Magrolimab is a monoclonal antibody that blocks cluster of differentiation 47, a don't-eat-me signal overexpressed on cancer cells. Cluster of differentiation 47 blockade by magrolimab promotes macrophage-mediated phagocytosis of tumor cells and is synergistic with azacitidine, which increases expression of eat-me signals. We report final phase Ib data in patients with untreated higher-risk myelodysplastic syndromes (MDS) treated with magrolimab and azacitidine (ClinicalTrials.gov identifier: NCT03248479).
1075 Background: In the phase 3 TROPiCS-02 study, SG, a Trop-2–directed antibody-drug conjugate coupled to SN-38 as the payload, demonstrated clinically meaningful improvement in survival outcomes over chemotherapy in patients (pts) with pretreated HR+/HER2- mBC. SN-38 leads to double-stranded DNA damage, therefore we hypothesized that in tumors with defective DDR machinery, SG may provoke synthetic lethality. We report on comprehensive genomic analysis of DDR gene variants and the impact on SG clinical efficacy in this patient population. Methods: Pts with HR+/HER2– mBC who received prior taxane, endocrine therapy (ET), CDK4/6 inhibitor, and 2-4 prior lines of chemotherapy were randomized to receive SG (10 mg/kg IV days 1 and 8, every 21 days) or treatment of physician’s choice (TPC) until disease progression or unacceptable toxicity. DDR gene deleterious variants were identified using whole exome sequencing (WES) on archival or screening tumor tissues based on 142 DDR pathway genes annotated in the Kyoto Encyclopedia Genes and Genomes (KEGG) database and Human DNA Repair Gene database; association between these variants and clinical outcomes was evaluated using Cox regression model as Hazard Ratio (HR) with 95% Confidence Intervals (CI). Results: Of 543 patients included in the intent-to-treat (ITT) population, WES data was available for 195 (36%) – clinicopathological features were similar between ITT and WES dataset (median age = 57 vs 58 for SG and 55 vs 55 for TPC; prior lines of chemotherapy >2 lines = 59% vs 57% for SG and 58% vs 55% for TPC). Estrogen Receptor (ER)>10% and prior lines of chemotherapy were comparable between WT and MUT in SG arm and in TPC arm. Overall, 114 (58%) of tumor samples had ≥1 deleterious alteration with BRCA2, PRKDC, ATM being the most common alterations. The primary results are included (Table). Although all patients demonstrated improved efficacy with SG vs TPC, patients with DDR mutant MBC had numerically greater benefit in PFS vs WT (MUT HR= 0.61; WT HR= 0.76) and OS (MUT HR = 0.68; WT HR= 0.82). Conclusions: While SG benefit over TPC was observed in both DDR WT and DDR MUT HR+/HER2– mBC, numerically greater benefit was observed for patients with DDR deficient tumors, suggesting possible synergy between the DDR pathway and SG’s anti-tumor effect. Further study of the synergistic effects of SG in combination with agents targeting DDR pathway are warranted. Clinical trial information: NCT03901339 . [Table: see text]
Abstract. The meat rabbit industry in China relies on foreign breeds and synthetic lines; the development of superior domestic breeds has not yet been fully realised. We compared the meat quality of two Chinese local breeds of black rabbits (Laiwu black and Minxinan black) and Hyla commercial rabbits, to provide a reference for the utilisation of meat rabbit breeds. In the present study, 35 d old Laiwu black rabbits, Minxinan black rabbits, and Hyla rabbits (20 rabbits each) were selected and reared under identical feeding and management conditions for 7 weeks, after which 10 randomly selected rabbits from each group were slaughtered for the analysis of meat quality. The a∗ (redness) value of the two local breeds was significantly higher than that of Hyla rabbits (p<0.01). The shearing force and drip loss of Laiwu black rabbits were significantly lower than those of the other groups (p<0.05). The two local breeds exhibited significantly higher myoglobin levels than Hyla rabbits (p<0.01), while melanin was highest in the meat of Minxinan black rabbits. The essential amino acids (valine, isoleucine, leucine and lysine) were significantly lower in Minxinan black rabbits than in the other groups (p<0.05). Aldehyde (heptanal, octanal) contents in Minxinan black meat were significantly higher than those of the other groups (p<0.01); however, nucleotide (guanine, adenine) contents were significantly lower (p<0.01). Unsaturated fatty acids (oleic, linoleic, α-linolenic) were significantly higher in the meat of Laiwu black rabbits than in those of the other groups (p<0.05). Both Laiwu black and Minxinan black rabbits have certain advantages in terms of nutritional indicators while also having good meat colour and flavour. The results of this study provide a theoretical reference for the research and development of meat rabbit breeds.
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)
'%3e%3cpath fill='%23012169' d='M0 0v30h60V0z'/%3e%3cpath stroke='%23fff' stroke-width='6' d='m0 0 60 30m0-30L0 30'/%3e%3cpath stroke='%23C8102E' stroke-width='4' d='m0 0 60 30m0-30L0 30' clip-path='url(%23b)'/%3e%3cpath stroke='%23fff' stroke-width='10' d='M30 0v30M0 15h60'/%3e%3cpath stroke='%23C8102E' stroke-width='6' d='M30 0v30M0 15h60'/%3e%3c/g%3e%3c/svg%3e)