- |||||||||| Clinical guideline, Review, Journal: 2023 guidelines on the management of psoriasis by the Dermatological Society of Singapore. (Pubmed Central) - Oct 7, 2024
Therapeutic implica-tions in special populations, such as pregnant/ lactating women, children, the elderly, those undergo-ing surgery and those suffering from specific infections and cancer were addressed. These guidelines were developed for dermatologists, family physicians, rheumatologists and other specialists to support their selection of appropriate management options.
- |||||||||| Ibrance (palbociclib) / Pfizer
Journal, Metastases: Prognostic value of the 21-Gene Breast Recurrence Score (Pubmed Central) - Oct 6, 2024
However, clinicians should consider the occurrence of minor AEs (e.g., injection-site reactions). We found a distinct prognostic value of the 21-Gene Breast Recurrence Score
- |||||||||| Prolia (denosumab) / Amgen, Focus V (anlotinib) / Advenchen, Sino Biopharm
Journal: Clinical-proteomic classification and precision treatment strategy of chordoma. (Pubmed Central) - Oct 6, 2024
Notably, these approaches demonstrate positive treatment outcomes for each subtype in vitro and in vivo. Altogether, this work sheds light on the clinical-proteomic characteristics of chordoma and provides a candidate precision treatment strategy for chordoma according to molecular classification, underscoring their potential for clinical application.
- |||||||||| Tepezza (teprotumumab-trbw) / Roche, Amgen, Actemra IV (tocilizumab) / Roche, JW Pharma
Journal: Survey of the management of moderate to severe active Graves' orbitopathy at 28 metropolitan centers of excellence in France (Pubmed Central) - Oct 6, 2024
This study highlights the variability in practices and the importance of a multidisciplinary approach, while calling for national standardization of practices. Despite disparities in the application of recommendations, the emergence of second-line treatments such as tocilizumab and teprotumumab indicates a steady evolution in therapeutic options, although obstacles in terms of accessibility and cost remain.
- |||||||||| Adult ALL Advancements: Optimizing Cure in 2024 (Ballroom 20AB (San Diego Convention Center); Virtual) - Oct 5, 2024 - Abstract #ASH2024ASH_687;
More recently, blinatumomab and inotuzumab have shown promising results in the upfront treatment of patients with B-cell ALL...Finally, Dr. Kebriaei will review the optimal sequence for transplant within the context of CAR T therapy.
- |||||||||| MODULE 4: Future Directions in the Management of MF (Manchester Grand Hyatt San Diego, Seaport Ballroom EFGH; In-Person; Virtual) - Oct 5, 2024 - Abstract #ASH2024ASH_130;
Kebriaei will review the optimal sequence for transplant within the context of CAR T therapy. This program is supported by educational grants from CTI BioPharma, a Sobi Company, Geron Corporation, GSK, Incyte Corporation and Karyopharm Therapeutics.Mechanism of antitumor activity of navitoclax and biological rationale for its evaluation for MF Available efficacy and safety findings from the Phase III TRANSFORM-1 study of navitoclax in combination with ruxolitinib versus ruxolitinib alone for patients with previously untreated MF Potential role of navitoclax in the up-front setting and ongoing evaluation for relapsed/refractory (R/R) disease in the Phase III TRANSFORM-2 study Rationale for the evaluation of BET inhibitors for MF; updated findings from the Phase III MANIFEST-2 study combining pelabresib to ruxolitinib for JAK inhibitor-na
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen, Lunsumio (mosunetuzumab-axgb) / Roche, ERY974 / Roche
Organ-specific delivery of a mRNA-encoded bispecific T cell engager targeting Glypican-3 in hepatocellular carcinoma (Grand Ballroom AB - George R. Brown Convention Center) - Oct 4, 2024 - Abstract #SITC2024SITC_1755;
Background Bispecific T-cell engaging antibodies (BiTEs) have been clinically validated (e.g., blinatumomab, mosunetuzumab) but are mostly limited to hematological cancers...MTS105, at dose levels associated with a significantly lower peripheral BiTE Cmax (maximum concentration) and AUC (area under the curve), achieved a better anti-tumor efficacy than the Fc-domain-containing antibody-based BiTE (ERY974)...Conclusion The mRNA-encoded BiTE demonstrated optimal tissue/tumor-specific PK, safety and potent anti-tumor activity in preclinical models. MTS105 is currently in early human trials to assess its safety and preliminary efficacy.
- |||||||||| etrumadenant (AB928) / Arcus Biosci, Gilead
The adenosine receptor antagonist etrumadenant reduces tumor adenosine-regulated NR4A gene expression and increases mCRC inflammation in patients from the ARC-9 trial (Exhibit Halls AB - George R. Brown Convention Center) - Oct 4, 2024 - Abstract #SITC2024SITC_1588;
P1/2
Etruma, in combination with zimberelimab (Z) (anti-PD-1 antibody), FOLFOX, and bevacizumab (bev) (EZFB regimen) demonstrated an impressive overall survival (OS) benefit compared to the regorafenib (rego) control arm in third-line, chemo-resistant mCRC in the primary analysis of the ARC-9 study (NCT04660812)...Consistent with an adenosine-targeting MoA, EZFB provided significantly improved PFS and OS compared to rego for patients with CD73 IHC-positive tumors. Ethics Approval All patients were provided the most recent copy of the Informed Consent form describing the study and associated interventions, which the patient or their legally authorized representative were required to sign and date prior to participating in the study.
- |||||||||| Imlygic (talimogene laherparepvec) / Amgen, Opdivo (nivolumab) / BMS
Interim analysis of a phase II study of talimogene laherparepvec (T-VEC) followed by combination T-VEC + nivolumab in non-melanoma skin cancers and refractory cutaneous lymphoma (NCI#10057) (Exhibit Halls AB - George R. Brown Convention Center) - Oct 4, 2024 - Abstract #SITC2024SITC_1470;
Conclusions Analysis of data from Part I of this clinical trial suggests that T-VEC monotherapy did not translate to broad clinical efficacy across all tumor types, though may show activity in patients without visceral metastases. MCC and CSCC expansion cohorts (Part II) will be reported separately.View this table:View inline View popup Download powerpoint Abstract 621 Table 1 Best response to T-VEC monotherapyDownload figure Open in new tab Download powerpoint Abstract 621 Figure 1 Elderly female with at least 4 in-transit metastases from MCC on the left lower leg, who achieved a durable PR on T-VEC monotherapy
- |||||||||| Novel dual MEK inhibitors for RAS-mutated colorectal cancer as a single agent or in combination with known therapies including aPD-1 (Exhibit Halls AB - George R. Brown Convention Center) - Oct 4, 2024 - Abstract #SITC2024SITC_1372;
In a CRC SW837 (KRAS-G12C, insensitive to Adagrasib) model, ABM-4218 showed synergic effect with Adagrasib, as well as the EGFR antibody Cetuximab...Conclusions In summary, A series of novel dual MEK inhibitors have been studied for the possible treatment of colorectal cancer by modulating the pERK level via the MEK1/2 kinase, which is the mechanism for the EGFR negative feedback loop. Good in vivo efficacies are observed in several CRC animal models, including the combination with immunotherapy.
- |||||||||| Actimmune (interferon gamma-1 b) / Clinigen, Amgen
The battle within: AML (Exhibit Halls AB - George R. Brown Convention Center) - Oct 4, 2024 - Abstract #SITC2024SITC_1318;
as a cytokine impairing T-cell function. Ethics Approval Samples from healthy donors and samples from AML patients were collected with written consent in accordance with the Declaration of Helsinki and with approval from the Institutional Review Board of LMU Munich.
- |||||||||| CT-0525 / CARISMA Therap, CT-0508 / CARISMA Therap
A phase 1, first-in-human study of autologous monocytes engineered to express an anti-HER2 chimeric antigen receptor (CAR) in participants with HER2 overexpressing solid tumors (Exhibit Halls AB - George R. Brown Convention Center) - Oct 4, 2024 - Abstract #SITC2024SITC_1202;
We previously developed human chimeric antigen receptor macrophages (CAR-Macrophage) and have shown potent anti-tumor activity in pre-clinical solid tumor models.1 The anti-HER2 CAR-Macrophage cell therapy product, CT-0508, was evaluated in a Phase 1 trial as a monotherapy and in combination with pembrolizumab...Methods This Phase 1, first-in-human study evaluates the preliminary safety, feasibility, tolerability, trafficking, TME activation, and initial evidence of efficacy of the investigational CAR-Monocyte product CT-0525 in pts with locally advanced unresectable/metastatic solid tumors overexpressing HER2...Filgrastim mobilized autologous CD14+ monocytes are collected by apheresis, followed by manufacturing and cryopreservation...Correlative assessments include pre- and post-treatment biopsies and blood samples for safety, immunogenicity, pharmacokinetics, tumor trafficking, TME modulation, epitope spreading, and other translational biomarkers. Ethics Approval The study has obtained ethics approval with local IRBS at enrolling clinical sites and all participants gave informed consent before being enrolled in the study.
- |||||||||| Differently specific BTK inhibitors impair anti-tumor T-cell immunity (Exhibit Halls AB - George R. Brown Convention Center) - Oct 4, 2024 - Abstract #SITC2024SITC_826;
Methods To evaluate the impact of BTKi, we used spectral flow cytometry to assess T-cell activation and tumor-killing in vitro, with transgenic T-cells, CD3xCD19 bsAb blinatumomab(blina) and CAR-T cells from murine models, healthy controls and lymphoma patients...Results In vitro, Ibrut markedly reduced CD8 proliferation, activation and lymphoma killing, whereas Zanubrutinib and Acalabrutinib(acala) had minimal effects...While many datasets indicate improved global T-cell health in Ibrut-treated patients during therapy, these reports may be confounded by the T-cell suppressive effects of heavy tumor burden and immune benefits of tumor debulking. Rigorous comparison of differently specific BTKi suggests that avoiding inhibition of ITK, and possibly RLK, may yield combination BTKi/T-cell therapies with optimal anti-tumor effects in our patients.
- |||||||||| Blincyto (blinatumomab) / Astellas, Amgen, Lunsumio (mosunetuzumab-axgb) / Roche, ERY974 / Roche
Organ-specific delivery of a mRNA-encoded bispecific T cell engager targeting Glypican-3 in hepatocellular carcinoma (Exhibit Halls AB - George R. Brown Convention Center) - Oct 4, 2024 - Abstract #SITC2024SITC_804;
Background Bispecific T-cell engaging antibodies (BiTEs) have been clinically validated (e.g., blinatumomab, mosunetuzumab) but are mostly limited to hematological cancers...MTS105, at dose levels associated with a significantly lower peripheral BiTE Cmax (maximum concentration) and AUC (area under the curve), achieved a better anti-tumor efficacy than the Fc-domain-containing antibody-based BiTE (ERY974)...Conclusion The mRNA-encoded BiTE demonstrated optimal tissue/tumor-specific PK, safety and potent anti-tumor activity in preclinical models. MTS105 is currently in early human trials to assess its safety and preliminary efficacy.
- |||||||||| Nutlin-3 / EMD Serono, navtemadlin (KRT-232) / Kartos Therap
Anticancer effects and mechanisms of herbs used in traditional Chinese medicine on human lung carcinoma and hepatoma cells (Exhibit Halls AB - George R. Brown Convention Center) - Oct 4, 2024 - Abstract #SITC2024SITC_705;
Besides, we found that although P. chinensis affected different pathways in A549 and Huh7 cells, the triggered transcriptional factors were similar and they were associated with the cell cycle regulation. Conclusions We conclude that P. chinensis has a significant anticancer effect on both A549 and Huh7 cells, signifying its potential for clinical translation in cancer treatment after additional preclinical and clinical studies.Download figure Open in new tab Download powerpoint Abstract 701 Figure 1
- |||||||||| Luminescent reporter assays for ADCP and ADCC characterization of immunotherapies targeting primary effector cells (Exhibit Halls AB - George R. Brown Convention Center) - Oct 4, 2024 - Abstract #SITC2024SITC_564;
A physiologically relevant FcgR bioassay was also qualified using Cetuximab and Rituximab against A549 and Raji target cells...Differentiated macrophages were used in a thaw-and-use format against Ramos or SK-BR-3 target cells to measure ADCP activity of ritixumab and trastuzumab respectively...Conclusions These bioassays are both robust and user-friendly and adhere to ICH guidelines with pre-qualification. Collectively, these innovative reporter bioassays furnish a sturdy, high-throughput toolkit to expedite the exploration and advancement of immunotherapies targeting macrophage effector functions.
- |||||||||| Imdelltra (tarlatamab-dlle) / Amgen
DLL3-TOPAbody: a next-generation trispecific T cell engager with 4 (Exhibit Halls AB - George R. Brown Convention Center) - Oct 4, 2024 - Abstract #SITC2024SITC_542;
DLL3-CD3 bispecific T cell engager Tarlatamab has received accelerated approval for the treatment of extensive stage small cell lung cancer (ES-SCLC)...Conclusions DLL3-TOPAbody represents a novel DLL3-targeted T cell engager with potent and durable anti-tumor activity. Together, these results underscore the potential of DLL3-TOPAbody as a novel therapeutic agent against DLL3+ cancers and support its advancement into clinical development.
- |||||||||| Monjuvi (tafasitamab-cxix) / Incyte, Blincyto (blinatumomab) / Astellas, Amgen, Gazyva (obinutuzumab) / Roche, Biogen
A feasible alternative to CD19-CAR T lymphocytes: the potential of Cytokine-Induced Killer (CIK) cells combined with anti-CD19/20 antibodies (Exhibit Halls AB - George R. Brown Convention Center) - Oct 4, 2024 - Abstract #SITC2024SITC_446;
The heatmaps illustrate the cytokine concentrations in all experimental conditionsDownload figure Open in new tab Download powerpoint Abstract 396 Figure 6 In vivo Therapy. The combined CIK + Tafa therapy was able to reduce tumor growth and significantly prolong the survival of treated mice, both in the Burkitt lymphoma model (Raji) and in the mantle cell lymphoma model (Granta-519)
- |||||||||| conatumumab (AMG 655) / Amgen
Journal: The generation of stable microvessels in ischemia is mediated by endothelial cell derived TRAIL. (Pubmed Central) - Oct 4, 2024
Single-cell RNA sequencing revealed heparin-binding EGF-like growth factor in mediating EC-pericyte communications dependent on TRAIL. These studies highlight unique TRAIL-dependent mechanisms mediating neo-angiogenesis and vessel stabilization and the potential of repurposing TRAIL-R2 agonists to stimulate stable and functional microvessel networks to treat ischemia in PAD.
- |||||||||| Clinical, Review, Journal: Preventive drug treatments for adults with chronic migraine: a systematic review with economic modelling. (Pubmed Central) - Oct 4, 2024
The adverse events review included 40 randomised controlled trials with 25,891 participants; 3 additional drugs, amitriptyline, atogepant and rimegepant, were included...Consensus was reached on the top three recommendations for future research on medications to prevent chronic migraine: (1) calcitonin gene-related peptide monoclonal antibodies and Botox versus calcitonin gene-related peptide monoclonal antibodies, (2) candesartan versus placebo and (3) flunarizine versus placebo...63. See the NIHR Funding and Awards website for further award information.
- |||||||||| Prolia (denosumab) / Amgen
Journal: Giant cell tumor of the cervical spine: A very uncommon cause for cervical spine compression. (Pubmed Central) - Oct 4, 2024
She was proposed for adjuvant treatment based on Denosumab...Meanwhile, she experienced a pulmonary embolism leading to her demise. This case underscores the importance of considering giant cell tumors in the differential diagnosis of cervical spine lesions and emphasizes the successful and prompt management through a multidisciplinary approach involving surgical intervention and adjuvant therapy.
- |||||||||| Lumakras (sotorasib) / Amgen
Trial primary completion date: A Phase 1/2, Study Evaluating the Safety, Tolerability, PK, and Efficacy of Sotorasib (AMG 510) in Subjects With Solid Tumors With a Specific KRAS Mutation (CodeBreaK 100) (clinicaltrials.gov) - Oct 4, 2024
P1/2, N=713, Active, not recruiting,
Despite maximum-tolerated doses of statins from age 32, combined with ezetimibe and evolocumab, her LDL-C levels remained critically elevated at 12-14 Trial primary completion date: Oct 2027 --> May 2028
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