6010 Background: Indoleamine 2,3-dioxygenase 1 (IDO1) is a tryptophan-catabolizing enzyme that induces immune tolerance by T-cell suppression. IDO1 overexpression has been associated with poor survival in SCCHN. Epacadostat (E) is a potent, selective oral IDO1 inhibitor. ECHO-202/KEYNOTE-037 is an open-label, phase I/II (P1/2) study evaluating E plus PD-1 inhibitor pembrolizumab (P) in multiple tumor types. We report preliminary P1/2 efficacy, safety, and tolerability findings in the SCCHN cohort as of a 29OCT2016 data cutoff. Methods: Eligible adult patients (pts) had metastatic SCCHN and received ≥1 prior chemotherapy regimen that included a platinum agent. Prior checkpoint inhibitor therapy (tx) was not permitted, and pts with carcinoma of the nasopharynx or salivary gland were excluded. In P1 dose escalation (3+3+3), pts received E (25, 50, 100, or 300 mg PO BID) + P (2 mg/kg or 200 mg IV Q3W); MTD was not exceeded. E (100 mg BID) + P (200 mg Q3W) dosing was selected for P2 cohort expansion. Response was assessed in RECIST 1.1 evaluable pts. Results: A total of38 pts (P1, n = 2; P2, n = 36) were evaluated. Median age was 63 years, 87% of pts were men, 95% were white, and 66% received prior cetuximab. Of 36 efficacy-evaluable pts, 81% (n = 29) received 1–2 prior lines of tx and 19% (n = 7) received ≥3 prior lines of tx. ORR (CR+PR) and DCR (CR+PR+SD) for pts with 1–2 prior tx were 34% (2 CR, 8 PR) and 62% (8 SD), respectively; for pts with ≥3 prior tx, ORR and DCR were 14% (1 PR) and 43% (2 SD). Response was observed regardless of HPV status. At data cutoff, 9/11 responses were ongoing (range, 1+ to 563+ days). PFS and biomarker analyses are ongoing. The most common TRAEs in all 38 pts were fatigue (24%), nausea (11%), and decreased weight (11%). Grade ≥3 TRAEs occurred in 11% of pts; only increased amylase and lipase (both asymptomatic) were grade ≥3 TRAEs that occurred in > 1 pt. TRAEs led to discontinuation in 1 pt (increased amylase and lipase). Conclusions: In pts with advanced SCCHN, E + P was generally well tolerated and associated with encouraging response rates, particularly in pts with 1–2 prior lines of tx. A phase III SCCHN study is planned. Clinical trial information: NCT02178722.

4515 Background: Epacadostat (E) is a potent oral inhibitor of indoleamine 2,3-dioxygenase 1 (IDO1), a tryptophan-catabolizing enzyme that induces immune tolerance by T-cell suppression. Preclinical and clinical data suggest that epacadostat has antitumor activity when combined with checkpoint inhibitors, including the PD-1 inhibitor pembrolizumab (P). ECHO-202/KEYNOTE-037 is an ongoing open-label, phase 1/2 (P1/2) study evaluating E + P in multiple tumor types. We report preliminary P1/2 efficacy and safety data for the advanced renal cell carcinoma (RCC) cohort as of a 29OCT2016 data cutoff. Methods: Eligible patients (pts) had advanced clear-cell RCC, prior antiangiogenic therapy (tx), and no prior checkpoint inhibitor tx. In P1 dose escalation (3+3+3), pts received E (25, 50, 100, or 300 mg PO BID) + P (2 mg/kg or 200 mg IV Q3W); MTD was not exceeded. E (100 mg BID) + P (200 mg Q3W) dosing was selected for P2 cohort expansion. Response was assessed in RECIST 1.1 evaluable pts. Safety/tolerability was assessed in pts receiving ≥1 E + P dose. Results: 33 pts (P1, n = 11; P2, n = 22) were enrolled (median age, 63 years; 70% men; 97% white; MSKCC criteria of favorable, intermediate, and poor in 6%, 64%, and 12% of pts, respectively). Of 30 efficacy-evaluable pts, 63% (n = 19) had 0–1 prior tx and 37% (n = 11) had ≥2 prior tx for advanced disease. ORR (CR+PR) and DCR (CR+PR+SD) for pts with 0–1 prior tx was 47% (9/19; 1 CR, 8 PR) and 58% (11/19; 1 CR, 8 PR, 2 SD), respectively; for pts with ≥2 prior tx, ORR and DCR were 0% and 36% (4/11; all SD). At data cutoff, 9/9 responses were ongoing (range, 1+ to 372+ days). PFS and biomarker analyses are ongoing. TRAEs occurring in ≥10% of the 33 pts included fatigue and rash (36% each); and arthralgia, diarrhea, pruritus, and pyrexia (12% each). Grade ≥3 TRAEs occurred in 15% of pts (none in > 1 pt). Two pts discontinued due to TRAEs (grade 3 autoimmune hepatitis, n = 1; grade 3 aseptic meningitis/headache/nausea/vomiting/anxiety, n = 1). Conclusions: E + P was generally well tolerated and associated with encouraging response outcomes in advanced RCC pts with 0–1 prior line of tx. E + P represents a novel immunotherapeutic strategy. A phase 3 RCC study is planned. Clinical trial information: NCT02178722.

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Background: Antimicrobial resistance is a major concern especially in urinary tract infections in children as improperly treated urinary tract infections (UTIs) on long term can cause renal scarring in young children, which leads to long term morbidities like hypertension, chronic renal disease and pre-eclampsia. The empirical therapy for UTI varies regionally due to their varied sensitivities and resistance pattern. This study aims to facilitate policy making in empirical antibiotic therapy of pediatric patients with urinary tract infections.Methods: A cross sectional study, which included a group of 140 children’s (6 months to 3 years) with fever were included in the study. All patients with colony count >1 lakh CFU/ml or colony count >50,000 CFU/ml, with leukocyturia (>5 WBCs/HPF in centrifuged urine) or colony count >1000 CFU/ml with urinary symptoms were diagnosed to be positive for urinary tract infection.Results: The prevalence of UTI in febrile children less than 3 years in our study was 0.1%. Out of 140 patients with fever, 35 were UTI positive. E. coli was the most commonly isolated organism (60%), followed by MRSA (14.2%) and Enterococci (11.4 %). E. coli was found to be most sensitive to nitrofurantoin (85.7%), followed by gentamicin (61.9%) and norfloxacin (38%). E. coli showed high resistance to cefuroxime (76.2%) and ceftriaxone (71.4%). MRSA was found to be most sensitive to linezolid and vancomycin, and resistant to norfloxacin.Conclusions: The data shows the increased resistance of E. coli to commonly prescribed antibiotics like cefuroxime and ceftriaxone. So, this study shows the empirical treatment of UTI in our region and the importance of having antibiotic prescription policies in every region.

Background Epacadostat, an oral, selective inhibitor of IDO1, has shown activity when administered with pembrolizumab. We evaluated the addition of chemotherapy to epacadostat and pembrolizumab in patients with advanced or metastatic solid tumors. One proposed mechanism of resistance to PD-1 checkpoint inhibition is through immunosuppression mediated by L-kynurenine. IDO1, indoleamine-2,3-dioxygenase 1 is the rate-limiting enzyme catalyzing the conversion of L-tryptophan to L-kynurenine. If IDO1 is a mechanism of tumor escape from checkpoint inhibition, then addition of an IDO1 inhibitor with a PD-1 checkpoint inhibitor could enable tumor response to immunotherapy. Methods Patients received one of 7 tumor-appropriate chemotherapy regimens. Pembrolizumab 200 mg was infused intravenously every 3 weeks. Epacadostat 100 mg was administered orally twice daily. The primary objectives of phase I were determining safety/tolerability and defining the maximum tolerated or pharmacologically active dose of epacadostat. Phase II of the study was designed to enroll efficacy-expansion cohorts and to assess changes in the tumor and tumor microenvironment via mandatory-biopsy cohorts. Results A total of 70 patients were enrolled. Twelve patients were enrolled in the phase II mandatory-biopsy cohorts. Due to early study closure, efficacy expansion did not enroll. Grades 3 and 4 treatment-emergent adverse events (TEAEs) occurred in 78.6% of patients. Neutropenia and disease progression were the only grades 3 and 4 TEAEs reported in ≥10.0% of patients. One treatment-related death was reported. The ORR was 31.4% across all treatment groups. Conclusion The combination of epacadostat 100 mg bid with pembrolizumab and chemotherapy had an acceptable safety profile. This regimen showed antitumor activity across multiple types of advanced or metastatic solid tumors (ClinicalTrials.gov Identifier: NCT03085914).

Health-care providers must be cautious about the adverse effects of drugs, especially Stevens-Johnson syndrome, which is a potentially fatal condition. Several drugs are at high risk of inducing Stevens-Johnson syndrome including allopurinol, sulfonamides, cephalosporins, quinolones, phenytoin, carbamazepine, and nonsteroidal anti-inflammatory drugs. Owing to high risk of mortality, management of patients requires rapid diagnosis, identification and discontinuation of the causative drug, and specialized support care.

Background: Acute Coronary Syndrome (ACS) is an emergency condition where usage of many drugs during its management in ICCU is common. This could be a potential cause for Polypharmacy, Potential Drug-Drug Interactions and increased Cost Burden on patients. The objective of the study was WHO criteria for prescription like, 1) Average number of drugs per prescription, 2) Percentage of drugs prescribed by Generic name, 3) Percentage of drugs with Injections prescribed, 4) Percentage of prescriptions with Antibiotics and 5) Percentage of drugs prescribed from the WHO Essential Drugs List.Methods: After obtaining approval from Institutional Ethics Committee, an observational study was carried out among 125 patients in a tertiary care hospital, Mysore. Patients diagnosed with ACS admitted in Intensive Cardiac Care Unit (ICCU) for initial 48 hrs were included in the study. The prescriptions were analyzed for WHO criteria for prescription. The results were analyzed using Descriptive Statistics and T- test.Results: In our present study the most common diagnoses were found to be ACS- Anterior wall myocardial infarction (36.8%) and ACS-Inferior wall myocardial infarction (32.8%). Hypertension (35.2%) and Type 2 diabetes mellitus (29.6%) were the frequently associated co-morbid conditions. Antiplatelet drugs (100%) and Hypolipidemic drugs (100%) were the most commonly prescribed, followed by Anti coagulants (94.4%). The average number of drugs per prescription was 9.09±2.17. Percentage of drugs prescribed by generic names was 37.29%. The percentage of drugs prescribed from essential drug list was 50.84%.Conclusions: The present study provides valuable insight about the overall pattern of drugs used in Acute Coronary syndrome. Physician should be encouraged to prescribe drugs with generic name.

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