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e17535 Background: High-grade serous ovarian carcinoma (HGSOC) is the most frequent and deadliest type of ovarian cancer (OC). With the recent advances in transcriptomic and epigenomic profiling of cancer at single cell resolution, it has become clear that intra-tumor heterogeneity driven by genetic and epigenetic factors may be the basis of drug resistance. Current treatments are not homogeneously effective against all the cancer cell subpopulations, thus enabling resistance. With single cell sequencing technology, characterization of cell signatures and regulatory mechanisms may translate to prognostic markers and novel drug targets. Methods: The transcriptomic and epigenomic landscape of HGSOC was mapped for five tumor samples from debulking surgeries and one tissue patient-derived xenograft (PDX) using the 10X genomics sequencing platform. This strategy permits the combination of single cell ATAC-seq and single cell RNA-seq within the same nucleus (Multiome). Isolation of nuclei, library preparation and sequencing were performed following 10X genomics protocols. Sample quality and library quality were assessed by nuclear morphology and fragment size analysis, respectively. Sequenced reads were mapped to the human genome and downstream analysis including copy number variant prediction, pathway enrichment, motif enrichment and gene regulatory network analysis were performed. The sampled patients continue to be followed for clinical outcomes, such as response to therapy. Clinical data including patient age, grade, and stage of cancer, debulking status, CA-125 levels, and neoadjuvant status, were used in conjunction with the genomics data to characterize patient specific molecular regulatory signatures. Results: Cells from the six samples (total N= 26,421) were projected via UMAP. Immune and stromal cells were shown to cluster by cell-type while cancer cells clustered by patient. Cancer cells were identified as cycling cells, ciliated cells, cells with enrichment of the JAK-STAT signaling pathway, and cells exhibiting cancer stemness signatures. Transcription factor motifs and binding-site enrichment in open chromatin regions reveal transcription regulation-based subpopulations. Using the combined gene expression and open chromatin information from these cells, there is potential to uncover the genetic regulatory network(s) that drives treatment resistance. Conclusions: With single cell technology, specific clusters of cancer and tumor microenvironment cells can be classified. Beyond characterizing patient specific signatures, multiome enables the discovery of genomic, transcriptomic and epigenomic signatures that provide insight in tumor progression and treatment resistance.

TPS5634 Background: The prognosis for women with recurrent or persistent EC after progressing on first-line chemotherapy is poor, with a median overall survival (OS) of 12 months, highlighting the need for more efficacious therapies for this population. Immune checkpoint inhibitors either as monotherapy or when combined with kinase inhibitors have recently demonstrated encouraging response rates in pts with microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR) and MS-stable (MSS)/MMR-proficient (MMRp) EC, respectively. Atezo is a humanized monoclonal anti-programmed cell death ligand 1 (PD-L1) inhibitor that has demonstrated monotherapy antitumor activity with an acceptable safety profile in relapsed recurrent EC. Atezo has shown compelling clinical efficacy for pts with certain solid tumors (e.g., urothelial, NSCLC, triple negative breast cancer) as monotherapy and as part of combinatorial therapy. The AFT-50 EndoMAP trial is a platform trial designed to evaluate the efficacy and safety of Atezo in combination with biomarker-defined targeted agents in pts with recurrent or persistent EC. Recognizing pts may have either progressed through or received a checkpoint inhibitor in a prior line of therapy, a non atezo cohort will also be open to enrollment. Methods: This is a phase IB/II non-randomized, multicenter, multicohort, biomarker-driven platform study consisting of two cohorts: A (atezo containing) and B (non atezo). Eligible pts have recurrent or persistent EC and have received no more than 2 prior lines of therapy. FoundationOne CDx (F1CDx) NGS assay will be used for genomic tumor profiling. In cohort A, pts may be eligible for one of the following doublets: Atezo+ipatasertib (PIK3CA/PTEN/AKT1-altered cancers), Atezo+talazoparib (tumors with genomic loss of heterozygosity (LOH) ≥16%), Atezo+Trastuzumab emtansine (ERBB2/HER2 mutated and/or amplified tumors), Atezo+Tiragolumab (MSI-H and/or TMB>10 mut/MB), and Atezo+bevacizumab (biomarker unmatched). Pts will receive Atezo in addition to the targeted agent (at the study approved dosing schedule) until progression, unacceptable toxicity, pt or physician decision to withdraw from the study, death, or study termination. Pts in cohort B, will be eligible for inavolisib (PIK3CA/PTEN/AKT1-altered cancers) + letrozole. Each cohort will enroll ~20 pts; however, the exact size of the cohort may be adjusted. The primary endpoint for Cohort A is confirmed overall response rate (ORR) for each cohort, and for Cohort B is progression free survival at 6 months. Secondary endpoints include disease control rate, duration of response, OS, safety and tolerability, 6-month PFS (cohort A). As a platform study, additional arms may be added, as supported by evolving understanding of EC and molecular targets. EndoMAP is actively enrolling at 17 sites in the US with a target of 25 sites nationwide. Clinical trial information: NCT04486352 .

5606 Background: The National Comprehensive Cancer Network (NCCN) recommends that patients with endometrial cancer under age 50 undergo germline genetic testing. Despite this recommendation, completion rates are suboptimal for patients with gynecologic malignancies. The reasons for failure to complete testing are unknown, but oncology providers may not refer patients to genetic counselors, who frequently order this testing. Best practice advisories (BPAs) in electronic medical records can alert providers of patients who meet guideline-based treatments and testing criteria. It is unknown how oncology providers interact with a BPA indicating patients with endometrial cancer meet NCCN germline testing criteria. The objective of this study is to evaluate genetic counseling referral patterns after implementing a BPA. Methods: Our team developed a BPA to prompt oncology providers to order genetic counseling referrals for patients diagnosed with endometrial or uterine cancer under age 50. We reviewed all provider-BPA interactions between go-live (January 2022) and January 2023. Patient demographic, histopathologic, and cancer treatment data were collected. Provider actions, including BPA cancellation and order placement, were collected. The Chi-Square goodness of fit test was used to identify differences in referral rates by patient or disease characteristics. Results: The BPA displayed 1121 times for 103 patients. Attending physicians received 535 alerts, fellow physicians – 269, and advanced practice providers (APPs) – 317. The median number of alerts per patient was 7 (range 1-87). Of the 103 patients, 23 were excluded from analysis due to no diagnosis of endometrial cancer, patient declined referral, previously completed, or a lack of provider visits within the study period. Of the 80 eligible patients, 36 (45%) received referrals; 18 were placed by attending physicians, 17 by fellows, and one by an APP. Patients under age 40 versus age 40-49 were more likely to be referred (65% vs. 35%; p = 0.011). Patients with active disease were more likely to be referred than those in surveillance (65% vs. 18%; p < 0.001). There were no differences in referral rates by primary language, race, body mass index ≥40, fertility-sparing versus definitive treatment, stage I versus stage II-IV disease, or grade 1-2 versus three tumors. Conclusions: Despite implementing a BPA, only 45% of eligible patients received indicated referrals. Attending and fellow physicians frequently manage patients with active disease and often order referrals; however, APPs frequently manage patients in surveillance and infrequently place referrals, highlighting an opportunity for education. In addition, patients aged 40-49 are less likely to be referred, suggesting a need for new strategies to improve referral rates. Further research is indicated to identify referral barriers for patients undergoing active treatment.

5554 Background: Epithelial ovarian cancer (EOC) is characterized by chemoresistant recurrences primarily confined to the intraperitoneal cavity, frequently leading to malignant small bowel obstructions. Intraperitoneal (IP) chemotherapy has been incorporated in EOC, but only in the first-line setting. Pressurized intraperitoneal aerosolized chemotherapy (PIPAC) is a novel IP drug delivery method that optimizes tissue penetration depth and drug distribution, to treat recurrent peritoneal malignancies. Recent trials outside the U.S. demonstrated partial to stable response following PIPAC in recurrent EOC. To date, no clinical trials have been completed investigating the role of PIPAC in EOC in the United States. Methods: We performed a multicenter prospective phase I trial using IP cisplatin 10.5 mg/m2 and doxorubicin 2.1 mg/m2 via PIPAC at 6-week intervals. Patients were eligible if they had recurrent disease with peritoneal metastasis; extraperitoneal metastasis was allowed. The primary endpoint was dose-limiting toxicity (DLT). Secondary endpoints included progression free survival, PCI scoring, RECIST measurements, and quality of life (QoL). The patients with gastric and uterine cancers’ toxicity data were used but given inherent prognostic differences the treatment efficacy for these patients were not used in this analysis. Adverse event (AE) monitoring was graded using CTCAE spanning 18 weeks. Following completion of treatment (³2 PIPACs) patients were followed up every 12 weeks. QoL was measured using patient-reported assessments at 0, 6, 12, and 18 weeks. Baseline demographics were summarized. Mean change in PCI was calculated between cycle (C) 1 and 2, and cycle 2 and 3. Toxicities attributed to the surgery or PIPAC were reported with highest grade for each patient. Results: Nine heavily pretreated, recurrent patients were enrolled in the trial: 7 with platinum-resistant recurrent EOC, 1 with uterine cancer, and 1 with gastric cancer. PIPAC completion rate was 71.4%. Median age of participants was 65 years. Median prior lines of chemotherapy were 4 (range 2 - 10). No surgical complications occurred in the cohort. Two patients came off study: one for G3 abdominal pain and the other for G3 anorexia. For the EOC cohort, the median PCI reduction was -1.4% (C1 to C2) and -2.8% (C1 to C3). One low-grade serous EOC patient demonstrated a partial response based on RECIST criteria and received 6 cycles. Two EOC patients showed an initial response based on PCI reduction, but progressed following Cycle 2. Overall, QoL was stable. Conclusions: PIPAC with cisplatin/doxorubicin in platinum-resistant ovarian cancer is well tolerated. Intraperitoneal responses were seen in a subset of low-grade serous ovarian cancer patients, which may warrant further study. Heavily pretreated, platinum-resistant high-grade EOC patients derived limited intraperitoneal control from PIPAC monotherapy. Clinical trial information: NCT04329494 .

5512 Background: The multicenter, open-label, randomized phase 2 NCI-9944 study (NCT02595892) demonstrated that addition of ATR inhibitor (ATRi) berzosertib to gemcitabine increased progression-free survival (PFS) compared to gemcitabine alone (HR = 0.57, one-sided log-rank p = 0.044, which met the one-sided significance level of 0.1 used for sample size calculation). Final overall survival (OS) and corresponding biomarker analyses are reported here. Methods: Patients (pts) with platinum-resistant high-grade serous ovarian cancer and unlimited previous lines of cytotoxic therapy in the platinum-sensitive setting but no more than one line of cytotoxic therapy in the platinum-resistant setting, were randomized 1:1 to gemcitabine/berzosertib versus gemcitabine alone. Randomization was stratified based on platinum free interval (PFI), PFI≤3 months versus > 3 months. Crossover from gemcitabine to gemcitabine/berzosertib was allowed upon disease progression by RECIST 1.1. OS was a secondary endpoint while preplanned exploratory correlative studies included assessment of DNA repair pathways and replication stress (RS) alterations by targeted gene sequencing and/or immunohistochemistry (IHC). Results: Seventy pts were randomly assigned to treatment with gemcitabine/berzosertib (34 pts) or gemcitabine alone (36 pts); 15 pts crossed over from gemcitabine to gemcitabine/berzosertib. At the final OS analysis (92.9% maturity), median follow-up was 53.2 weeks in the gemcitabine/berzosertib and 43 weeks in the gemcitabine alone groups. Median OS in the intent-to-treat (ITT) population was 59.4 weeks in the gemcitabine/berzosertib group versus 43.0 weeks in the gemcitabine alone group (HR 0.79, 90% CI 0.52-1.2, one-sided p = 0.18). However, when patients who crossed over to gemcitabine/berzosertib were excluded from analysis, a significant OS benefit was observed with gemcitabine/berzosertib (HR 0.60, 90%CI 0.37−0.97); HR was 0.26 (90% CI 0.1−0.7) in pts with PFI≤3 months and 0.89 (90%CI 0.50−1.59) in pts with PFI > 3 months. Furthermore, significant OS benefit was observed in pts with RS-low tumors (HR 0.39, 90%CI 0.17−0.91, defined as tumors harboring no genomic RS alterations related to loss of RB pathway regulation and/or oncogene-induced RS) but not in pts with RS-high tumors (HR 0.74, 90%CI 0.35−1.56). Additional targeted gene sequencing and IHC analyses as well as analyses adjusting for patient crossover will be reported at the meeting. Conclusions: In the ITT population, gemcitabine/berzosertib did not significantly improve OS versus gemcitabine alone. Pts with PFI≤3 months and pts with RS-low tumors may derive a survival advantage from addition of berzosertib to gemcitabine in the platinum-resistant setting. Clinical trial information: NCT02595892 .

e17057 Background: Results from the VISION trial (NCT03511664) led to the approval of lutetium-177 (177Lu)–PSMA-617 for the treatment of metastatic castration-resistant prostate cancer (mCRPC). This trial excluded patients with baseline cytopenias, thus safety in this frequently encountered patient population is unknown. We aimed to use real-world data to describe the tolerability of radioligand therapy in those with poorer bone marrow reserve. Methods: We retrospectively reviewed the records of all patients, who received a first dose of 177Lu–PSMA-617 at Mayo Clinic in the interval of April 26, 2022, to December 1, 2022. Patients were categorized as having poor marrow reserve on the basis of pre-treatment hematologic parameters, including: (1) an anemia cohort with hemoglobin (Hg) less than 9 g/dL, (2) a thrombocytopenia cohort with platelets (Plt) less than 100 x 109/L, (3) a leukopenia cohort with white blood cell count (WBC) less than 2.5 x 109/L, and (4) a multiple cytopenia cohort. These were exclusionary parameters from the VISION trial. Longitudinal laboratory data and clinical outcomes were collected and analyzed using descriptive statistics. Results: At data cutoff, 185 patients had received one or more doses of 177Lu, including 26 (14%) with at least one baseline cytopenia prior to their first cycle of treatment. In total, there were 19 (73%) patients with anemia, 3 (12%) with thrombocytopenia, 2 (8%) with leukopenia, and 2 (8%) with multiple cytopenias at baseline. The median number of cycles received thus far is 3, including 14 (54%) who are still receiving therapy and 12 (46%) who have permanently discontinued treatment. Median longitudinal changes in blood counts for the anemia cohort are presented in Table 1. Reasons for treatment discontinuation include: toxicity (n = 2), disease progression (n = 5), death (n = 4), or other (n = 1). Dose reductions or treatment delays for worsening myelosuppression were utilized in 3 (12%) and 5 (19%) patients, respectively. Transfusions of packed red blood cells or platelets were required for 16 (62%) patients. A total of 6 (23%) received care in the emergency department or were hospitalized. Conclusions: Treatment discontinuation for toxicity was rare among men with mCRPC and baseline cytopenias, while receiving 177Lu; however, these patients have an overall poor prognosis. [Table: see text]

e17009 Background: Decreased circulating levels of ether lipids (glycerophospholipids with an ether-linked fatty alcohol, e.g. plasmalogens) have been observed in obesity, diabetes and cardiovascular disease. In vitro and in vivo studies suggest that ether lipids are anti-inflammatory and protective against obesity. A recent landmark study revealed that ether lipids can kill cancer cells through ferroptosis. However, the role of ether lipids in prostate cancer has not been thoroughly investigated despite the known association of dysregulated lipid metabolism with poorer clinical outcomes. The aim of this study was to assess the relationship between the circulating profiles of ether lipids and clinical outcomes in localised and metastatic prostate cancer. Methods: The profiles of ~150 ether lipids (8 lipid classes) in plasma lipidomic data from localised prostate cancer (389 men in Australia) and metastatic castration-resistant prostate cancer (mCRPC)(2 cohorts –147 men in USA, 128 men in Australia) were analysed for associations with disease progression or overall survival (OS). Open-access genomic data of mCRPC tumours (108 men, CbioPortal) were analysed for aberrations in genes associated with ether lipid metabolism in relation to clinical outcome. Results: Previously in these study cohorts, we had identified men with poorer prognosis based on their plasma lipidome and our validated sphingolipid signature. These men with poorer prognosis have lower plasma levels of ether lipids than those with better prognosis (t-test p < 0.05, localised disease – 110 ether lipids, mCRPC – 54 ether lipids). Decreased plasma levels of up to 46 ether lipid species were associated with higher rates of clinical relapse in localised disease (hazard ratio (HR) range 0.37-0.73, p-value range 0.006-0.049), shorter radiological progression-free survival in mCRPC (HR range 0.35-0.73, p-value range 0.00009-0.049), and shorter OS in mCRPC (HR range 0.33-0.79, p-value range 0.000004-0.0497). Chromosomal loss of tumour GNPAT, an essential gene in ether lipid synthesis, was associated with shorter OS in mCRPC (HR = 1.36, 95% CI 1.02-1.81, p = 0.03). Conclusions: Lower circulating levels of ether lipids were associated with worse prognosis in localised and metastatic prostate cancer, suggesting that these lipids are protective against disease progression. Further research is required to understand the role of ether lipids in disease progression, and to determine if modulation of ether lipid levels through supplementation is beneficial.

5094 Background: In prior studies, basal vs. luminal differentiation portends differential response to a) androgen suppression (AS) duration for high-risk prostate cancer (PCa) (NRG-GU-TS006) and b) docetaxel chemotherapy (CT) and AS for metastatic hormone-sensitive disease (CHAARTED). In NRG-GU-TS006, basal tumors appeared to benefit the most from longer duration of AS while those with luminal subtype did not whereas, in CHAARTED, luminal subtype had greater benefit from addition of CT. Herein, we examined basal-luminal subtyping to predict differential response to the addition of CT in the setting of high-risk PCa treated with AS and definitive radiotherapy (AS + RT) in NRG/RTOG 0521. Methods: Per pre-specified and approved NCI analysis plan (Navigator #1061), we obtained available NRG biobank biopsy specimens from patients enrolled on the NRG/RTOG 0521 phase III trial, which randomized patients to AS + RT +/- CT. The highest-grade tumors were profiled on clinical-grade whole-transcriptome arrays (Veracyte, San Diego, CA). Basal-luminal subtypes were generated using a 215-gene PCa subtyping classifier (PSC), a second generation PAM50 basal-luminal model. Treatment effects in Luminal Proliferating (LP) and non-LP subtypes were examined with Cox (for overall survival, OS, and metastasis-free survival, MFS) and Fine & Gray (for distant metastasis, DM) multivariable (MVA) models adjusted for age and trial risk stratification, as well as with restricted mean survival times (RMST). Results: Of 183 samples available for analysis (91 from control and 92 from the CT arm), 52 (28%) were classified as LP subtype. Median follow-up for OS was 9.9 years. No significant differences in clinical or pathological variables were observed between LP and non-LP subtypes. In MVA, we did not detect any significant LP subtype-by-CT treatment interaction but observed evidence of non-proportional hazards (Grambsch-Therneau test, p<0.05). In unselected patients, 5- and 10-year RMST difference between the arms was 0.9 (95% CI [-1.5, 3.4], p=0.46) and 5.7 (95% CI [-2.5, 13.9], p=0.17) months of OS. Stratifying by tumor subtype, at 5 years the RMST difference in months was 3.8 (95% CI [0.3, 7.2], p=0.03) for LP and -0.2 ([-3.4, 2.9], p=0.89) for non-LP. The RMST difference in months at 10-years was 13.7 (95% CI [-0.2, 27.5], p=0.053) for LP and 2.5 ([-7.6, 12.5], p=0.63) for non-LP. Conclusions: In pre-treatment biopsy samples from a Phase 3 trial cohort of localized high-risk men, luminal-basal subtyping of tumors demonstrated differential response to docetaxel CT. Similar to results from the CHAARTED trial of metastatic disease, LP tumors may derive greater benefit from addition of CT. Validation of these findings may enable effective earlier use of CT in men with PCa.

5077 Background: In the phase 3 PRESTO study, intensified androgen deprivation therapy (ADT) with apalutamide (Apa) with or without abiraterone acetate plus prednisone (AAP), administered for a finite treatment period of 52 weeks, prolonged prostate-specific antigen progression-free survival (PSA PFS) in pts with high-risk biochemically relapsed prostate cancer (BRPC). We evaluated the association between PSA nadir within 3 months of treatment initiation with subsequent PSA PFS in this study. Methods: PRESTO is a randomized phase 3, open-label trial in pts with BRPC following radical prostatectomy (RP) and PSA doubling time (PSADT) ≤ 9 months, without distant metastases on conventional imaging (NCT03009981). Pts were randomized 1:1:1 to receive a finite 52-week treatment course with ADT, ADT + Apa, or ADT + Apa + AAP, stratified by PSADT (< 3 vs 3–9 months), with post-treatment follow-up. The association between PSA nadir within the first three months on treatment with subsequent PSA PFS was analyzed in a post hoc fashion. Results: 504 pts were randomized to ADT alone (N = 167), ADT + Apa (N = 168) or ADT + Apa + AAP (N = 169). 463 pts were evaluable for PSA nadir at 3 months. Across the three treatment arms, a PSA nadir of less than 0.1, between 0.1 – 0.2, and ≥ 0.2 ng/mL within the first three months of treatment was observed in 86.3%, 4.4%, and 9.3% of patients, respectively. A PSA nadir of < 0.2 ng/mL was reached within 3 months of treatment initiation in 79.8%, 96.9%, and 95.0% of pts randomized to the ADT, ADT + Apa, and ADT + Apa + AAP arms, respectively. The association between time to PSA nadir and subsequent PSA PFS was -0.30 (standard error = 0.03, Kendall’s tau modified for bivariate censoring), and median time to PSA nadir was 2.0 months (interquartile range 1.12 – 4.76 months). Failure to reach a PSA nadir < 0.2 ng/mL within the first three months of treatment was associated with a significantly shorter PSA PFS compared to pts with a PSA nadir ≤ 0.1 ng/mL (median PSA PFS of 13.9 vs. 22.8 months from 3 months post-treatment initiation; hazard ratio = 5.60, 95% CI: 3.58 – 8.75, p < 0.0001). There was also a significant difference in PSA PFS in those with a three-month PSA nadir between 0.1 – 0.2 vs ≤ 0.1 ng/mL (median PSA PFS 17.4 vs 22.8 months, HR = 2.63, 95:CI: 1.49 – 4.63, p = 0.0008). Conclusions: Using a landmark analysis at 3 months, a failure to reach PSA nadir less than 0.1 ng/mL within three months following initiation of ADT in BRPC is associated with shorter time to subsequent progression following treatment discontinuation. Follow-up is ongoing to integrate genomic profiling of primary prostate cancer tissues and whole blood RNA in pts with suboptimal PSA nadir to identify potential markers of relative androgen pathway inhibitor resistance. Clinical trial information: NCT03009981 .

5074 Background: Analysis of phase 3 studies of patients (pts) with mHSPC in the era of ADT, including in combination with docetaxel and/or androgen receptor axis targeted therapies have established PSA-7mo as a key prognostic marker. Our objective was to evaluate the association between PSA-3mo, PSA 7-mo and OS measured in the phase 3 S1216 trial in mHSPC comparing ADT + orteronel (treatment arm) vs ADT + bicalutamide (control arm) [NCT01809691]. Methods: Pts enrolled in the S1216 trial with available PSA-3mo & PSA-7mo were included in this analysis. PSA responses were defined as complete response (CR) if PSA ≤ 0.2 ng/mL, partial response (PR) for PSA >0.2 and ≤ 4ng/mL, and no response (NR) as PSA >4 ng/mL at month 3 or 7. Landmark OS was measured and Cox regression model applied adjusting for stratification (performance status, extent of disease, early vs late start of treatment, treatment arm). Results: 1251 pts were alive and evaluable for PSA-3mo and 1231 pts were evaluable at 7 mo, out of a total of 1279 pts. The median age was 67 (range: 43-92), 10% of patients were black, 96% had a Zubrod performance status of 0-1. Median PSA at baseline was 29 ng/ml (range: 2-6710). Of pts on treatment vs.control arm, PSA-3mo CR, PR, and NR occurred in 52% vs 35%; 31% vs 42%, and 17% vs 23%, respectively. Of pts on treatment vs control arm, PSA-7mo CR, PR, and NR occurred in 61% vs 46%, 20% vs 26%, and 19% vs 29%, respectively. CR or PR at either timepoint led to significantly better outcomes than those with NR. No interaction between treatment arm and PSA response was observed in terms of OS. Conclusions: PSA-3mo and PSA-7mo are strong prognostic markers for pts with mHSPC. More pts on ADT with orteronel achieved CR at 3 and 7 mo. In addition to its use in counseling patients in the clinic, PSA-3mo and PSA-7mo may be used as parameters for designing future trials in pts with mHSPC, utilizing the next generation of intensification or de-intensification treatment regimens. Clinical trial information: NCT01809691 . [Table: see text]