dacetuzumab (SGN-40) / Pfizer - LARVOL DELTA

Primary biliary cholangitis: a summary of pathogenesis and therapies. (PubMed, Ann Gastroenterol) - "First-line therapy includes ursodeoxycholic acid (UDCA), which improves liver biochemistry and slows disease progression, with obeticholic acid (OCA) as an option for non-responders. Emerging therapies, such as peroxisome proliferator-activated receptor-α agonists, biologics such as dacetuzumab and rituximab, and experimental approaches such as stem-cell therapy, offer promising advances in managing PBC. Liver transplantation remains a final treatment option for advanced cases."

Journal • Review • Hepatology • Immunology • Inflammation • Primary Biliary Cholangitis • Transplantation

Crystal structures of human CD40 in complex with monoclonal antibodies dacetuzumab and bleselumab. (PubMed, Biochem Biophys Res Commun) - "Our results offer important insights for future structural and functional studies of CD40 and provide clues to understanding the mechanism of biological response. These data can be applied to developing new strategies for designing antibodies with more therapeutic efficacy."

Journal • Oncology • CD40 • CD40LG • TNFA

Updated results of a phase 1 study of SEA-CD40, gemcitabine, nab-paclitaxel, and pembrolizumab in patients with metastatic pancreatic ductal adenocarcinoma (PDAC; SGNS40-001). (ASCO-GI 2023) - P1 | "The combination of SEA-CD40 + GnP + pembro has an acceptable safety profile and shows evidence of antitumor activity in pts with PDAC. This regimen may warrant further evaluation. Clinical trial information: NCT02376699."

Clinical • Metastases • P1 data • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • CD40

JNJ-64457107, a CD40 Agonist, Induces Cell Death in BCL6hiIRF4neg GCB Subtype of DLBCL (ASH 2018) - P1; "It was also reported that a CD40 agonist, SGN-40, induced direct cytotoxicity in diffuse large B cell lymphoma (DLBCL) cell lines (Burlington 2011), and clinical responses have been noted in this indication (Advani 2009). p65 and p52 fold induction was determined by Western blot of whole lysates. Representative data of 2 independent experiments are shown."

Biosimilar • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Immune Modulation • Inflammation • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Phase 2 study of SEA-CD40 combination therapies in advanced malignancies (SGNS40-002, trial in progress) (SITC 2022) - P1, P2 | "Five indication-specific cohorts will explore 2 different regimens: cohorts 1–3 will receive SEA-CD40 with pembrolizumab while cohorts 4 and 5 will receive SEA-CD40, pembrolizumab, carboplatin, and pemetrexed. All patients will provide written informed consent. Consent All patients will provide written informed consent."

Combination therapy • IO biomarker • P2 data • Eye Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Uveal Melanoma • CD40 • TNFA

Preliminary results of a phase 1 study of sea-CD40, gemcitabine, nab-paclitaxel, and pembrolizumab in patients with metastatic pancreatic ductal adenocarcinoma (PDAC). (ASCO-GI 2022) - P1 | "We present data from an ongoing Phase 1 study (SGNS40-001) in a PDAC cohort evaluating the combination of SEA-CD40, GnP, and pembrolizumab (pembro). The combination of SEA-CD40 + GnP + pembro demonstrated a tolerable safety profile. Evidence of immune activation was observed, consistent with the proposed mechanism of action. Follow-up for response and survival are ongoing."

Clinical • IO biomarker • P1 data • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • CD40 • CD8

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

[VIRTUAL] Phase I study of SEA-CD40, gemcitabine, nab-paclitaxel, and pembrolizumab in patients with metastatic pancreatic ductal adenocarcinoma (PDAC). (ASCO 2020) - P1 | "An ongoing Phase 1 study (SGNS40-001) is evaluating SEA-CD40 as monotherapy and in combination with pembrolizumab in patients with advanced solid or hematologic malignancies. Enrollment to this cohort began in November 2019. Research Funding: Seattle Genetics, Inc."

Clinical • P1 data • Hematological Malignancies • Immune Modulation • Inflammation • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • CD40

[VIRTUAL] Phase I study of SEA-CD40, gemcitabine, nab-paclitaxel, and pembrolizumab in patients (pts) with metastatic pancreatic ductal adenocarcinoma (PDAC) (trial in progress). (ASCO-GI 2021) - "A Phase 1 study (SGNS40-001) is evaluating SEA-CD40 monotherapy and in combination with other agents in pts with advanced solid or hematologic malignancies. Assessment of dose-limiting toxicity will occur initially in groups of 6 pts to identify the recommended phase 2 dose of SEA-CD40 for the cohort. Enrollment to this cohort began in November 2019."

Clinical • P1 data • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma

Investigational Monoclonal Antibodies in the Treatment of Multiple Myeloma: A Systematic Review of Agents under Clinical Development. (PubMed, Antibodies (Basel)) - "Combination therapy using mAbs such as indatuximab, pembrolizumab, lorvotuzumab, siltuximab or dacetuzumab with chemotherapy agents produced better outcomes as compared to monotherapies. Further clinical trials investigating mAbs targeting CD38 used in combination therapy are warranted."

Clinical • Journal • Review • Hematological Disorders • Hematological Malignancies • Immune Modulation • Inflammation • Multiple Myeloma • Oncology

Updating targets for natural killer/T-cell lymphoma immunotherapy. (PubMed, Cancer Biol Med) - "Clinical activity of targeted antibodies, such as daratumumab (anti-CD38 antibody) and brentuximab vedotin (anti-CD30 antibody), have been reported in NKTCL. Additionally, dacetuzumab and Campath-1H have demonstrated promising results...Cellular immunotherapy may be used either as maintenance therapy following initial induction chemotherapy or in cases of relapsed/refractory disease. The present review outlines the known immunotherapy targets for the treatment of NKTCL."

IO biomarker • Journal • Review • Epstein-Barr Virus Infection • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma • Transplantation • CCR4 • GZMB • IL10 • NCAM1 • PD-L1

Network meta-analysis of targeted therapies for diffuse large B cell lymphoma. (PubMed, BMC Cancer) - "This study provides the best treatment strategy for DLBCL patients in terms of overall survival, events-free survival, and overall response rate. The findings of this study require validation with further large-scale RCTs."

Journal • Retrospective data • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Thrombocytopenia

Innovative Therapeutic Approaches in Primary Cutaneous B Cell Lymphoma. (PubMed, Front Oncol) - "Newer options are monoclonal anti-CD40 antibody dacetuzumab, anti-PD-1 and anti-PD-L1 checkpoint inhibitors, and Bruton tyrosine kinase inhibitors...In aggressive PCDLCBCL, LT, rituximab with polychemotherapy is recommended. Innovative therapies include intralesional oncolytic virotherapy, systemic monoclonal antibodies, and small molecules."

Journal • Review • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Trial to define the safety and tolerability of SGN-40, rituximab, and gemcitabine in patients with DLBCL (clinicaltrials.gov) - P1, N=29; Completed; Completion date: NA -> Feb ‘10

Completion date • Hematological Malignancies

A phase 2b trial comparing dacetuzumab 1 R-ICE vs placebo + R-ICE in patients with relapsed diffuse large B-cell lymphoma (ICML 2011) - P2b, N=151; A planned futility analysis, conducted after 50% of planned pts (N=112) were treated, revealed a similar CR rate (36% dacetuzumab vs. 42% PBO) & OR rate (64% vs. 68%); After following pts ±1 year, there is a trend toward improved FFS (HR=0.789) & OS (HR=0.714) for dacetuzumab pts

P2b data • Hematological Malignancies

Role of investigational monoclonal antibodies in the treatment of multiple myeloma: A systematic review. (ASCO 2019) - "...Isatuximab (anti-CD38) and F50067 (anti-CXCR4) were the only MoAbs which produced encouraging results as monotherapy with ORR of 66.7% and 32% respectively. Isatuximab use in combination with Len-Dex produced CBR of 83%, and in combination with pomalidomide and dexamethasone CBR of 73%... CD38 remains an important target for further clinical trials in combination therapy. Trials using indatuximab, pembrolizumab, lorvotuzumab, siltuximab, and dacetuzumab in combination therapy produced better outcomes as compared to monotherapies. Surface receptor targeting antibodies in relapsed refractory multiple myeloma."

Review

Comparison of salvage therapies for relapsed or refractory diffuse large B-cell lymphoma (DLBCL): Network meta-analysis. (ASCO 2019) - "The salvage therapies investigated were rituximab plus ifosfamide, carboplatin, and etoposide(R-ICE), rituximab plus dexamethasone, high dose cytarabine, cisplatin(R-DHAP), rituximab plus gemcitabine, dexamethasone, cisplatin(R-GDP), ofatumumab plus dexamethasone, cytarabine, and cisplatin(O-DHAP), ifosfamide plus ofatumunab, carboplatin, and etoposide(O-ICE), dacetuzumab plus rituximab, ifosfamide, carboplatin and etoposide(DR-ICE). R-DHAP, R-GDP, O-ICE and O-DHAP were found to have no difference in treatment effect in achieving complete response in comparison to R-ICE. R-DHAP and O-DHAP are associated with higher number of severe adverse events in comparison with R-ICE. Outcomes mentioned above should be interpreted in the context of drugs and other factors involved in the disease."

Retrospective data

Emerging immune targets for the treatment of multiple myeloma. (PubMed, Immunotherapy) - "...Other monoclonal antibodies that have shown efficacy in combination therapy include siltuximab (OR: 66%), indatuximab (OR: 78%), isatuximab (OR: 64.5%), pembrolizumab (OR: 60%), bevacizumab (OR: 70%), dacetuzumab (OR: 39%) and lorvotuzumab (OR: 56.4%). No OR was observed with monotherapy using BI-505, siltuximab, bevacizumab, AVE-1642, figitumumab, atacicept, milatuzumab, dacetuzumab, lucatumumab, IPH2101, lorvotuzumab, BT062 and nivolumab...A recent experience of CAR T-cell (B-cell maturation antigen) therapy in advanced MM has shown global response of 100%. The future of monoclonal antibodies and adoptive T cells for MM treatment seems promising."

Journal