ALBERT

Description: In this article, we analyze how pregnant and breastfeeding women perceive the inside of their bodies as well as their thoughts regarding the accumulation and elimination of chemical compounds present in food, and how these are then transmitted to the fetus. We explore different social perceptions of risk regarding the circulation of chemical compounds inside the body using qualitative research based on the technique of body mapping, comprised of women’s figures of their bodies in combination with comments on the figures, food diaries and narratives from in-depth interviews. We examine how these 41 women (21 pregnant and 20 breastfeeding) perceive the body’s internal mechanisms during the stages of pregnancy and breastfeeding, as well as the circulation of chemical contaminants within it. The body mapping technique allowed us to analyze participants’ knowledge of internal pollution, a little-understood process in society. Thanks to these pregnant and breastfeeding women, who made an effort to represent and reflect on these new risks, this study shows that scientists and obstetricians need to collaborate with women in order to better understand and publicize the risks of internal pollution.

Description: Acute myeloid leukemia (AML) is an aggressive hematologic malignancy with most patients relapsing even after initial therapies. Despite recent advances in treatment, the development of efficacious novel treatments remains an unmet need. CD47 is a myeloid checkpoint upregulated by tumor cells to evade the host immune response, and its blockade enhances anti-tumor immunity (Weiskopf, 2017). Recently, pre-clinical and clinical studies that explored the use of CD47 targeting agents in combination with azacitidine, a hypomethylating chemotherapeutic, demonstrated robust anti-cancer activity (Feng, ASH 2018 and Sallman, ASH 2019). ALX148 is an engineered fusion protein comprised of a high affinity CD47 blocker linked to an inactive human immunoglobulin Fc region. In preclinical studies, ALX148 bridges innate and adaptive immunity by promoting macrophage phagocytosis, dendritic cell activation and a shift of tumor-associated macrophages towards an inflammatory phenotype, leading to increased anti-tumor activity when combined with various anti-cancer therapeutics (Kauder, 2018). ALX148 has previously been shown to be well tolerated in patients with both solid tumor and hematological malignancies with encouraging anti-tumor responses reported in combination with anti-cancer therapeutics (EHA 2020, #EP1247 and ASCO 2020, #3056). Recently, the combination of azacitidine with venetoclax, a BCL2 inhibitor, has shown increased efficacy compared to azacitidine alone in patients with AML (EHA 2020, #LB2601). We observed in vitro treatment with azacitidine or venetoclax increased the cell surface expression of both CD47 and calreticulin, a pro-phagocytic marker, in multiple AML cell lines. We thereby hypothesize that combining ALX148 with either azacitidine or venetoclax would enhance the therapeutic efficacy against AML and report our preclinical findings here. In vitro treatment with ALX148 led to enhanced phagocytic engulfment by human monocyte-derived macrophages across multiple AML cell lines treated with azacitidine or venetoclax, including those harboring TP53 and FLT3 mutations, compared to either treatment alone. Our in vitro findings correlated with enhanced in vivo antileukemic activity in several murine AML xenograft models. Mice were inoculated via tail vein or implanted subcutaneously with AML cells, and when tumors reached exponential growth, mice were randomized to receive the following: vehicle control, azacitidine, venetoclax, ALX148 alone or ALX148 in combination. Cohorts receiving ALX148 combination therapies demonstrated significantly greater inhibition of tumor progression with evidence of tumor eradication, leading to markedly enhanced survival over any single agent therapy. Together, these in vitro and in vivo results provide rationale that ALX148 combinations may benefit AML and MDS patients. Clinical trials with ALX148 in patients with MDS (NCT04417517) and AML are currently planned. Disclosures Chen: ALX Oncology: Consultancy, Current equity holder in publicly-traded company, Ended employment in the past 24 months; Tallac Therapeutics: Current Employment, Current equity holder in private company. Harrabi:ALX Oncology Inc: Consultancy, Current equity holder in publicly-traded company, Ended employment in the past 24 months; Tallac Therapeutics: Current Employment, Current equity holder in private company. Fong:ALX Oncology Inc: Current Employment, Current equity holder in publicly-traded company. Ruffner:ALX Oncology Inc: Current Employment, Current equity holder in publicly-traded company. Forgie:ALX Oncology Inc.: Current Employment, Current equity holder in publicly-traded company; Pfizer Inc.: Ended employment in the past 24 months. Sim:ALX Oncology Inc: Consultancy, Current equity holder in publicly-traded company, Ended employment in the past 24 months; Tallac Therapeutics: Current Employment, Current equity holder in private company. Randolph:ALX Oncology Inc.: Current Employment, Current equity holder in publicly-traded company. Wan:Tallac Therapeutics: Current Employment, Current equity holder in private company; ALX Oncology Inc: Consultancy, Current equity holder in publicly-traded company, Ended employment in the past 24 months. Pons:ALX Oncology Inc.: Current Employment, Current equity holder in publicly-traded company. Kuo:ALX Oncology Inc: Consultancy, Current equity holder in publicly-traded company, Ended employment in the past 24 months; Tallac Therapeutics: Current Employment, Current equity holder in private company.

Description: Background: CD47 is a myeloid checkpoint upregulated by tumor cells to evade the host's immune response. The high affinity CD47 blocker fusion protein, ALX148, is linked to an inactive immunoglobulin Fc region to minimize toxicity. ALX148 is half the size of an antibody, has been well tolerated, and enhances the innate and adaptive immune response against cancer in combination with anticancer therapeutics across solid and hematologic tumors (ASCO 2020 #3056, EHA 2020 #EP1247). Characterization of ALX148's tolerability profile and antitumor activity in combination with rituximab are reported in patients (pts) with non-Hodgkin Lymphoma (NHL). Methods: Patients with relapsed or refractory CD20-positive B-cell NHL for which no curative therapy was available received ALX148 (10 mg/kg QW or 15 mg/kg QW) in combination with rituximab (375 mg/m2 weekly for 4 doses followed by once monthly for 8 doses). The primary endpoint for the safety population was dose limiting toxicity (DLT). Tumor response, pharmacokinetic (PK), and pharmacodynamic (PD) markers were assessed in all pts. Data are reported as of 30Jun2020 in these fully enrolled cohorts with final data to be updated at the time of presentation. Results: A total of 33 patients with NHL were administered ALX148 in combination with rituximab. Twenty-two pts with median age of 66 years (range 32-80) were administered ALX148, 10 mg/kg QW (ALX10), in combination with rituximab [DLBCL, n=11; mantle cell lymphoma (MCL), n=4; follicular lymphoma (FL), n=5; and marginal zone lymphoma (MZL), n=2]. Eleven pts with median age of 64 years (range 53-78) were administered ALX148, 15 mg/kg QW (ALX15), in combination with rituximab (DLBCL, n=6; MCL, n=1; FL, n=3; and MZL, n=1). There have been no DLTs reported in the fully enrolled safety cohorts, and the MTD of ALX148 in combination with rituximab has not been reached. The maximum ALX148 administered dose is 15 mg/kg QW. Twenty-eight pts experienced any AE, while 16 pts reported mostly low grade treatment-related adverse events (TRAE). The most common TRAEs were rash (21%, n=7), fatigue (9%, n=3), anemia, nausea, neutropenia, and pruritus (6%, n=2 each). With a median follow up of 14 months, objective responses were observed across all histologies in response-evaluable ALX10 pts: 40.9% ORR (4CR,5PR, 6SD, n=22 total) and with a median follow up of 9 months in ALX15 pts: 63.6% ORR (3CR, 4PR, 1SD, n=11 total). Preliminary results indicate favorable ALX148 PK and near complete CD47 receptor occupancy across the dosing interval. Final results will be updated at time of presentation. Conclusions: ALX148 demonstrates excellent tolerability with durable responses in combination with rituximab in patients with relapsed/refractory NHL. The MTD of ALX148 in combination with rituximab was not reached. Encouraging preliminary activity and favorable PK/PD characteristics in combination with rituximab were observed at all dose levels with greater objective response rates reported at the MAD of 15 mg/kg QW. Disclosures Kim: Boryung: Consultancy; Voronoi: Consultancy; F. Hoffmann-La Roche Ltd/Genentech, Inc.: Consultancy; Sanofi: Consultancy; Novartis: Consultancy; Takeda: Consultancy; AstraZeneca and Korea Health Industry Development Institute: Research Funding; AstraZeneca: Consultancy. Lakhani:incyte: Research Funding; merck: Research Funding; mersana: Research Funding; northern biologics: Research Funding; odonate: Research Funding; pfizer: Research Funding; ikena: Research Funding; symphogen: Research Funding; taiRx: Research Funding; tesaro: Research Funding; livzon: Research Funding; loxo: Research Funding; macrogenics: Research Funding; inhibRx: Research Funding; cytomx: Research Funding; formation biologics: Research Funding; forty seven inc: Research Funding; alexion Pharmaceuticals: Research Funding; Alpine Biosciences: Research Funding; ALX Oncology Inc.: Research Funding; Apexian: Research Funding; asana biosciences: Research Funding; ascentage pharma: Research Funding; beigene: Research Funding; celgene: Research Funding; cerulean pharma: Research Funding; constellation pharma: Research Funding; coordination therapeutics: Research Funding; regeneron: Research Funding; sapience therapeutics: Research Funding; shattuck labs: Research Funding; innovent bio: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; jounce therapeutics: Research Funding. Gainor:theravance: Consultancy; adaptimmune: Research Funding; ariad: Research Funding; astrazeneka: Research Funding; blueprint medicines: Research Funding; lily: Consultancy; gilead sciences: Consultancy; merck: Consultancy, Research Funding; moderna therapeutics: Consultancy, Research Funding; tesaro: Research Funding; blueprint medicines: Consultancy; novartis: Research Funding; oncorus: Consultancy; regeneron: Consultancy; bristol-myers Squibb: Consultancy, Research Funding; amgen: Consultancy; array biopharma: Consultancy, Research Funding; agios: Consultancy; ironwood pharmaceuticals: Consultancy; takeda: Consultancy; genentech: Consultancy, Research Funding; jounce therapeutics: Consultancy, Research Funding. Kamdar:Roche: Research Funding. Fanning:ALX Oncology Inc.: Current Employment, Current equity holder in publicly-traded company. Squifflet:ALX Oncology Inc.: Consultancy; IDDI: Current Employment. Jin:ALX Oncology Inc.: Current Employment. Forgie:ALX Oncology Inc.: Current Employment, Current equity holder in publicly-traded company; Pfizer Inc.: Ended employment in the past 24 months. Wan:Tallac Therapeutics: Current Employment, Current equity holder in private company; ALX Oncology Inc.: Consultancy, Current equity holder in publicly-traded company. Pons:ALX Oncology Inc.: Current Employment, Current equity holder in publicly-traded company. Randolph:ALX Oncology Inc.: Current Employment, Current equity holder in publicly-traded company. Kim:F. Hoffmann-La Roche: Research Funding; Pfizer: Research Funding; JJ: Research Funding; Celltrion: Research Funding; Kyowa Kirn: Research Funding; Donga: Research Funding; Mundipharma: Research Funding.