Bariatric surgery is recognized as the most clinically and cost-effective treatment for people with severe and complex obesity. Many people presenting for surgery have pre-existing low vitamin and mineral concentrations. The incidence of these may increase after bariatric surgery as all procedures potentially cause clinically significant micronutrient deficiencies. Therefore, preparation for surgery and long-term nutritional monitoring and follow-up are essential components of bariatric surgical care. These guidelines update the 2014 British Obesity and Metabolic Surgery Society nutritional guidelines. Since the 2014 guidelines, the working group has been expanded to include healthcare professionals working in specialist and non-specialist care as well as patient representatives. In addition, in these updated guidelines, the current evidence has been systematically reviewed for adults and adolescents undergoing the following procedures: adjustable gastric band, sleeve gastrectomy, Rouxen-Y gastric bypass and biliopancreatic diversion/duodenal switch. Using methods based on Scottish Intercollegiate Guidelines Network methodology, the levels of evidence and recommendations have been graded. These guidelines are comprehensive,

PURPOSE Glofitamab is a T-cell–engaging bispecific antibody possessing a novel 2:1 structure with bivalency for CD20 on B cells and monovalency for CD3 on T cells. This phase I study evaluated glofitamab in relapsed or refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL). Data for single-agent glofitamab, with obinutuzumab pretreatment ( Gpt) to reduce toxicity, are presented. METHODS Seven days before the first dose of glofitamab (0.005-30 mg), all patients received 1,000 mg Gpt. Dose-escalation steps were determined using a Bayesian continuous reassessment method with overdose control. Primary end points were safety, pharmacokinetics, and the maximum tolerated dose of glofitamab. RESULTS Following initial single-patient cohorts, 171 patients were treated within conventional multipatient cohorts and received at least one dose of glofitamab. This trial included heavily pretreated patients with R/R B-NHL; most were refractory to prior therapy (155; 90.6%) and had received a median of three prior therapies. One hundred and twenty-seven patients (74.3%) had diffuse large B-cell lymphoma, transformed follicular lymphoma, or other aggressive histology, and the remainder had indolent lymphoma subtypes. Five (2.9%) patients withdrew from treatment because of adverse events. Cytokine release syndrome occurred in 86 of 171 (50.3%) patients (grade 3 or 4: 3.5%); two (1.2%) patients experienced grade 3, transient immune effector cell–associated neurotoxicity syndrome-like symptoms. The overall response rate was 53.8% (complete response [CR], 36.8%) among all doses and 65.7% (CR, 57.1%) in those dosed at the recommended phase II dose. Of 63 patients with CR, 53 (84.1%) have ongoing CR with a maximum of 27.4 months observation. CONCLUSION In patients with predominantly refractory, aggressive B-NHL, glofitamab showed favorable activity with frequent and durable CRs and a predictable and manageable safety profile.

No abstract

A novel application of near-infrared (near-IR) spectroscopy for the on-line determination of nanoparticle size of a drug compound in a high solids dispersion is described. The on-line spectroscopic technique provides real-time data for process monitoring and control and overcomes the limitations that are encountered using laboratory-based instrumentation for nanoparticle size determination. Near-IR spectroscopy is capable of providing an accuracy of 2.4 nm near the endpoint of particle production, where the volume-weighted D90 particle size is determined to be 200-220 nm. The accuracy is adequate for endpoint control, which minimizes excess processing and provides control over the particle size throughout nanoparticle production.

Despite advancements in outcomes with the introduction of anti-CD20 monoclonal antibody therapy, a substantial proportion of B-cell Non-Hodgkin's Lymphoma (B-NHL) patients do not sustain a durable response to standard of care treatment. T-cell bispecific antibodies (TCBs) represent a new class of disease-targeting agents shown to activate T-cells to kill cancer cells, offering this exciting mechanism of action with 'off the shelf' availability. CD20-TCB (RG6026) is a novel T-cell-engaging bispecific antibody whose "2:1" format possesses two CD20 binders in addition to a CD3 binder, enabling increased tumor antigen avidity, rapid T-cell activation, and enhanced tumor cell killing. NP30179 is a multicenter phase I dose escalation trial investigating the safety, tolerability, pharmacokinetics (PK), biomarker responses, and antitumor activity (assessed by overall response rate [ORR] and complete response rate [CR] per Lugano 2014 criteria) of single agent CD20-TCB. Patients receive escalating doses of CD20-TCB as intravenous infusions with dose escalation guided by a model implementing the Bayesian continuous reassessment method with overdose control. In order to reduce the potential risk of cytokine release syndrome (CRS) induced by CD20-TCB mediated systemic T-cell activation, a single dose of 1000 mg obinutuzumab (G) pretreatment (Gpt) is administered seven days prior to start of CD20-TCB and has preclinically been shown to debulk peripheral B cells and reduce systemic cytokine release (Bacac et al. Clin Canc Res 2018). As of July 29th 2018 a total of 64 patients (pts) with aggressive r/r B-NHL (DLBCL/PMBCL/trFL/Richter´s transformation (n=47)) and indolent r/r B-NHL (FL(n=17)) received CD20-TCB doses ranging from 5 µg to 1800 µg in a Q2W schedule. Median age was 64 years (range 28-82), 61% were male, median prior lines of therapy was 3 (range 1-10). A single DLT (myocardial infarction) was observed at 220 µg and until the maximum tested dose CD20-TCB was well tolerated. The most reported AEs were pyrexia (n=14, all Gr 1 and 2), neutropenia (all grades n=17, Gr 3 and 4 n=14) and cytokine release syndrome (CRS, n=14, all Grade 1-2 according to the criteria by Lee et al. Blood 2014). Two patients received tocilizumab for CRS management all CRS events were manageable and resolved, without leading to dose reduction or study withdrawal. No CNS toxicity was reported so far in this study. Fifty-five pts had at least one post-baseline response assessment and were eligible for efficacy analysis. Responses were observed from 15 µg onwards, and complete responses (CR) occurred from 300 µg onwards following two cycles of treatment. At doses of 300 µg or above (n=29) the ORR and CR rate by investigator assessment was 38% and 24%, respectively (FL: 3/5 pts and 2/5 pts respectively, aggressive B-NHL: 8/24 pts and 5/24 pts respectively). All CRs are sustained thus far with a median follow up 96 days (range 26-152). Responses were seen across various NHL subtypes and across prognostic factors such as prior lines of therapy, refractoriness to the most recent line of therapy, tumor burden, and IPI or FLIPI. CD20-TCB exposure and receptor occupancy increased dose-dependently across the investigated dose range; dose-escalation is continuing to optimize these factors. No anti-drug-antibodies have occurred. CD20-TCB is a novel 2:1 format T-cell-engaging bispecific antibody which already at suboptimal doses displays promising clinical activity in heavily-pretreated B-NHL. In addition, Gpt has shown clinical proof of principle as an approach to efficiently mitigate CRS. An update on safety and efficacy as well as biomarker data will be presented. Disclosures Hutchings: Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche/Genentech: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Iacoboni:Celgene: Other: Travel funding; Roche: Honoraria. Morschhauser:Janssen: Other: Scientific Lectures; BMS: Membership on an entity's Board of Directors or advisory committees; Epizyme: Consultancy; Roche: Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees. Sureda:Takeda: Consultancy, Honoraria, Speakers Bureau; Roche: Honoraria; Merck: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Sanofi: Honoraria. Salles:Janssen: Honoraria; Merck: Honoraria; Gilead Sciences: Honoraria; Epizyme: Honoraria; Amgen: Honoraria; Acerta: Honoraria; Abbvie: Honoraria; Celgene: Honoraria, Research Funding; Roche: Honoraria, Research Funding; Novartis: Consultancy, Honoraria; Morphosys: Honoraria; Pfizer: Honoraria; Servier: Honoraria; Takeda: Honoraria. Carlo-Stella:Rhizen Pharmaceuticals: Research Funding; Boehringer Ingelheim: Consultancy; Sanofi: Consultancy; MSD: Other: Advisory Board; Genenta Science: Other: Advisory Board; BMS: Other: Advisory Board; Amgen: Other: Advisory Board; Janssen: Other: Advisory Board; AstraZeneca: Other: Advisory Board; ADC Therapeutics: Other: Advisory Board. Martinez Lopez:Celgene: Research Funding, Speakers Bureau; BMS: Research Funding, Speakers Bureau; Jansen: Research Funding, Speakers Bureau; Novartis: Research Funding, Speakers Bureau. Thomas:Roche: Employment, Equity Ownership. Morcos:Roche: Employment, Equity Ownership. Quackenbush:Roche: Employment. Ferlini:Roche: Employment. Bacac:F. Hoffmann-La Roche Ltd.: Employment, Other: stock, Patents & Royalties. Broeske:Roche: Employment, Equity Ownership. Dimier:Roche: Employment, Equity Ownership. Moore:Roche: Employment. Weisser:Roche: Employment, Equity Ownership, Patents & Royalties. Dickinson:GSK: Consultancy.

CD20-TCB (RG6026) is a novel T-cell-engaging bispecific (TCB) antibody with a '2:1' molecular format comprising two fragment antigen binding regions that bind CD20 (on the surface of B cells) and one that binds CD3 (on the surface of T cells). CD20-TCB offers the potential for increased tumor antigen avidity, rapid T-cell activation, and enhanced tumor cell killing versus other bispecific formats, and the ability to combine with another CD20-targeted agent. Preclinical studies of concurrent therapy with CD20-TCB plus obinutuzumab (G) in diffuse large B-cell lymphoma (DLBCL) models demonstrate strong and sustained tumor regression driven by multiple mechanisms of action. These include induction of direct tumor cell death and antibody-dependent cellular cytotoxicity/cellular phagocytosis mediated by G, as well as recruitment of T-cells into the tumor and T-cell cytotoxicity mediated by CD20-TCB. NP30179 (NCT03075696) is a multicenter Phase I/Ib dose-escalation trial investigating the safety, tolerability, pharmacokinetics, biomarker responses, and anti-tumor activity (assessed by objective response rate [ORR] and complete response [CR] rate per modified Lugano 2014 criteria) of CD20-TCB in relapsed or refractory (R/R) B-cell non-Hodgkin lymphoma (NHL) patients (pts). For the first time, we report preliminary data from Arm B, evaluating dual CD20-targeted therapy with concurrent CD20-TCB and G. All pts receive a single dose of 1000mg G as pre-treatment (Gpt) 7 days before the start of CD20-TCB therapy (Cycle 1) to mitigate cytokine release syndrome (CRS). From Cycle 2 onwards, 1000mg G is administered on the same day as CD20-TCB, which constitutes the start of an initial 28-day dose-limiting toxicity (DLT) window, in 3-weekly cycles. Pts receive escalating doses of CD20-TCB, guided by a model implementing the Bayesian continuous reassessment method with overdose control. As of May 22, 2019, a total of 28 pts with R/R aggressive (a) NHL (DLBCL/primary mediastinal large B-cell lymphoma/transformed follicular lymphoma [FL]/mantle cell lymphoma/Richter´s transformation; n=22) or FL (n=6) had received concurrent G in combination with CD20-TCB doses ranging from 0.6 to 16mg for 8-12 cycles. Median age was 65 years (range, 34-81), 15 (54%) were male, 19 (68%) were refractory to prior therapy, and median prior lines of therapy was 2 (range, 1-6). Twenty-three CRS events (according to Lee criteria, Lee et al. Blood 2014) occurred in 16 (57%) pts (maximum Grade [Gr]: Gr 1, 5 [18%]; Gr 2, 9 [32%]; Gr 3, 1 [4%]; Gr 4, 1 [4%]). CRS events were confined to Cycle 1 in all but two pts. Neurotoxicity was rare (Gr 1, 4 [14%]; Gr 2, 2 [7%]; Gr 3, 1 [4%]) and all events resolved. Apart from CRS, the most frequent adverse events were anemia (all Gr, 6 [21%]; Gr 3, 3 [11%]), thrombocytopenia (all Gr, 6 [21%]; Gr ≥3, 3 [11%]; no hemorrhages reported), neutropenia (all Gr, 4 [14%]; Gr ≥3, 3 [11%]), pyrexia (all Gr, 4 [14%], all Gr 1-2), and hypokalemia (all Gr, 4 [14%]; Gr ≥3, 1 [4%]). No DLTs were reported and no new safety signals were observed. The overall safety profile overlapped with that reported in the single arm of the same study. Twenty-one pts reached their first response assessment or withdrew early and were eligible for efficacy analysis. Overall, the ORR and CR rate by investigator assessment was 48% [10/21 pts] and 43% [9/21], respectively (aNHL: ORR, 38% [6/16]; CR, 31% [5/16]; FL: ORR and CR, 80% [4/5]). CD20-TCB exposure and receptor occupancy (RO%) increased dose-dependently across the investigated dose range, and consistent with the RO%-efficacy model (Djebli et al. ASH 2019), clinically relevant CD20-TCB RO% and increased clinical activity was observed at a dose of 16mg when combined with concurrent G. In the 16mg cohort that included 10 R/R pts, 70% of whom were refractory to prior therapy and median prior lines of therapy was 4, the ORR and CR rate were 90% (9/10 pts) and 80% (8/10), respectively (aNHL: CR, 71% [5/7]; FL: CR, 100% [3/3]), and all CRs were ongoing at the time of abstract submission. This is the first study to demonstrate that CD20-TCB can be safely combined with an anti-CD20 monoclonal antibody and further supports the promise of the '2:1' format for allowing combination therapy with therapeutic levels of other anti-CD20 antibodies, such as G. CD20-TCB plus G provides highly promising clinical activity in heavily pre-treated R/R B-cell NHL. Updated clinical and biomarker data will be presented. Disclosures Morschhauser: Janssen: Honoraria; BMS: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees; Epizyme: Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Carlo-Stella:AstraZeneca: Honoraria; ADC Therapeutics: Consultancy, Other: Travel, accommodations, Research Funding; Servier: Consultancy, Honoraria, Other: Travel, accommodations; Rhizen Pharmaceuticals: Research Funding; Boehringer Ingelheim: Consultancy; Novartis: Consultancy, Research Funding; Janssen Oncology: Honoraria; Takeda: Other: Travel, accommodations; Sanofi: Consultancy, Research Funding; Genenta Science srl: Consultancy; F. Hoffmann-La Roche Ltd: Honoraria, Other: Travel, accommodations, Research Funding; Amgen: Honoraria; MSD: Honoraria; Janssen: Other: Travel, accommodations; Celgene: Research Funding; BMS: Honoraria. Salles:Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Educational events; Autolus: Consultancy, Membership on an entity's Board of Directors or advisory committees; Epizyme: Consultancy, Honoraria; Roche, Janssen, Gilead, Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Educational events; BMS: Honoraria; Novartis, Servier, AbbVie, Karyopharm, Kite, MorphoSys: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Educational events; Merck: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Other: Educational events. Hutchings:Janssen: Research Funding; Pfizer: Research Funding; Incyte: Research Funding; Celgene: Research Funding; Genmab: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Iacoboni:Celgene: Honoraria; Janssen: Honoraria; Novartis: Consultancy, Honoraria; Abbvie: Honoraria; Roche: Honoraria. Sureda:Amgen: Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Speakers Bureau; Roche: Honoraria; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria; Sanofi: Honoraria; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support; Gilead: Honoraria; Novartis: Honoraria. Crump:Servier: Consultancy; F. Hoffmann-La Roche Ltd: Consultancy, Research Funding; Kite/Gilead: Consultancy. Martinez-Lopez:Novartis: Honoraria, Other: Advisory boards; Janssen: Honoraria, Other: Advisory boards and Non-Financial Support ; Incyte: Honoraria, Other: Advisory boards; VIVIA Biotech: Honoraria; Celgene: Honoraria, Other: Advisory boards and Non-Financial Support ; Amgen: Honoraria, Other: Non-Financial Support ; F. Hoffmann-La Roche Ltd: Honoraria; BMS: Honoraria, Other: Advisory boards. Thomas:F. Hoffmann-La Roche Ltd: Employment, Equity Ownership. Morcos:Roche: Employment, Equity Ownership. Ferlini:Roche: Employment, Equity Ownership. Keelara:F. Hoffmann-La Roche Ltd: Employment, Equity Ownership. Bröske:Roche: Employment, Equity Ownership. Bacac:Roche: Employment, Equity Ownership, Patents & Royalties: Patents, including the one on CD20-TCB. Dimier:F. Hoffmann-La Roche Ltd: Employment, Equity Ownership. Moore:F. Hoffmann-La Roche Ltd: Employment, Equity Ownership. Weisser:Pharma Research and Early Development Roche Innovation Center Munich: Employment, Equity Ownership, Patents & Royalties. Dickinson:Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; GlaxoSmithKline: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Merck Sharpe and Dohme: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. OffLabel Disclosure: CD20-TCB (also known as RG6026, RO7082859) is a full-length, fully humanized, immunoglobulin G1 (IgG1), T-cell-engaging bispecific antibody with two fragment antigen binding ('Fab') regions that bind to CD20 (on the surface of B cells) and one that binds to CD3 (on the surface of T cells) (2:1 format). The 2:1 molecular format of CD20-TCB, which incorporates bivalent binding to CD20 on B cells and monovalent binding to CD3 on T cells, redirects endogenous non-specific T cells to engage and eliminate malignant B cells. CD20-TCB is an investigational agent.

with R/R DLBCL, 2/11 (18%) had responses at doses between 5-12 mg, 6/11 (55%) had responses at doses between 18-40 mg, and 2/2 (100%) had responses at the 80 mg dose, with both of these latter being CRs. Elevated levels of serum cytokines were observed w/ dosing; however, no correlation was observed w/ clinical efficacy.Immunohistological analysis of malignant lymph node tissue demonstrated that pts w/ high and low CD20 achieved clinical response.Relapse among responders was seen w/ either maintenance or loss of CD20 expression, suggesting antigen-dependent and independent disease escape mechanisms. Conclusions: R1979 was well tolerated in pts w/ R/R B-NHL. No DLTs and no significant neurological toxicity were observed. Tx w/ R1979 showed impressive efficacy w/ 100% ORR in R/R FL starting at doses ≥5 mg. More resistant tumors such as R/R DLBCL are showing benefit w/ increasing doses. Based on these efficacy findings, a Phase 2 study in R/R FL Gr 1-3a, R/R DLBCL, and other R/R B-NHL subtypes is planned.Introduction: CD20-TCB (RG6026) is a T-cell-engaging bispecific antibody with a novel "2:1" molecular format which preclinically showed greater avidity for CD20 antigen, combinability with other anti-CD20 antibodies, and greater efficacy as compared to other CD20-CD3 bispecific formats. NP30179 is an ongoing multicenter phase I dose escalation trial investigating the safety, tolerability, pharmacokinetics (PK), biomarkers and antitumor activity of CD20-TCB. Methods: Patients receive escalating doses of CD20-TCB as intravenous infusions guided by a model implementing a Bayesian CRM method with overdose control. To reduce the risk of cytokine release syndrome (CRS), a single dose of obinutuzumab as pretreatment (Gpt) is administered seven days prior to CD20-TCB to debulk B cells in peripheral blood and normal tissues (Bacac et al Clin Canc Res 2018).Updated data at clinically-relevant doses of 600 μg and above are reported.Results: As of February 13 th 2019 a total of 87 pts with r/r aggressive (a)NHL (DLBCL/PMBCL/trFL/Richter´s transformation; n=79) and r/r FL (n=8) received CD20-TCB doses ranging from 600 μg to 25mg in a Q2W or Q3W schedule. Median age was 61 years (range 22-84), 92 ABSTRACT median prior lines of therapy was 3 (range 1-13), and 86% pts were refractory to prior therapy. CRS (according to the criteria by Lee et al.Blood 2014) occurred in 45 patients (23% G1, 24% G2, 3% G3, 1% G4). At the highest dose cohort (25 mg) >G3 CRS occurred in 3/8 pts at cycle 1, thereby preventing further dose escalation. One patient in the 25 mg cohort died of upper GI bleeding after an episode of severe CRS. All other CRS events were manageable and resolved, and patients were retreated without delay at the same dose at cycle 2, where only one additional CRS event was seen (G1).In the efficacy evaluable pts (n=84) the ORR and CR rate by investigator assessment (Lugano 2014 criteria) in aNHL (n=76) was 46% and 29%, and in FL (n=8) 63% and 50%, respectively. In the highest dose cohorts (10-25 mg) the ORR and CR rate in aNHL (n...

In an effort to clarify and expand the theoretical foundation for behavioral researches on androgyny the present study, through an extensive literature review, attempted to establish personality structure as a function of masculine instrumentality (M) and feminine expressivity (F) in females. Results were strong and confirming, suggesting that considerable relationship may exist between certain sex role socialization practices and general personality development. In addition, the implications of instrumentality and expressivity for adjustment were investigated through a planned contrast of clinical and normal groups, with the expectation that feminine females would appear more frequently in the clinical group. However, results clarified that it is the lack of masculine instrumentality in the personality, not the feminine role per se, which is implicated in mental illness. These findings lend clarity to previous researches on androgyny and adjustment. Implications for feminine socialization and ego psychology are considered.