicalTrials.gov ID, NCT02083484) was a global expanded access program that allowed access to pembrolizumab, an antiprogrammed death 1 antibody, for patients with advanced melanoma before its regulatory approval. Patients with unresectable stage III/IV melanoma that progressed after standard-of-care therapy, including ipilimumab and, if BRAF mutant, a BRAF inhibitor, were eligible to receive pembrolizumab 2 mg/kg every 3 weeks. Response was assessed by immune-related response criteria by investigator review. Adverse events (AEs) were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. In the United States, 979 patients enrolled between April and September 2014. Of the 947 evaluable patients, 621 (65.6%) remained on treatment and transitioned to receive commercial pembrolizumab following approval by the Food and Drug Administration, whereas 326 (34.4%) discontinued, most commonly for disease progression (39.6%) or death (26.4%). Objective response rate was 14.5% (95% confidence interval, 12.2%-16.8%) in the treated population (n=947) and 22.1% (95% confidence interval, 18.8%-25.5%) in patients who had ≥1 response assessment reported (n=619). Twelve patients achieved complete response. One hundred eighty-one (19.1%) patients experienced ≥1 treatment-related AE, most commonly general disorders (8.0%), skin/subcutaneous tissue disorders (7.3%), and gastrointestinal disorders (6.4%); 29 (3.1%) patients experienced ≥1 grade 3/4 treatment-related AE. Immune-mediated AEs were also reported. There were no treatment-related deaths. The safety and efficacy observed in this expanded access program were consistent with those previously reported for similar populations and support the use of pembrolizumab for patients with advanced melanoma.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/60z5g7xzTest

المؤلفون: Ribas, Antoni, Puzanov, Igor, Dummer, Reinhard, Schadendorf, Dirk, Hamid, Omid, Robert, Caroline, Hodi, F Stephen, Schachter, Jacob, Pavlick, Anna C, Lewis, Karl D, Cranmer, Lee D, Blank, Christian U, O'Day, Steven J, Ascierto, Paolo A, Salama, April KS, Margolin, Kim A, Loquai, Carmen, Eigentler, Thomas K, Gangadhar, Tara C, Carlino, Matteo S, Agarwala, Sanjiv S, Moschos, Stergios J, Sosman, Jeffrey A, Goldinger, Simone M, Shapira-Frommer, Ronnie, Gonzalez, Rene, Kirkwood, John M, Wolchok, Jedd D, Eggermont, Alexander, Li, Xiaoyun Nicole, Zhou, Wei, Zernhelt, Adriane M, Lis, Joy, Ebbinghaus, Scot, Kang, S Peter, Daud, Adil

المصدر: The Lancet Oncology. 16(8)

مصطلحات موضوعية: Clinical Trials and Supportive Activities, Cancer, Clinical Research, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Adolescent, Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized, Antineoplastic Agents, Antineoplastic Combined Chemotherapy Protocols, Disease Progression, Disease-Free Survival, Drug Resistance, Neoplasm, Female, Humans, Intention to Treat Analysis, Ipilimumab, Kaplan-Meier Estimate, Male, Melanoma, Middle Aged, Skin Neoplasms, Time Factors, Treatment Outcome, Young Adult, Oncology and Carcinogenesis, Oncology & Carcinogenesis

الوصف: BackgroundPatients with melanoma that progresses on ipilimumab and, if BRAF(V600) mutant-positive, a BRAF or MEK inhibitor or both, have few treatment options. We assessed the efficacy and safety of two pembrolizumab doses versus investigator-choice chemotherapy in patients with ipilimumab-refractory melanoma.MethodsWe carried out a randomised phase 2 trial of patients aged 18 years or older from 73 hospitals, clinics, and academic medical centres in 12 countries who had confirmed progressive disease within 24 weeks after two or more ipilimumab doses and, if BRAF(V600) mutant-positive, previous treatment with a BRAF or MEK inhibitor or both. Patients had to have resolution of all ipilimumab-related adverse events to grade 0-1 and prednisone 10 mg/day or less for at least 2 weeks, an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and at least one measurable lesion to be eligible. Using a centralised interactive voice response system, we randomly assigned (1:1:1) patients in a block size of six to receive intravenous pembrolizumab 2 mg/kg or 10 mg/kg every 3 weeks or investigator-choice chemotherapy (paclitaxel plus carboplatin, paclitaxel, carboplatin, dacarbazine, or oral temozolomide). Randomisation was stratified by ECOG performance status, lactate dehydrogenase concentration, and BRAF(V600) mutation status. Individual treatment assignment between pembrolizumab and chemotherapy was open label, but investigators and patients were masked to assignment of the dose of pembrolizumab. We present the primary endpoint at the prespecified second interim analysis of progression-free survival in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01704287. The study is closed to enrolment but continues to follow up and treat patients.FindingsBetween Nov 30, 2012, and Nov 13, 2013, we enrolled 540 patients: 180 patients were randomly assigned to receive pembrolizumab 2 mg/kg, 181 to receive pembrolizumab 10 mg/kg, and 179 to receive chemotherapy. Based on 410 progression-free survival events, progression-free survival was improved in patients assigned to pembrolizumab 2 mg/kg (HR 0·57, 95% CI 0·45-0·73; p

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/8j23r3pnTest