scholarly journals Programmed Death-Ligand 1 Expression and Response to the Anti–Programmed Death 1 Antibody Pembrolizumab in Melanoma

2016 ◽  
Vol 34 (34) ◽  
pp. 4102-4109 ◽  
Author(s):  
Adil I. Daud ◽  
Jedd D. Wolchok ◽  
Caroline Robert ◽  
Wen-Jen Hwu ◽  
Jeffrey S. Weber ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Objective Response Rate ◽  
Response Rate ◽  
Objective Response ◽  
Progression Free Survival ◽  
Hazard Ratio ◽  
Tumor Biopsy ◽  
Programmed Death Ligand 1 ◽  
Programmed Death ◽  
Programmed Death 1

Purpose Expression of programmed death-ligand 1 (PD-L1) is a potential predictive marker for response and outcome after treatment with anti–programmed death 1 (PD-1). This study explored the relationship between anti–PD-1 activity and PD-L1 expression in patients with advanced melanoma who were treated with pembrolizumab in the phase Ib KEYNOTE-001 study (clinical trial information: NCT01295827). Patients and Methods Six hundred fifty-five patients received pembrolizumab10 mg/kg once every 2 weeks or once every 3 weeks, or 2 mg/kg once every 3 weeks. Tumor response was assessed every 12 weeks per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by independent central review. Primary outcome was objective response rate. Secondary outcomes included progression-free survival (PFS) and overall survival (OS). Membranous PD-L1 expression in tumor and tumor-associated immune cells was assessed by a clinical trial immunohistochemistry assay (22C3 antibody) and scored on a unique melanoma (MEL) scale of 0 to 5 by one of three pathologists who were blinded to clinical outcome; a score ≥ 2 (membranous staining in ≥ 1% of cells) was considered positive. Results Of 451 patients with evaluable PD-L1 expression, 344 (76%) had PD-L1–positive tumors. Demographic and staging variables were equally distributed among PD-L1–positive and –negative patients. An association between higher MEL score and higher response rate and longer PFS (hazard ratio, 0.76; 95% CI, 0.71 to 0.82) and OS (hazard ratio, 0.76; 95% CI, 0.69 to 0.83) was observed ( P < .001 for each). Objective response rate was 8%, 12%, 22%, 43%, 57%, and 53% for MEL 0, 1, 2, 3, 4, and 5, respectively. Conclusion PD-L1 expression in pretreatment tumor biopsy samples was correlated with response rate, PFS, and OS; however, patients with PD-L1–negative tumors may also achieve durable responses.

scholarly journals PD-1 Blockade in Advanced Adrenocortical Carcinoma

2020 ◽  
Vol 38 (1) ◽  
pp. 71-80 ◽  
Author(s):  
Nitya Raj ◽  
Youyun Zheng ◽  
Virginia Kelly ◽  
Seth S. Katz ◽  
Joanne Chou ◽  
...  
Keyword(s):  
Objective Response Rate ◽  
Response Rate ◽  
Treatment Options ◽  
Objective Response ◽  
Progression Free Survival ◽  
Clinical Activity ◽  
Programmed Death Ligand 1 ◽  
Prior Therapy ◽  
Programmed Death ◽  
Adrenocortical Carcinomas

PURPOSE Adrenocortical carcinomas (ACC) are rare and aggressive malignancies with limited treatment options. This study was undertaken to evaluate the immunogenicity of ACC. PATIENTS AND METHODS Patients with advanced ACC were enrolled in a phase II study to evaluate the clinical activity of pembrolizumab 200 mg every 3 weeks, without restriction on prior therapy. The primary end point was objective response rate. Efficacy was correlated with tumor programmed death-ligand 1 expression, microsatellite-high and/or mismatch repair deficient (MSI-H/MMR-D) status, and somatic and germline genomic correlates. RESULTS We enrolled 39 patients with advanced ACC and herein report after a median follow-up of 17.8 months (range, 5.4 months to 34.7 months). The objective response rate to pembrolizumab was 23% (nine patients; 95% CI, 11% to 39%), and the disease control rate was 52% (16 patients; 95% CI, 33% to 69%). The median duration of response was not reached (lower 95% CI, 4.1 months). Two of six patients with MSI-H/MMR-D tumors responded. The other seven patients with objective responses had microsatellite stable tumors. The median progression-free survival was 2.1 months (95% CI, 2.0 months to 10.7 months), and the median overall survival was 24.9 months (95% CI, 4.2 months to not reached). Thirteen percent of patients (n = 5) had treatment-related grade 3 or 4 adverse events. Tumor programmed death-ligand 1 expression and MSI-H/MMR-D status were not associated with objective response. CONCLUSION MSI-H/MMR-D tumors, for which pembrolizumab is a standard therapy, are more common in ACC than has been recognized. In advanced ACC that is microsatellite stable, pembrolizumab provided clinically meaningful and durable antitumor activity with a manageable safety profile.

scholarly journals Nivolumab for Newly Diagnosed Advanced-Stage Classic Hodgkin Lymphoma: Safety and Efficacy in the Phase II CheckMate 205 Study

2019 ◽  
Vol 37 (23) ◽  
pp. 1997-2007 ◽  
Author(s):  
Radhakrishnan Ramchandren ◽  
Eva Domingo-Domènech ◽  
Antonio Rueda ◽  
Marek Trněný ◽  
Tatyana A. Feldman ◽  
...  
Keyword(s):  
Response Rate ◽  
Objective Response ◽  
Progression Free Survival ◽  
Advanced Stage ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Programmed Death Ligand 1 ◽  
Classic Hodgkin Lymphoma ◽  
Immune Mediated ◽  
Programmed Death

PURPOSE Nivolumab, an anti–programmed death-1 monoclonal antibody, has demonstrated frequent and durable responses in relapsed/refractory classic Hodgkin lymphoma (cHL). We report results from Cohort D of the CheckMate 205 trial, which assessed nivolumab monotherapy followed by nivolumab plus doxorubicin, vinblastine, and dacarbazine (N-AVD) for newly diagnosed cHL. METHODS Patients 18 years of age or older with untreated, advanced-stage (defined as III to IV and IIB with unfavorable risk factors) cHL were eligible for Cohort D of this multicenter, noncomparative, phase II trial. Patients received nivolumab monotherapy for four doses, followed by 12 doses of N-AVD; all doses were every 2 weeks, and nivolumab was administered at 240 mg intravenously. The primary end point was safety. Efficacy end points included objective response rate and modified progression-free survival, defined as time to disease progression/relapse, death, or next therapy. Chromosome 9p24.1 alterations and programmed death-ligand 1 expression were assessed in Hodgkin Reed-Sternberg cells in evaluable patients. RESULTS A total of 51 patients were enrolled and treated. At diagnosis, 49% of patients had an International Prognostic Score of 3 or greater. Overall, 59% experienced a grade 3 to 4 treatment-related adverse event. Treatment-related febrile neutropenia was reported in 10% of patients. Endocrine immune-mediated adverse events were all grade 1 to 2 and did not require high-dose corticosteroids; all nonendocrine immune-mediated adverse events resolved (most commonly, rash; 5.9%). At the end of therapy, the objective response rate (95% CI) per independent radiology review committee was 84% (71% to 93%), with 67% (52% to 79%), achieving complete remission (five patients [10%] were nonevaluable and counted as nonresponders). With a minimum follow-up of 9.4 months, 9-month modified progression-free survival was 92%. Patients with higher-level Hodgkin Reed-Sternberg programmed death-ligand 1 expression had more favorable responses to N-AVD ( P = .041). CONCLUSION Nivolumab followed by N-AVD was associated with promising efficacy and safety profiles for newly diagnosed, advanced-stage cHL.

scholarly journals Nivolumab for Relapsed/Refractory Classic Hodgkin Lymphoma After Failure of Autologous Hematopoietic Cell Transplantation: Extended Follow-Up of the Multicohort Single-Arm Phase II CheckMate 205 Trial

2018 ◽  
Vol 36 (14) ◽  
pp. 1428-1439 ◽  
Author(s):  
Philippe Armand ◽  
Andreas Engert ◽  
Anas Younes ◽  
Michelle Fanale ◽  
Armando Santoro ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Objective Response Rate ◽  
Hematopoietic Cell Transplantation ◽  
Response Rate ◽  
Objective Response ◽  
Classic Hodgkin Lymphoma ◽  
Programmed Death ◽  
Programmed Death 1 ◽  
Autologous Hematopoietic Cell Transplantation

Purpose Genetic alterations causing overexpression of programmed death-1 ligands are near universal in classic Hodgkin lymphoma (cHL). Nivolumab, a programmed death-1 checkpoint inhibitor, demonstrated efficacy in relapsed/refractory cHL after autologous hematopoietic cell transplantation (auto-HCT) in initial analyses of one of three cohorts from the CheckMate 205 study of nivolumab for cHL. Here, we assess safety and efficacy after extended follow-up of all three cohorts. Methods This multicenter, single-arm, phase II study enrolled patients with relapsed/refractory cHL after auto-HCT treatment failure into cohorts by treatment history: brentuximab vedotin (BV)–naïve (cohort A), BV received after auto-HCT (cohort B), and BV received before and/or after auto-HCT (cohort C). All patients received nivolumab 3 mg/kg every 2 weeks until disease progression/unacceptable toxicity. The primary end point was objective response rate per independent radiology review committee. Results Overall, 243 patients were treated; 63 in cohort A, 80 in cohort B, and 100 in cohort C. After a median follow-up of 18 months, 40% continued to receive treatment. The objective response rate was 69% (95% CI, 63% to 75%) overall and 65% to 73% in each cohort. Overall, the median duration of response was 16.6 months (95% CI, 13.2 to 20.3 months), and median progression-free survival was 14.7 months (95% CI, 11.3 to 18.5 months). Of 70 patients treated past conventional disease progression, 61% of those evaluable had stable or further reduced target tumor burdens. The most common grade 3 to 4 drug-related adverse events were lipase increases (5%), neutropenia (3%), and ALT increases (3%). Twenty-nine deaths occurred; none were considered treatment related. Conclusion With extended follow-up, responses to nivolumab were frequent and durable. Nivolumab seems to be associated with a favorable safety profile and long-term benefits across a broad spectrum of patients with relapsed/refractory cHL.

scholarly journals Avelumab, an Anti–Programmed Death-Ligand 1 Antibody, In Patients With Refractory Metastatic Urothelial Carcinoma: Results From a Multicenter, Phase Ib Study

2017 ◽  
Vol 35 (19) ◽  
pp. 2117-2124 ◽  
Author(s):  
Andrea B. Apolo ◽  
Jeffrey R. Infante ◽  
Ani Balmanoukian ◽  
Manish R. Patel ◽  
Ding Wang ◽  
...  
Keyword(s):  
Adverse Events ◽  
Urothelial Carcinoma ◽  
Response Rate ◽  
Objective Response ◽  
Progression Free Survival ◽  
Free Survival ◽  
Programmed Death Ligand 1 ◽  
Phase Ib ◽  
Programmed Death ◽  
Metastatic Urothelial Carcinoma

Purpose We assessed the safety and antitumor activity of avelumab, a fully human anti–programmed death-ligand 1 (PD-L1) IgG1 antibody, in patients with refractory metastatic urothelial carcinoma. Methods In this phase Ib, multicenter, expansion cohort, patients with urothelial carcinoma progressing after platinum-based chemotherapy and unselected for PD-L1 expression received avelumab 10 mg/kg intravenously every 2 weeks. The primary objectives were safety and tolerability. Secondary objectives included confirmed objective response rate (Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1), progression-free survival, overall survival (OS), and PD-L1–associated clinical activity. PD-L1 positivity was defined as expression by immunohistochemistry on ≥ 5% of tumor cells. Results Forty-four patients were treated with avelumab and followed for a median of 16.5 months (interquartile range, 15.8 to 16.7 months). The data cutoff was March 19, 2016. The most frequent treatment-related adverse events of any grade were fatigue/asthenia (31.8%), infusion-related reaction (20.5%), and nausea (11.4%). Grades 3 to 4 treatment-related adverse events occurred in three patients (6.8%) and included asthenia, AST elevation, creatine phosphokinase elevation, and decreased appetite. The confirmed objective response rate by independent central review was 18.2% (95% CI, 8.2% to 32.7%; five complete responses and three partial responses). The median duration of response was not reached (95% CI, 12.1 weeks to not estimable), and responses were ongoing in six patients (75.0%), including four of five complete responses. Seven of eight responding patients had PD-L1–positive tumors. The median progression-free survival was 11.6 weeks (95% CI, 6.1 to 17.4 weeks); the median OS was 13.7 months (95% CI, 8.5 months to not estimable), with a 12-month OS rate of 54.3% (95% CI, 37.9% to 68.1%). Conclusion Avelumab was well tolerated and associated with durable responses and prolonged survival in patients with refractory metastatic UC.

scholarly journals Pivotal Trial of Enfortumab Vedotin in Urothelial Carcinoma After Platinum and Anti-Programmed Death 1/Programmed Death Ligand 1 Therapy

2019 ◽  
Vol 37 (29) ◽  
pp. 2592-2600 ◽  
Author(s):  
Jonathan E. Rosenberg ◽  
Peter H. O’Donnell ◽  
Arjun V. Balar ◽  
Bradley A. McGregor ◽  
Elisabeth I. Heath ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Response Rate ◽  
Objective Response ◽  
Locally Advanced ◽  
Programmed Death Ligand 1 ◽  
Programmed Death ◽  
Duration Of Response ◽  
Metastatic Urothelial Carcinoma ◽  
Programmed Death 1 ◽  
Previously Treated

PURPOSE Locally advanced or metastatic urothelial carcinoma is an incurable disease with limited treatment options, especially for patients who were previously treated with platinum and anti–programmed death 1 or anti–programmed death ligand 1 (PD-1/L1) therapy. Enfortumab vedotin is an antibody–drug conjugate that targets Nectin-4, which is highly expressed in urothelial carcinoma. METHODS EV-201 is a global, phase II, single-arm study of enfortumab vedotin 1.25 mg/kg (intravenously on days 1, 8, and 15 of every 28-day cycle) in patients with locally advanced or metastatic urothelial carcinoma who were previously treated with platinum chemotherapy and anti–PD-1/L1 therapy. The primary end point was objective response rate per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by blinded independent central review. Key secondary end points were duration of response, progression-free survival, overall survival, safety, and tolerability. RESULTS Enfortumab vedotin was administered to 125 patients with metastatic urothelial carcinoma. Median follow-up was 10.2 months (range, 0.5 to 16.5 months). Confirmed objective response rate was 44% (95% CI, 35.1% to 53.2%), including 12% complete responses. Similar responses were observed in prespecified subgroups, such as those patients with liver metastases and those with no response to prior anti–PD-1/L1 therapy. Median duration of response was 7.6 months (range, 0.95 to 11.30+ months). The most common treatment-related adverse events were fatigue (50%), any peripheral neuropathy (50%), alopecia (49%), any rash (48%), decreased appetite (44%), and dysgeusia (40%). No single treatment-related adverse events grade 3 or greater occurred in 10% or more of patients. CONCLUSION Enfortumab vedotin demonstrated a clinically meaningful response rate with a manageable and tolerable safety profile in patients with locally advanced or metastatic urothelial carcinoma who were previously treated with platinum and anti–PD-1/L1 therapies.

scholarly journals Efficacy of Pembrolizumab in Patients With Noncolorectal High Microsatellite Instability/Mismatch Repair–Deficient Cancer: Results From the Phase II KEYNOTE-158 Study

2020 ◽  
Vol 38 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Aurelien Marabelle ◽  
Dung T. Le ◽  
Paolo A. Ascierto ◽  
Anna Maria Di Giacomo ◽  
Ana De Jesus-Acosta ◽  
...  
Keyword(s):  
Adverse Events ◽  
Microsatellite Instability ◽  
Mismatch Repair ◽  
Phase Ii ◽  
Objective Response Rate ◽  
Response Rate ◽  
Objective Response ◽  
Programmed Death ◽  
Programmed Death 1 ◽  
Previously Treated

PURPOSE Genomes of tumors that are deficient in DNA mismatch repair (dMMR) have high microsatellite instability (MSI-H) and harbor hundreds to thousands of somatic mutations that encode potential neoantigens. Such tumors are therefore likely to be immunogenic, triggering upregulation of immune checkpoint proteins. Pembrolizumab, an anti‒programmed death-1 monoclonal antibody, has antitumor activity against MSI-H/dMMR cancer. We report data from the phase II KEYNOTE-158 study of pembrolizumab in patients with previously treated, advanced noncolorectal MSI-H/dMMR cancer. PATIENTS AND METHODS Eligible patients with histologically/cytologically confirmed MSI-H/dMMR advanced noncolorectal cancer who experienced failure with prior therapy received pembrolizumab 200 mg once every 3 weeks for 2 years or until disease progression, unacceptable toxicity, or patient withdrawal. Radiologic imaging was performed every 9 weeks for the first year of therapy and every 12 weeks thereafter. The primary end point was objective response rate per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, as assessed by independent central radiologic review. RESULTS Among 233 enrolled patients, 27 tumor types were represented, with endometrial, gastric, cholangiocarcinoma, and pancreatic cancers being the most common. Median follow up was 13.4 months. Objective response rate was 34.3% (95% CI, 28.3% to 40.8%). Median progression-free survival was 4.1 months (95% CI, 2.4 to 4.9 months) and median overall survival was 23.5 months (95% CI, 13.5 months to not reached). Treatment-related adverse events occurred in 151 patients (64.8%). Thirty-four patients (14.6%) had grade 3 to 5 treatment-related adverse events. Grade 5 pneumonia occurred in one patient; there were no other treatment-related fatal adverse events. CONCLUSION Our study demonstrates the clinical benefit of anti–programmed death-1 therapy with pembrolizumab among patients with previously treated unresectable or metastatic MSI-H/dMMR noncolorectal cancer. Toxicity was consistent with previous experience of pembrolizumab monotherapy.

scholarly journals CheckMate-032 Study: Efficacy and Safety of Nivolumab and Nivolumab Plus Ipilimumab in Patients With Metastatic Esophagogastric Cancer

2018 ◽  
Vol 36 (28) ◽  
pp. 2836-2844 ◽  
Author(s):  
Yelena Y. Janjigian ◽  
Johanna Bendell ◽  
Emiliano Calvo ◽  
Joseph W. Kim ◽  
Paolo A. Ascierto ◽  
...  
Keyword(s):  
Gastroesophageal Junction ◽  
Objective Response ◽  
Locally Advanced ◽  
Survival Rates ◽  
Progression Free Survival ◽  
The United States ◽  
Phase Iii ◽  
Programmed Death Ligand 1 ◽  
Programmed Death ◽  
Esophagogastric Cancer

Purpose Metastatic esophagogastric cancer treatments after failure of second-line chemotherapy are limited. Nivolumab demonstrated superior overall survival (OS) versus placebo in Asian patients with advanced gastric or gastroesophageal junction cancers. We assessed the safety and efficacy of nivolumab and nivolumab plus ipilimumab in Western patients with chemotherapy-refractory esophagogastric cancers. Patients and Methods Patients with locally advanced or metastatic chemotherapy–refractory gastric, esophageal, or gastroesophageal junction cancer from centers in the United States and Europe received nivolumab or nivolumab plus ipilimumab. The primary end point was objective response rate. The association of tumor programmed death-ligand 1 status with response and survival was also evaluated. Results Of 160 treated patients (59 with nivolumab 3 mg/kg, 49 with nivolumab 1 mg/kg plus ipilimumab 3 mg/kg, 52 with nivolumab 3 mg/kg plus ipilimumab 1 mg/kg), 79% had received two or more prior therapies. At the data cutoff, investigator-assessed objective response rates were 12% (95% CI, 5% to 23%), 24% (95% CI, 13% to 39%), and 8% (95% CI, 2% to 19%) in the three groups, respectively. Responses were observed regardless of tumor programmed death-ligand 1 status. With a median follow-up of 28, 24, and 22 months across the three groups, 12-month progression-free survival rates were 8%, 17%, and 10%, respectively; 12-month OS rates were 39%, 35%, and 24%, respectively. Treatment-related grade 3/4 adverse events were reported in 17%, 47%, and 27% of patients in the three groups, respectively. Conclusion Nivolumab and nivolumab plus ipilimumab demonstrated clinically meaningful antitumor activity, durable responses, encouraging long-term OS, and a manageable safety profile in patients with chemotherapy-refractory esophagogastric cancer. Phase III studies evaluating nivolumab or nivolumab plus ipilimumab in earlier lines of therapy for esophagogastric cancers are underway.

Effects of adding necitumumab to first-line chemotherapy in patients with stage IV non-small-cell lung cancer: Meta-analysis

2019 ◽  
Vol 26 (6) ◽  
pp. 1331-1342
Author(s):  
Irena Ilic ◽  
Sandra Sipetic ◽  
Jovan Grujicic ◽  
Milena Ilic
Keyword(s):  
Overall Survival ◽  
Objective Response Rate ◽  
Advanced Nsclc ◽  
Response Rate ◽  
Meta Analysis ◽  
Objective Response ◽  
Stage Iv ◽  
Progression Free Survival ◽  
First Line ◽  
Free Survival

Introduction Almost half of patients with non-small-cell lung cancer (NSCLC) are diagnosed at an advanced stage. Our aim was to assess the effects of adding necitumumab to chemotherapy in patients with stage IV NSCLC. Material and methods A comprehensive literature search was performed according to pre-specified inclusion and exclusion criteria. Data on overall survival, progression-free survival, objective response rate and adverse events were extracted. A meta-analysis was performed to obtain pooled hazard ratios (HR) and corresponding 95% confidence intervals (CI) for time-to-event data and pooled odds ratio (OR) with 95% CI for dichotomous outcomes. Results The meta-analysis included four randomized clinical trials with 2074 patients. The pooled results showed significant improvement for overall survival (HR = 0.87 (95% CI 0.79–0.95), p = 0.004) when necitumumab was added to chemotherapy in patients with advanced NSCLC. No statistically significant improvement was noted for progression-free survival and objective response rate (HR = 0.83 (95% CI 0.69–1.01), p = 0.06 and OR = 1.46 (95% CI 0.90–2.38), p = 0.13, respectively). Subgroup analysis showed that in patients with non-squamous NSCLC, there was no benefit in overall survival and objective response rate. Patients with advanced NSCLC who received necitumumab were at the highest odds of developing a skin rash (OR = 14.50 (95% CI 3.16–66.43), p = 0.0006) and hypomagnesaemia (OR = 2.77 (95% CI 2.23–3.45), p < 0.00001), while the OR for any grade ≥3 adverse event was 1.55 (95% CI 1.28–1.87, p < 0.00001). Conclusions The addition of necitumumab to standard chemotherapy in a first-line setting in patients with stage IV NSCLC results in a statistically significant improvement in overall survival, while the results were not significant for progression-free survival and objective response rate.

scholarly journals Phase Ib/II Study of Pembrolizumab and Pegylated-Interferon Alfa-2b in Advanced Melanoma

2018 ◽  
Vol 36 (35) ◽  
pp. 3450-3458 ◽  
Author(s):  
Diwakar Davar ◽  
Hong Wang ◽  
Joe-Marc Chauvin ◽  
Ornella Pagliano ◽  
Julien J. Fourcade ◽  
...  
Keyword(s):  
Overall Survival ◽  
Objective Response Rate ◽  
Response Rate ◽  
Objective Response ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Pegylated Interferon ◽  
Gene Signature ◽  
Advanced Melanoma ◽  
Phase Ib

Purpose Objective responses are reported in 34% to 37% of patients with programmed death-1 (PD-1)–naïve advanced melanoma treated with PD-1 inhibitors. Pre-existing CD8+ T-cell infiltrate and interferon (IFN) gene signature correlate with response to PD-1 blockade. Here, we report a phase Ib/II study of pembrolizumab/pegylated (PEG)-IFN combination in PD-1–naïve advanced melanoma. Patients and Methods PEG-IFN (1, 2, and 3 μg/kg per week) was dose escalated using a modified toxicity probability interval design in three cohorts of four patients each, whereas pembrolizumab was dosed at 2 mg/kg every 3 weeks in the phase Ib portion. Thirty-one patients were enrolled in the phase II portion. Primary objectives were safety and incidence of dose-limiting toxicities. Secondary objectives included objective response rate, progression-free survival (PFS), and overall survival. Results Forty-three patients with stage IV melanoma were enrolled in the phase Ib and II portions of the study and included in the analysis. At the data cutoff date (December 31, 2017), median follow-up duration was 25 months (range, 1 to 38 months). All 43 patients experienced at least one adverse event; grade 3/4 treatment-related adverse events occurred in 21 of 43 patients (48.8%). Objective responses were seen at all three dose levels among 43 evaluable patients. The objective response rate was 60.5%, with 46.5% of patients exhibiting ongoing response. Median PFS was 11.0 months in all patients and unreached in responders, whereas median overall survival remained unreached in all patients. The 2-year PFS rate was 46%. Conclusion Pembrolizumab/PEG-IFN demonstrated an acceptable toxicity profile with promising evidence of clinical efficacy in PD-1–naïve metastatic melanoma. These results support the rationale to further investigate this pembrolizumab/PEG-IFN combination in this disease.

Sign in / Sign up

Export Citation Format

Share Document