BACKGROUND: Although immune checkpoint inhibitor-based therapy has improved the outcomes of many patients with metastatic renal cell carcinoma (mRCC), most eventually develop disease progression. Newer agents that modulate immune response can possibly potentiate checkpoint inhibitor therapy. The ITK/ETK/BTK inhibitor ibrutinib has been reported to inhibit myeloid derived suppressor cells in preclinical models and to potentiate immunotherapy. We conducted an investigator-initiated trial of ibrutinib plus the PD1 inhibitor nivolumab in mRCC patients, particularly in those previously exposed to immune checkpoint inhibitors. METHODS: Eligible patients had mRCC of any histologic subtype, completed at least one line of prior systemic therapy which could have included prior immunotherapy, and had acceptable end-organ function with ECOG performance status of 0–2. Treatment consisted of nivolumab 240 mg intravenously every 2 weeks plus ibrutinib 560 mg (dose level 0) or 420 mg (dose level -1) orally once daily. Cycle length was 28 days. Dose limiting toxicity (DLT) was defined as any Grade 3 or higher adverse event (AE) attributable to therapy. After identification of the recommended phase 2 dose (RP2D), up to 19 patients were enrolled to an expansion cohort to further evaluate toxicities and any early evidence of efficacy. The primary endpoints of the trial were establishment of RP2D and progression-free survival (PFS). RESULTS: A total of 31 patients were enrolled, 6 to dose level 0, 7 (of which one was not evaluable for DLT) in dose level -1, and 18 in the expansion cohort. Median age was 60 years (range, 36–90), most had clear cell histology (n = 27; 87%), and most had prior immune checkpoint inhibitor therapy (n = 28; 90%). Three patients experienced one DLT each, all in dose level 0 (all Grade 3), namely elevated lipase, hypoalbuminemia, and nausea. No DLTs were seen in dose level –1 which was declared the RP2D. The most common Grade 3 or higher AEs include anemia (n = 5), lymphocyte count decrease (4), nausea (2), and hypotension (2). Of 28 patients evaluable for response, one patient (3.6%) had a complete response, 2 (7.1%) had a partial response, and 11 (39.2%) had stable disease, for an objective response rate of 10.7%(95%CI: 3.7%–27.2%) and a disease control rate of 50%(95%CI: 32.6%–67.4%). All responders had received prior immune checkpoint inhibitor therapy. Median PFS was 2.5 months (95%CI, 1.9 –4.8) while median OS was 9.1 months (95%CI, 6.6 –19.0). CONCLUSIONS: Ibrutinib at a dose of 420 mg orally once daily in combination with nivolumab 240 mg IV every 2 weeks is feasible and tolerable in mRCC patients. No unique immune-related AEs were observed. Anti-tumor activity was seen in patients previously exposed to PD-1 targeted therapy.

Niclosamide has preclinical activity against a wide range of cancers. In prostate cancer, it inhibits androgen receptor variant 7 and synergizes with abiraterone. The approved niclosamide formulation has poor oral bioavailability. The primary objective of this phase Ib trial was to identify a maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of a novel reformulated orally-bioavailable niclosamide/PDMX1001 in combination with abiraterone and prednisone in men with castration-resistant prostate cancer (CRPC). Eligible patients had progressing CRPC, adequate end-organ function, and no prior treatment with abiraterone or ketoconazole. Patients were treated with escalating doses of niclosamide/PDMX1001 and standard doses of abiraterone and prednisone. Peak and trough niclosamide plasma levels were measured. Common Terminology Criteria for Adverse Events (CTCAE) v4.0 and Prostate Cancer Working Group 2 criteria were used to evaluate toxicities and responses. Nine patients with metastatic CRPC were accrued, with no dose-limiting toxicities observed at all dose levels. The recommended Phase II dose of niclosamide/PDMX1001 was 1200 mg orally (PO) three times daily plus abiraterone 1000 mg PO once daily and prednisone 5 mg PO twice daily. Trough and peak niclosamide concentrations exceeded the therapeutic threshold of > 0.2 µM. The combination was well tolerated with most frequent adverse effects of diarrhea. Five out of eight evaluable patients achieved a PSA response; two achieved undetectable PSA and radiographic response. A novel niclosamide/PDMX1001 reformulation achieved targeted plasma levels when combined with abiraterone and prednisone, and was well tolerated. Further study of niclosamide/PDMX1001 with this combination is warranted.

5054 Background: Preclinical models have shown that autophagy is a cell survival mechanism to overcome treatment-induced stress and facilitate progression and resistance in CRPC. Metformin (met) demonstrates autophagy inhibition and resensitizes CRPC tumors to enzalutamide (enza) as a combination in in vitro models. A Phase Ib/II trial was conducted to evaluate the combination. Methods: Eligible patients (pts) had established CRPC, ECOG 0-2, adequate hematologic and organ function, and ≤ 2 prior treatments for CRPC. Major exclusion criteria included prior enza or met treatment, presence of brain metastases, history of DM2 or seizures. An initial cohort of 3 pts were treated with enza 160 mg PO daily and met 500 mg PO bid (DL1), with met dose escalated to 1000 mg PO bid (DL2) in subsequent 3 pts if dose-limiting toxicity (DLT) was observed in ≤1 pt in DL 1, and cycles of 28 days. Once primary objective of maximum tolerated dose (MTD) was established, additional pts were enrolled at MTD for a total of 24 evaluable pts. Secondary objectives of the study included PSA response and safety. Results: From 8/24/16-12/31/18, a total of 3 pts were enrolled to DL1, with no DLTs observed in that cohort, with an additional 21 enrolled to DL2; 12 remain on trial. Median age was 71, with 8/24 (33%) and 3/24 (12.5%) with prior docetaxel and abiraterone treatment, respectively. One DLT due to Grade 3 abdominal pain was observed at DL2 prior to establishing MTD. Grade 3 AEs observed in 1/24 (4%) of pts were diarrhea, fatigue, hypertension, lower GI bleed, myalgia; 2/24 (8%) had abdominal pain. One pt had Grade 4 hallucinations. Among pts who discontinued, 8 were discontinued for progression, 3 withdrew consent, and 1 experienced an SAE (seizure). Pts received median of 11 cycles (1-31) of treatment. PSA response ≥ 50% was observed in 19/24 (79%) pts. Conclusions: The combination of enzalutamide 160 mg PO daily and metformin 1000 mg PO bid is well-tolerated, and clinically active. Clinical trial information: NCT02339168.

600 Background: Immune checkpoint inhibitor therapy (CPI) has transformed the management of pts with mRCC, with a fraction experiencing durable tumor responses. However, most eventually develop disease progression after either an initial response to CPI or while on CPI. Newer agents that modulate immune response can possibly potentiate CPI therapy. The ITK/ETK/BTK inhibitor ibrutinib has been reported to inhibit myeloid derived suppressor cells in preclinical models and to potentiate CPI. We conducted an investigator-initiated pilot trial of ibrutinib plus the PD1 inhibitor nivolumab in mRCC pts, particularly in those previously exposed to CPI. Here we report initial safety and efficacy results from the dose-finding cohort. Methods: Pts with mRCC of any histologic subtype and who have completed at least one line of prior systemic therapy including prior CPI were eligible. Pts must have acceptable end-organ function and Zubrod PS of 0-2. Treatment consisted of nivolumab 240 mg IV q2 weeks plus ibrutinib 560 mg (dose level 0) or 420 mg (dose level -1) orally once daily. Cycle length was 28 days. Dose limiting toxicity (DLT) was defined as any Grade(Gr) 3+ adverse event (AE) attributable to therapy. Results: As of 9/18/17, 12 pts have been enrolled, six to each dose level. Patient characteristics: Mean age = 62 years (range 44-78); Male sex = 7 (58%); White race = 9 (75%); Prior CPI = 11 (92%). Three pts experienced one DLT each in dose level 0 (all Gr3): elevated lipase, hypoalbuminemia, & nausea. Only 1 DLT has been seen thus far in dose level -1 (Gr3 infection). The most common Gr3+ AEs include anemia (n = 5), ALT elevation (4), AST elevation (3), nausea (3), hypoalbuminemia (2), esophagitis, infection, lipase increase, and vomiting (1 each). Two pts with prior CPI had partial tumor response (1 confirmed, 1 unconfirmed). Conclusions: Ibrutinib at a dose of 420mg orally once daily in combination with nivolumab 240mg IV q 2 weeks appears feasible and tolerable in mRCC patients. No unique immune-related AEs have been seen thus far. Anti-tumor activity was seen in 2 pts previously exposed to PD1-targeted therapy. Further evaluation of this combination is warranted. (Supported by Pharmacyclics and UCDCCC). Clinical trial information: NCT02899078.

525 Background: We previously reported tolerability of pembrolizumab plus either docetaxel or gemcitabine in platinum-treated metastatic urothelial cancer patients (pts), given the hypothesis that chemotherapy might enhance tumoral neoantigen expression and modulate immunogenicity of tumor cells, potentially enhancing the response to anti-PD-1 therapy. Herein we report further results from an expansion cohort. Methods: Eligible pts had Zubrod PS 0-1, adequate end-organ function, and up to 2 prior lines of chemotherapy (at least one platinum based). Patients were treated with pembrolizumab 200 mg IV on D1 q3weeks plus either docetaxel 75 mg/m2 IV on D1 (Arm A) or gemcitabine 1000 mg/m2 IV on D1 & D8 (Arm B). Primary endpoint was safety; secondary endpoints were overall response rate (RR) and progression free-survival (PFS). Results: A total of 20 pts have enrolled, 9 in Arm A, 11 in Arm B. Mean age was 66 (range 31-84). Most common AEs ≥ Grade 3 were hyponatremia (8/20), anemia (5/20), fatigue (5/20), neutropenia (4/20), leukopenia (4/20) acute kidney injury (3/20), hypophosphatemia (3/20). There were no treatment-related deaths; 13 died from tumor progression (PD). In total, 1 pt had complete response (CR), 5 pts had partial responses (PR), 3 pts had minor responses (MR), 4 had stable disease (SD), and 7 progressed (PD); overall RR was 45% and Disease Control Rate (DCR) was 65%. Arm A had overall RR of 44%, DCR 56%. Arm B had overall RR of 45%, DCR 73%. Median PFS (overall, Arm A & Arm B) was 7, 13.3, and 5.9 months. Conclusions: The combination of pembrolizumab with either docetaxel or gemcitabine is tolerated with expected adverse effects, with evidence of efficacy. Expanded cohorts continue to enroll. Clinical trial information: NCT02437370.

TPS394 Background: Enzalutamide (Enza) and abiraterone (Abi) are commonly used to treat CRPC. Resistance is the most common cause of treatment failure. We discovered that a critical steroidogenic enzyme AKR1C3 was significantly elevated and contributed to intratumoral androgen synthesis in Enza-resistant prostate cancer cells and tumors. Overexpression of AKR1C3 induced androgen receptor variant 7 (AR-V7) expression, while inhibition of AKR1C3 downregulated AR-V7. We then discovered that indomethacin (Indo) inhibited AKR1C3 activation and sensitized resistant CRPC cells to Enza and Abi. One patient accidentally took Indo and achieved biochemical as well as radiological response of his prostate cancer. These findings prompted us to design a clinical trial to test the combination of Indo with Enza for the treatment of CRPC and to study the underlying mechanisms of action and resistance. Methods: This investigator-initiated single-arm Phase Ib/II trial enrolls patients with progressive CRPC after Abi, adequate vital organ function, ECOG performance status 0-2, and serum testosterone < 50 ng/dl. Major exclusion criteria include prior Enza treatment, brain metastasis and history of seizure. In the Phase Ib cohort, patients receive Enza 160 mg po qd and Indo 50 mg po tid to determine toxicity. The Phase II expansion will enroll 26 patients with 21 evaluable patients. This sample size provides 90% power to detect, at the 0.05 level (1-sided), the difference between a PSA response rate of 50% expected with the study treatment and a historical control of 20% with Enza alone. Co-primary endpoints are safety and PSA response of ≥50% decrease. Secondary endpoints include overall response rate as determined by the Prostate Cancer Working Group 2 criteria (PCWG2), progression-free survival and overall survival. Molecular correlative studies are exploratory endpoints. Serum and intratumoral androgen levels, full-length AR, AR-V7 and AKR1C3 will be measured to assess the effect of the combination therapy. To date, 4 patients have been enrolled to the trial (clinicaltrials.gov Identifier No: NCT02935205; this trial is funded by DoD Prostate Cancer Research Program IMPACT award). Clinical trial information: NCT02935205.

281 Background: Preclinical models have shown that autophagy is a resistance mechanism of enzalutamide (enza), a small molecule suppressing the androgen pathway approved for treatment of CRPC. Metformin, an autophagy inhibitor, enhances preclinical therapeutic responses when combined with Enza, thus prompting a Phase I clinical trial evaluating the combination. We present results to date. Methods: Eligible patients (pts) had established CRPC, ECOG 0-2, adequate hematologic and organ function, and ≤ 2 prior treatments for CRPC. Major exclusion criteria included prior enza or metformin treatment, presence of brain metastases, history of DM2 or seizures. An initial cohort of 3 pts were treated with enza 160 mg PO qdaily and metformin 500 mg PO bid (DL1), with metformin dose escalated to 1000 mg PO bid (DL2) in subsequent 3 pts if dose-limiting toxicity (DLT) was observed in ≤1 pt in DL1. Primary objective was to establish the maximum tolerated dose (MTD), with secondary objectives of evaluating PSA response of ≥ 50%, PSA progression, and safety. Results: A total of 12 pts have been enrolled to date; mean age was 77 (range 60-95). No DLTs were observed at DL1; 1 DLT due to Grade 3 abdominal pain was observed at DL2, with an additional 6 pts subsequently enrolled in expansion. The only adverse effects ≥ Grade 3 were: syncope (1/12), hallucinations (1/12), and abdominal pain (2/12). One pt withdrew consent, 2 required dose reduction of metformin, and 1 died of progressive disease. Of 10 evaluable pts, PSA response was seen in 8 pts. Conclusions: The combination of enza 160 mg qdaily and metformin 1000 mg PO bid is safe and well-tolerated. Efficacy results to date support continued study of the combination in pts with CRPC. Clinical trial information: NCT02339168.

Although immune checkpoint inhibitor therapy has led to modest response rates in patients with advanced urothelial cancer, the combination of chemotherapy with immune checkpoint inhibition has not been previously clinically studied. In this phase I study, we found that the combination of pembrolizumab with either docetaxel or gemcitabine in patients with platinum-refractory advanced urothelial cancer was feasible and active. Introduction: Cytotoxic chemotherapy might prime urothelial cancer (UC) to checkpoint inhibition, prompting a trial of chemotherapy with the programmed death receptor-1 inhibitor pembrolizumab. Patients and Methods: Patients with advanced, platinum-refractory UC received pembrolizumab and either docetaxel (arm A) or gemcitabine (arm B). Primary end points were assessments of maximum tolerated dose and dose-limiting toxicity (DLT). Secondary end points were overall response rate (ORR) and progression-free survival (PFS). Results: Twelve patients were enrolled in the initial cohorts; 6 in each arm. One DLT was seen in each arm: Grade 3 hypophosphatemia (arm A), Grade 3 diarrhea (arm B). Adverse events of Grade >3 were observed in 7 (54%), the most common being anemia (6; 50%), fatigue (6; 50%), hyponatremia (4; 33%) and neutropenia (3; 25%), with no treatment-related deaths. There were 5 confirmed responses (1 complete, 4 partial), with an ORR of 42% and disease control rate (DCR) of 58%. Arm A had an ORR of 50% and DCR of 67%, whereas arm B had an ORR of 33% and DCR of 50%. Median PFS was 4.8, 5.7, and 3.7 months for the overall cohort, arm A, and arm B, respectively. Conclusion: Pembrolizumab with either docetaxel or gemcitabine is feasible for treatment of platinum-refractory advanced UC patients. Preliminary efficacy was observed. Further examination is warranted. (C) 2018 Elsevier Inc. All rights reserved.

5031 Background: The androgen receptor (AR) variant AR-V7 lacks the ligand binding domain, constitutively activates the AR pathway, and confers resistance to Abiraterone (Abi) and enzalutamide (Enza). We discovered that the anti-helminthic drug niclosamide targets AR-V7 and sensitizes resistant CRPC to Enza and Abi. We hypothesize that niclosamide/PDMX1001 potentiates the efficacy of Abi against CRPC. Methods: Eligible patients (pts) have progressive CRPC with serum testosterone < 50 ng/dl. No prior Abi was allowed. In the Phase Ib cohort, pts received Abi 1000 mg PO qd, prednisone 5 mg PO bid, with intrapatient dose-escalation of niclosamide/PDMX1001 from 400 mg PO bid to 1600 mg PO tid. Trough niclosamide/PDMX1001 levels were measured. The Phase II cohort will enroll 27 patients with detectable AR-V7 in the peripheral blood. Co-primary endpoints include toxicity and response as determined by the Prostate Cancer Working Group 2 criteria. Results: Of 6 pts (age 74-83) in the Phase Ib cohort, five pts tolerated a niclosamide/PDMX1001 dose of 1,600 mg po tid without dose limiting toxicity; per protocol, this is the recommended Phase II dose. Niclosamide/PDMX1001 trough level was 0.305-0.648 µM in the three pts analyzed thus far, higher than the target level of 0.1µM required for anti-cancer activity. Of 6 pts, two pts achieved undetectable PSA ( < 0.01 ng/ml) for over 16 cycles and are still going on, compared to historical control 0/30 pts treated with Abi alone; two with partial PSA response (≥50% decrease). Of the remaining two pts, one was prematurely taken off from the study after one cycle because of rising PSA, and the other had PSA decrease of 17.1%, but biopsy of the only enlarged lymph node showed all necrotic tissue. No dose-limiting toxicity was observed. The Phase II cohort will now enroll. Molecular correlative studies will be presented. Conclusions: The combination of niclosamide/PDMX1001, Abi and prednisone is well tolerated with promising safety and efficacy data. Targeted serum trough levels of niclosamide are clinically achievable. Clinical trial information: NCT02807805.

398 Background: Metastatic urothelial cancer (mUC) is only modestly responsive to checkpoint inhibitor immunotherapy; e.g., the PDL1 inhibitor atezolizumab confers only a 16% tumor response rate (RR) in platinum-treated mUC. Chemotherapy is hypothesized to enhance tumoral neoantigen expression thus priming response to PD1-directed immunotherapy. Here we report results from the initial cohort of an investigator-initiated trial of Pembro plus either docetaxel or gemcitabine in platinum-treated mUC patients (pts). Methods: Primary endpoint was safety; secondary endpoints were overall RR and progression-free survival (PFS). Eligible pts had Zubrod PS 0-1, adequate end-organ function, and up to 2 prior lines of chemo (at least 1 platinum-based). Dose limiting toxicity (DLT) was any grade (Gr) 3+ non-heme toxicity, Gr3+ neutropenia w/ fever or infection, or Gr4 platelets (plts), or Gr3 plts with bleeding. In dose level (DL) 1, treatment consisted of Pembro 200 mg IV on D1 q3 weeks plus either docetaxel 75 mg/m2 on D1 (Arm 1) or gemcitabine 1000 mg/m2 on D1&D8 (Arm 2). Results: Overall 12 pts were enrolled in DL1, six in each arm. Median age was 69 years (range 45-84), 8 (67%) male, & 10 (83%) of white race. One pt in each arm had DLT: Gr3 hypophosphatemia in Arm 1, Gr3 diarrhea in Arm 2. Attributable Gr3+ toxicities were seen in 7 (54%). Most common Gr3+ AEs were anemia (5, 38%), fatigue (4, 31%), & neutropenia (4, 31%). There were no treatment related deaths; 3 died from tumor progression (PD). As of 10/2016, 4 pts remain on active therapy. In total 4 pts had confirmed response (1 CR, 3 PR), 2 had stable disease (SD), and 6 had PD for an overall RR of 33% and Disease Control Rate (DCR) of 50%. Arm 1 had an overall RR of 50% (1CR, 2PR, 1SD) and DCR of 67%. Arm 2 had an overall RR of 17% (1PR, 1SD) and DCR of 33%. Median PFS (overall, Arm 1 & 2) were 4.8, 5.7, and 3.7 months. Conclusions: Pembro 200 mg IV q3 weeks plus either full-dose docetaxel or gemcitabine is feasible in platinum-treated mUC pts. Encouraging anti-tumor activity for chemo-immunotherapy was seen in this ongoing study, particularly with Pembro+docetaxel. Further investigation of this approach is warranted. Clinical trial information: NCT02437370.

This paper demonstrates an automated computer vision system for outdoor tree crop enumeration in a seedling nursery. The complete system incorporates both hardware components (including an embedded microcontroller, an odometry encoder, and an uncalibrated digital color camera) and software algorithms (including microcontroller algorithms and the proposed algorithm for tree crop enumeration) required to obtain robust performance in a natural outdoor environment. The enumeration system uses a three-step image analysis process based upon: (1) an orthographic plant projection method integrating a perspective transform with automatic parameter estimation; (2) a plant counting method based on projection histograms; and (3) a double-counting avoidance method based on a homography transform. Experimental results demonstrate the ability to count large numbers of plants automatically with no human effort. Results show that, for tree seedlings having a height up to 40 cm and a within-row tree spacing of approximately 10 cm, the algorithms successfully estimated the number of plants with an average accuracy of 95.2% for trees within a single image and 98% for counting of the whole plant population in a large sequence of images.

227 Background: Ketoconazole (keto), a known CYP17 inhibitor, is a traditional systemic treatment for CRPC. However, most of the published data has been in the pre-chemo setting; its efficacy in the post-chemo setting has not been as widely reported. Chemo-naive patients treated with attenuated doses of keto (200-300 mg TID) had prostate specific antigen (PSA) response rate (> 50% decline) ranges from 21%-62% and treatment was well tolerated. We hypothesized that low dose keto would likewise possess efficacy and tolerability in the CRPC post-chemo state. Methods: CRPC patients with ECOG PS 0-3, adequate end organ function, who had received at least one chemo were treated with low-dose keto (200 mg PO TID) and HC (20 mg PO q AM and 10 mg PO q PM) until progression, as defined by either RECIST or PSA rise > 50% from nadir or baseline. Primary endpoint was PSA response rate (> 50% reduction from baseline). A Simon minimax design was used. PSA response of > 25% was to be considered promising for further study (versus null rate of < 5%); 25 patients were required. Secondary endpoints included PSA response > 30%, progression-free survival (PFS), duration of stable disease, and evaluation of adverse events (AE). Results: 29 patients were accrued: median age was 71 (range 55-86) and median pretreatment PSA was 76 ng/mL (range 7-11,420 ng/ml); all had prior docetaxel-based chemotherapy. 28 patients were evaluable for response; all were evaluable for toxicity. PSA response of >50% was seen in 48% of patients and 59% of patients had a PSA response of > 30%. Median PFS was 138 days; median duration of stable disease was 123 days. 12 patients had grade 3 or 4 toxicity on treatment. Of the 17 grade 3 AEs, only 3 were considered ‘probably’ or ‘possibly’ related to treatment, while none of the 2 grade 4 AEs were considered related to treatment. Conclusions: In docetaxel pre-treated CRPC patients, low-dose keto + HC is a well-tolerated, relatively inexpensive and clinically active treatment option. PSA response with low-dose keto appears comparable to that of abiraterone in this patient context. A prospective randomized study of available post-chemo options is needed to assess comparative efficacy. Clinical trial information: NCT00895310.

Abstract Background: We previously showed that the mTOR pathway is activated in castrate resistant prostate cancer (CRPC) while inhibition of this pathway upregulated androgen receptor (AR) signaling. Based on these data, a phase I/II clinical trial was designed to determine the efficacy and tolerability of the combination of the AR inhibitor bicalutamide and the mTOR inhibitor everolimus in CRPC patients compared with bicalutamide alone. Methods: Eligible patients had histologically confirmed disease and disease progression (PSA or radiographically) while on androgen deprivation therapy (failed the therapy); and could have less than 2 months of bicalutamide at the initiation of androgen deprivation to prevent flare. The primary endpoint is PSA response. Complete response (CR) was defined as complete disappearance of all measurable and non-measurable disease. Results: In all, 19 patients were enrolled in the study, but data from only 18 have been included because one patient passed away before he could be started on the drugs. No unexpected toxicity was observed in the 18 patients enrolled in this study. 5 patients were on placebo+bicalutamide and 13 were on everolimus+bicalutamide. Of the 13 patients on everolimus+bicalutamide, nine (69.23%) had partial response (PR, a decline in PSA by at least 30%), one (7.69%) unconfirmed PR (patients have PSA response less than two cycles), and three (23.08%) had stable disease (SD, no symptomatic deterioration, PSA increase <100%, and not CR/PR). In contrast, of the 5 patients on Placebo+bicalutamide, 1 (20%) had PR, 1 (20%) unconfirmed PR, 2 SD (40%) and one (20%) had disease progression. The mean time to relapse (days from start of treatment to patient withdrawal) was 220 days for patients on everolimus+bicalutamide and 109 days for patients on Placebo+bicalutamide. Recent publications indicate ErbB3 increases with mTOR inhibition. Therefore, to investigate the difference in the patients on everolimus+bicalutamide who responded to the treatment, vs those who did not, serum from 8 patients on everolimus+bicalutamide, of which 4 responded to this combination (PSA decrease >50%) and 4 did not, were further analyzed for levels of ErbB3. Significantly, ErbB3 levels were increased in the serum from patients who did not show any decline or partial decline in PSA, but not in the ones who responded well to the drug combination. Conclusions: The combination of everolimus+bicalutamide doubled the time to relapse in patients who had failed androgen deprivation therapy, compared to bicalutamide alone. Relapse in these patients may be related to the increase in ErbB3, hence an ErbB3 inhibitor in combination with everolimus may further benefit this group of patients. We intend to investigate in the future whether expression of ErbB3 in the serum can be used to predict whether a patient will respond to the treatment or not. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5750. doi:1538-7445.AM2012-5750