bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasma biomarkers of amyloid, tau, axonal, and neuroinflammation pathologies in dementia with Lewy bodies
Authors: Vrillon Agathe , Bousiges Olivier , Götze Karl , Demuynck Catherine , Muller Candice , Ravier Alix , Schorr Benoît , Philippi Nathalie , Hourregue Claire , Cognat Emmanuel , Dumurgier Julien , Lilamand Matthieu , Cretin Benjamin , Blanc Frédéric , Paquet Claire 
Published: July 2024

Abstract
Background
Increasing evidence supports the use of plasma biomarkers of amyloid, tau, neurodegeneration, and neuroinflammation for diagnosis of dementia. However, their performance for positive and differential diagnosis of dementia with Lewy bodies (DLB) in clinical settings is still uncertain.

Methods
We conducted a retrospective biomarker study in two tertiary memory centers, Paris Lariboisière and CM2RR Strasbourg, France, enrolling patients with DLB (n = 104), Alzheimer’s disease (AD, n = 76), and neurological controls (NC, n = 27). Measured biomarkers included plasma Aβ40/Aβ42 ratio, p-tau181, NfL, and GFAP using SIMOA and plasma YKL-40 and sTREM2 using ELISA. DLB patients with available CSF analysis (n = 90) were stratified according to their CSF Aβ profile.

Results
DLB patients displayed modified plasma Aβ ratio, p-tau181, and GFAP levels compared with NC and modified plasma Aβ ratio, p-tau181, GFAP, NfL, and sTREM2 levels compared with AD patients. Plasma p-tau181 best differentiated DLB from AD patients (ROC analysis, area under the curve [AUC] = 0.80) and NC (AUC = 0.78), and combining biomarkers did not improve diagnosis performance. Plasma p-tau181 was the best standalone biomarker to differentiate amyloid-positive from amyloid-negative DLB cases (AUC = 0.75) and was associated with cognitive status in the DLB group. Combining plasma Aβ ratio, p-tau181 and NfL increased performance to identify amyloid copathology (AUC = 0.79). Principal component analysis identified different segregation patterns of biomarkers in the DLB and AD groups.

Conclusions
Amyloid, tau, neurodegeneration and neuroinflammation plasma biomarkers are modified in DLB, albeit with moderate diagnosis performance. Plasma p-tau181 can contribute to identify Aβ copathology in DLB.
Associations of activity, sedentary and sleep behaviors with prevalent steatotic liver disease in middle-aged and older adults: the ELSA-Brasil study
Authors: de Paula Danilo , Feter Natan , dos Reis Rodrigo Citton Padilha , Griep Rosane Harter , Duncan Bruce Bartholow , Schmidt Maria Inês 
Published: July 2024

Abstract
Background
Steatotic liver disease (SLD) is a prevalent metabolic disease. While single component movement behaviors have been related to its development, comprehensive assessments of their joint associations are scarce.

Objective
To investigate the single-component and multi-component associations of moderate and vigorous physical activity (MVPA), light physical activity (LPA), sedentary behavior (SB), and sleep with prevalent SLD in Brazilian adults.

Methods
A cross-sectional analysis using data from the third wave of the ELSA-Brasil cohort (2017–2019). Participants wore an ActiGraph wGT3X-BT in the waist for seven days and completed a sleep diary. SLD was defined by a Fatty Liver Index ≥ 60. To investigate single-component and multi-component associations, we used three exposure modeling approaches based on Poisson models: multivariable-adjusted regression, restricted cubic splines, and compositional data analysis.

Results
Among 8569 participants (55.7% women, mean age 59.2 ± 8.60), 43.9% had SLD. Total activity volume adjusted for covariates was inversely associated with prevalent SLD. Every 1 mg/day increase in total activity volume was associated with a PR of 0.95 in individuals sleeping < 7 h/day (95% CI 0.94–0.97) and 0.95 (95% CI 0.93–0.96) in those sleeping ≥ 7 h/day. Increasing 30 min/day of MVPA was associated with decreasing prevalence of SLD (sleep ≥ 7 h/day [PR 0.83; 95% CI 0.77–0.89]; sleep ≥ 7 h/day [PR 0.78; 95% CI 0.74–0.83]). Sleep, SB, and LPA were not associated with SLD. Associations of total activity volume and MVPA were more pronounced among females. Adjustment with adiposity markers attenuated the associations.

Conclusions
In adults, total activity volume and MVPA were inversely associated with SLD in a dose–response fashion. Substituting lower-intensity behaviors with MVPA was associated with a lower prevalence of SLD independent of sleep duration, sex, and age.
Multi-ethnic genome-wide association study to identify a novel locus for susceptibility to immune-related adverse events from immune checkpoint inhibitors.
Authors: Huang Yiqing , Zhao Joseph J , Wong Alvin , Tay Sen Hee , Ang Yvonne Li'en , Goh Boon Cher , Soo Ross A. , Aminkeng Folefac 
Published: July 2024

3090 Background: Immune-related adverse events (IrAEs) arising from immune checkpoint inhibitors (ICIs) can be unpredictable. As genomic variation underlies both disease susceptibility and drug responses, genomic markers may predict for the development of IrAEs. We perform a pioneering pharmacogenomic study across a multi-ethnic Asian patient population to uncover genomic biomarkers associated with IrAEs from ICIs. Methods: From March 2018 – July 2023, cancer patients treated with ICIs from the National University Cancer Institute Singapore and Tan Tock Seng Hospital were recruited. IrAEs were characterized and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5. DNA was extracted and genotyped by Infinium Global Screening Array (700K markers). Statistical analyses were performed by SVS/HelixTree, PLINK and R. Genetic association was performed by logistic regression (additive model), accounting for all possible confounding factors. Bonferroni corrected P < 1.28E-07 (0.05/390,925 SNPs passed QC) was considered statistically significant. Results: Genome-wide association study (GWAS) was conducted amongst 507 patients of Asian Ancestry (Chinese, Malay, Indian and Others). Median age was 63. Majority were male (66.5%), Chinese (76.7%), ECOG PS 0-1 (40.1%) and had stage IV cancer at diagnosis (67.2%). Non-small cell lung cancer (37.1%), renal cell carcinoma (12.2%) and hepatocellular carcinoma (7.7%) were the three most common cancers. Top four ICIs used were pembrolizumab, nivolumab, durvalumab and atezolizumab, respectively (47.1%, 23.9%, 12.5%, 11.3%). 0.8% of patients received dual ICIs concurrently. Median duration of treatment was 142 days and median follow-up was 147 days. IrAEs were seen in 43.7% of patients. Skin (24.1%), endocrine (8.1%) and hepatotoxicity (6.1%) were the most common IrAEs. 4.9% of patients had grade ≥3 toxicity, of which skin (3.6%), hepatotoxicity (3.0%) and pulmonary toxicity (1.8%) were the most common. Multi-ethnic GWAS analysis identified one potential novel genetic locus associated with CTCAE grade ≥3 IrAEs. chr3:163402331 rs146525069; P = 7.29E-08, OR (95%CI) = 17.08 (5.40- 54.04); minor allele = A, 10.91% in Cases vs 0.71% in Controls. Conclusions: This pharmacogenomics GWAS uncovered a novel locus for susceptibility to serious immune-related adverse events from immune checkpoint inhibitors. Further pharmacogenomic discovery/replication and functional validation studies are currently on-ongoing. Our study provides a potential biological mechanism for IrAEs and a step towards more effective clinical translation of pharmacogenetic testing to personalize ICI use.
Characterization of diverse targetable ERBB2 alterations in 512,993 patients with solid tumors.
Authors: Liu Dazhi , Keller-Evans Rachel B , Schrock Alexa B. , Drilon Alexander E. , Jee Justin , Li Bob T. 
Published: July 2024

3129 Background: Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate (ADC) that has demonstrated activity against a range of HER2-expressing and HER2-mutant (mut) solid tumors. We present an extensive landscape of ERBB2 alterations (alt) that may predict sensitivity to HER2-targeted therapies in development with a focus on mutations and cancer types without approved indications. Methods: We queried institutional databases (MSKCC and Foundation Medicine, Inc.) of comprehensive genomic profiling (CGP) performed on solid tumor tissue samples using either MSK-IMPACT (N=83,332; MSK) or FoundationOne/FoundationOne CDx (N=429,661; FMI) and on patient-matched liquid biopsies using FoundationOne Liquid CDx (N=1,922). ctDNA tumor fraction (ctDNA TF) on FoundationOne Liquid CDx was estimated using a composite algorithm. Clinicopathological characteristics and treatment outcomes were annotated for MSK-IMPACT samples. Results: ERBB2 activating alt were detected in 6.6% (n=28,508) and 5.0% (n=4,133) of tumors in the FMI and MSK cohorts, respectively. In FMI tissue samples, ERBB2 alt were most prevalent in gastroesophageal (GEC; 18.1%), bladder (18.0%), salivary gland (14.1%), breast (12.7%), and uterine (12.1%) cancers. The cancer types with the largest number of ERBB2mut tumors, specifically, included NSCLC (n=1,618, 1.9%), breast (n=1,565, 3.5%), colorectal (CRC; n=1,221, 2.3%), bladder (n=855, 8.8%), and GEC (n=660, 3.4%). Across these 5 cancers, ERBB2 mut were most commonly located in the kinase domain (KD; 58%), followed by the extracellular domain (ECD; 28%) and transmembrane domain (TMD; 2%). Rare splice site mut and in-frame deletions resulting in exon 16 loss (Ex16Alt) were also observed (n=76, <0.1%). ERBB2 mut were found to be mutually exclusive with other RTK/MAPK driver oncogenes including: EGFR, KRAS, ALK, MET, BRAF, and RET in NSCLC; FGFR1 in breast cancer; BRAF in CRC; and FGFR3 in bladder cancer. In patient-matched liquid biopsy samples, sensitivity for detecting ERBB2 amplifications (amp; 33.3%, 43/129) was lower than for detecting ERBB2 mut (72.3%, 47/65) across select cancers. However, sensitivity for detection of both alts was improved in liquid samples with elevated ctDNA TF (≥1%), increasing to 52.6% (40/76) for amp and 97.3% (36/37) for mut. In the MSK cohort, 110 of 986 (11.2%) patients with ERBB2 mut non-NSCLC tumors received one or more HER2-targeted therapies, including ADCs. Clinical responses to HER2-targeted therapies were observed in patients harboring KD mut (n=10), ECD mut (n=6), TMD mut (V659E, n=1), and in 1 patient with a V697L mut. Conclusions: CGP detects diverse ERBB2activating alt at a high incidence in solid tumor types beyond NSCLC. These represent patient populations who may benefit from HER2-directed therapies. Trials of novel HER2-targeted agents are necessary to refine our understanding of the biological dependency of HER2 alterations.
Triplet combination treatments with pembrolizumab (pembro) for anti–PD-(L)1–refractory advanced melanoma: Preliminary results of the phase 1/2 KEYMAKER-U02A study.
Authors: Dummer Reinhard , Grob Jean-Jacques , Robert Caroline , Shapira-Frommer Ronnie , Lebbe Celeste , Ascierto Paolo Antonio , Dalle Stéphane , Hamid Omid , Meyer Nicolas , Khattak Muhammad Adnan , Hill Andrew Graham , Cohen Jonathan , Curigliano Giuseppe , Di Giacomo Anna Maria , Del Vecchio Michele , Jang Sekwon , Singh Rohini , Peng Xuan , Diede Scott J. , Long Georgina V. 
Published: July 2024

9506 Background: Anti–PD-(L)1–refractory melanoma is a major challenge, and immunotherapy combination treatment may be useful in this patient population. The phase 1/2 KEYMAKER-U02A (NCT04305041) is a multi-arm, open-label, adaptive umbrella study designed to evaluate pembro + investigational agents for the treatment of anti–PD-(L)1–refractory melanoma. We report results from arm 1 (pembro + quavonlimab [qmab] (anti-CTLA4) + vibostolimab [vibo] (anti-TIGIT)), arm 2 [pembro + qmab + lenvatinib [len] (TKI)), and arm 3 (pembro + ATRA [all-trans retinoic acid]) of KEYMAKER-U02A. Methods: In all arms, adults had stage III/IV melanoma, ≥1 measurable lesion per RECIST v1.1, an Eastern Cooperative Oncology Group performance status score of 0 or 1, and disease progression on anti–PD-(L)1 therapy alone or in combination. Pts were randomized equally to open arms. In arm 1, pts received pembro 200 mg IV Q3W + qmab 25 mg IV Q6W + vibo 200 mg IV Q3W. In arm 2, pts received pembro 400 mg IV Q6W + qmab 25 mg IV Q6W + len 20 mg PO QD. In arm 3, pts received pembro 400 mg IV Q6W + ATRA 150 mg/m2/day PO for 3 days Q3W. Pts received treatment for up to 2 y or until intolerable toxicity, disease progression, or pt withdrawal. Primary end points were safety and ORR per RECIST v1.1 by blinded independent central review (BICR). DOR per RECIST v1.1 by BICR was the secondary end point. PFS per RECIST v1.1 by BICR and OS were exploratory end points. Enrollment was planned for a maximum of 20 pts in each arm and enrollment could continue to up to 40 pts if an ORR of > 20% (5/20) was observed. Enrollment would then continue up to 100 pts if an ORR of ≥35% (14/40) was observed. Results: At data cutoff (Oct 18, 2022), 40 pts had been assigned to arms 1 and 2 and 20 pts to arm 3. Median (range) follow-up was 18.4 (1.7-24.5) mo in arm 1, 18.5 mo (1.6-25.4) in arm 2, and 2.7 mo (0.8-3.5) in arm 3. Efficacy is reported in the table. Treatment-related adverse events (TRAEs) occurred in 35 pts (88%) in arm 1, 38 pts (95%) in arm 2, and 15 pts (75%) in arm 3. Grade 3-5 TRAEs occurred in 11 pts (28%) in arm 1, 23 pts (58%) in arm 2, and 3 pts (15%) in arm 3; 1 pt in arm 2 died from a grade 5 TRAE (immune-mediated nephritis). Conclusions: Although objective responses were observed in some pts with anti–PD-(L)1–refractory melanoma, protocol-prespecified criteria for enrollment expansion were not met in any arm. The safety profile was manageable. Additional arms will be reported for this pt population with a high unmet need. Clinical trial information: NCT04305041 . [Table: see text]
Length of treatment after partial or complete remission in immunotherapy for metastatic melanoma: An EUMelaReg real world study.
Authors: Asher Nethanel , Mohr Peter , Ellebaek Eva , Bender Marc , Mangana Joanna , Kandolf Lidija , Gavrilova Iva , Ascierto Paolo Antonio , Gogas Helen , Rutkowski Piotr , Schadendorf Dirk , Bastholt Lars , Weichenthal Michael ,   EUMelaReg Consortium
Published: July 2024

9531 Background: A significant proportion of patients (pts) with non-resectable melanoma treated with immune checkpoint inhibitors (ICI) achieve durable remissions, but there is limited data on the optimal duration of ICI therapy in these pts. Therefore, the influence of the duration and maintenance of ICI therapy in pts with a partial (PR) or complete remission (CR) on further outcome was investigated. Methods: Primary objectives was the survival outcome after achieving PR or CR in non-resectable stage III/IV melanoma in relation to baseline prognostic variables and duration of maintenance treatment with ICIs in 1st line. This retrospective study evaluated melanoma cases from the EUMelaReg treatment registry, who achieved a best overall response (BOR) of PR or CR with either single agent anti-PD1 or combined anti-PD1/anti-CTLA4 in 1st line. Cases were stratified according to treatment duration after achieving a PR or CR: < 6 months (M), 6-12 M, > 12 M. To address immortal time bias, cases with early progression were cloned into all respectively compatible strata. These synthetical strata were further analyzed and compared by propensity score weighting, and robust confidence intervals were retrieved by bootstrapping techniques. Results: A total of 1,291 pts were included in the analysis. After cloning, 2,144 cases could be stratified to the synthetical arms of <6 M (26.5%), 6-12 M (31.4%) or >12 M (42.1%) treatment continuation after achieving PR or CR. Adjusted Kaplan-Meier estimates showed that treatment until progressive disease (PD) or > 12 M after remission resulted in prolonged progression-free (PFS) and overall survival (OS) compared to the < 6 M arm (hazard ratio (HR): 0.82 [95% confidence interval (CI): 0.6-0.9] and HR: 0.67 [95% CI: 0.5-0.9], respectively).This effect was more pronounced in PR (HR 0.66 for OS) than in (HR 0.84 for OS). Treatment for 6-12 M compared to < 6 M also showed a trend towards prolonged PFS and OS (HR: 0.85 [95% CI: 0.7-1.1] and HR: 0.82 [95% CI: 0.6-1.1], respectively). Conclusions: This study showed PFS and OS benefit for pts continuing on treatment for > 12 M or until progression after achieving PR or CR compared to pts treated for < 6 M. [Table: see text]
Using serial 18F-FDG PET/CT PERCIST response to predict responses to immune check point inhibitors in patients with advanced cutaneous squamous cell carcinoma.
Authors: Ladwa Rahul , Kenyon Sarrinder , Jagger Gillian , McGrath Margaret Louise , Cuscaden Claire 
Published: July 2024

9548 Background: The role of serial 18F-FDG-PET/CT imaging in predicting long term efficacy of PD-1 targeted immune checkpoint inhibitor (ICI) in advanced cutaneous squamous cell carcinoma (cSCC) is unknown. This study aims to correlate PET PERCIST response with time to progressive disease. Methods: This was a single-centre retrospective study of patients treated with ICI for advanced cSCC who had baseline and serial FDG-PET/CT within 4-months of commencement of ICI. PERCST 1.0 was calculated by two radiologists independently and classified into complete metabolic response (CMR), partial metabolic response (PMR), stable metabolic disease (SMD), and progressive metabolic disease (PMD). The primary endpoint was time to progression from commencement of ICI. Progression was determined by a multidisciplinary team combining clinical and radiological assessments. Results: Of the 242 patients treated with ICI for advanced cSCC during 2018-2023, 83 (34%) patients had a serial FDG PET. Of these, 53 patients met the inclusion criteria of ≤4-months from ICI to second PET. CMR (54.7%), PMR (15.1%), SMD (11.3%) and PMD (18.9%) were seen as initial responses by PERCST 1.0. With a median follow-up of 8-months (1-55), progressive disease as determined by the multidisciplinary team was observed in 11 patients (21%). For these 11 patients, the 4-month PERCST 1.0 response was measured as CMR (n=1), PMR (N=1), SMD (N=2) and PMD (N=7). The median TTP was significantly higher in CMR/ PMR vs SMD/PMD (55 vs 4-Months, P<0.001). At data cut off, 94.6% (N=35) of patients with a 4-month PET PERCST 1.0 CMR/ PMR assessment did not progress clinically. Clinical response was maintained at a minimum of 12-months in 94.7% (n=18) of those responding. Conclusions: Rate of CMR and PMR in advanced cSCC is high with ICI. Early PET CMR/ PMR appears to predict long term durable responses. Incorporation of PET/CT into the assessment of response in cSCC may help guide treatment decisions by early identification of those patients not responding to ICI.
Atezolizumab (A), cobimetinib (C), and vemurafenib (V) in patients (pts) with BRAFV600 mutation–positive melanoma with central nervous system (CNS) metastases (mets): Final results and exploratory biomarker analysis from the phase 2 TRICOTEL study.
Authors: Dummer Reinhard , Levesque Mitchell , Bellini Elisa , Chen Marissa , Hu Youyou , Wong Tiffany , Stassen Katja , Duhard Pauline , Yan Yibing , Tawbi Hussein A. 
Published: July 2024

9550 Background: Primary analysis results from the phase 2 TRICOTEL study showed intracranial activity with the triplet combination of A + C + V in pts with BRAFV600-mutated melanoma with CNS mets (1). Here, we report final analysis results and exploratory biomarker analyses for pts with BRAFV600-mutated melanoma in the triplet combination cohort from TRICOTEL. Methods: Eligible pts were aged ≥18 y and had melanoma, MRI-confirmed CNS mets ≥5 mm in ≥1 dimension, and no prior systemic treatment for metastatic disease. Pts received A (840 mg on days 1 and 15 of each 28-d cycle) + C (60 mg once daily for 21 d on, 7 d off) + V (720 mg twice daily) except in cycle 1, during which A was withheld. Tumor tissue and circulating tumor DNA (ctDNA) samples collected at baseline (cycle 1, day 1) and ctDNA at the time of progressive disease (PD) were profiled for mutations using next-generation sequencing. Tumor tissue was profiled using a pipeline programmed for MelArray, and ctDNA was measured based on the tissue genetic profile. Results: A total of65 pts were enrolled in the triplet combination cohort. At final analysis, median follow-up was 12.4 mo. Per independent review committee (IRC) assessment, intracranial ORR (confirmed by assessments ≥4 wk apart) was 38% (95% CI, 27–51) and median intracranial PFS was 5.1 mo (95% CI, 3.7–6.9) (Table). Median OS was 13.4 mo (95% CI, 10.7–16.9). No new safety signals were observed since primary analysis. Mutations were detected in baseline ctDNA samples of 60 pts (5 pts not reported) and showed high prevalence of NF1, NRAS, and GNAI2 mutations; relative to tumor tissue, 11 additional BRAF mutations were detected in ctDNA at baseline. Acquired mutations in AKT1 were detected in ctDNA at PD. Median OS shortened in pts with >2 versus ≤2 mutated MAPK pathway genes in ctDNA at baseline (9.1 vs 14.5 mo; hazard ratio, 2.0 [95% CI, 1.0–3.7]; p<0.05). In tumor tissue, baseline mutations in PIK3C2A and PLEKHG4 were enriched in nonresponders, while RAD51B mutations were enriched in responders. Conclusions: Combination A + C + V had clinical intracranial activity in pts with BRAFV600-mutated melanoma with CNS mets. Exploratory biomarker analyses in this small cohort demonstrate the presence of ctDNA in pts with melanoma and CNS mets and provide insight into mutations associated with response and resistance to the triplet combination. 1. Dummer R et al, Lancet Oncol 2023. Clinical trial information: NCT03625141 . [Table: see text]
The efficacy and safety of toripalimab combined with anlotinib in the first-line treatment of Chinese patients with metastatic melanoma.
Authors: Ye Ting , Li Linqing , Fan Li , Cao Rubo , Li Xianan , Chen Jing 
Published: July 2024

9560 Background: Acral, mucosal and non-CSD melanoma are the major subtypes in Chinese melanoma patients, with poor response to antiprogrammed cell death-1 (PD-1) monotherapy. Anti PD-1 monoclonal antibodies combined with anti-angiogenesis agent have showed synergistic effects mechanically and a promising response rate. Here, we report efficacy and safety of toripalimab combined with anlotinib in Chinese patients with metastatic melanoma. Methods: Patients with metastatic acral, mucosal and non-CSD melanoma received toripalimab 240mg intravenously every 3 weeks combined with anlotinib 12 mg orally once a day for first 2 weeks every 3 weeks as first-line treatment, until disease progression or unacceptable toxicity. All patients were enrolled from the Cancer Center of Union Hospital, affiliated to Tongji Medical College of Huazhong University of Science and Technology and Hunan Cancer Hospital. Results: From January 2021 to January 2024, a total of 47 patients were enrolled in this study. Subtypes were 16 patients with acral melanoma, 21 patients with mucosal melanoma, and 10 patients with non-CSD melanoma. Average age was 59.7 ±10.1 years old. The median follow-up was 26.5 months (95% CI: 20.6, 32.4 months). Among the 46 efficacy evaluable patients, the objective response rate (ORR) and disease control rate (DCR) were 23.9% and 80.4%, respectively. Median duration of response was 14.4 months (95% CI: 7.5, 21.3). The median progression-free survival (PFS) of all 47 patients was 5.7 months (95% CI 4.2 to 7.2 months); and the median OS was 14.4 months (95% CI 7.3 to 21.5 months). The median PFS of patients with M1a stage is 24.4 months, statistically longer than M1b (5.1 months), M1c (6.6 months) and M1d (4.0 months). The median PFS of acral, mucosal and non-CSD melanoma were 6.6m, 5.1m, 5.2m respectively with no statistical difference, and these is no difference of PFS between gender and age. In terms of safety, treatment-related adverse events (TRAEs) for all grades occurred in 76.6% (36/47) of patients, and grade 3 or 4 occurred in 4.3% (2/47) of patients. The incidence of immune-related adverse reactions (irAE) was 23.4% (11/47) for all grades, the most common irAEs (≥2%) included hypothyroidism, immune-associated hepatitis and rash. Conclusions: Toripalimab combined with anlotinib displays good efficacy and well-tolerant safety profiles in the treatment of patients with metastatic melanoma. Further biomarker analysis was ongoing.