General Research Support Research Articles

La seminoteca del herbario TFC (SEGAI): desempolvando un pequeño gran tesoro

T he seed library (“seminoteca”) of the Herbarium TFC, belonging to the General Research Support Service (SEGAI) of the University of La Laguna, is an accessory collection started in 1974 at the initiative of Dr Wildpret. Until 1985, it carried out exchanges through an Index Seminum (Department of Botany, 1974-1976 and 1978-1985). Subsequently, its activity ceased to focus on the conservation of the Herbarium main collections, and the seed collection, made up of 3061 samples, was left unused, except for some taxonomic queries. Now, we have undertaken the improvement of the general conservation of the collection, and we want to make it known to the scientific community. Taxonomic, spatial, and temporal coverage of the 1565 seed samples collected in the Canary Archipelago has been analysed, and an evaluation of the quality of the sample data has been carried out.

국내 인문사회기반 융합연구의 학술 및 과학기술 성과 분석에 대한 연구

This study examined academic and scientific and technological achievements through actual humanities and social science-based convergence research in a situation where the importance of humanities and social science-based convergence research is continuously expanding. As a result of the analysis, in the case of academic and science and technology achievements, it was found that the results of the publication of papers in professional academic journals and the presentation of papers at domestic and international academic conferences were mainly, and overall performance was decreasing. This seems to be because the interdisciplinary convergence research support project was integrated into a general joint research support project in 2019, and the general joint research support project (convergence) has yet to produce results in the early stages. In addition, since performance input is not mandatory, performance is expected to be omitted, and empirical research should be conducted to investigate and analyze academic and scientific performance for researchers carrying out general joint research support projects (convergence).

ENPAC: phase II trial with safety lead of enzalutamide in combination with paclitaxel and carboplatin for advanced or recurrent endometrioid endometrial adenocarcinoma

Objectives: The androgen receptor (AR) is more widely expressed than the estrogen or progesterone receptor in endometrial cancer (EC), including up to 90% of endometrioid type. Enzalutamide binds to the AR thereby nuclear translocation of receptors and blocking the association of the AR with DNA. We sought to evaluate the efficacy of paclitaxel, carboplatin and enzalutamide in a phase II study of advanced or recurrent endometrioid EC. Methods: Women with chemo-naïve, advanced-stage or recurrent endometrioid EC with measurable disease and adequate end organ function were eligible. Documented AR expression was not required. A safety lead in of the triplet was performed to confirm dose. In phase II, patients received 28 days of enzalutamide (160mg daily) as a single agent before starting triplet therapy. Pre- and post-treatment biopsies were obtained during the single agent lead in for evaluation of molecular markers including AR receptor expression and activation, expression of AR-related genes/proteins, and DNA copy number alterations and mutations. Patients then received carboplatin (AUC 6 IV Q3wk), paclitaxel (175 mg/m2), and enzalutamide (160mg daily). Response per RECIST 1.1 was assessed every 3 cycles for a maximum of 9 cycles. Evaluable patients received at least 6 cycles of triplet therapy. Progression free survival (PFS) was calculated from date of treatment initiation to earliest date of progression, death, or last contact. This study was approved and funded in part by the National Comprehensive Cancer Network (NCCN) Oncology Research Program from general research support provided by Astellas Pharma Global Development, Inc. Results: Conclusions: The combination of enzalutamide, carboplatin, and paclitaxel was tolerable and had promising clinical outcomes in chemo-naïve advanced or recurrent endometrioid EC. Further analyses are ongoing regarding predictors of response and resistance to androgen-inhibitor therapy. Clinical Trials Registration: NCT02684227. The androgen receptor (AR) is more widely expressed than the estrogen or progesterone receptor in endometrial cancer (EC), including up to 90% of endometrioid type. Enzalutamide binds to the AR thereby nuclear translocation of receptors and blocking the association of the AR with DNA. We sought to evaluate the efficacy of paclitaxel, carboplatin and enzalutamide in a phase II study of advanced or recurrent endometrioid EC. Women with chemo-naïve, advanced-stage or recurrent endometrioid EC with measurable disease and adequate end organ function were eligible. Documented AR expression was not required. A safety lead in of the triplet was performed to confirm dose. In phase II, patients received 28 days of enzalutamide (160mg daily) as a single agent before starting triplet therapy. Pre- and post-treatment biopsies were obtained during the single agent lead in for evaluation of molecular markers including AR receptor expression and activation, expression of AR-related genes/proteins, and DNA copy number alterations and mutations. Patients then received carboplatin (AUC 6 IV Q3wk), paclitaxel (175 mg/m2), and enzalutamide (160mg daily). Response per RECIST 1.1 was assessed every 3 cycles for a maximum of 9 cycles. Evaluable patients received at least 6 cycles of triplet therapy. Progression free survival (PFS) was calculated from date of treatment initiation to earliest date of progression, death, or last contact. This study was approved and funded in part by the National Comprehensive Cancer Network (NCCN) Oncology Research Program from general research support provided by Astellas Pharma Global Development, Inc. The combination of enzalutamide, carboplatin, and paclitaxel was tolerable and had promising clinical outcomes in chemo-naïve advanced or recurrent endometrioid EC. Further analyses are ongoing regarding predictors of response and resistance to androgen-inhibitor therapy.

A phase I study of mirvetuximab soravtansine (MIRV) and gemcitabine (G) in patients (Pts) with selected frα-positive solid tumors: Results in the ovarian cancer (EC) cohort.

5542 Background: Mirvetuximab soravtansine (MIRV) is an ADC comprising a FRα-binding antibody, cleavable linker, and the maytansinoid DM4, a potent tubulin-targeting agent. MIRV has promising single agent activity in FRα-positive medium/high expression epithelial ovarian cancer (EOC), at 6 mg/kg, based on adjusted ideal body weight (AIBW) IV every (q) 21 days. This study evaluated MIRV and G in recurrent EOC, endometrial and triple negative breast cancer. The recommended phase 2 dose (RP2D) was established at MIRV 6 mg/kg AIBW IV, day 1 and G 800 mg/m2 IV, d1, 8 q21 days (J Clin Oncol 37, 2019, Abs. #3009). Here we report the results from the EOC cohort. Methods: Patients (pts) with FRα-positive platinum resistant EOC with ≤4 prior chemotherapy (CT) regimens, were eligible. FRα positivity was initially defined as ≥ 25% of cells with PS2+ staining intensity (low to high FRα expression) and was subsequently revised to require medium/high FRα expression (≥50%/ ≥75% of cells with PS2+ staining intensity). Results: From 10/2017 to 12/2020, 113 EOC pts underwent FRα screening, with 74 FRα-positive results. Thirty total EOC pts (with median 3 prior lines of therapy) were treated; 8 pts during dose escalation and 22 EOC pts at the RP2D (all evaluable for response). Fifteen (50%) pts had high FRα, 10 pts (33%) medium FRα, and 5 pts (17%) low FRα expression. Eleven (36%) of the 30 EOC pts achieved a partial response (PR), 15 pts (50%) had SD and 4 pts (13%) progressed. Among the 11 responders, 5 pts had high FRα, 4 pts medium FRα and 2 pts low FRα expression. Non-heme clinically significant adverse events (AEs) included: G2 sensory neuropathy (4 pts) G3 diarrhea (3 pts), G3 fatigue (2 pts), G3 pneumonitis (2 pts), and 1 pt with G5 respiratory failure (secondary to pneumonia but drug-induced pneumonitis could not be ruled out). Conclusions: MIRV in combination with G has promising clinical activity in late line platinum resistant FRα-positive EOC, with best responses observed in high FRα expression. The regimen is well tolerated with expected AEs based on the known toxicities of each agent. This study was approved and funded by the National Comprehensive Cancer Network (NCCN) Oncology Research Program from general research support provided by ImmunoGen Corp and Cancer Center Support Grant P30CA033572. Clinical trial information: NCT02996825.

Association Between Physician Industry Payments and Cost of Anterior Cervical Discectomy and Fusion in Medicare Beneficiaries

Neurosurgical spine specialists receive considerable amounts of industry support that may impact the cost of care. The aim of this study was to evaluate the association between industry payments received by spine surgeons and the total hospital and operating room (OR) costs of an anterior cervical discectomy and fusion (ACDF) procedure among Medicare beneficiaries. All ACDF cases were identified among the Medicare carrier files from January 1, 2013, to December 31, 2014, and matched to the Medicare inpatient baseline file. The total hospital and OR charges were obtained for these cases. Charges were converted to cost using year-specific cost-to-charge ratios. Surgeons were identified among the Open Payments database, which is used to quantify industry support. Analyses were performed to examine the association between industry payments received and ACDF costs. Matching resulting in the inclusion of 2209 ACDF claims from 2013-2014. In 2013 and 2014, the mean total cost for an ACDF was $21,798 and $21,008, respectively; mean OR cost was $5878 and $6064, respectively. Mann-Whitney U test demonstrated no significant differences in the mean total or OR cost for an ACDF based on quartile of general industry payment received (P= 0.21 and P= 0.54), and linear regression found no association between industry general payments, research support, or investments on the total hospital cost (P= 0.41, P= 0.13, and P= 0.25, respectively), or OR cost for an ACDF (P= 0.35, P= 0.24, and P= 0.40, respectively). This study suggests that spine surgeons performing ACDF surgeries may receive industry support without impacting the cost of care.

Phase II randomized trial of carboplatin + pemetrexed + bevacizumab, +/- atezolizumab in stage IV non-squamous non-small lung cancer (NSCLC) patients who harbor a sensitizing EGFR mutation or have never smoked.

TPS9629 Background: Stage IV NSCLC patients who are never-smokers or with EGFR-mutated tumors generally do not benefit from single-agent immunotherapy. Retrospective subgroup analyses from recent phase III trials suggest that immunotherapy-chemotherapy +/- VEGF inhibition may overcome resistance to PD-L1 inhibitors in these patients, however prospective research on this is needed. This trial will examine a patient population with stage IV non-squamous disease who either have tumors that possess an EGFR exon 19 or 21 mutation or who are never-smoker wild-types, to determine whether the PD-L1 inhibitor atezolizumab in combination with pemetrexed, carboplatin, and bevacizumab can improve outcomes. Methods: This is a randomized, phase II, multi-center, open-label trial to assess pemetrexed/carboplatin and bevacizumab +/- atezolizumab in 117 subjects with stage IV non-squamous NSCLC. Randomization will be 2:1 favoring the + atezolizumab arm. Patients are stratified by EGFR mutation status (i.e. EGFR exon 19 or 21 vs. never-smoker wild-type). Never-smoker wild-type is defined as smoking < 100 cigarettes in a lifetime and without any EGFR mutation or ALK or ROS1 rearrangement. Patients with EGFR exon 19 or 21 mutated tumors must have progression of disease or intolerance of treatment with one or more prior TKIs. Primary endpoint is progression-free survival (PFS). Secondary endpoints include overall survival (OS), overall response rate, duration of response, and time to response. Primary objective is to compare PFS between arms. Secondary objectives include a safety analysis in all treated subjects, and comparisons of PFS and OS between arms for the patient subset with EGFR-mutated tumors. Correlative studies include interrogating flow cytometry-based peripheral blood biomarkers, examining the role of desmoplasia in local tumor immunosuppression, and assessing the contribution of estrogen metabolites to tumorigenesis. This study opened in August 2019 with 2 patients enrolled at the time of submission. Twenty U.S. sites through the NCCN are participating. This study was approved and funded by the National Comprehensive Cancer Network (NCCN) Oncology Research Program from general research support provided by Genentech, Inc. Clinical trial information: NCT03786692 .

Phase II trial of trifluridine/tipiracil and irinotecan for the treatment of advanced refractory biliary tract cancer.

TPS594 Background: Effective treatment options are very limited for patients with advanced refractory biliary tract cancer (BTC). Fluoropyrimidine-based chemotherapy regimen such as 5-fluorouracil and irinotecan are frequently utilized for these patients after first-line therapy despite lack of FDA approval. Trifluridine/tipiracil (FTD/TPI) is a novel oral nucleoside with antitumor activity in both fluoropyrimidine sensitive and resistant tumors due to its unique mechanisms of action. Given early toxicity and efficacy data from our previous study on single-agent trifluridine/tipiracil (FTD/TPI) in advanced BTC, the clinical evaluation of its combination with irinotecan represents a rational approach for the treatment of advanced refractory BTC. Methods: This is a single-arm phase II trial with a two-stage design to assess the efficacy of trifluridine/tipiracil (FTD/TPI) and irinotecan in advanced refractory BTC. Key eligibility criteria include histologically confirmed advanced, unresectable BTC who have progressed on at least one line of systemic therapy and have measurable disease per RECIST v1.1. Target accrual is 25. Treatment includes trifluridine/tipiracil (FTD/TPI) 25 mg/m2 on days 1-5 and irinotecan 180 mg/m2 on day 1 in 14-day cycles. Patients will be evaluated for response every 4 cycles and in the absence of disease progression, therapy may be given up to 2 years. The primary end point is the progression-free survival rate at 16 weeks. Secondary endpoints include overall response rate, disease control rate, progression-free survival, overall survival, and incidence of adverse events. Correlative biomarker studies include evaluations of circulating tumor DNA and circulating tumor cells at baseline, after 4 cycles and at progression; and development of patient-derived tumor organoids from pre-treatment biopsies for parallel treatments. This study was approved and funded in part by the National Comprehensive Cancer Network (NCCN) Oncology Research Program from general research support provided by Taiho Oncology, Inc. Clinical trial information: NCT 04072445.

A phase II study of trifluridine/tipiracil, irinotecan, and bevacizumab in pretreated metastatic colorectal cancer (TABAsCO).

TPS275 Background: Colorectal cancer (CRC) is the second leading cause of cancer-related death in US. The majority of US patients (pts) receive first-line therapy (Rx) with FOLFOX [Folinic acid (FA), 5-fluorouracil (5-FU) and oxaliplatin (Ox)] + a biologic, making FOLFIRI [FA+ 5-FU+ irinotecan (Iri)] + bevacizumab (Bev) a common second-line Rx. This regimen has a median progression-free survival (PFS) of approximately 6 months (mo) and overall survival (OS) of 12 mo. Further gains are desperately needed. Trifluridine/tipiracil (FTD/TPI) is an oral combination Rx of a thymidine-based nucleoside analogue, FTD, and a phosphorylase inhibitor, TPI. FTD/TPI has a distinct mechanism of action from 5-FU and in preclinical models can overcome 5-FU resistance via DNA incorporation, base excision repair pathway and glycosylation responses to DNA damage. Further, there is an additive effect in combination with Iri. FTD/TPI was FDA approved for use in refractory metastatic CRC (mCRC) based on phase III RECOURSE trial. Phase I data showed combination of FTD/TPI, Iri and Bev to be safe, and an efficacy signal was seen in dose-expansion cohort (NCT01916447). A 12.5% response rate, 83.4 % disease control rate and PFS of 7.9 mo was achieved. As this study largely assessed refractory pts, one might expect a greater efficacy in Iri naïve pts. To test this hypothesis, we are conducting a multi-center phase II study of FTD/TPI, Iri and Bev as second-line Rx in mCRC pts. Methods: Eligible pts have mCRC and received first-line Ox based Rx. Rx to be given in 28-day cycles: Iri (180 mg/m2) and Bev (5 mg/kg) on D1 & 15, and FTD/TPI (25 mg/m2) twice daily on D2-6 & 16-20. Response assessment via CT/MRI to be done q8 wks (RECIST 1.1). Rx to continue until disease progression or unacceptable toxicity. The primary objective is to estimate PFS. Secondary objectives include ORR, OS, and safety. Final analysis to be done either 12 mo after enrollment of the final pt or once all pts have progression, whichever occurs earlier. A total of 40 pts to be accrued, and enrollment to start in January 2020. This study was approved and funded by the National Comprehensive Cancer Network (NCCN) Oncology Research Program from general research support provided by Taiho Oncology, Inc.

Androgen Receptor Targeting with Enzalutamide for Mantle Cell Lymphoma: Safety and Efficacy

BACKGROUND: Mantle cell lymphoma (MCL) demonstrates a male to female ratio of 4:1. While the pathobiology underlying this gender-distribution imbalance is unknown, anecdotal clinical observations, as well as in vitro evidence of relative androgen receptor (AR) overexpression in MCL cell lines and response to androgen blockade, implicate the AR signaling axis as a potential driver of lymphomagenesis in MCL (Mostaghel et al. Experimental Hematology 2017). Thus, we hypothesized that blocking the AR axis could be a potential treatment strategy for MCL. Here, we report results from our pilot study using the second-generation AR antagonist enzalutamide for treatment of MCL. METHODS: A single arm pilot study was carried out at the Fred Hutchinson Cancer Research Center/University of Washington/Seattle Cancer Care Alliance. Patients ≥ 18 years, with relapsed/refractory or untreated MCL, metabolically active disease > 1.5 cm in long axis, ECOG ≤ 2, ANC ≥ 1000/mm3 & platelet ≥ 50,000/mm3, and acceptable liver and renal function were eligible. Enzalutamide 160 mg was administered daily until disease progression, intolerance, or decision of patient or physician to stop study drug. The primary endpoint was overall response rate (ORR) including complete response (CR) and partial response (PR). The secondary endpoints were time to treatment failure (TTF), progression free survival (PFS), overall survival (OS), adverse events (AEs) as measured by NCI-CTCAE version 4.0, and disease control rate. Correlative studies included impact of AR expression and changes in sex hormone levels on clinical outcomes. RESULTS: Eight patients were enrolled between September 2015 and January 2018. Median age at enrollment was 60 (range 47-79), six were male, median number of prior treatments was 2.5 (range 0-5), three received prior Bruton's tyrosine kinase (BTK) inhibitor therapy, and four had a prior autologous stem cell transplant. Mantle cell lymphoma international prognostic index (MIPI) scores were low (1), intermediate (4) and high (3). The median Ki-67 was 28% (range < 5 to 60). Patients were treated for a median of 3.5 28-day cycles. Reasons for discontinuation included progressive disease (6) and development of rash at day 10 (1). One patient remains on study and without disease progression at 16 months. Best responses in the six response-evaluable patients included three with stable disease (ranging from 5 to 8 months) and three with progressive disease. Low response rates led to closure of the study. Median PFS and OS were 157 days (range 38 to 248) and 1168 days (range 187 to 1289), respectively (figure 1). All patients had tumor AR expression available for review and stained positive (6 variably positive, 1 uniformly positive, and 1 weakly focally positive). No clinical factor, AR staining nor baseline or changes in hormone levels were correlated with response or PFS, though the single patient with ongoing disease control >15 months is the only evaluable female on study who is receiving enzalutamide as first-line therapy. Two grade 3 (abdominal pain, agitation) and one grade 4 (leukocytosis) AEs were reported. CONCLUSIONS: Blocking the AR axis with enzalutamide in the treatment of MCL was well tolerated but did not appear to translate into a meaningful ORR despite supportive preclinical data. This study was approved and funded in part by the National Comprehensive Cancer Network (NCCN) Oncology Research Program from general research support provided by Astellas. Disclosures Smith: Merck Sharp & Dohme Corp: Consultancy, Research Funding; Pharmacyclics: Research Funding; Incyte Corporation: Research Funding; Genentech: Research Funding; Denovo Biopharma: Research Funding; Portola Pharmaceuticals: Research Funding; Ayala (spouse): Research Funding; Bristol-Myers Squibb (spouse): Research Funding; Seattle Genetics: Research Funding; Ignyta (spouse): Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding; Acerta Pharma BV: Research Funding. Till:Mustang Bio: Patents & Royalties, Research Funding. Graf:AstraZeneca: Research Funding; TG Therapeutics: Research Funding; BeiGene: Research Funding. Gopal:Teva, Bristol-Myers Squibb, Merck, Takeda, Seattle Genetics, Pfizer, Janssen, Takeda, and Effector: Research Funding; Seattle Genetics, Pfizer, Janssen, Gilead, Sanofi, Spectrum, Amgen, Aptevo, BRIM bio, Acerta, I-Mab-pharma, Takeda, Compliment, Asana Bio, and Incyte: Honoraria; Seattle Genetics, Pfizer, Janssen, Gilead, Sanofi, Spectrum, Amgen, Aptevo, BRIM bio, Acerta, I-Mab-pharma, Takeda, Compliment, Asana Bio, and Incyte.: Consultancy. OffLabel Disclosure: Enzalutamide is FDA approved for metastatic and non-metastatic castration-resistant prostate cancer.

A Phase 1b Dose Escalation Trial of Carfilzomib in Combination with Bendamustine and Rituximab in Patients with Relapsed or Refractory Non-Hodgkin Lymphoma

Background Despite advances in therapy, relapsed or refractory (RR) non-Hodgkin lymphoma (NHL) remains a major treatment challenge. Preclinical data support the activity of proteasome inhibitors against lymphoma through multiple mechanisms including activation of the endoplasmic reticulum (ER) stress response and reduction in the threshold for apoptosis in response to chemotherapy. Clinically, proteasome inhibiton with bortezomib added to bendamustine yielded promising results in patients (pts) with indolent NHL with limited additional toxicity. Compared to bortezomib, carfilzomib is a more target specific and potent proteasome inhibitor with less neurotoxicity. We embarked on a multicenter, phase 1b dose escalation trial to assess the combination of carfilzomib with bendamustine and rituximab in pts with RR aggressive or indolent NHL. Methods The primary objective of the study is to determine the maximum tolerated dose (MTD) and recommended phase II dose of carfilzomib when combined with bendamustine and rituximab. The secondary objective is to evaluate the preliminary antitumor activity of the combination in select NHL histologies. Correlative studies examine markers of ER stress and apoptosis in response to treatment. Here we report the preliminary results of the dose escalation phase expected to be completed in Fall 2019. We followed a standard 3+3 design with escalation of the carfilzomib dose in 4 dose level cohorts combined with bendamustine dosed at 90 mg/m2 IV on Days 1 and 2 and Rituximab dosed at 375 mg/m2 IV on Day 9 of cycle 1 and Day 1 of subsequent cycles. Initially, carfilzomib was dosed twice a week with dose level 1 at 15 mg/m2 IV on days 1,2,8,9, 15, and 16. Subsequently, we explored weekly dosing schedules with carfilzomib at 36 mg/m2 (dose level 2), 56 mg/m2 (dose level 3), and 70 mg/m2 (dose level 4) on days 9 and 16 with a 20 mg/m2 starting dose on day 2. Dose limiting toxicity (DLT) was defined as Gr4 or specific Gr3 events attributable to the combination. Pts are treated for up to 6 cycles with an interim PET/CT after cycle 3. Results To date, 10 pts have been treated on the dose escalation phase with one patient currently on study treatment. Overall, 5 pts had diffuse large B-cell lymphoma (DLBCL), 3 mantle cell lymphoma (MCL), 1 follicular lymphoma (FL), and 1 marginal zone lymphoma (MZL). Pts received a median of 3 prior lines of therapy. Four pts were treated on dose level 1, 3 on dose level 2, and 3 on dose level 3. Treatment-emergent Grade 2-4 adverse events included thrombocytopenia in 1 pt (Gr 4), neutropenia in 1 pt (Gr 4), febrile neutropenia in 1 pt (Gr 3), culture negative fevers in 1 pt (Gr 3), nausea/vomiting in 2 pts (Gr 2 and 3), other GI toxicities in 1 pt (Gr 2), lower back pain in 1 pt (Gr 2), arthralgias in 1 pt (Gr 2), and cerebrevoascular ischemia in 1 pt (Gr 2). Two pts had treatment related-SAEs (Gr3 culture negative fevers; Gr 3 febrile neutropenia and Gr 3 vomiting) at dose level 2 and 3 respectively. One patient experienced DLT (Gr 3 febrile neutropenia) at dose level 3. There were no treatment related deaths. Of 10 evaluable pts to date, the overall response rate (ORR) is 40% with 3 pts achieving complete remission (one with FL, one with DLBCL and one with MCL) and one pt with MCL achieving a partial remission. The responder with FL had relapsed disease after achieving prior complete remission with rituximab and bendamustine alone. For the 9 pts who completed study treatment, median duration of treatment was 2.4 months, median progression free survival was 1.9 months and median overall survival was 11.6 months. The median duration of response for the 3 responders who completed therapy was 21.8 months. Conclusion Carfilzomib in combination with bendamustine and rituximab is a safe and well-tolerated treatment for pts with RR NHL. The MTD has not been reached and enrollmemt continues, with dose escalation phase anticipated to complete in Fall 2019. Preliminary data indicate that this combination may have efficacy with an acceptable side effect profile in this heavily pre-treated patient population with limited treatment options. Disclosure: This study was approved and funded by the National Comprehensive Cancer Network (NCCN) Oncology Research Program with general research support provided by Amgen. Disclosures Tuscano: Spectrum: Research Funding; Celgene: Honoraria, Research Funding; Novartis: Research Funding; Pharmacyclics: Research Funding; Seattle Genetics: Honoraria; Amgen: Honoraria; Takada: Research Funding; Abbvie: Research Funding; Genentech: Research Funding. Wieduwilt:Celgene: Membership on an entity's Board of Directors or advisory committees; Amgen, Leadiant, Merck, Servier: Research Funding; Daiichi Sankyo: Membership on an entity's Board of Directors or advisory committees; Reata Pharmaceuticals: Equity Ownership. Andreadis:Genentech: Equity Ownership, Other: Spouse is Employee; Novartis: Honoraria, Research Funding; Amgen: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Gilead: Consultancy; Jazz Pharmaceuticals: Consultancy; Bayer: Consultancy.

CLO19-036: Folate Receptor alpha Expression in Metastatic Triple-Negative Breast Cancer (TNBC)

Background: Folate receptor alpha (FRα) is a glycosyl phosphatidylinositol (GPI)-anchored cell surface protein that binds and internalizes folate, which is a cofactor required for DNA/RNA synthesis and cell growth and proliferation. There is a marked up-regulation of FRα in many solid tumors; in contrast, FRα has a minimal expression in adult normal tissue. Mirvetuximab soravtansine is an antibody drug conjugate (ADC) consisting of a maytansinoid, N2'-Deacetyl-N2'-(4-mercapto-4-methyl-1-oxopentyl)-maytansine (DM4), conjugated to an anti-FRα antibody, M9346A. Once bound to the FRα and internalized, the anti-mitotic agents are released and inhibit tubulin polymerization and microtubule assembly, leading to cell death. Here we report the expression of FRα+ on residual tumor samples in metastatic TNBC. Methods: 68 patients (Pts) with stage IV TNBC underwent prescreening to determine if residual tumor tissue expressed FRα. Formalin fixed paraffin embedded (FFPE) samples were sent to Ventana Translational Diagnostics CAP/CLIA Laboratory for analysis using an in-house developed assay, Ventana OptiView DAB Detection kit, and the Ventana BenchMark Ultra automated slide stainer. FRα expression was evaluated by board certified pathologists using a scoring scale 1+ (low), 2+ (medium), and 3+ (high). For the purposes of study entry, FRα expression on cell surface was required to be low, defined as >25% of cells having 1+ expression. Results: 12% (8/68) of evaluated TNBCs had moderate to high rates of FRα expression. The median age of pts screened for FRα was 53 years. Moderate to high FRα expression rates were more common in Black and Asian patients (Table 1). Conclusion: Our prospective study has demonstrated that moderate to high expression of FRα in metastatic TNBC is 12%, which is lower than previously reported. An ongoing phase II study will determine efficacy for mirvetuximab soravtansine in advanced TNBC. Acknowledgement: This study was approved and funded in part by the NCCN Oncology Research Program from general research support provided by ImmunoGen, Inc.

Final Safety Results of a Phase 1 Clinical Trial of Afatinib in Combination With Docetaxel and Postoperative Radiation Therapy for High-Risk Squamous Cell Carcinoma of the Head and Neck

Afatinib is an oral, irreversible EGFR/ErbB family receptor inhibitor with clinical activity in recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN). Previously, EGFR-inhibition with cetuximab in combination with docetaxel and postoperative radiation therapy (PORT) was shown in RTOG 0234 to be well tolerated with higher rates of disease-free survival compared to historical results with cisplatin and PORT. We therefore aimed to assess the tolerability of afatinib in combination with docetaxel and PORT in a cohort of patients with high-risk pathologic features after definitive surgery. This was an open label, non-randomized, phase 1, 3+3 dose-escalation study. Eligible patients had resected stage III-IV SCCHN of the oral cavity, oropharynx, larynx, or hypopharynx with high-risk features of either positive margins (tumor at ink), extracapsular nodal extension, N3 nodal stage, or T4 tumor with bone invasion. Patients received afatinib at an initial dose of 30 mg daily for 1 week prior to PORT and then daily during PORT. Docetaxel 15 mg/m2 was given weekly during PORT. The maximum PORT dose was 66 Gy, 2 Gy/fraction. Toxicities were scored using CTCAE v4.0. Eleven patients (6 women) were enrolled with a median age of 61 years (44-66 yrs), AJCC stage of III (n = 2) or IV (n = 9) and oral cavity (n = 10) and larynx (n = 1) primary tumors. Seven patients received the starting 30 mg dose including 2 patients that withdrew consent after starting treatment, and 2 that experienced hypersensitivity reactions due to docetaxel and were taken off-study. There were 2 dose-limiting toxicity (DLT) events of grade 3 diarrhea and mucositis at the initial 30 mg dose. Four patients receive the de-escalated 20 mg dose. There were 2 DLT’s (grade 3 mucositis). There were no grade 4 or 5 events. The most common toxicity was diarrhea occurring in 9 of 11 patients (grade 3 in 2 patients), and mucositis occurring in 8 of 11 patients (grade 3 in 4 patients). The combination of afatinib with both PORT and docetaxel for mucosal SCCHN was shown to be difficult to tolerate with a high rate of grade 3 toxicity, mostly mucositis, in this cohort of patients requiring postoperative chemoradiation to the oral cavity. Afatinib may be better tolerated with PORT alone and this is currently being tested in a prospective phase 1 trial in an intermediate-risk cohort. This study was approved and funded by the National Comprehensive Cancer Network (NCCN) Oncology Research Program from general research support provided by Boehringer Ingelheim Pharmaceuticals, Inc.

Abstract CT142: A single arm, single stage phase II trial of trametinib (GSK1120212) and GSK2141795 in persistent or recurrent cervical cancer

Abstract Introduction: In the US, invasive cervical cancer (CC) will affect 12,710 women/year with approximately 4,290 deaths. While screening has reduced cases in the developed world, CC remains a leading cause of cancer death globally with 275,000 women dying of CC/year. Though treatment options for recurrent/metastatic (met) CC have improved by adding bevacizumab to platinum-based chemotherapy, patients with met CC will eventually have cancer progression and therapies are few. PIK3CA and KRAS mutations are found in both adenocarcinomas and squamous cell cancers of the cervix. Thus, therapies targeting the PI3K/AKT and RAS-ERK pathways have rationale for treating metastatic CC; pre-clinical studies support dual PI3K inhibition and MEK inhibition given pathway redundancy and negative feedback loops. This phase II study tested a MEK and an AKT inhibitor combination. Study Design: Trametinib (GSK1120212) is a reversible/selective inhibitor of MEK1 and MEK2. GSK2141795 is an AKT1-3 inhibitor. Objectives included RECIST 1.1 activity of trametinib and GSK2141795 in pts with recurrent CC (primary objective). Other objectives included toxicities and duration of response. Translational objectives included description of mutation and co-mutation rates of PI3K and RAS-ERK signaling pathway genes using hybrid-capture and massively parallel sequencing assay at Dana-Farber Cancer Institute. Eligibility: recurrent or met CC (any histology), receipt of 1 prior chemotherapy, and up to 1 additional regimen, no prior use of PI3K or RAS-ERK pathway inhibitor, ECOG PS 0-2, normal organ function, and availability of FFPE tissue. The treatment regimen was: trametinib 1.5 mg and GSK2141795 50 mg, both given PO daily; cycle length: 28 days. RR was assessed every 2 cycles. This study (NCT01958112) was approved and funded in part by the National Comprehensive Cancer Network (NCCN) Oncology Research Program from general research support provided by Novartis Pharmaceuticals Corporation. Results: 16 pts were enrolled and 14 received study drug. The study was closed prior to accrual completion because of Novartis’ decision to stop 1) developing this combination because of lack of activity across several cancer types and observed toxicities and 2) manufacturing GSK2141795. Of the 14 patients who received study drug, one patient had a partial response lasting 108 days, 8 had stable disease, 3 had progression at their first evaluation and 2 pts were unevaluable. Related serious adverse events included a thromboembolic event (grade 3), acneiform rash (grade 3), retinal detachment (grade 2), and hypophosphatemia (grade 3). There were no grade 4 or 5 drug related toxicities. Conclusions: This combination of an AKT and MEK inhibitor was tolerated by patients. Anti-cancer activity was minimal in the enrolled patients, but the study was terminated early due to discontinuation of the AKT inhibitor GSK2141795. Citation Format: Ursula A. Matulonis, Alexi Wright, Susana Campos, Panagiotis Konstantinopoulos, Ariana Peralta, Kimberley MacNeill, Stephanie Morrissey, Christin Whalen, Joyce Liu. A single arm, single stage phase II trial of trametinib (GSK1120212) and GSK2141795 in persistent or recurrent cervical cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr CT142. doi:10.1158/1538-7445.AM2017-CT142

A phase I/II study of nintedanib and capecitabine in refractory metastatic colorectal cancer.

759 Background: Refractory metastatic colorectal cancer patients (mCRC) have a poor prognosis with median survival of 4-6 months. Nintedanib is a TKI which inhibits VEGFR, PDGFR, and FGFR with preclinical efficacy in bevacizumab resistant CRC. This phase I/II study sought to evaluate the recommended phase II dose (RP2D) and efficacy of nintedanib and capecitabine in refractory mCRC patients. Methods: Key eligibility criteria included histologically proven mCRC, ECOG PS of 0 or 1, progression/intolerance to a fluoropyrimidine, oxaliplatin, irinotecan, and anti-EGFR therapy for RAS wt patients. Prior regorafenib, uncontrolled hypertension ( ≥ 160/90), recent clinically significant thrombosis/hemorrhage, or prior intolerance to capecitabine were exclusionary. Doses were escalated across 2 planned dose levels (DL) in a standard 3+3 design, with escalating doses of capecitabine. DLT observation window was the first 3 weeks after dosing. The primary endpoint was establishment of the RP2D. Results: 10 patients were enrolled across 2 dose levels. 1 patient withdrew consent and was replaced. 5 (50%) were PS 0. No grade 4 or 5 AEs were observed. No DLTs were observed. 2/10 (20%) of patients experienced a grade 3 AE, including hyperbilirubinemia (10%), AST elevation (10%), diarrhea (10%), dehydration (10%), and weakness (10%). The most common treatment-related AEs included palmar-plantar eythrodysesthesia (PPE) (50%), diarrhea (40%), stomatitis (30%), nausea (20%), vomiting (20%), and fatigue (20%). The RP2D was determined to be capecitabine 1000 mg/m2 divided bid and nintedanib 200 mg bid. PK data will be presented. Conclusions: Treatment was well tolerated. Most of the observed AEs were grade 1 or 2, without a marked difference between DLs. PPE was readily managed with dose adjustments. The phase II study is ongoing at the RP2D. This study was approved and funded by the National Comprehensive Cancer Network (NCCN) Oncology Research Program from general research support provided by Boehringer Ingelheim Pharmaceuticals, Inc. Clinical trial information: NCT02393755.

How Rigged Are Stock Markets? Evidence from Microsecond Timestamps

We use new timestamp data from the two Securities Information Processors (SIPs) to examine SIP reporting latencies for quote and trade reports. Reporting latencies average 1.13 milliseconds for quotes and 22.84 milliseconds for trades. Despite these latencies, liquidity-taking orders gain on average $0.0002 per share when priced at the SIP-reported national best bid or offer (NBBO) rather than the NBBO calculated using exchanges’ direct data feeds. Trading surrounding SIP-priced trades shows little evidence that fast traders initiate these liquidity-taking orders to pick-off stale quotes. These findings contradict claims that fast traders systematically exploit traders who transact at the SIP NBBO. Statement of Financial Disclosure and Conflict of Interest: Neither author has any financial interest or affiliation (including research funding) with any commercial organization that has a financial interest in the findings of this paper. The authors are grateful to the University of California, Berkeley School of Law, for providing general faculty research support.

Phase II trial of temsirolimus (TEM) plus sorafenib (SOR) in hepatocellular carcinoma (HCC).

TPS501 Background: The multikinase inhibitor SOR prolongs survival in patients with HCC not amenable to curative therapies. In HCC preclinical models, the combination of SOR with an inhibitor of the mammalian target of rapamycin (mTOR) pathway is synergistic, though single-agent mTOR inhibition did not improve survival in HCC patients after failure of SOR in a phase III trial. We previously completed a phase I study of the mTOR inhibitor TEM combined with SOR in 25 HCC patients which identified the maximum tolerated dose as TEM 10 mg IV weekly and SOR 200 mg PO BID. This two-center, phase II study was developed to examine the efficacy of the combination and to explore candidate biomarkers. The study was approved and funded by the National Comprehensive Cancer Network (NCCN) Oncology Research Program from general research support, with activation October 2012. Methods: The study is registered on ClinicalTrials.gov (NCT01687673). Design: Single-arm, one stage phase II trial. Primary endpoint: Time to progression (TTP) by RECIST 1.1. Other endpoints: Progression-free survival, response rate, overall survival, proportion with alpha fetoprotein decline ≥ 50%, toxicity, hepatitis B virus reactivation rate, and exploratory biomarkers including mTOR pathway protein expression in tumor, circulating tumor cells, and blood and tumor micro-RNA profiles. Sample size: 25 evaluable patients are required to detect a difference between the null hypothesis of median TTP < 3 months versus alternate hypothesis of median TTP ≥ 6 months (a clinically-meaningful outcome in advanced HCC), with 1-sided significance level of 10% and power 88% under the exact test. Main eligibility criteria: HCC not amenable to curative therapies, histologically-confirmed, ≥ 1 untreated, radiographically-measurable site of disease. No prior systemic therapy. ECOG ≤ 1. Child-Pugh score ≤ 7 with bilirubin ≤ 2 mg/dL. Treatment and procedures: TEM 10 mg IVweekly plus SOR 200 mg PO BID in 28-day cycles, with collection of archival tumor samples and blood samples at baseline, on treatment, and at progression. Accrual:Sixteen of 25 planned evaluable patients have enrolled. An interim analysis for safety after 30% enrollment met pre-specified target to continue. Clinical trial information: NCT01687673.

A phase II trial of pralatrexate (P) plus oxaliplatin (O) in advanced esophagogastric cancer (aEGC).

152 Background: Advanced EGC is an aggressive cancer with limited treatment (Rx) options. In preclinical studies P has demonstrated increased cellular uptake and polyglutamylation relative to other anti-folates plus is synergistic with platinum. We evaluated combination P plus O in aEGC and examined pharmacogenomics and tumor microRNA profiling to identify predictive signatures for response and toxicity. Here we report on clinical outcome data for the entire cohort. Methods: Objective response (OR) following P+O was assessed in an exact 2-stage design, including early stopping for futility and a safety lead-in cohort of 6 patients (pts) with provisions for dose de-escalation for dose limiting toxicity (DLT). Eligibility included metastatic/unresectable, therapy-naïve EGC pts with adequate organ and functional status and < G2 neuropathy. Rx consisted of biweekly O (85mg/m2) plus P (Dose level [D] 1, 120mg/m2; dose level -1 [D-1] 100 mg/m2). O was stopped after 12 cycles. Secondary endpoints were toxicity, survival and molecular correlates. Results: The study met its interim efficacy threshold and proceeded to full accrual. 35 pts, median age 67 yrs (39-83), 32 males, mostly adenocarcinoma (29) were accrued. 2/4 pts at D1 developed DLTs (1 G3 diarrhea, 1 G3 mucositis). All remaining pts were treated at D-1, which had no DLTs in the safety cohort. G4 toxicity included neutropenia (2) and myocardial infarction (1). The most common G3 events were mucositis (5), dehydration and neutropenia (4 each), anorexia, neuropathy, fatigue and nausea/vomiting (all 3 each). Including G1 and 2 events, myelosuppression, mucositis and neuropathy were the most common toxicities. Median # of P cycles administered at D-1 was 8 (1, 17). In an intent to treat analysis, confirmed OR was 23% (8/35) and 16 pts (46%) had stable disease. 3 pts were non-evaluable for response. Conclusions: Combination O and P administered biweekly at 85mg/m2 and 100 mg/m2 respectively is safe, well-tolerated and has modest efficacy in aEGC. Survival analysis results will be available for the meeting. This study was approved and funded by the NCCN from general research support provided by Allos Therapeutics, a subsidiary of Spectrum Pharmaceuticals, Inc. Clinical trial information: NCT01178944.

A phase I multicenter study of the combination of temozolomide and pazopanib in advanced pancreatic neuroendocrine tumors (PNET).

TPS492 Background: Everolimus and sunitinib targeted therapy have proven efficacy in advanced PNET, with ORR 5-9% and PFS HR < 0.5 compared to placebo.Additionally, a single arm phase II study showed promising activity with temozolomide and capecitabine combination with an ORR of 70%. Rationale:PNETs are distinguished by their vascularlity and up-regulation of VEGF factors. In the preclinical setting, the combination of temozolomide and sunitinib appears to act synergistically by altering the tumor microenvironment enhancing activity of temozolomide. Pazopanib has shown activity in a single arm phase II study in advanced PNETs with a 6-month PFS rate of 80% and ORR of 17%. There is sufficient preclinical and clinical evidence suggesting that the combination of an anti-angiogenic agent with temozolomide is more efficacious, hence, our rationale for the current study. Methods: Objectives: (1) Determine the MTD and toxicity profile of temozolomide + pazopanib. (2) Describe the PK profile of this combination. (3) Observe the ORR. Trial Design:Open label Phase I study to determine the MTD and safety profile employing a 3+3 dose-escalation model of the combination of temozolomide and pazopanib in patients with advanced PNET who have received between 1-4 prior therapies. Cohort 1: temozolomide at 150 mg/m2 on Days 1-7 and 15-21, and pazopanib 400 mg orally once daily continuously throughout cycle of 28 days. Once MTD is determined, PK sampling will be performed in 6 additional patients enrolled at the MTD. To date, eleven patients have been enrolled in cohort 1 and cohort -1. Cohort -1 is currently accruing at the reduced dose level of temozolomide 100mg/m2 and pazopanib 400mg daily for the duration of the cycle. The trial is funded to proceed to a single arm phase II with exploratory end points: (1) Correlation of MGMT expression by IHC to ORR and PFS (2) tumor blood flow (perfusion CT imaging) relationship with ORR. (This study was approved and funded by the National Comprehensive Cancer Network (NCCN) Oncology Research Program from general research support provided by GlaxoSmithKline.) Clinical Trial information: NCT01465659. Clinical trial information: NCT01465659.

Abstract B279: A phase I study determining the safety and tolerability of combination therapy with Pazopanib (P), a VEGFR/PDGFR/Raf inhibitor, and GSK1120212 (Trametinib: T), a MEK inhibitor, in advanced solid tumors with expansion cohorts in advanced differentiated thyroid cancer (DTC), cholangiocarcinoma (ChCA), and soft tissue sarcoma (STS).

Abstract Background: P is a small molecule tyrosine kinase inhibitor that selectively inhibits VEGFR1-3, PDGFR-α, PDGFR-β, c-kit, and FGFR 1-3 and is approved for renal cancer and STS. T is a potent, highly selective, allosteric inhibitor of MEK1/2 approved for BRAF-mutated advanced melanoma. Increased signaling of growth factor receptor tyrosine kinases have been shown to be important to cell survival in multiple tumor types, and their inhibition has been effective therapeutically in STS, DTC, and ChCa. In addition, increased RAS/RAF/MEK/ERK signaling plays a critical role in the development of many different types of cancers, including ChCA and DTC. We hypothesized that combination therapy with P and T would be tolerable and effective for this range of tumor types. Methods: We designed a phase I, open label, dose escalation trial with P+T open to patients with advanced solid tumors. The study was a standard 3+3 design with an expansion cohort of 25 pts each for advanced DTC, STS, and ChCA for correlative endpoints and PK studies. Pts were treated with T held constant at 1 mg QD and P at 400 mg QD (DL1), 600 mg QD (DL2)and 800 mg QD (DL3); T was then escalated to 1.5 mg QD (DL4) and 2 mg QD (DL5). Eligibility included adequate end organ function, PS 0-1, and PD within 6 months in the expansion cohort of DTC. The primary objective was to determine the safety and tolerability of P+T and to find the MTD. Secondary objectives include assessing preliminary efficacy and exploration of PK/PD endpoints with tumor biopsies. Results: We report the results of the dose escalation component of the study. 26 pts were accrued to 5 dose levels and treated for a median of 3 cycles (range <1-9.5). MTD was defined as DL5. There was one DLT on DL1 with gr3 fatigue and muscle weakness. There were no gr4 AEs at least possibly attributable to study therapy. Grade 3 AES attributable to study therapy were diarrhea and elevated transaminases (15%), HTN (12%), fatigue (8%), and proteinuria, muscle weakness, rash, or abdominal cramping (4%). Common gr1-2 AES included diarrhea (73%), nausea and rash (54%), fatigue (46%), HTN (38%), anorexia or vomiting (27%). 7 pts discontinued study tx due to AEs. 9 pts had dose reductions at a median of cycle 2 (range 1-9) due to HTN (3), diarrhea (3), fatigue (2), elevated transaminases or glaucoma exacerbation (1). Out of 25 evaluable pts, 3 had a partial response (ChCA, ovarian, DTC) and were treated 4-9.5 cycles and 16 had stable disease at least through first reassessment. Conclusions: P+T is a tolerable combination with some preliminary signs of efficacy. Accrual to expansion cohorts in DTC, STS, and ChCA for further exploration of efficacy and correlative endpoints is ongoing. This study was approved and funded by the National Comprehensive Cancer Network (NCCN) from general research support provided by GlaxoSmithKline. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):B279. Citation Format: Nilofer Azad, Douglas Ball, Steven Sherman, Michelle Rudek, Gerald Falchook, Barry Nelkin, Filip Janku, Nicholas Papadopoulos, Ashley O'Conner, Shabina Ahmed, Breelyn Wilky, Susan Markus, Jing Gong, David Cosgrove, Marianna Zahurak, Ralph Zinner, Razelle Kurzrock. A phase I study determining the safety and tolerability of combination therapy with Pazopanib (P), a VEGFR/PDGFR/Raf inhibitor, and GSK1120212 (Trametinib: T), a MEK inhibitor, in advanced solid tumors with expansion cohorts in advanced differentiated thyroid cancer (DTC), cholangiocarcinoma (ChCA), and soft tissue sarcoma (STS). [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr B279.

Phase I study of weekly albumin-bound paclitaxel (ab-P) plus weekly cetuximab (Cet) plus intensity-modulated radiation therapy (IMRT) in patients with stage III/IVb head and neck squamous cell carcinoma (HNSCC).

6034 Background: There is a clinical need to improve the efficacy of standard Cet + concurrent RT for pts with stage III/IVB HNSCC. Taxanes have potent activity against HNSCC, and ab-P may offer therapeutic advantages in comparison with other drugs of this class. Methods: This was a single institution phase I study with a modified 3 + 3 design. 4 dose levels (DLs) of weekly ab-P were explored (30, 45, 60, and 80 mg/m2) during IMRT. Standard Cet (450 mg/m2 loading dose followed by 250 mg/m2 weekly) concurrent with IMRT (total dose, 70 Gy) was prescribed for all pts. The maximum-tolerated dose (MTD) would be exceeded if >2/6 pts experienced DLTs at a given dose level. NCI CTCAE v.3 was used, and DLT monitoring extended until 2 wks after IMRT. Results: 25 eligible pts (20M, 5F) enrolled, with median age 58 years (range, 46-84) and median KPS 90 (range 80-100). Primary tumor sites were oropharynx, 20 (10 HPV pos, 5 HPV neg, 5 not done); neck node with unknown primary, 2; and larynx, oral cavity, and maxillary sinus, 1 each. Two pts never received ab-P and were deemed inevaluable. At DL 1 (ab-P, 30 mg/m2), there was one DLT (g.4 pneumonia) among 6 pts. At DL2 (ab-P, 45 mg/m2), there were 2 DLTs (g.4 cerebrovascular accident; g.3 decrease in L. ventricle ejection fraction/CHF exacerbation) among 6 pts. At DL3 (ab-P, 60 mg/m2), there was 1 DLT (g.3 supraventricular tachycardia) among 6 pts. MTD was exceeded at DL4 (ab-P, 80 mg/m2) with 3 DLTS (g.3 neuropathy, g.3 dehydration, g.3 anemia) among 5 evaluable pts. For the entire study population, most common ≥ g3 AEs were: lymphopenia 100%, functional mucositis, 56%, and pain in throat/oral cavity, 52%. There were no treatment-related deaths. Among 23 evaluable pts at a median follow up of 29 months, 2y PFS rate is 64% (95% CI: 41-80%) and 2y OS rate is 90% (95% CI: 66-97). Conclusions: The recommended phase II dose is ab-P 60 mg/m2 weekly when given concurrently with IMRT and standard weekly Cet. This regimen merits further study as an alternative to IMRT + Cet alone for pts who require a non-platinum regimen. This study was approved and funded by the NCCN from general research support provided by Celgene, Inc. Clinical trial information: NCT00736619.