bluuebunny/crossref_metadata_2025_split huggingface dataset:
Updated safety and clinical activity of durvalumab monotherapy in previously treated patients with stage IIIB/IV NSCLC.
Authors: Balmanoukian Ani Sarkis , Antonia Scott Joseph , Hwu Wen-Jen , Hamid Omid , Gutierrez Martin , Jamal Rahima , Jerusalem Guy Heinrich Maria , Ahn Myung-Ju , Kim Dong-Wan , Cunningham David , Kim Sang-We , Brahmer Julie R. , Lutzky Jose , Weiss Jared , Jin Xiaoping , Antal Joyce , Gupta Ashok Kumar , Segal Neil Howard 
Published: September 2018

9085 Background: Preliminary analyses of an ongoing Phase 1/2 study of single-agent durvalumab showed antitumor activity and a tolerable safety profile in advanced NSCLC, with higher ORR and longer OS in pts with high vs. low/negative PD-L1 tumor expression. Here we present updated safety analyses (primary endpoint) for all NSCLC pts and clinical activity based on investigator-assessed RECIST v1.1 in pts who had received prior treatment for advanced NSCLC. Methods: Durvalumab (10 mg/kg q2w) was given until unacceptable toxicity or disease progression, or for up to 12 mos; retreatment was permitted upon disease progression after completion of 12 mos of treatment. PD-L1 expression was assessed using the Ventana PD-L1 (SP263) Assay (PD-L1 high = ≥25% and PD-L1 low/negative = <25% of tumor cells with membrane staining). Results: As of 24 Oct 2016, 245 pts with previously treated NSCLC (53% squamous) received durvalumab and were followed for a median of 29.2 (range 0.3–40.5) mos; 142 pts (58%) had treatment-related adverse events (AEs), most frequent: fatigue (18%), decreased appetite (9%), and nausea, rash, and diarrhea (each 8%). 25 pts (10%) had treatment-related Grade 3/4 AEs, most frequent: fatigue and hyponatremia (each 2%); there were no treatment-related deaths. 4% had treatment-related serious AEs including colitis and pneumonitis (each 2%). In the overall population, 12 mo OS rate was 47% (95% CI 40–53) and 18 mo OS rate was 38% (95% CI 31–45). Antitumor activity and survival by PD-L1 status are shown in the table. Conclusions: Consistent with earlier reports, durvalumab had a manageable safety profile in Stage IIIB/IV NSCLC, with encouraging clinical activity as 2L+ therapy. Higher tumor PD-L1 expression enriched clinical benefit of response rate and survival endpoints. Clinical trial information: NCT01693562. [Table: see text]
Baseline-derived neutrophil-to-lymphocyte ratio (dNLR) and lactate dehydrogenase (LDH) to predict the benefit of immune checkpoint inhibitors (ICI) in advanced non-small cell lung cancer (NSCLC) patients.
Authors: Mezquita Laura , Auclin Edouard , Ferrara Roberto , Audigier-Valette Clarisse , Tessonnier Laurent , Charrier Melinda , Boucher Marie Eve , Lahmar Jihene , Caramella Caroline , Remon Jordi , Planchard David , Adam Julien , Gazzah Anas , Chaput Nathalie , Soria Jean-Charles , Besse Benjamin 
Published: September 2018

9089 Background: dNRL (Neutrophils/Leucocytes-Neutrophils) and LDH were recently correlated to ICI benefit in melanoma. We tested if dNLR and LDH could have the same role in NSCLC patients. Methods: Baseline dNLR and LDH were collected in 234 patients treated with PD1/PDL1 inhibitors from Nov. 2013 to Dec. 2016, in a discovery (D) cohort (N = 161) from Gustave Roussy and an independent validation (V) cohort (N = 73) from 2 centers. ICI benefit was analyzed according to overall survival (OS), progression free survival (PFS) and response rate (RR) by RECIST 1.1. Kaplan-Meier and Cox regression were performed. Results: In the D cohort, 100 patients (62%) were males, 136 (85%) smokers and PS ≤1, with median age 61.5; 133 patients (81%) stage IV; 100 (62%) had adenocarcinoma and 46 (29%) squamous cells carcinoma; 35 (22%) were KRASmut, 13 (8%) EGFRmut and 3 (2%) ALKpositive. PDL1 expression was positive in 43 (75%), negative in 14 (25%) and unknown in 78. 132 (82%) patients received PD1 inhibitors; the median of prior lines was 1 (1-11). dNLR > 3 and LDH > upper normal limit (UNL) were independent factors for poor OS (HR 4,67, p = 0.011 and HR 2,65, p = 0.002, respectively) and poor PFS (HR 4,71, p = 0.001 and HR 1,68, p = 0.042 respectively). The median follow-up (FU) was 12 months (m) [95% CI 11-14], the median PFS 3m [2-4] and the median OS 10m [8-13]. In the V cohort, with a median FU of 11m [8-14], dNLR > 3 and LDH > UNL were significantly associated with poor OS (both p = 0.001), with a trend toward association with PFS (p = 0.06, p = 0.08, respectively). A Lung Immune Predictive Index (LIPI) was tested considering dNLR > 3 and LDH > UNL, with three groups. In D cohort, the median OS for good (no factor), intermediate (one factor) and poor (two factors) was 34m [17-NR], 10m [8-NR], 3m [1-NR], respectively (p = 0.0001), and PFS was similarly correlated (p = 0.001). Same results were demonstrated in the V cohort. Conclusions: Baseline dNLR > 3 and LDH > UNL can predict the benefit of ICI in advanced NSCLC patients. The LIPI at baseline is an easy tool to identify the candidates to immunotherapy. Confirmation cohorts are ongoing to validate the predictive role of the LIPI.
Re-challenge with BRAF-directed treatment: A multi-institutional retrospective study.
Authors: Valpione Sara , Carlino Matteo S. , Mangana Joanna , Mooradian Meghan , McArthur Grant A. , Schadendorf Dirk , Hauschild Axel , Long Georgina V. , Arance Ana M. , Ascierto Paolo Antonio , Maio Michele , De Rosa Francesco , Larkin James M. G. , Park John J. , Goldinger Simone M. , Flaherty Keith , Xu Wen , Livingstone Elisabeth , Weichenthal Michael , Lorigan Paul ,   Project Collaborators' Group (Gaba L, MD; Rajat R, MD; Sullivan R, MD; Di Giacomo AM, MD; Dummer R, MD)
Published: September 2018

9512 Background: Most patients treated with BRAF inhibitors (BRAFi) +/- MEK inhibitors (MEKi) eventually progress on treatment. Along with genetic acquired resistance, epigenetic mechanisms that could be reversed after BRAFi discontinuation have been described. The purpose of this study was to analyse outcomes for patients (pts) retreated with BRAF-directed therapy. Methods: 116 pts who received BRAFi based therapy and, after a break, were re-challenged with BRAFi +/- MEKi treated at 14 centres in Europe, US, and Australia were analysed for progression free survival (PFS) and response rate (RR), as well as factors predicting overall survival (OS) (demographics, disease stage, treatment, LDH level, duration of first BRAFi treatment, reason for first BRAFi discontinuation and interval between BRAFi stop and re-challenge). Multivariate Cox regression, regression trees and Kaplan Meier method were used. Results: Median duration of 1st BRAFi +/- MEKi treatment was 9.4 months (mts) and 7.7 mts for the subsequent treatment after discontinuation (immunotherapy 72%, other 17 %, drug holiday 11%). Brain metastases were present in 51 pts (44%). RR to re-challenge with BRAFi +/- MEKi was 43%: complete response (CR) 3%, partial response (PR) 39%, stable disease 24% and progressive disease (PD) 30%, 4% missing. Of 80 pts who previously discontinued BRAFi for PD, 31 (39%) responded (30 PR and 1 CR). Median OS from retreatment was 9.8 mts. Independent prognostic factors for survival at re-challenge included number of metastatic sites (HR = 1.32 for each additional organ with metastases, p < .001), LDH (HR = 1.37 for each multiple of the upper normal limit, p < .001), while combination of BRAFi+MEKi conferred a better prognosis vs BRAFi alone (HR = 0.5, p = .006). Pts with < 3 metastatic sites treated with BRAFi and MEKi had a better survival (median OS not reached) and pts with ≥ 3 metastatic sites and raised LDH treated with BRAFi alone had the worse outcome (median OS 4 mts). Number of metastatic sites (HR = 1.44, p < .001) and combination of BRAFi and MEKi (HR = 0.45, p < .001) were independent prognostic factors for PFS (median 5.0 mts). Conclusions: Re-challenge with BRAFi +/- MEKi induces a clinically significant response and should be considered for selected cases.
Quantitative spatial profiling of PD-1/PD-L1 interaction and HLA-DR/IDO1 to predict outcomes to anti-PD-1 in metastatic melanoma (MM).
Authors: Johnson Douglas Buckner , Bordeaux Jennifer , Kim Ju Young , Vaupel Christine , Rimm David L. , Ho Thai Huu , Joseph Richard Wayne , Daud Adil , Conry Robert Martin , Gaughan Elizabeth M , Dimou Anastasios , Balko Justin M. , Smithy James William , Witte John S , McKee Svetlana B , Dominiak Nicole , Dabbas Bashar , Hall Jeff , Dakappagari Naveen ,   Navigate BioPharma Leadership
Published: September 2018

9517 Background: Although PD-1/L1 axis directed therapies induce durable responses in some mm patients (pts), biomarkers of response remain elusive. We hypothesized that quantifying key immune suppression mechanisms within the tumor microenvironment would provide superior predictors of response to anti-PD-1 compared with single marker assessment. Methods: Pre-treatment tumor biopsies from 124 mm pts treated with anti-PD-1 at 7 academic centers were fluorescently stained with multiple immune markers in discovery (n = 24) and validation (n = 100) cohorts. Selected biomarker signatures, PD-1/PD-L1 interaction score (proportion of PD-1+ cells co-localized with PD-L1) and IDO1/HLA-DR co-expression were evaluated for anti-PD-1 treatment response and survival. Slides were imaged using Vectra; biomarker positive cells and their co-localization were objectively quantified in pathologist-selected regions using novel Automated Quantitative Analysis (AQUA) algorithms. Results: In the discovery cohort, high levels of PD-1/PD-L1 interaction score and/or IDO1/HLA-DR coexpression was strongly positively associated with response to anti-PD-1 (p = 0.0005). In contrast, other individual biomarkers (PD-1, PD-L1, CD8) were not associated with response or survival (p > 0.10). This finding was replicated in the validation cohort: pts with high PD-1/PD-L1 and/or IDO1/HLA-DR were more likely to respond to treatment (p = 0.009). These pts also experienced a three-fold increase in progression free survival (hazards ratio (HR) = 0.33; p = 0.003) and overall survival (HR = 0.34; p = 0.004). Multivariate analyses revealed that these findings were independent of BRAF mutation, stage, LDH and prior therapy. In the combined cohort (n = 124), 80% of responding pts had higher levels of PD-1/PD-L1 interaction scores and/or IDO1/HLA-DR. In contrast, PD-L1 expression alone (≥1% or ≥50%) was not predictive of PFS or OS (p > 0.1). Conclusions: This novel multiplexed method profiling key tumor-immune suppression pathways identified mm pts likely to respond to anti-PD-1 therapy. This method could help stratify patients for PD-1 monotherapy and be useful in guiding future clinical trials.
Phase 1b/2 trial of ribociclib+binimetinib in metastatic NRAS-mutant melanoma: Safety, efficacy, and recommended phase 2 dose (RP2D).
Authors: Schuler Martin H. , Ascierto Paolo A. , De Vos Filip Yves Francine Leon , Postow Michael Andrew , Van Herpen Carla M.L.- , Carlino Matteo S. , Sosman Jeffrey A. , Berking Carola , Long Georgina V. , Weise Amy , Gutzmer Ralf , Kaatz Martin , McArthur Grant A. , Schwartz Gary , Daud Adil , Maharry Kati , Yerramilli-Rao Padmaja , Zimmer Lisa , Bozon Viviana , Amaria Rodabe Navroze 
Published: September 2018

9519 Background: Simultaneous inhibition of MEK and CDK4/6 may suppress MAPK pathway activation and cell-cycle checkpoint dysregulation in NRAS-mutant melanoma, resulting in enhanced antitumor activity. Phase 1b data are reported. Methods: The phase 1b primary objective was to determine maximum tolerated dose (MTD)/RP2D. A 28-d cycle of oral ribociclib (RIBO) once daily (QD) for 21 d + oral binimetinib (BINI) twice daily (BID) for 28 d, and a 21-d cycle of RIBO QD + BINI BID, both for 14 d per cycle, were evaluated. Secondary objectives were to evaluate efficacy, safety and pharmacodynamics. Results: Based on dose escalation (van Herpen, ESMO 2015), MTD was 600mg RIBO/45mg BINI for the 21-d and 200/45 for the 28-d regimens. Due to promising activity, the 28-d cycle was selected as RP2D(unconfirmed partial response [PR] with limited follow-up occurred in 35% of pts). This finding was supported by comparable and manageable safety and the Bayesian logistic regression model.As of Jan 2017, the RP2D was received by 16 pts in phase 1b (ECOG PS 0/1/2, 63%/31%/6%; elevated lactate dehydrogenase, 44%; stage IVM1c disease, 50%; prior ipilimumab [ipi], 44%; prior anti–programmed death [PD]-1/PD-L1, 31%). Median (range) exposure was 4 (0–13) mo. Common adverse events (AEs) were increased blood creatine phosphokinase, elevated AST, peripheral edema, acneiform dermatitis, diarrhea and fatigue. Common grade 3/4 AEs were elevated AST and ALT (19%/6%), nausea (19%/0%), rash (19%/0%), vomiting (6%/6%) and neutropenia (12%/0%). Confirmed PR (cPR) occurred in 4 pts (25%; time to response, 48–168 d), stable disease in 7 pts (44%), disease progression in 3 pts (19%); 2 pts (12%) were not evaluable. Among cPR pts, 3 had prior ipi and/or anti–PD-1/PD-L1. Median progression-free survival (mPFS) was 6.7 (95% CI, 3.5–9.2) mo. Sequence analysis of synchronous non- RAS genetic alterations will be presented. Conclusions: Combined RIBO/BINI at the selected RP2D had a manageable safety profile and favorable efficacy (based on mPFS) for NRAS-mutant melanoma in phase 1b. Based on these promising data, the phase 2 expansion is underway to assess antitumor activity at the RP2D. Clinical trial information: NCT01781572.
Immune-related tumor response dynamics in melanoma patients (pts) treated with pembrolizumab: Identifying markers for clinical outcome and treatment decisions.
Authors: Nishino Mizuki , Giobbie-Hurder Anita , Manos Michael P , Bailey Nancy , Buchbinder Elizabeth Iannotti , Ott Patrick Alexander , Ramaiya Nikhil H. , Hodi F. Stephen 
Published: September 2018

9521 Background: PD-1 inhibitors have shown marked efficacy in advanced melanoma and are associated with unique response patterns. We aimed to characterize the tumor burden dynamics and identify quantitative imaging markers for overall survival (OS) in melanoma pts treated with pembrolizumab. Methods: The study included 107 advanced melanoma pts (63 males; median age: 63) treated with pembrolizumab monotherapy at DFCI. Tumor burden dynamics were assessed on serial CT scans during therapy by irRECIST, which uses unidimensional measurements and includes new lesions in tumor burden [Clin Cancer Res. 2013;19:3936-43]. The relationships between tumor burden dynamics and OS were studied. Results: Among 107 pts, 96 pts had measurable tumor burden at baseline and 11 had non-target lesions alone at baseline. Among the 96 pts, maximal tumor shrinkage ranged from -100% to 567% (median:-18.5%). Overall response rate was 44% (42/96; irCR in 5, irPR in 37). Tumor burden remained < 20% increase from baseline throughout therapy in 57 pts (55%). Using a 3-month landmark analysis, pts with < 20% tumor burden increase from baseline at 3 months had longer OS than pts with ≥ 20% increase (12-month OS rate: 82 vs. 53%). In extended Cox models, pts with < 20% tumor burden increase during therapy had significantly reduced hazards of death (HR = 0.19, 95%CI: 0.08–0.43, p < 0.0001 univariate; HR = 0.18, 95%CI: 0.08-0.41, p < 0.0001, multivariable). Five pts (5%) experienced pseudoprogression; 3 pts had increase of target lesions with subsequent response, which was noted after confirmed irPD on consecutive scans. Two pts with no measurable tumor burden progressed with new/non-target lesions that subsequently regressed. Conclusions: Tumor burden increase of < 20% from the baseline during pembrolizumab therapy was associated with longer OS, proposing a practical prognostic marker to guide treatment decisions. Pseudoprogressors may experience response after confirmed irPD, indicating a limitation of the current strategy for immune-related response assessment. Evaluations of non-measurable tumor burden may require further attention in the clinical setting of immuno-oncology.
Updated 5-y landmark analyses of phase 2 (BREAK-2) and phase 3 (BREAK-3) studies evaluating dabrafenib monotherapy in patients with BRAF V600–mutant melanoma.
Authors: Chapman Paul B. , Ascierto Paolo Antonio , Schadendorf Dirk , Grob Jean Jacques , Ribas Antoni , Kiecker Felix , Dutriaux Caroline , Demidov Lev V. , Lebbe Celeste , Rutkowski Piotr , Blank Christian U. , Gutzmer Ralf , Millward Michael , Kefford Richard , Huang Yingjie , Zhang Ying , Squires Matthew , Mookerjee Bijoyesh , Hauschild Axel 
Published: September 2018

9526 Background: Prior analyses of phase 2 (BREAK-2; NCT01153763) and phase 3 (BREAK-3; NCT01227889) trials showed that durable clinical benefit and tolerability lasting ≥ 3 y are achievable with the BRAF inhibitor dabrafenib in some patients (pts) with BRAFV600–mutant metastatic melanoma. Here, we report 5-y landmark analyses for BREAK-2 and BREAK-3. Methods: BREAK-2, a single-arm, phase 2 study, evaluated dabrafenib 150 mg twice daily in pts with stage IV BRAF V600E/K–mutant MM. BREAK-3, an open-label, randomized (3:1), phase 3 study, assessed dabrafenib 150 mg twice daily vs dacarbazine 1000 mg/m2 every 3 weeks in pts with previously untreated BRAFV600E–mutant unresectable stage III or stage IV MM. Updated analyses were performed to describe ≥ 5-y outcomes in each study. Results: BREAK-2 enrolled 92 pts (V600E, n = 76; V600K, n = 16), of whom most (90%) had prior systemic anticancer therapy. At data cutoff (17 Jun 2016), all pts had discontinued, mostly due to progression (84%). In V600E pts, 5-y progression-free survival (PFS) was 11%, and 5-y overall survival (OS) was 20%. Postprogression immunotherapy was received by 22% of enrolled pts. In BREAK-3 (data cutoff, 16 Sep 2016), median follow-up was 18.6 mo for the dabrafenib arm (n = 187) and 12.8 mo for the dacarbazine arm (n = 63). Follow-up for the 37 dacarbazine-arm pts (59%) who crossed over to receive dabrafenib was based on the initial assignment of dacarbazine. The 5-y PFS was 12% vs 3% and 5-y OS was 24% vs 22% for the dabrafenib and dacarbazine arms, respectively. A subset of pts in each respective arm received postprogression anti–CTLA-4 (24% vs 24%) and/or anti–PD-1 (8% vs 2%) therapy, whereas 31% vs 17% did not receive any further therapy following study treatment. No new safety signals were observed in either study with long-term follow-up. Additional characterization of pts using cfDNA analysis will be presented. Conclusions: These data provide the longest reported PFS and OS follow-up for BRAF inhibitor monotherapy in BRAF V600–mutant MM. Both BREAK-2 and BREAK-3 showed that 11%-12% of pts initially treated with single-agent dabrafenib remained progression free at 5 y. Clinical trial information: NCT01153763; NCT01227889.
Intra-patient escalation dosing strategy with IMCgp100 results in mitigation of T-cell based toxicity and preliminary efficacy in advanced uveal melanoma.
Authors: Sato Takami , Nathan Paul D. , Hernandez-Aya Leonel Fernando , Sacco Joseph J , Orloff Marlana M. , Truscello Jessica , McAlpine Cheryl , Hulstine Ann-Marie , Lanasa Mark C. , Coughlin Christina Marie , Carvajal Richard D. 
Published: September 2018

9531 Background: IMCgp100 is a bispecific biologic capable of redirecting T cells against the melanocyte-associated antigen gp100. In the first-in-human (FIH) clinical trial, preliminary efficacy of IMCgp100 in advanced uveal melanoma (UM) was observed; however, cases of severe T cell-mediated toxicities with the first 2 doses limited dosing to 50 mcg QW. This phase 1 study was designed to implement intra-patient escalation to mitigate toxicity and maximize exposure of IMCgp100. Methods: Using a 3+3 design, HLA-A2+ pts with metastatic UM were treated with low weekly (QW) dosing of IMCgp100 iv at Cycle 1, Day 1 (C1D1) (20 mcg) and C1D8 (30 mcg), followed by the escalated cohort dose administered at C1D15 and beyond. Results: Nineteen metastatic UM pts with a median of 3 prior lines of therapy (range 0 - 8) were treated across 4 target dose cohorts (60, 70, 80, and 75 mcg). Fifteen of 19 pts remain on treatment at the data cutoff (25Nov16). Enrollment completed 15Sep16. DLT was observed in 1 of 6 pts in the 70-mcg cohort (LFT elevation), and 2 of 4 pts treated at 80 mcg QW (LFT and bilirubin elevation). The 80 mcg dose level was not tolerated and a 75 mcg cohort was enrolled. Six pts were treated at 75 mcg without DLT; this dose was identified as the MTD and RP2D. All 3 DLT resolved without corticosteroids and all pts resumed IMCgp100. Frequent related AE included pruritus (84%), pyrexia (84%), fatigue (74%), hypotension (74%) and peripheral edema (63%). Gr 3/4 drug-related AE include AST increased (15%), erythema (15%) and hypotension (15%). Preliminary efficacy data (RECIST v1.1) from 17 evaluable pts (2 pts had insufficient follow-up) showed no objective responses; 12 pts had a BOR of SD (63%) including 4 pts (24%) with a ≥10% reduction in target lesions. With median follow-up of 1.8 mo, the disease control rate (16 wks) was 32%. Conclusions: The intra-patient escalation regimen of IMCgp100 results in a 50% increase in dose above the FIH Phase 1, acceptable safety profile, and preliminary efficacy in UM pts. Considering the dismal prognosis of metastatic UM, the PFS observed in this study is encouraging. A Phase 2 expansion cohort and separate pivotal trial of IMCgp100 in advanced UM are ongoing. Clinical trial information: NCT02570308.
Phase 1b/2, open label, multicenter, study of intratumoral SD-101 in combination with pembrolizumab in anti-PD1 naïve & experienced metastatic melanoma patients.
Authors: Leung Abraham C.F. , Kummar Shivaani , Agarwala Sanjiv S. , Nemunaitis John J. , Gonzalez Rene , Drabick Joseph J. , Schmidt Emmett V. , Chartash Elliot , Xing Biao , Currie Graeme , Janssen Robert , Ribas Antoni 
Published: September 2018

9550 Background: SD-101 is a synthetic CpG-ODN agonist of TLR 9 that stimulates dendritic cells to release IFN-alpha and mature into antigen presenting cells to activate T cell anti-tumor responses. Pembro is a PD-1 inhibitor approved for the treatment of metastatic melanoma. This study, MEL-01 (NCT02521870), assesses the safety and preliminary efficacy of SD-101 in combination with pembro in stage IIIC-IV melanoma. Methods: A modified 3+3 design was used for SD-101 dose escalation of 1, 2, 4, and 8 mg injected in a single tumor lesion Q1W x 4 then Q3W x 7 in combination with pembro (200 mg IV Q3W). Tumor responses were assessed per investigator using RECIST v1.1. Results: In phase Ib, 22 pts were enrolled: median age 64 y/o, male 68%, white 82%, Stage IV/IIIc 86%/14%, LDH > 1 ULN 27%, ≥ 3 prior lines therapy 36%, anti-PD-1 naïve (n = 9) and experienced (n = 13). There has been no dose limiting toxicity (DLT) to date. The most common (≥20%) treatment-related AEs (TRAEs) were transient low-grade fatigue, myalgia, headache, chills and injection site reactions. Grade ≥ 3 TRAEs were observed in 59.1% pts (most common: myalgia 13.6% and injection site pain 13.6%). Immune-related AEs occurred in 2 pts. One had a G2 pneumonitis on Day 23 resulting in drug withdrawal and the other G3 hypophysitis (85 days after last treatment). No deaths occurred. Responses were observed at all doses in PD-1 inhibitor naïve pts, both at the injected and non-injected lesions. A response was seen at the 8 mg dose in PD-1 inhibitor experienced pts. With median f/u of 97 days (max 382), the ORR was 66.7% in the PD-1 inhibitor naïve patients with best overall response of CR 22.2% (n = 2), PR 44.4% (n = 4), SD 11.1% (n = 1), PD 11.1% (n = 1), and NE 11.1% (n = 1). In the PD-1 inhibitor experienced pts: PR 7.7% (n = 1) and SD 38.5% (n = 5). Conclusions: The combination of SD-101 and pembro was well tolerated and demonstrates no worsening of the expected toxicities of each of the individual monotherapies. These interim data support enhanced activity of adding SD-101 to pembro in anti-PD-1 naive metastatic melanoma as well as potential activity in anti-PD-1 experienced pts. Additional follow up data through May 15, 2017 will be presented. Clinical trial information: NCT02521870.