427 Efficacy and safety of AK112, an anti-PD-1/VEGF-A bispecific antibody, in patients with platinum-resistant/refractory epithelial ovarian cancer in a Phase 1 study

BackgroundPlatinum-resistant/refractory epithelial ovarian cancer (PROC) is a high unmet medical need with limited treatment options and a median survival of 12–15 months.1 Single agent PD-(L)1 inhibitors have objective response rates (ORR) of less than 10%.2 3 However, combination of nivolumab plus bevacizumab yields a higher ORR of 16.7% in platinum-resistant patients (pts), indicating synergistic activity between PD-1 inhibition and anti-angiogenic therapy in this disease.4 Here, we present initial efficacy and safety data for AK112, a bispecific antibody targeting PD-1 and VEGF-A, in pts with PROC.MethodsPts with PROC were enrolled in an ongoing Phase 1a/1b study of AK112 (NCT04047290). Tumor assessments based on RECIST v1.1 were performed once every 8 weeks/2 cycles for the first 12 months, and every 12 weeks thereafter.ResultsAs of 16 July 2021, 19 PROC pts, of which 6 had platinum-refractory disease, have received AK112 at doses ranging from 3 mg/kg to 30 mg/kg Q2W. Seventeen pts (89.5%) had ≥2 lines of prior therapy in the recurrent/metastatic setting and 7 pts (36.8%) had prior bevacizumab. Seventeen pts had at least 1 post-baseline tumor assessment. Median duration of follow-up was 4.5 months. ORR was 29.4% (5/17; 2 clear cell, 3 high-grade serous]). Among the 5 responders, 3 pts received 20mg/kg Q2W AK112 and 1 pt each had 3mg/kg and 10mg/kg Q2W AK112. Median duration of response was not reached. One pt, who had clear cell PROC and received prior immune checkpoint inhibitor (ICI) therapy, had tumor shrinkage of 70% and continued treatment for more than 17 months. Another pt, who had high-grade serous ovarian cancer and prior treatment with bevacizumab, had tumour shrinkage of 65% and continued treatment for more than 4 months. Disease control rate (DCR) was 76.5% (13/17), with tumor shrinkage observed in 11 pts (64.7%). Twelve out of 19 (63.2%) pts experienced treatment-related adverse events (TRAEs). Three pts (15.8%) experienced Grade 3 TRAEs (hypertension and transaminitis in 1 pt; and hypertension and colitis). There were no Grade 4–5 TRAEs. Commonly reported TRAEs were hypertension (15.8%), arthralgia (15.8%), fatigue (15.8%), hypothyroidism (10.5%) and rash (10.5%).ConclusionsThe initial results from Study AK112-101 demonstrate that AK112 garners an encouraging anti-tumor activity and a favorable safety profile in patients with platinum-resistant/refractory epithelial ovarian cancer. AK112 will be further evaluated for the treatment of platinum-resistant/refractory epithelial ovarian cancer in a Phase 2 study.AcknowledgementsAkeso Biopharma, Inc would like to thank the patients, investigators and site staff for their participation in this study.Trial RegistrationClinicalTrials.gov Identifier: NCT04047290ReferencesPujade-Lauraine E, Banerjee S, Pignata S. Management of platinum-resistant, relapsed epithelial ovarian cancer and new drug perspectives. J Clin Oncol 2019; 37:2437–2448.Disis ML, Taylor MH, Kelly K, et al. Efficacy and Safety of Avelumab for Patients With Recurrent or Refractory Ovarian Cancer: Phase 1b Results From the JAVELIN Solid Tumor Trial. JAMA Oncol 2019; 5:393–401.Matulonis UA, Shapira-Frommer RS, Santin A, et al. Antitumor activity and safety of pembrolizumab in patients with advanced recurrent ovarian cancer: Interim results from the phase 2 KEYNOTE-100 study. J Clin Oncol 2018; 36: suppl abstr 5511.Liu JF, Herold C, Gray KP, et al. Assessment of Combined Nivolumab and Bevacizumab in Relapsed Ovarian Cancer: A Phase 2 Clinical Trial. JAMA Oncol 2019;5:1731–1738.Ethics ApprovalThis study received ethics approval from Bellberry Human Research Ethics Committee (HREC) on 05 Nov 2019 (Application number 2019-05-459-AB). In accordance with ICH Good Clinical Practice Guidelines and the Declaration of Helsinki, study participants gave informed consent voluntarily before participating in this study.

The use of aluminothermic slags for the production of chemically resistant refractory composite materials

Приведены результаты исследований по получению новых составов химически стойких огнеупорных композиционных материалов на основе отходов Ключевской обогатительной фабрики ― продуктов плавленых глиноземистых марок ППГ-50ТП и ППГ-65ТП. Высокие химическая стойкость, огнеупорность, механическая прочность, твердость и износостойкость позволяют применять их для изготовления огнеупорных изделий, бетонов, масс для защиты футеровки.

Production of chemically resistant refractory concrete mix from metallurgical waste and their physical and chemical properties

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A PSMA-targeted theranostic approach is unlikely to be efficient in serous ovarian cancers

Purpose Until now, results evaluating the expression of PSMA in ovarian cancer were sparse and contradictory. The aim was to reinvestigate the feasibility of a PSMA targeted theranostic approach in epithelial ovarian cancers with data from the tumour bank of a referring cancer centre. Materials and methods The OvaRessources Biological Resources Center database was screened from January 2004 to December 2017 to seek patients referred for the initial management of a serous epithelial ovarian cancer and for whom peritoneal histological samples were available in the tumour bank. Immunodetection of PSMA was performed to assess its cellular and neovascular expression. Slides were controlled by a certified pathologist, recorded as tiled tiff images and processed to compute the proportion of DAB stained surface. Results Of the 51 patients identified by the database screening, 32 patients were included resulting in 57 samples (32 pre-chemotherapy and 25 post-chemotherapy histological samples). Nine patients were chemo-sensitive, 10 were partially chemo-sensitive and 13 were chemo-resistant/refractory. In the entire dataset, the expression of PSMA was quasi-inexistent: %DABPSMA = 0.04 (± 0.12) %. There was no significant difference in the %DABPSMA of sensitive, partially sensitive and resistant/refractory patients. There was also no significant difference in %DABPSMA in tumours before and after chemotherapy in the 25 patients for whom both samples were available. Conclusion The present work demonstrates that PSMA expression is negligible and a fortiori non-sufficient to ensure its usefulness as a prognosticator or a target for a theranostic strategy in ovarian cancers.