Background: In this first-in-human phase 1 study (NCT02964013; MK-7684-001), we investigated the safety and efficacy of the anti-TIGIT (T cell immunoglobulin and ITIM domain) antibody vibostolimab as monotherapy or in combination with pembrolizumab. Patients and methods: Part A enrolled patients with advanced solid tumors, and part B enrolled patients with nonsmall-cell lung cancer (NSCLC). Patients received vibostolimab 2.1-700 mg alone or with pembrolizumab 200 mg in part A and vibostolimab 200 mg alone or with pembrolizumab 200 mg in part B. Primary endpoints were safety and tolerability. Secondary endpoints included pharmacokinetics and objective response rate (ORR) per RECIST v1.1. Results: Part A enrolled 76 patients (monotherapy, 34; combination therapy, 42). No dose-limiting toxicities were reported. Across doses, 56% of patients receiving monotherapy and 62% receiving combination therapy had treatmentrelated adverse events (TRAEs); grade 3-4 TRAEs occurred in 9% and 17% of patients, respectively. The most common TRAEs were fatigue (15%) and pruritus (15%) with monotherapy and pruritus (17%) and rash (14%) with combination therapy. Confirmed ORR was 0% with monotherapy and 7% with combination therapy. In part B, 39 patients had anti-PD-1 (programmed cell death protein 1)/PD-L1 (programmed death-ligand 1)-naive NSCLC (all received combination therapy), and 67 had anti-PD-1/PD-L1-refractory NSCLC (monotherapy, 34; combination therapy, 33). In patients with anti-PD-1/PD-L1-naive NSCLC: 85% had TRAEsethe most common were pruritus (38%) and hypoalbuminemia (31%); confirmed ORR was 26%, with responses occurring in both PD-L1-positive and PD-L1-negative tumors. In patients with anti-PD-1/PD-L1-refractory NSCLC: 56% receiving monotherapy and 70% receiving combination therapy had TRAEsethe most common were rash and fatigue (21% each) with monotherapy and pruritus (36%) and fatigue (24%) with combination therapy; confirmed ORR was 3% with monotherapy and 3% with combination therapy. Conclusions: Vibostolimab plus pembrolizumab was well tolerated and demonstrated antitumor activity in patients with advanced solid tumors, including patients with advanced NSCLC.

BACKGROUND AND PURPOSE:Placement of a covered stent to control carotid blowout (CB) in malignant tumors of the head and neck has been reported to be an effective treatment. However, it is not uncommon to encounter recurrent hemorrhage. The purpose of this study was to evaluate the follow-up results of patients treated with covered stents.

Current smoking was significantly associated with symptoms of asthma, such as having recent wheezing and recent exercise-induced wheezing, especially for non-atopics, in Korean adolescent population. Current smoking was further associated with lower pulmonary function, but not BHR.

Belotecan was active in SCLC patients as a single agent, warranting further investigations of belotecan in combination with platinum or other active agents.

Pts with previously treated recurrent/advanced NSCLC were enrolled; those who received prior antiePD-1 therapy were excluded. Pts received dostarlimab 500 mg Q3W for cycles 1e4 and 1000 mg Q6W until disease progression. The primary endpoint was immune-related objective response rate (irORR) assessed by immunerelated Response Evaluation Criteria in Solid Tumors. Tumor PD-L1 expression was measured on tumor samples collected prior to enrollment, and PD-L1 tumor proportion scores were categorized as <1%, 1e49%, and 50%.Results: A total of 67 pts were enrolled; 3% of pts were epidermal growth factor receptor (EGFR)-positive; 18% had unknown EGFR status. No patient had a known anaplastic lymphoma kinase (ALK) translocation; 22% had unknown ALK status. Confirmed irORR was 27% with 2 complete responses (Table ). Median follow-up was 13.8 months; median duration of response was 11.6 months (range, 2.8e19.4). Fortyfive (67%) pts experienced a treatment-related adverse event (TRAE). Eight (12%) pts experienced a grade 3 TRAE: fatigue (4%) and decreased appetite (3%) were most common. Nineteen (28%) pts had immune-related TRAEs (irTRAEs). Five (7%) pts had grade 3 irTRAEs. Six (9%) pts had any grade pneumonitis, 1 (1%) had grade 3 pneumonitis. Four (6%) pts discontinued treatment due to a TRAE; 3 (4%) were due to irTRAEs. There were 2 deaths due to adverse events; none were assessed as related to dostarlimab.Conclusions: Dostarlimab demonstrated durable antitumor activity in pts with previously treated recurrent/advanced NSCLC. TRAEs were characteristic of antiePD-1 agents.Clinical trial identification: NCT02715284.