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Summary Background Gemogenovatucel-T is an autologous tumour cell vaccine manufactured from harvested tumour tissue, which specifically reduces expression of furin and downstream TGF-β1 and TGF-β2. The aim of this study was to determine the safety and efficacy of gemogenovatucel-T in front-line ovarian cancer maintenance. Methods This randomised, double-blind, placebo-controlled, phase 2b trial involved 25 hospitals in the USA. Women aged 18 years and older with stage III/IV high-grade serous, endometrioid, or clear cell ovarian cancer in clinical complete response after a combination of surgery and five to eight cycles of chemotherapy involving carboplatin and paclitaxel, and an Eastern Cooperative Oncology Group status of 0 or 1 were eligible for inclusion in the study. Patients were randomly assigned (1:1) to gemogenovatucel-T or placebo by an independent third party interactive response system after successful screening using randomly permuted block sizes of two and four and stratified by extent of surgical cytoreduction and neoadjuvant versus adjuvant chemotherapy. Gemogenovatucel-T (1 × 107 cells per injection) or placebo was administered intradermally (one per month) for a minimum of four and up to 12 doses. Patients, investigators, and clinical staff were masked to patient allocation until after statistical analysis. The primary endpoint was recurrence-free survival, analysed in the per-protocol population. All patients who received at least one dose of gemogenovatucel-T were included in the safety analysis. The study is registered with ClinicalTrials.gov , NCT02346747 . Findings Between Feb 11, 2015, and March 2, 2017, 310 patients consented to the study at 22 sites. 217 were excluded. 91 patients received gemogenovatucel-T (n=47) or placebo (n=44) and were analysed for safety and efficacy. The median follow-up from first dose of gemogenovatucel-T was 40·0 months (IQR 35·0–44·8) and from first dose of placebo was 39·8 months (35·5–44·6). Recurrence-free survival was 11·5 months (95% CI 7·5–not reached) for patients assigned to gemogenovatucel-T versus 8·4 months (7·9–15·5) for patients assigned to placebo (HR 0·69, 90% CI 0·44–1·07; one-sided p=0·078). Gemogenovatucel-T resulted in no grade 3 or 4 toxic effects. Two patients in the placebo group had five grade 3 toxic events, including arthralgia, bone pain, generalised muscle weakness, syncope, and dyspnea. Seven patients (four in the placebo group and three in the gemogenovatucel-T group) had 11 serious adverse events. No treatment-related deaths were reported in either of the groups. Interpretation Front-line use of gemogenovatucel-T immunotherapy as maintenance was well tolerated but the primary endpoint was not met. Further investigation of gemogenovatucel-T in patients stratified by BRCA mutation status is warranted. Funding Gradalis.

Covalent BTK inhibitors (BTKi) have transformed the management of mantle cell lymphoma (MCL), but most patients will require additional treatment. Pirtobrutinib is a highly selective, non-covalent (reversible) BTKi that inhibits both wild-type and C481-mutated BTK with equal low nM potency.To evaluate pirtobrutinib safety and efficacy in patients with MCL.BRUIN is an ongoing multicenter phase 1/2 study (NCT03740529) of pirtobrutinib monotherapy.Global; community hospitals, academic medical centers.Patients with advanced B-cell malignancies.Oral pirtobrutinib, phase 1 dose-escalated in a standard 3+3 design, phase 2 continuous therapy, 28-day cycles.The primary phase 1 objective was to determine the recommended phase 2 dose (RP2D) and the primary phase 2 objective was overall response rate (ORR); secondary objectives included duration of response, progression-free survival, overall survival, safety/tolerability, and pharmacokinetics.As of 27 September 2020, 323 patients (170 CLL/SLL, 61 MCL, 26 WM, 26 DLBCL, 13 MZL, 12 FL, 9 RT, and 6 other NHL) were treated on 7 dose levels (25-300mg QD). No DLTs were reported and MTD was not reached (n=323). 200mg QD was selected as the RP2D. Fatigue (20%), diarrhea (17%) and contusion (13%) were the most frequent treatment-emergent adverse events regardless of attribution or grade seen in10% of patients. The most common adverse event of grade ≥3 was neutropenia (10%). Five (1%) patients discontinued due to treatment-related adverse events. 52 prior BTKi treated MCL patients were efficacy evaluable with an ORR of 52% (95% CI 38-66; 13 CR [25%], 14 PR [27%], 9 SD [17%]), 11 PD [21%] and 5 [10%] discontinued prior to first response assessment). Median follow-up was 6 months (0.7-18.3+). Responses were observed in 9/14 patients (64%) with prior autologous or allogeneic stem cell transplant, and 2/2 with prior CAR-T cell therapy.Pirtobrutinib demonstrated promising efficacy in heavily pretreated, poor-prognosis MCL following multiple prior lines of therapy, including a covalent BTKi. Pirtobrutinib was well tolerated and exhibited a wide therapeutic index. Updated data, including approximately 60 new patients with MCL and an additional 10 months since the prior data-cut will be presented.

Context: Despite the marked efficacy of covalent BTK inhibitors (BTKi) in CLL/SLL, the development of resistance and discontinuation for adverse events can lead to treatment failure. Low oral bioavailability or short half-life of these agents can lead to suboptimal BTK target coverage and ultimately result in acquired resistance in some patients (pts). Pirtobrutinib (LOXO-305) is a highly selective, non-covalent BTKi that inhibits both WT and C481-mutated BTK with equal, low nM potency. Objective: To evaluate pirtobrutinib safety and efficacy in pts with CLL/SLL. Design: BRUIN is an ongoing multi-center phase 1/2 trial (NCT03740529). Enrollment was initiated 21 March 2019. Setting: Global: community hospitals, and academic medical centers. Patients: As of 27 September 2020, 323 previously treated pts with B-cell malignancies (170 CLL/SLL, 61 MCL, 26 WM, and 66 other B-cell lymphomas) were enrolled. Interventions: Oral pirtobrutinib (7 dose escalation levels: 25–300mg once daily) in 28-day cycles. Main Outcomes Measures: Determining the maximum tolerated dose/recommended phase 2 dose (RP2D), safety profile, and efficacy based on response assessment using disease-specific criteria (iwCLL2018 for CLL/SLL) per protocol. Results: Pirtobrutinib demonstrated high oral exposures, with doses ≥100mg QD exceeding BTK IC90 for the entirety of the dosing interval. No DLTs occurred. The only treatment-emergent adverse events, regardless of attribution or grade seen in ≥10% of pts (n=323), were fatigue (20%), diarrhea (17%), and contusion (13%). An RP2D of 200 mg QD was selected for future studies. The ORR (per iwCLL 2018) was 63%, with 69 PRs, 19 PR-Ls, 45 SDs, 1 PD, and 5 discontinued prior to first response assessment. Responses deepened over time among pts with ≥10 months of follow-up (n=29; 86% ORR). ORR was not influenced by the reason for prior BTKi discontinuation (i.e., progression vs intolerance) or other classes of prior therapy received (including a covalent BTK and a BCL2 inhibitor). The longest followed responding pt continues on treatment for 17.8+ months. Conclusions: Pirtobrutinib showed promising efficacy in pre-treated CLL/SLL pts, was well-tolerated, and exhibited a wide therapeutic index.

Context Despite the marked efficacy of covalent BTK inhibitors (BTKi) in MCL, WM, and MZL, the development of resistance and discontinuation for adverse events can lead to treatment failure. Low oral bioavailability or short half-life of these agents can lead to suboptimal BTK target coverage and ultimately result in acquired resistance in some patients (pts). Pirtobrutinib (LOXO-305) is a highly selective, non-covalent BTKi that inhibits both WT and C481-mutated BTK with equal, low nM potency. Objective To evaluate safety and efficacy of pirtobrutinib in pts with MCL/NHLs. Design BRUIN is an ongoing multi-center phase 1/2 trial (NCT03740529). Enrollment was initiated 21 March 2019. Setting Global: community hospitals, academic medical centers. Patients Previously treated pts with advanced B-cell malignancies. Interventions Oral pirtobrutinib (7 dose escalation levels: 25–300mg once daily) in 28-day cycles. Main Outcomes Measures Determining the maximum tolerated dose/recommended phase 2 dose (RP2D), safety profile, and efficacy based on response assessment using disease-specific criteria per protocol. Results As of 27 September 2020, 323 pts with B-cell malignancies (170 CLL/SLL, 61 MCL, 26 WM, and 66 other B-cell lymphomas) were treated on 7 dose levels (25–300mg QD). Pirtobrutinib demonstrated high oral exposures, with doses ≥100 mg QD exceeding the BTK IC90 for the entirety of the dosing interval. No DLTs occurred. The only TEAEs, regardless of attribution or grade in ≥10% of pts (n=323), were fatigue (20%), diarrhea (17%) and contusion (13%). A RP2D of 200mg QD was selected. At the efficacy cutoff date, 35 (57%) MCL pts, 18 (69%) WM pts, and 34 (52%) other NHL pts remained on therapy. Among the 52 efficacy evaluable prior BTKi treated MCL pts, the ORR was 52%. Among the 19 efficacy evaluable pts with WM, the ORR was 68%. For the other 55 efficacy evaluable NHL pts, ORR was 24% (DLBCL), 50% (FL), 22% (MZL), and 75% (Richter's transformation). Conclusion Pirtobrutinib demonstrated promising efficacy in MCL and other NHL pts, was well-tolerated and exhibited a wide therapeutic index.

Ewing's sarcoma is a devastating rare pediatric cancer of the bone. Intense chemotherapy temporarily controls disease in most patients at presentation but has limited effect in patients with progressive or recurrent disease. We previously described preliminary results of a novel immunotherapy, FANG (Vigil) vaccine, in which 12 advanced stage Ewing's patients were safely treated and went on to achieve a predicted immune response (IFNγ ELISPOT). We describe follow-up through year 3 of a prospective, nonrandomized study comparing an expanded group of Vigil-treated advanced disease Ewing's sarcoma patients (n = 16) with a contemporaneous group of Ewing's sarcoma patients (n = 14) not treated with Vigil. Long-term follow-up results show a survival benefit without evidence of significant toxicity (no ≥ grade 3) to Vigil when administered once monthly by intradermal injection (1 × 10e(6) cells/injection to 1 × 10e(7) cells/injection). Specifically, we report a 1-year actual survival of 73% for Vigil-treated patients compared to 23% in those not treated with Vigil. In addition, there was a 17.2-month difference in overall survival (OS; Kaplan-Meier) between the Vigil (median OS 731 days) and no Vigil patient groups (median OS 207 days). In conclusion, these results supply the rational for further testing of Vigil in advanced stage Ewing's sarcoma.

Background The poor outcomes associated with current therapies for recurrent epithelial ovarian cancer (EOC) are thought to reflect the existence of drug-resistant ovarian cancer stem cells (OCSCs). TRX-E-002-1 is a novel, third generation benzopyran molecule that induces caspase-dependent and -independent apoptosis in CD44 positive ovarian cancer stem-like cells and CD44 negative ovarian somatic cancer cells. The dose escalation phase of a progressive design trial investigating intraperitoneal (IP)-administered TRX-E-002-1 monotherapy and in combination with standard of care for recurrent EOC (NCT02903771) has been completed with a Maximum Tolerated Dose (MTD) of 5 mg/kg established. Methods Women with platinum resistant, persistent or recurrent EOC were enrolled into the dose escalation phase of the study (Part A) in which TRX-E-002-1 monotherapy was administered IP weekly for 2 three-week cycles, after which combination with standard intravenous chemotherapy was allowed to a maximum of 8 cycles. Subjects were followed up for 3 months after the end of treatment. The study objectives were to establish the MTD and to evaluate safety, tolerability, pharmacokinetics and anti-tumour activity of TRX-E-002-1. Results A total of 9 subjects were evaluable for efficacy. Four of 9 patients completed 8 cycles (6 months); 2 remained progression-free at the 3-month endpoint post-treatment (9 months). Preliminary data on activity include 1 partial response (during combination treatment) and 5 patients with stable disease on monotherapy per RECIST criteria. The most common drug-related adverse events, not generally dose limiting, were abdominal pain (27%), fatigue (13%), vomiting (10%) and nausea (10%). There was limited accumulation of TRX-E-002-1 with multiple dosing across multiple concentration‐time points. PK profiles were comparable between all subjects with plasma concentrations progressively declining to Conclusions IP administered TRX-E-002-1 as a first-in-class, dual acting, anti-cancer therapy has demonstrated preliminary activity for the treatment of platinum resistant ovarian cancer. Clinical trial identification NCT02903771. Editorial acknowledgement Dr Caroline Markey, Markey Medical Consulting. Legal entity responsible for the study Kazia Therapeutics Limited. Funding Kazia Therapeutics Limited. Disclosure J. Coward: Honoraria (institution): Takeda Pharmaceuticals; Research grant / Funding (self): AstraZeneca; Leadership role, Overseas Trainee Sub-committee member: Royal Australasian College of Physicians. K. Moore: Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Clovis; Advisory / Consultancy, Research grant / Funding (institution): Immunogen; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Tesaro; Advisory / Consultancy: Pfizer; Advisory / Consultancy, Research grant / Funding (self): Merck; Advisory / Consultancy: Aravive; Advisory / Consultancy, Research grant / Funding (institution): OncoMed; Advisory / Consultancy: Samumed; Advisory / Consultancy: Eisai; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Genentech/Roche; Advisory / Consultancy: Janssen; Advisory / Consultancy: Cue; Research grant / Funding (self): Lilly; Research grant / Funding (self): PTC Therapeutics; Research grant / Funding (institution): Regeneron; Research grant / Funding (institution): Agenus; Leadership role, Chair: NRG Oncology OVarian Committee; Leadership role, Associate Director: GOG Partners. D. Berg: Full / Part-time employment: Kazia Therapeutics Limited. J. Garner: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment, Officer / Board of Directors: Kazia Therapeutics Limited. D. Dizon: Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Kazia Therapeutics; Honoraria (self): AstraZeneca; Honoraria (self), Advisory / Consultancy: Tesaro; Honoraria (self): Regeneron; Advisory / Consultancy: iMab. All other authors have declared no conflicts of interest.

Stathmin1 (STMN1) is a microtubule modulator that is expressed in multiple cancers and correlates with poor survival. We previously demonstrated in vivo safety of bifunctional (bi) shRNA STMN1 bilamellar invaginated vesicle (BIV) and that systemic delivery correlated with antitumor activity. Patients with superficial advanced refractory cancer with no other standard options were entered into trial. Study design involved dose escalation (four patients/cohort) using a modified Fibonacci schema starting at 0.7 mg DNA administered via single intratumoral injection. Biopsy at baseline, 24/48 hours and resection 8 days after injection provided tissue for determination of cleavage product using next-generation sequencing (NGS) and reverse transcription quantitative polymerase chain reaction (RT-qPCR), 5′ RLM rapid amplification of cDNA ends (RACE) assay. Serum pharmacokinetics of circulating plasmid was done. Twelve patients were entered into three dose levels (0.7, 1.4, 7.0 mg DNA). No ≥ grade 3 toxic effects to drug were observed. Maximum circulating plasmid was detected at 30 seconds with less than 10% detectable in all subjects at 24 hours. No toxic effects were observed. Predicted cleavage product was detected by both NGS (n = 7/7 patients analyzed, cohorts 1, 2) and RLM RACE (n = 1/1 patients analyzed cohort 3). In conclusion, bi-shRNA STMN1 BIV is well tolerated and detection of mRNA target sequence-specific cleavage product confirmed bi-shRNA BIV mechanism of action.

Background SL-801 is a novel, oral, small molecule that reversibly inhibits Exportin-1 (XPO-1), a nuclear export protein, overexpressed in a variety of solid and hematologic malignancies. XPO-1 is a mediator of nuclear-cytoplasmic transport of over 200 nuclear proteins and has been associated with aggressive tumor behavior and poor prognosis. SL-801 has demonstrated potent in vitro and in vivo activity. Interim results from the dose-escalation stage are reported. Methods STML-801-0115 is a first-in-human, multicenter dose and schedule finding study in patients with localized unresectable, or metastatic solid tumors that are refractory to or are relapsed after treatment with standard therapy. Objectives are to identify the maximum tolerated dose or optimal dose/schedule, and assess pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity. SL-801 was initially orally administered on days 1-4 and 8-11 of a 21-day cycle (Schedule A). The dosing schedule has been amended to potentially allow a longer recovery time between dosing periods while maintaining dose intensity. Patients are now receiving SL-801 once daily on days 1-2, 8-9, 15-16 and 22-23 of a 28-day cycle (Schedule B). The starting dose in the study was 5 mg/day in Schedule A; current study dose level is 70 mg/day in Schedule B. Results 45 patients received 5-65 mg/day of SL-801 in Schedule A (median age 63 YO [range: 39-83], 51% females, median number of prior systemic therapies, 4 [range: 2-10]; 57% received 3 or more. Common treatment-emergent adverse events (TEAEs) were nausea (62%), vomiting (64%), fatigue (44%), decreased appetite (33%), and diarrhea (29%). Grade 3 TEAEs included nausea (9%), anemia (7%), and fatigue, diarrhea, hyponatremia and hypophosphatasemia (each 4%). Most TEAEs were grade 1-2; no grade 4-5 toxicities reported. 12 patients (27%) had stable disease (SD) and remained on study for 2-11 months including 5 with SD for 4+ months. 1 patient with basal cell carcinoma had SD for 11 months. 3 patients had radiographic tumor shrinkage of 14-20% in target lesions. Conclusions SL-801 reversibly binds XPO1, a clinically validated target in oncology. To date 27% of heavily pre-treated patients have achieved SD as best response. Enrollment and dose escalation continue. Clinical trial identification NCT02667873. Legal entity responsible for the study Stemline Therapeutics. Funding Stemline Therapeutics. Disclosure J. Wang: Speaker Bureau / Expert testimony: AstraZeneca. E. Chiorean: Research grant / Funding (institution): Boehringer-Ingelheim, Merck, BMS, Lilly, Stemline, Ignyta/Roche, Incyte, Halozyme; Advisory / Consultancy: AstraZeneca, Array, Ipsen, Eisai, Halozyme, Seattle Genetics, Vicus, Five Prime. P. LoRusso: Advisory / Consultancy: abbvie; Advisory / Consultancy, data safety monitoring board: agios; Advisory / Consultancy: alexion; Advisory / Consultancy: ariad; Advisory / Consultancy, data safety monitoring committee: Five prime; Advisory / Consultancy: GenMab; Advisory / Consultancy: Glenmark; Advisory / Consultancy, data safety monitoring: Halozyme; Advisory / Consultancy: Menarini; Advisory / Consultancy: Novartis; Advisory / Consultancy: Genentech; Advisory / Consultancy: CytomX; Advisory / Consultancy: Omniox; Advisory / Consultancy: Ignyta; Advisory / Consultancy: Takeda; Advisory / Consultancy: Sotio; Advisory / Consultancy, data safety monitoring committee: Tyme. K. Courtney: Advisory / Consultancy: Janssen; Research grant / Funding (institution): Astellas Pharma; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Medivation; Research grant / Funding (institution): Aragon; Research grant / Funding (self): Astellas Pharma; Research grant / Funding (institution): PSMA Development; Research grant / Funding (institution): Stemline; Research grant / Funding (institution): Peloton; Research grant / Funding (institution): Merck Sharp & Dohme; Research grant / Funding (institution): Corvus Pharmaceuticals; Research grant / Funding (institution): Clovis Oncology; Research grant / Funding (institution): Proacta; Spouse / Financial dependant, Receives patent royalties: Athena Diagnostics, Inc. D. Qi: Advisory / Consultancy: stemline. J. Bullington: Shareholder / Stockholder / Stock options, Full / Part-time employment: Stemline. M. Sardone: Shareholder / Stockholder / Stock options, Full / Part-time employment: Stemline. J. Chen: Shareholder / Stockholder / Stock options, Full / Part-time employment: Stemline. C. Brooks: Shareholder / Stockholder / Stock options, Full / Part-time employment: Stemline. S. Shemesh: Shareholder / Stockholder / Stock options, Full / Part-time employment: Stemline. T.M. Bauer: Full / Part-time employment: Tennessee Oncology; Advisory / Consultancy: Ignyta; Advisory / Consultancy: Guardant Health; Advisory / Consultancy: Loxo; Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Speaker Bureau / Expert testimony: Bayer; Research grant / Funding (institution): Daiichi Sankyo; Research grant / Funding (institution): Medpacto, Inc; Research grant / Funding (institution): Incyte; Research grant / Funding (institution): Mirati Therapeutics; Research grant / Funding (institution): MedImmune; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): MabVax; Research grant / Funding (institution): Stemline Therapeutics; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): GlaxoSmithKline; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Amgen. All other authors have declared no conflicts of interest.

Selective delivery of therapeutic molecules to primary and metastatic tumors is optimal for effective cancer therapy. A liposomal nanodelivery complex (scL) for systemic, tumor-targeting delivery of anticancer therapeutics has been developed. scL employs an anti-transferrin receptor (TfR), scFv as the targeting molecule. Loss of p53 suppressor function, through mutations or inactivation of the p53 pathway, is present in most human cancers. Rather than being transiently permissive for tumor initiation, persistence of p53 dysfunction is a continuing requirement for maintaining tumor growth. Herein, we report results of a first-in-man Phase I clinical trial of restoration of the normal human tumor suppressor gene p53 using the scL nanocomplex (SGT-53). Minimal side effects were observed in this trial in patients with advanced solid tumors. Furthermore, the majority of patients demonstrated stable disease. One patient with adenoid cystic carcinoma had his status changed from unresectable to resectable after one treatment cycle. More significantly, we observed an accumulation of the transgene in metastatic tumors, but not in normal skin tissue, in a dose-related manner. These results show not only that systemically delivered SGT-53 is well tolerated and exhibits anticancer activity, but also supply evidence of targeted tumor delivery of SGT-53 to metastatic lesions.

We performed a phase I trial of FANG vaccine, an autologous tumor-based product incorporating a plasmid encoding granulocyte-macrophage colony-stimulating factor (GMCSF) and a novel bifunctional short hairpin RNAi (bi-shRNAi) targeting furin convertase, thereby downregulating endogenous immunosuppressive transforming growth factors (TGF) β1 and β2. Patients with advanced cancer received up to 12 monthly intradermal injections of FANG vaccine (1 × 10(7) or 2.5 × 10(7) cells/ml injection). GMCSF, TGFβ1, TGFβ2, and furin proteins were quantified by enzyme-linked immunosorbent assay (ELISA). Safety and response were monitored. Vaccine manufacturing was successful in 42 of 46 patients of whom 27 received ≥1 vaccine. There were no treatment-related serious adverse events. Most common grade 1, 2 adverse events included local induration (n = 14) and local erythema (n = 11) at injection site. Post-transfection mean product expression GMCSF increased from 7.3 to 1,108 pg/10(6) cells/ml. Mean TGFβ1 and β2 effective target knockdown was 93.5 and 92.5% from baseline, respectively. Positive enzyme-linked immunospot (ELISPOT) response at month 4 was demonstrated in 9 of 18 patients serially assessed and correlated with survival duration from time of treatment (P = 0.025). Neither dose-adverse event nor dose-response relationship was noted. In conclusion, FANG vaccine was safe and elicited an immune response correlating with prolonged survival. Phase II assessment is justified.

This phase II, multicenter, single-arm, two-stage study in platinum-resistant, advanced epithelial ovarian or primary peritoneal cancer evaluated the efficacy, safety, and tolerability of weekly single-agent volociximab. Pharmacokinetic/pharmacodynamic (PK/PD) studies were also performed.Sixteen patients were enrolled in Stage 1. Volociximab was administered at 15mg/kg IV qwk until progression of disease or drug intolerability. Tumor response was assessed every 8weeks. Serum samples for PK or whole blood for the evaluation of circulating tumor cells, endothelial cells, and endothelial progenitor cells were obtained on Days 1, 8, 15, 29, and 50. Ascites from one patient was collected for volociximab concentration analysis. Archived tumor tissue was analyzed by immunohistochemistry (IHC) for α5 integrin expression.Safety data are available on all 16 patients; 14 were evaluable for efficacy. One patient had stable disease at 8weeks. The remaining 13 progressed on treatment. Twelve patients (75%) experienced study-related adverse events (AEs); the most common (≥20%) were headache and fatigue. Three patients experienced possible study-related serious AEs (SAEs): reversible posterior leukoencephalopathy syndrome, pulmonary embolism, and hyponatremia. Peak serum concentrations of volociximab increased 2-3 fold from Day 1 to Day 50. Clinically relevant trough levels were achieved (150μg/mL). IHC analysis of archived tumor sections showed low-to-moderate expression of α5 integrin on all ovarian cancer tissue evaluated.Despite insufficient clinical activity in this refractory patient population to continue the study, weekly volociximab was well tolerated, and the gained understanding of the mechanism of action of volociximab will inform future development efforts.