ocaratuzumab (AME-133v) / Mentrik, Eli Lilly - LARVOL DELTA

EXAMINING THE ASSOCIATIONS BETWEEN GROCERY STORE FACTORS AND FOOD ALLERY LABEL COMPLIANCE (ACAAI 2024) - "The findings suggest that grocery store size influences the accuracy of food allergen labeling, with larger stores more likely to label products correctly. Targeted interventions are needed to improve labeling practices, especially in smaller grocery stores. Frequency Table of Correct Labeling within Food Categories, by Grocery Store Category Allergen Store Category P Large Small N Pct N Pct Gluten 133 100% 110 100% N/A Correct Incorrect 0 0% 0 0% Sesame 133 100% 109 99.1% 0.4257 Correct Incorrect 0 0% 1 0.9% Milk 133 100% 109 99.1% 0.0292 Correct Incorrect 0 0% 1 0.9% Egg 124 93.2% 93 84.6% 0.5912 Correct Incorrect 9 6.8% 17 15.5% Fish 132 99.25% 108 98.2% 0.2039 Correct Incorrect 1 0.75% 2 1.8% Shellfish 133 100% 108 98.2% 0.4527 Correct Incorrect 0 0% 2 1.8% Tree Nuts 133 100% 109 99.1% 0.3811 Correct Incorrect 0 0% 1 0.9% Peanuts 129 97% 109 99.1% 0.2039 Correct Incorrect 4 3% 1 0.9% Wheat 133 100% 108 98.2% 0.0246 Correct Incorrect 0 0 2 1.8% Soybeans 132 99.25% 103..."

Compliance • Food Hypersensitivity • Immunology

Immunotherapy in indolent Non-Hodgkin's Lymphoma. (PubMed, Leuk Res Rep) - "Other than that, a resistance mechanism to rituximab emerged by inducing a failure in the apoptosis mechanism...Here came the development of 90Y-ibritumomab tiuxetan and 131I-tositumomab. After it, humanized anti-CD20 emerged ofatumumab, IMMU106 (veltuzumab) in 2005, and ocrelizumab which are considered as second generation anti-CD20 and 3 generation anti-CD20 include AME-133v (ocaratuzumab), PRO131921 and GA101 (obinutuzumab). Also multiple other agents emerged targeting different surface cell antigens like CD52 (alemtuzumab), CD22 (unconjugated epratuzumab and calicheamicin conjugated CMC-544 [inotuzumab ozogamicin]), CD80 (galiximab), CD2 (MEDI-507 [siplizumab]), CD30 (SGN-30 and MDX-060 [iratumumab], Brentuximab vedotin), CD40 (SGN-40), and CD79b (Polatuzumab). Other agents include MAB targeting T-Cells like mogamulizumab, Denileukin Diftitox and BiTEs or bispecific T cell engagers like Mosunetuzumab, Glofitamab, and Epcoritamab...Another important aspect in..."

Journal • Allergy • Chronic Lymphocytic Leukemia • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Immune Modulation • Indolent Lymphoma • Inflammation • Leukemia • Lymphoma • Lymphoplasmacytic Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Waldenstrom Macroglobulinemia • CD22 • CD40 • CD52 • CD79B • TNFRSF8

Epitope Mapping of Rituximab Using HisMAP Method. (PubMed, Monoclon Antib Immunodiagn Immunother) - "Specific anti-CD20 monoclonal antibodies (mAbs), such as rituximab, ofatumumab, veltuzumab, and ocaratuzumab, have been developed. In this study, we tried to determine the binding epitope of rituximab for CD20 using histidine-tag insertion for epitope mapping (HisMAP) method. The results showed that two regions of CD20 (-PANPSE- and -CYSIQ-) are important for rituximab-binding for CD20."

Journal • Hematological Malignancies • Immunology • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Efficacy of ocaratuzumab (AME-133v) in relapsed follicular lymphoma patients refractory to prior rituximab (ASCO 2012) - Presentation time: Mon, Jun 4; 1:15 PM - 5:15 PM; Anticipated presentation at ASCO 2012

Anticipated P1/2 data presentation • Hematological Malignancies

A phase 1 study of AME-133v (LY2469298) an Fc-engineered humanized monoclonal antibody in FcγRIIIa-genotyped patients with previously treated follicular lymphoma (Clin Cancer Res) - P1/2, N=23; AME 06.133v.A; AME-133v demonstrated non-linear PK with properties similar to rituximab; Selective reduction of B-cells during & after AME-133v treatment was demonstrated by flow cytometry of peripheral blood; A PR or CR was observed in 5 of 23 (22%) pts & the mPFS was 25.4 weeks

P1 data • Hematological Malignancies • Non-Hodgkin’s Lymphoma

Ocaratuzumab, an Fc-engineered antibody demonstrates enhanced antibody-dependent cell-mediated cytotoxicity in chronic lymphocytic leukemia (MAbs) - "In extended allogeneic ADCC E:T titration, ocaratuzumab (0.1 µg/mL) demonstrated 19.4% more cytotoxicity than rituximab (E:t = 0.38:1; P = 0.0066) and 21.5% more cytotoxicity than ofatumumab (E:t = 1.5:1; P = 0.0015). In autologous ADCC, ocaratuzumab (10 µg/mL) demonstrated ~1.5-fold increase in cytotoxicity compared with rituximab or ofatumumab at all E:T ratios tested (E:Ts = 25:1,12:1,6:1; all P<0.001)."

Preclinical • Hematological Malignancies • Non-Hodgkin’s Lymphoma

Efficacy of ocaratuzumab (AME-133v) in relapsed follicular lymphoma patients refractory to prior rituximab (ASCO 2012) - Presentation time: Monday June 4, 1:15 PM to 5:15 PM; P1, N=56; AME 06.133v.A; Prolonged PFS in selected pts following ocaratuzumab suggests that the increased binding affinity to CD16 and improved antibody-dependent cell-mediated cytotoxicity (ADCC) of this antibody is clinically relevant; As a single agent, ocaratuzumab may provide prolonged clinical benefit in relapsed FL pts and a clinical trial comparing ocaratuzumab to rituximab is in preparation

P1 data • Hematological Malignancies • Non-Hodgkin’s Lymphoma

Results of a phase 1 study of AME-133v (LY2469298), an Fc-engineered humanized monoclonal anti-CD20 antibody, in FcγRIIIa-genotyped patients with previously treated follicular lymphoma (Clin Cancer Res) - P1, N=23; AME-133v showed a 13- to 20-fold greater binding affinity for CD20 & was 5- to 7-fold more potent than rituximab in ADCC assays; Cell binding assays showed AME-133v and rituximab competed for an overlapping epitope on the CD20 antigen, & AME-133v inhibited binding of biotinylated rituximab to CD20 in a concentration-dependent manner; PR or CR was observed in 5 of 23 (22%) pts and the mPFS was 25.4 wks

P1 data • Hematological Malignancies • Non-Hodgkin’s Lymphoma

Anti-CD20 Therapy Reliance on Antibody-Dependent Cellular Phagocytosis Affects Combination Drug Choice (ASH 2019) - "To directly compare ADCC versus ADCP, we previously used a panel of anti-CD20 mAbs (rituximab, ofatumumab, obinutuzimab, ocaratuzumab) to test cytotoxicity of paired human NK cells and monocyte-derived macrophages (hMDM) against CLL cells in vitro...Our initial studies showed that ibrutinib (IBR), but not acalabrutinib (Acala), significantly decreased anti-CD20 ADCP as measured by a flow cytometry-based assay that measures single timepoint cell collections...IBR off-target candidates include other tyrosine kinases in the TEC (tyrosine kinase expressed in hepatocellular carcinoma) family. These data suggest that a a highly selective BTK inhibitor with little effect on ADCP could be a more suitable drug to combine with therapeutic mAb(s)."

Cellular Cytotoxicity of Next Generation CD20 Monoclonal Antibodies. (PubMed, Cancer Immunol Res) - "...ADCP and ADCC induction by rituximab, ofatumumab, obinutuzumab, or ocaratuzumab was measured using treatment-naïve chronic lymphocytic leukemia (CLL) target cells and either human monocyte-derived macrophages (for ADCP) or natural killer (NK) cells (for ADCC). Specific effects on ADCP were evaluated for clinically relevant drug combinations using BTK inhibitors (ibrutinib and acalabrutinib), PI3Kδ inhibitors (idelalisib, ACP-319, and umbralisib), and the BCL2 inhibitor venetoclax...Overall, ADCP was a better measure of clinically relevant mAb-induced cellular cytotoxicity, and next generation mAbs could activate ADCP at significantly lower concentrations, suggesting the need to test a wide-range of dose sizes and intervals to establish optimal therapeutic regimens. Complement activation by mAbs can contribute to ADCP, and venetoclax, acalabrutinib, and umbralisib are preferred candidates for multi-drug therapeutic regimens."

Journal

Evaluation of a Novel Medicolegal Death Investigator-Based Suicide Surveillance System to the National Violent Death Reporting System. (PubMed, Am J Forensic Med Pathol) - "...To evaluate the performance of each surveillance system, differences in the prevalence of suicide risk factor data from SRFSS were compared with the county OR-VDRS subset for the same 133 suicides occurring in 2014-2015...The prevalence was significantly different between the 2 surveillance systems for 21 (78%) of 27 variables. This study demonstrates the truly exceptional data quality and timeliness of MDI information over traditional sources."

Journal

ECONOMIC EVALUATIONS OF SUBCUTANEOUSLY ADMINISTERED ONCOLOGY THERAPIES- A HEALTH TECHNOLOGY ASSESSMENT (HTA) LANDSCAPE REVIEW (ISPOR 2019) - "...METHODS A structured literature review was conducted of HTA recommendations on oncology therapies that have transitioned from intravenous to subcutaneous administration: trastuzumab, rituximab, alemtuzumab, bortezomib, daratumumab, pertuzumab, and ocaratuzumab...Similarly, in published literature, subcutaneous trastuzumab and rituximab incurred lower direct and indirect drug administration costs...However, this is a conservative approach which may underestimate value, as additional benefits of subcutaneous administration, such as increased patient preference, may translate to higher quality-adjusted life-year (QALY) benefits that are not being captured in current health economic evaluations. Future modelling methods should consider these benefits in order to appropriately demonstrate the full value of subcutaneously administered oncology therapies."

HEOR