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Introduction : CD47, a cell-surface ligand overexpressed in various malignancies, binds to SIRPα on effector macrophages to promote tumor cell evasion of phagocytosis. Blockade of the CD47-SIRPα interaction provides a pro-phagocytic signal which enhances phagocytosis mediated by tumor-targeting antibodies such as rituximab. Agents targeting CD47 in combination with rituximab have demonstrated promising clinical activity in R/R NHL; however, the broad expression of CD47 leads to frequent on-target, off-tumor toxicities, including treatment-emergent hemolytic anemia. CC-95251 is a novel, fully human immunoglobulin G1 antibody that binds to SIRPα on monocytes and macrophages to potently block the CD47-SIRPα interaction. Here we report interim results from a phase 1 study evaluating CC-95251 combined with rituximab in patients (pts) with R/R NHL. Methods: CC-95251-ST-001 (NCT03783403) is a multicenter, open-label, phase 1, dose-escalation and expansion study of CC-95251 in pts with advanced solid tumors and CD20+ R/R NHL. The primary objectives of the dose-escalation stage presented here are to evaluate the safety and tolerability of escalating doses of CC-95251 combined with rituximab and to define the maximum tolerated dose (MTD) and/or recommended phase 2 dose for the combination in pts with R/R NHL. Pts with CD20+ NHL who had progressed on standard anticancer therapy or for whom no approved conventional therapy was available were eligible for inclusion. Dose-escalation was conducted using an adaptive, 2-parameter Bayesian logistic regression model with overdose control. Pts were treated in 28-day cycles with CC-95251 administered intravenously at 3, 10, or 20 mg/kg every week (QW) and rituximab 375 mg/m 2 given on days 1, 8, 15, and 22 of cycle 1, on day 1 of cycles 2-5, and on day 1 of every other cycle from cycle 6 to 24 until disease progression or unacceptable toxicity. Results: As of April 30, 2021, 18 pts were enrolled and 17 had received ≥ 1 dose of CC-95251 and rituximab. Median age of the enrolled study population was 69 (range 30-84) years. Treated pts had received a median of 4 (range 1-7) prior systemic therapies, including 14/17 (82%) pts with confirmed prior rituximab exposure. Enrolled tumor types included R/R diffuse large B-cell lymphoma in 14 (78%) pts, follicular lymphoma in 2 (11%), and mantle cell lymphoma and marginal zone lymphoma in 1 (6%) pt each. Of the pts with available response data for prior lines of therapy (LOT), 7 (41%) had disease confirmed to be refractory to any prior LOT, including 5 (29%) refractory to rituximab-containing regimens, and 5 (29%) to their last LOT. Pts received a median of 3 (range 1-12) cycles of CC-95251, with a median duration of treatment of 14.1 (range 1.1-47.3) weeks. There were no CC-95251 dose reductions. Five (29%) pts experienced ≥ 1 treatment-emergent adverse events (TEAEs) leading to CC-95251 dose interruption. To date, the MTD has not been reached for the combination of CC-95251 and rituximab. The most common (≥ 30%) TEAEs of any grade were neutropenia (11/17 [65%]), infections (9/17 [53%]), hypokalemia (6/17 [35%]), and hypomagnesemia (6/17 [35%]; Table). Grade ≥ 3 TEAEs reported in ≥ 2 pts were neutropenia (9/17 [53%]) and infections (4/17 [24%]). No treatment-related anemia, a notable toxicity of some anti-CD47 therapies, was reported with CC-95251 and there were no treatment-related deaths. The overall response rate was 41% (7/17), with 2/17 (12%) pts achieving a complete response (Figure). The median time to response was 7.6 weeks. Median duration of response has not been reached as responses are ongoing. Pharmacokinetic (PK) analysis showed that CC-95251 exhibited dose-proportional increases in exposure at doses > 3 mg/kg QW indicating saturation of nonlinear clearance pathways or target saturation. Full receptor occupancy on peripheral monocytes was achieved at doses > 3 mg/kg QW. The estimated terminal half-life when in the linear range of clearance was approximately 12 days. No substantial differences in PK were observed at the given dose levels for CC-95251 monotherapy versus CC-95251 combined with rituximab. Conclusions: CC-95251, a novel anti-SIRPα antibody, demonstrated a manageable safety profile and promising efficacy in combination with rituximab in pts with heavily pretreated CD20+ R/R NHL. The study continues to enroll in the dose-expansion phase. Updated safety and efficacy data will be presented. Figure 1 Figure 1. Disclosures Strati: Astrazeneca-Acerta: Research Funding; Roche-Genentech: Consultancy. Hawkes: Regeneron: Speakers Bureau; Specialised Therapeutics: Consultancy; Bristol Myers Squib/Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck KgA: Research Funding; Astra Zeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Other: Travel and accommodation expenses, Research Funding, Speakers Bureau; Janssen: Speakers Bureau; Antigene: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Merck Sharpe Dohme: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees. Ghosh: Karyopharma: Consultancy, Honoraria; Genmab: Consultancy, Honoraria; Gilead: Consultancy, Honoraria, Research Funding, Speakers Bureau; Bristol Myers Squibb: Consultancy, Honoraria, Research Funding, Speakers Bureau; Adaptive Biotech: Consultancy, Honoraria; Pharmacyclics LLC, an AbbVie Company: Consultancy, Honoraria, Research Funding, Speakers Bureau; TG Therapeutics: Consultancy, Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria, Speakers Bureau; Genentech: Research Funding; AbbVie: Honoraria, Speakers Bureau; Incyte: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Speakers Bureau; ADC Therapeutics: Consultancy, Honoraria; AstraZeneca: Consultancy, Honoraria, Speakers Bureau; Epizyme: Honoraria, Speakers Bureau. Tuscano: BMS, Seattle Genetics, Takeda, Achrotech, Genentech, Pharmacyclics, Abbvie: Research Funding. Chu: Abbvie: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Astellas: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria; BI: Consultancy, Honoraria; Astra Zeneca: Consultancy, Honoraria; Eli Lilly: Consultancy, Honoraria; Merck: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Merck KgaA: Other: DSMB. Patel: Bristol Myers Squibb: Current Employment. Burgess: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Hege: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Chhagan: Bristol Myers Squibb: Current Employment. Boyanapalli: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Day: Tracey Day: Current Employment. Shen: Bristol Myers Squibb: Current Employment. Mehta: Affirmed; Kite/Gilead; Roche-Genetech; Celgene/BMS; Oncotartis; Innate Pharmaceuticals; Seattle Genetics; Incyte; Takeda; Fortyseven Inc/Gilead; TG Therapeutics; Merck; Juno Pharmaceuticals/Bristol Myers Squibb: Research Funding; Seattle Genetics; Incyte; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Seattle Genetics; Incyte; TG Therapeutics: Consultancy.

Background HPV self-collection is a promising approach to improve uptake of cervical screening in under-screened women. The aim of this feasibility study was to measure uptake of HPV self-collection, HPV positivity, and screening history of street entrenched women in a rural region centre. Methods Women 30–69 years of age, attending drop-in community-based primary care and integrative reproductive health clinics in Northern British Columbia (BC), Canada and self-reported not having received cervix screening in the last 3 years, were offered self-collection for HPV testing. A convenience sample of all comers was administered a questionnaire and underwent a medical chart review, including the provincial cervix screening registry. Demographics, HIV status, and cervix screening history were collected. All women who tested HPV16/18 positive were referred for colposcopy. Results A total of 66 eligible women were analyzed (mean age 43.3 years), with population saturation reached after 3 months recruitment. An additional 11 women were deemed ineligible due to age or prior hysterectomy. 83% self-reported as Indigenous. Based on the provincial cervix screening registry, 48% of women were up-to-date on cervix screening based on triennial screening guidelines. All women undertook self-collection and the majority of women reported high perceived acceptability, safety, and accuracy of HPV self-collection. HPV 16/18 positivity was 7.6%, with 40% co-infected with HIV. Overall HIV prevalence was 16.4%, however, over 25% of women had unknown HIV status based on medical chart review. Conclusion HPV self-collection was highly acceptable as part of community-based integrative reproductive health services. Despite being a traditionally underserved population, and women self-reporting being overdue for screening, over half the women were up to date on cervix screening, albeit regular screening was lacking for many. The findings from this feasibility study will inform future implementation of HPV self-collection to improve and maintain regular cervix screening services in street entrenched women. Disclosure No significant relationships.

Mycobacterium tuberculosis (M.tb) is one of the most prevalent and deadly human pathogens. The molecular mechanisms determining the outcomes of infection with M.tb remain incompletely understood. Here we show that IL-1α-mediated signaling from infected macrophages is absolutely required for effective pathogen control in a model of pulmonary M.tb infection in mice. We further show that M.tb replication and survival of infected cells in vivo is controlled through an IL-1α-driven signaling to stroma cells that secrete in response TNF-α and enable cell-intrinsic resistance to the pathogen by limiting its replication at a single cell level. The lack of IL-1α leads to profound non-resolving inflammation that contributes to pathology, rather than to pathogen control. Restoration of IL-1α expression in CD11c-positive lung leukocytes in IL-1alpha-deficient mice alleviates inflammation and improves survival of animals after M.tb infection. Our study implicates IL-1α-driven leukocyte-stroma cell crosstalk as a key step in triggering M.tb control mechanisms that are critical for host survival. These data reveal fundamental role of innate immunity in M.tb pathogenesis and define novel molecular targets for the development of drugs to control tuberculosis epidemics.