9503 Background: The immunomodulatory receptor TIGIT is a novel inhibitory immune checkpoint present on activated T cells and NK cells in multiple cancers, including NSCLC. In a phase I study (GO30103), co-inhibition of TIGIT and PD-L1 signaling with tira plus atezo in CIT-naïve PD-L1 positive NSCLC potentially improved overall response rates (ORR) compared to historical ORR with PD-L1/PD-1 inhibitors. We conducted this phase II trial to confirm the efficacy and safety of tira plus atezo (TA) compared to placebo plus atezo (PA) in 1L NSCLC (GO40290, NCT NCT03563716). Methods: This prospective, randomized, double-blind, placebo-controlled trial enrolled patients (pts) with chemotherapy-naïve PD-L1+ (TPS ≥ 1% by 22C3 IHC pharmDx Dako assay) locally advanced or metastatic NSCLC with measurable disease, ECOG PS 0-1, and without EGFR or ALK alterations. Pts were randomized 1:1 to TA (tira 600 mg IV plus atezo 1200 mg IV) or PA (placebo plus atezo 1200 mg IV) on day 1 of every 3-week cycle. Stratification factors were PD-L1 status (TPS ≥ 50% vs TPS 1-49%), histology, and tobacco history. Co-primary endpoints were investigator assessed ORR and PFS, and additional endpoints were duration of response (DOR), OS, and safety. Exploratory endpoints were the effect of PD-L1 status on ORR and PFS. Results: 135 pts were randomized to PA (n = 68) or TA (n = 67). At primary analysis (30 Jun 2019), TA improved ORR and median PFS (mPFS) compared to PA, with median follow-up of 5.9 mo. In the safety population (68 in PA, 67 in TA), treatment-related AEs (TRAEs) occurred in 72% (PA) and 80.6% (TA); Grade ≥3 TRAEs occurred in 19.1% (PA) and 14.9% (TA). AEs leading to treatment withdrawal occurred in 10.3% (PA) and 7.5% (TA). Clinical trial information: NCT03563716 . With an additional six months of follow-up since the primary analysis (2 Dec 2019, median follow-up of 10.9 mo), improvement in ORR and mPFS was maintained in ITT for TA (37.3% [25.0, 49.6] and 5.6 mo [4.2, 10.4]) vs PA (20.6% [10.2, 30.9] and 3.9 mo [2.7, 4.5]). The safety profile remained tolerable. Conclusions: Treatment with TA compared to PA showed clinically meaningful improvement in ORR and PFS in ITT. The safety profile of TA was similar to PA. [Table: see text]

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Objective:The aim of this study was to investigate the incidence of carious lesions, the amount of salivary flow rate and pH value in patients with asthma and chronic obstructive pulmonary diseases (COPD), using inhalation therapy. The obtained results were compared with the results of adult healthy subjects, forming a control group.Material and Methods:The study included 80 participants aging between 18 and 65 years. The experimental group (EG) was comprised of 40 participants, previously diagnosed with asthma or COPD undergoing inhalation therapy for more than five years. The control group (CG), comprised of 40 participants, mirrored the same age and gender status of the EG. Dental status was determined by decayed, missing, and filled teeth (DMFT index). Quantity and pH value of saliva were determined in the laboratory.Results:In the EG, the mean value of the salivary flow rate and pH value were statistically significantly lower than in the CG (p<0.001). Patients in the EG had a higher value of DMFT index when compared with the CG, although the difference was not statistically significant (p=0.199). Mean number of decayed teeth, as well as missing teeth, in the EG was statistically significantly higher than in the CG (p<0.001). Mean number of filled teeth in the EG was statistically significantly lower than in the CG (p<0.001).Conclusion:It was found that patients undergoing inhalation therapy face increasing risk of dental caries due to the lower salivary flow rate and pH value along with the inhalation therapy. They should receive intensive preventive care, including oral hygiene instruction and dietary advice.

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