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Background HLX07 is a fully-humanised anti-epidermal growth factor receptor (EGFR) monoclonal antibody (mAb) with re-engineered Fab rendering its less immunogenic and better binding affinity than cetuximab. In-vivo studies of HLX07 demonstrated either equal or superior efficacy to cetuximab at the same dose level. Here, we present the data from the phase 1 study of HLX07 in advanced solid tumours. Methods We conducted an open-label, dose-escalation study to evaluate the safety, maximum tolerated dose (MTD), PK and clinical response of HLX07 in subjects with recurrent or metastatic solid tumours unamendable to standard therapy. Subjects received once weekly intravenous infusion of HLX07 at doses of 50, 100, 200, 400, 600 and 800 mg until disease progression, withdrawal of consent or development of toxicities. Dose-limiting toxicities (DLTs) were evaluated within 28 days after the first dose and CT/MRI scans were evaluated every 8 weeks after the first infusion for treatment response. Safety, immunogenicity, PK and clinical response evaluations were performed throughout the study period. Results HLX07 was first approved to initiate clinical trial by the Taiwan and US FDAs; subject recruitment began in late 2016. As of 13-June-2019, 19 subjects received HLX07 in the study with the longest follow-up period of over 224 days. Among the 16 subjects who had been evaluated for efficacy, 1 subject with advanced colon cancer in 600 mg cohort achieved partial response and 5 subjects in different cohorts achieved stable disease status. Particularly at the 400 mg dose level, 30% of patients were in stable disease status at week 16 evaluation. Possibly related to HLX07 AEs with grade >2 severity included skin rashes (10.6%), hypophosphatemia (5.3%), hypomagnesemia (5.3%) and hypocalcemia (5.3%). No novel safety signal was identified; no DLT was noted up to 800 mg cohort. The PK data up to 600 mg was described in the following table. Table: 68P PK parameter of HLX07 at 50, 100, 200, 400 and 600 mg dose levels Dose (mg)  Cmax (×μg/mL)   AUC0-t (×h*μg/mL)   t1/2 (MEAN CV%)(h)   -  1st dose  4th dose  1st dose  4th dose  1st dose  4th dose  50  15.0  15  351  311  31.08 (14.12%)  23.11(32.61%)  100  43.2  41  2067  3110  39.70 (37.61%)  55.87 (11.98%)  200  76.1  99  5793  9541  74.61 (12.49%)  154.56 (38.73%)  400  119  216  9085  23274  106.60 (19.68%)  131.28 (57.48%)  600  158  311  14278  69567  138.64 (10.49%)  210.27 (26.59%)  Dose (mg)  Cmax (×μg/mL)   AUC0-t (×h*μg/mL)   t1/2 (MEAN CV%)(h)   -  1st dose  4th dose  1st dose  4th dose  1st dose  4th dose  50  15.0  15  351  311  31.08 (14.12%)  23.11(32.61%)  100  43.2  41  2067  3110  39.70 (37.61%)  55.87 (11.98%)  200  76.1  99  5793  9541  74.61 (12.49%)  154.56 (38.73%)  400  119  216  9085  23274  106.60 (19.68%)  131.28 (57.48%)  600  158  311  14278  69567  138.64 (10.49%)  210.27 (26.59%)  Table: 68P PK parameter of HLX07 at 50, 100, 200, 400 and 600 mg dose levels Dose (mg)  Cmax (×μg/mL)   AUC0-t (×h*μg/mL)   t1/2 (MEAN CV%)(h)   -  1st dose  4th dose  1st dose  4th dose  1st dose  4th dose  50  15.0  15  351  311  31.08 (14.12%)  23.11(32.61%)  100  43.2  41  2067  3110  39.70 (37.61%)  55.87 (11.98%)  200  76.1  99  5793  9541  74.61 (12.49%)  154.56 (38.73%)  400  119  216  9085  23274  106.60 (19.68%)  131.28 (57.48%)  600  158  311  14278  69567  138.64 (10.49%)  210.27 (26.59%)  Dose (mg)  Cmax (×μg/mL)   AUC0-t (×h*μg/mL)   t1/2 (MEAN CV%)(h)   -  1st dose  4th dose  1st dose  4th dose  1st dose  4th dose  50  15.0  15  351  311  31.08 (14.12%)  23.11(32.61%)  100  43.2  41  2067  3110  39.70 (37.61%)  55.87 (11.98%)  200  76.1  99  5793  9541  74.61 (12.49%)  154.56 (38.73%)  400  119  216  9085  23274  106.60 (19.68%)  131.28 (57.48%)  600  158  311  14278  69567  138.64 (10.49%)  210.27 (26.59%)  Conclusions HLX07 is generally well tolerated without reaching the MTD up to 800 mg weekly cohort and exhibits antitumour activity with durable objective responses at various doses. These findings support the initiation of a phase 1b/2 study of HLX07 plus chemotherapy in advanced solid tumours with the longest follow-up time of over 275 days as of 20-June-2019. Additionally, HLX07 is currently under safety and efficacy investigation combined with anti-PD-1 antibody, HLX10, in squamous cell carcinoma of head and neck. Clinical trial identification HLX07-001 Phase 1 study (NCT02648490); HLX07-002 Phase 1b/2 study (NCT03577704). Legal entity responsible for the study Shanghai Henlius Biotech, Inc.; Taiwan Henlix Biotech Co. Ltd. Funding Shanghai Henlius Biotech, Inc. Disclosure M.M. Hou: Research grant / Funding (institution): Taiwan Henlix Biotech Co. Ltd. C.L. Ho: Research grant / Funding (institution): Taiwan Henlix Biotech Co. Ltd. H.Y. Lin: Research grant / Funding (institution): Taiwan Henlix Biotech Co. Ltd. W. Jiang: Full / Part-time employment: Shanghai Henlius Biotech, Inc. S. Liu: Full / Part-time employment: Shanghai Henlius Biotech,Inc. Y. Hong: Full / Part-time employment: Shanghai Henlius Biotech, Inc. A. LUK: Full / Part-time employment: Shanghai Henlius Biotech, Inc. S.F. Lin: Full / Part-time employment: Taiwan Henlix Biotech Co. Ltd. T.C. Hsieh: Full / Part-time employment: Taiwan Henlix Biotech Co. Ltd. E. Liu: Full / Part-time employment: Taiwan Henlix Biotech Co. Ltd. [ABSTRACT FROM AUTHOR]

Nivolumab plus ipilimumab demonstrated promising clinical activity and durable responses in sorafenib-treated patients with advanced hepatocellular carcinoma (HCC) in the CheckMate 040 study at 30.7-month median follow-up. Here, we present 5-year results from this cohort. Patients were randomized 1 : 1 : 1 to arm A [nivolumab 1 mg/kg plus ipilimumab 3 mg/kg Q3W (four doses)] or arm B [nivolumab 3 mg/kg plus ipilimumab 1 mg/kg Q3W (four doses)], each followed by nivolumab 240 mg Q2W, or arm C (nivolumab 3 mg/kg Q2W plus ipilimumab 1 mg/kg Q6W). The primary objectives were safety, tolerability, investigator-assessed objective response rate (ORR), and duration of response (DOR) per RECIST version 1.1. A total of 148 patients were randomized across treatment arms. At 60-month minimum follow-up (62.6-month median follow-up), the ORR was 34% (n = 17), 27% (n = 13), and 29% (n = 14) in arms A, B, and C, respectively. The median DOR was 51.2 months [95% confidence interval (CI) 12.6 months-not estimable (NE)], 15.2 months (95% CI 7.1 months-NE), and 21.7 months (95% CI 4.2 months-NE), respectively. The median overall survival (OS) was 22.2 months (34/50; 95% CI 9.4-54.8 months) in arm A, 12.5 months (38/49; 95% CI 7.6-16.4 months) in arm B, and 12.7 months (40/49; 95% CI 7.4-30.5 months) in arm C; 60-month OS rates were 29%, 19%, and 21%, respectively. In an exploratory analysis of OS by response (6-month landmark), the median OS was meaningfully longer for responders versus nonresponders for all arms. No new safety signals were identified with longer follow-up. There were no new discontinuations due to immune-mediated adverse events since the primary analysis. Consistent with the primary analysis, the arm A regimen of nivolumab plus ipilimumab continued to demonstrate clinically meaningful responses and long-term survival benefit, with no new safety signals in patients with advanced HCC following sorafenib treatment, further supporting its use as a second-line treatment in these patients. • After 5 years, nivolumab plus ipilimumab continued to show clinically meaningful benefit in sorafenib-treated advanced HCC. • The ORR in arm A [nivolumab 1 mg/kg + ipilimumab 3 mg/kg Q3W (four doses), then nivolumab 240 mg Q2W] was 34%. • Responses were durable (median DOR 51.2 months) and long-term survival benefit was achieved (5-year OS rate 29%) in arm A. • No new safety signals were identified, and there were no additional discontinuations due to immune-mediated adverse events since primary analysis. • These results further support the use of the arm A regimen of nivolumab plus ipilimumab for sorafenib-treated advanced HCC. [ABSTRACT FROM AUTHOR]

We retrospectively reviewed 102 patients with esophageal cancer (97.1% squamous cell carcinoma, 96.1% stage III) received FDG-PET staging and were treated by chemoradiotherapy with or without resection to assess whether the pretreatment [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) maximum standardized uptake value (SUVmax) of the primary tumor and metastatic lymph nodes can predict the prognosis of patients with esophageal cancer. Receiver operating characteristic analysis was performed to find the cutoff values for primary tumor SUVmax and nodal SUVmax. The influence of clinical factors including primary tumor SUVmax and nodal SUVmax on local progression-free survival, nodal progression-free survival (NPFS), distant metastasesfree survival (DMFS), and overall survival (OS) were evaluated using univariate and multivariate analyses. A total of 40 patients received esophagectomy after neoadjuvant chemoradiotherapy (trimodality), while 62 patients received definitive chemoradiotherapy (dCRT). The median follow-up was 26.4 months. The SUVmax of primary tumor had no significant predictive value on all outcomes, while the SUVmax of metastatic lymph nodes had predictive value on several outcomes. High nodal SUVmax (≥7) predicted for worse outcomes than low nodal SUVmax (<7) in the patients who received dCRT (two-year DMFS, 17% vs. 92%, P < 0.001; NPFS, 14% vs. 81%, P = 0.001; OS, 21% vs. 50%, P = 0.003), but not in those received trimodality. On multivariate analysis of patients receiving dCRT, nodal SUVmax was the strongest independent predictor on DMFS (hazard ratio [HR] 13.93, P < 0.001), NPFS (HR 3.99, P = 0.026), PFS (HR 2.90, P = 0.003), and OS (HR 3.80, P = 0.001). High pretreatment nodal SUVmax predicts worse treatment outcomes for the patients treated with dCRT. [ABSTRACT FROM AUTHOR]

Rice Xa21 gene encodes a receptor-like kinase that confers broad-spectrum resistance against Xanthomonas oryzae pv. oryzae (Xoo). Recently, a number of genes involved in the Xa21-mediated disease resistance pathway have been identified. Based on our previous data and the literature, we chose 16 candidate proteins and made corresponding antibodies. Using Western blotting, we systematically investigated the expression profile of the proteins in Xa21-mediated disease resistance response. We found nine proteins with altered expression. We further compared their expression in resistance, susceptible and mock responses, and found that GST expression was up-regulated during the resistance process, indicating GST is a positive regulator in resistance responses. ATPsB expression was down-regulated during both the resistance and susceptible response processes, although it was higher in the resistance response than that in the susceptible response. The total amount of MYB, GAPDH, CatB, Trx and NB-ARC proteins was lower in the resistance than in the susceptible response, but their abundance per unit bacteria in the resistance response was still higher than in the susceptible response, suggesting that these proteins might be positive regulators in the resistance response. In addition, expression of another ERF was induced by inoculation with bacterial blight pathogen, and expression of Zf-LSD1 was activated by wounding stress alone. Interestingly, most proteins showed similar altered expression patterns in the resistance and susceptible responses, but differed to some extents, implying that both responses might share common molecular mechanisms. This study revealed evidence of resistance-related protein expression, providing a foundation for better understanding of their functions. [ABSTRACT FROM AUTHOR]