Faculty Bibliography

Background: Standard of care (SOC) regimens may contribute to immunosuppression by elevating intratumoral levels of adenosine, which activates the A2a and A2b receptors (R) on immune cells. Extracellular adenosine is primarily produced by the enzyme CD73. In prostate cancer, the activity of the highly expressed protein, prostatic acid phosphatase, produces additional adenosine. AB928, which is the first clinical-stage small molecule dual antagonist of both A2aR and A2bR, is highly potent, pharmacodynamically active, and well tolerated in dose escalation studies in combination with chemo/immunotherapy. Targeting the adenosine axis in combination with SOC regimens or immunotherapy may have a more profound effect on activating and inducing sustained antitumor immunity in patients (pts) with metastatic castrate-resistant prostate cancer (mCRPC). Trial design: This is a phase (Ph) 1b/2, open-label, multicenter platform trial to evaluate the antitumor activity and safety of AB928-based combination therapy in pts with mCRPC. Eligibility for a specific treatment arm will be informed by prior anticancer therapy. Treatment arms will independently evaluate AB928 + zimberelimab (AB122; anti-PD-1 antibody) alone or in combination with an SOC backbone (enzalutamide or docetaxel) in earlier-line pts or AB928 + AB680 (CD73 inhibitor) +/- zimberelimab in later-line pts. Treatment arms will be conducted in 2 stages: Stage 1 (Ph1b) and Stage 2 (Ph2). In Ph1b, up to 15 pts will receive investigational product(s) at the single agent recommended dose with SOC per label guidance. Provided safety and futility stopping criteria are not met, further accrual in the earlier-line arms will involve randomization to SOC alone; in the later-line arms, upfront randomization to the all-experimental regimens will continue in Ph2. Investigator-assessed antitumor response (radiologic, prostate specific antigen [PSA]) will follow PCWG3 criteria. New treatment arms may be added via protocol amendment. ARC-6 is actively recruiting in the United States, and results will be shared in upcoming scientific conferences (NCT04381832). Clinical trial identification: NCT04381832. Legal entity responsible for the study: Arcus Biosciences.
Funding(s): Arcus Biosciences. Disclosure: S.K. Subudhi: Advisory/Consultancy, Research grant/Funding (self): Janssen Oncology; Advisory/Consultancy: Polaris; Advisory/Consultancy: Dendreon; Advisory/Consultancy, Shareholder/Stockholder/Stock options: Apricity Health; Advisory/Consultancy: Amgen; Advisory/Consultancy: Bayer; Advisory/Consultancy: Exelixis; Advisory/Consultancy, Research grant/Funding (self): AstraZeneca; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Dava Oncology; Advisory/Consultancy: Cancer Now; Advisory/Consultancy: MEDACorp; Honoraria (self): Parker Institute of Cancer Immunotherapy; Honoraria (self): SITC. D. Wise: Advisory/Consultancy: ScientiaCME; Advisory/Consultancy: OncLIve; Advisory/Consultancy: Foundation Medicine; Honoraria (self), Advisory/Consultancy: Best Doctors; Advisory/Consultancy: Leap Therapeutics; Advisory/Consultancy: Guidepoint Consulting; Advisory/Consultancy: GLG Consulting; Advisory/Consultancy: Silverlight; Advisory/Consultancy: Alphasights; Advisory/Consultancy: Pfizer. S.T. Liu: Advisory/Consultancy: Merck; Advisory/Consultancy: Exelixis; Advisory/Consultancy: Esai; Advisory/Consultancy: Seattle Genetics. A. Chaudhry: Speaker Bureau/Expert testimony, Research grant/Funding (institution): Bayer; Advisory/Consultancy, Research grant/Funding (institution): Exelixis; Advisory/Consultancy: Astellas Pharma; Shareholder/Stockholder/Stock options: Novartis; Research grant/Funding (institution): Arcus Biosciences; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Abbvie; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): BMS; Research grant/Funding (institution): Eli Lilly; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Beigene; Research grant/Funding (institution): BerGenBio; Research grant/Funding (institution): Blueprint; Research grant/Funding (institution): Alkermes; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): Gilead; Research grant/Funding (institution): Janssen; Research grant/Funding (institution): Millennium; Research grant/Funding (institution): Basilea; Research grant/Funding (institution): IunoCare; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): Novartis. J. Kim: Advisory/Consultancy: Sanofi; Advisory/Consultancy: EMD Serono; Advisory/Consultancy: Voluntis; Research grant/Funding (self): Immune Design. O. Gardner: Shareholder/Stockholder/Stock options, Full/Part-time employment: Arcus Biosciences; Shareholder/Stockholder/Stock options, Full/Part-time employment: Bellicum Pharmaceuticals; Full/Part-time employment: Aduro Biotech; Shareholder/Stockholder/Stock options, Full/Part-time employment: Janssen. H. Gilbert: Shareholder/Stockholder/Stock options, Full/Part-time employment: Arcus Biosciences; Advisory/Consultancy, Full/Part-time employment: Bellicum; Shareholder/Stockholder/Stock options, Full/Part-time employment: Roche/Genentech; Shareholder/Stockholder/Stock options: Denali; Shareholder/Stockholder/Stock options: Celgene; Shareholder/Stockholder/Stock options: BMS. M. Grady: Shareholder/Stockholder/Stock options, Full/Part-time employment: Arcus Biosciences; Full/Part-time employment: Bellicum; Full/Part-time employment: Biothera. M. Paoloni: Leadership role, Shareholder/Stockholder/Stock options, Full/Part-time employment: Arcus Biosciences; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy: Janssen Oncology; Advisory/Consultancy: Amgen. K. Krishnan: Leadership role, Shareholder/Stockholder/Stock options, Full/Part-time employment: Arcus Biosciences; Full/Part-time employment: Astex; Full/Part-time employment: Roche/Genentech; Full/Part-time employment: Five Prime. M. Carducci: Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy: Medivation; Advisory/Consultancy: Astellas; Advisory/Consultancy: Roche; Advisory/Consultancy: Abbvie; Advisory/Consultancy: Foundation Medicine; Advisory/Consultancy: Merck; Research grant/Funding (institution): EMD Serono; Research grant/Funding (institution): Exelixis; Research grant/Funding (institution): Gilead; Research grant/Funding (institution): Effector; Non-remunerated activity/ies: ECOG-ACRIN.
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Effective antiretroviral therapy initially resulted in large decreases in hospitalization rates of HIV-infected patients. The goal of this study was to determine whether these gains were being maintained in 2001. A cross-sectional study of hospital admission characteristics during four time periods was performed. All patients receiving care at the HIV clinics of New York Presbyterian Hospital-Cornell Medical Center (NYPH) in New York City were included. In 1995, 883 outpatients were receiving care for HIV infection at NYPH; this increased to 1990 outpatients by 2001. Demographic and laboratory information was obtained for these outpatients, and diagnoses were recorded for all patients requiring hospitalization on at NYPH during the time periods January 1 through June 30, in 1995, 1997, 1999, and 2001. The incidence of hospital admission declined in all four time periods: 1995 (95 per 100 patient-years [pt-yr]), 1997 (48 per 100 pt-yr), 1999 (38 per 100 pt-yr, p < 0.05), and 2001 (25 per 100 pt-yr). The incidence of bacterial pneumonia and opportunistic infections (OIs) decreased in all four time periods. The median hospitalization were CD4(+) cell count for outpatients increased from 231 (1995) to 364 (2001). Important predictors of hospitalization were CD4(+) < 200, and IVDU as an HIV risk factor. Since 1995 and the introduction of highly active antiretroviral therapy, continuing increases in CD4(+) cell counts of outpatients has been reflected in persistent declines in hospitalization rates. Large decreases in OIs and pneumonia have been minimally offset by stable rates of hospital admissions for diagnoses such as hepatitis, cirrhosis, and cellulitis

OBJECTIVE AND METHODS: This study was undertaken to find the role of fluorine-18-fluorodeoxyglucose (F18-FDG) in the diagnostic work-up of febrile Acquired Immune Deficiency Syndrome (AIDS) patients. Forty-seven (42 male and 5 female; mean age = 40.3 years) febrile patients with AIDS underwent imaging with F18-FDG by Dual Head Coincidence Imaging (DHCI). Findings were correlated with other imaging modalities.RESULTS: Our data show good sensitivity for scanning with F18-FDG by DHCI in determining the extent of Castleman's disease, lymphoma, Kaposi's sarcoma (KS), adenocarcinoma, and germ cell carcinoma. Various opportunistic infections also manifest with increased F18-FDG uptake.CONCLUSION: Total-body imaging can be done with F18-FDG with better resolution and a shorter procedure time compared to imaging with Gallium-67 (Ga-67). Furthermore, F18-FDG is more sensitive than Ga-67 for evaluating extent of involvement in various pathologies affecting AIDS patients. The new technology of DHCI is a good alternative for hospitals with no dedicated positron emission tomography (PET) scanner