Anderson, D K

e18026 Background: Immune checkpoint inhibitor (ICI) therapy is part of standard of care first-line therapy for recurrent or metastatic (R/M) HNSCC. However, less than 20% of patients (CPS ≥1) have an objective response to ICI monotherapy, and most tumors progress within ~3 months. We sought to improve the proportion of patients who benefit from a chemotherapy-free regimen by combining intratumoral (IT) VV1 oncolytic virus (VSV-IFNβ-NIS) injections with the anti-PD-1 antibody, cemiplimab. We report a pre-planned analysis of Simon's stage 1 results. Methods: We activated a phase 2 study testing the efficacy of first line IT VV1 plus cemiplimab in 1 st line patients with R/M HNSCC. A Simon's two-stage design was employed whereby 10 patients would be accrued in stage 1, and if 3 or more responses were observed, 12 additional patients would be accrued for stage 2. The primary endpoint was objective response rate (ORR) per investigator (RECIST 1.1). Eligible patients had untreated R/M HNSCC from primary oropharynx, oral cavity, hypopharynx, or larynx sites with CPS ≥1. Patients had to have at least one measurable lesion amenable to IT injection. Treatment comprised of IT injections to 1-5 lesions of oncolytic VV-1 virus and IV cemiplimab 350 mg on day 1, repeated every 21 days. Each lesion could be injected 3 times; a 4th injection was allowed if a partial response (PR) was achieved after 3 injections. Cemiplimab could be continued for up to 2 years until progression or unacceptable toxicity. Results: Patient and tumor characteristics, as well as efficacy and toxicity are summarized in the table below. Ten patients were treated at the time of Stage 1 analysis, with 3 showing a confirmed PR for ORR of 30%. Responder CPS scores were 45, 12 and 20%. Two of the responders subsequently showed progression after 6.2 and 9.9 months, the third has maintained PR at 7.7 months to date. Eight of 10 patients showed decrease in the sum of target lesion size (mean decrease of 16%; range -57 to 77%). One grade 2 event of ICI nephritis resolved with corticosteroid treatment. Conclusions: Three patients showed confirmed PR by RECIST 1.1 in Simon's stage 1, meeting criteria to proceed to Simon's stage 2. A total of 22 patients in the HNSCC will be enrolled. VV1 plus cemiplimab shows promise in first line R/M HNSCC based on these initial results. Clinical trial information: NCT04291105 . Patient demographics. N (treated) 10 Sex 20% female Median age (y) 60 (54 – 76) Oropharynx 7 HPV+ 7 Oral cavity 3 PD-L1 CPS median (range) 7.5 (1-45%) Locoregional injection 3 Distant injection 6 Local and distant injection 1 Best response (RECIST 1.1) PR 3 SD 5 PD 2 Adverse Events #pts any VV1/cemiplimab-related G3 AE 4 Lymphopenia 3 Elevated ALK 1

Abstract Most malignant effusions are mononuclear predominant, with only 16-20% being neutrophilic. Neutrophilic predominance should raise suspicion for secondary inflammatory process, particularly empyema. In absence of infection, elevated neutrophils can be a sign of tumor necrosis or tumor lysis. In malignant pleural effusions, markers such as low glucose, low pH, and high LDH may indicate a high tumor burden and are markers of poor outcomes. 64-year-old male with past medical history of metastatic mucinous lung adenocarcinoma status post diagnostic right lower lobe wedge resection and recurrent bilateral malignant pleural effusions, presented to outpatient clinic for therapeutic right-sided thoracentesis. 900 mL of viscus green-brown pleural fluid was removed, and initial fluid studies revealed a neutrophil-predominant exudate with 45,045 total nucleated cells (TNCs) and pH of 7.01. Given concern for infection the patient was admitted, and a right-sided 14 French pigtail pleural catheter was placed. Left-sided thoracentesis was also performed, with pleural fluid studies consistent with a lymphocytic exudate. Vitals on admission were all within normal limits and white blood cell count was 8.9. Chest computed tomography (CT) scan showed extensive bilateral lymphangitic metastases scattered throughout both lungs and bilateral hydropneumothoraces with evidence of a left-sided pleural rind. Infectious workup, including pleural fluid cultures and broad-range bacterial polymerase chain reaction (PCR) were all negative. Cytology of both left and right pleural fluid revealed malignant adenocarcinoma with a substantial amount of necrosis. Patient was discharged home on oral antibiotics with plan to follow up as outpatient for possible tunneled pleural catheter placement. Post-discharge, patient continued to receive intermittent therapeutic thoracenteses. Subsequently readmitted, again with concerns for empyema, bilateral tunneled pleural catheters were placed after infectious workup was again unrevealing. At one month follow up, he reported drainage of 300-500 mL of pleural fluid with alternating daily drainages without complication. Differentiating neutrophilic malignant pleural effusions from empyema is clinically difficult and can lead to delay in definitive pleural treatments. Although it is important to rule out infection, malignancy should remain on one’s differential diagnosis, particularly if the remainder of the patient’s history and presentation are inconsistent with an infectious etiology. This abstract is funded by: None

Abstract Introduction Superior vena cava (SVC) syndrome results from the obstruction or occlusion of the SVC, leading to a range of complications depending on severity, location, and chronicity with the development of collateral circulation. We present a case of a patient with prior facial edema and subsequent development of bilateral pleural effusions whose evaluation led to discovery of SVC stenosis and occlusion of bilateral brachiocephalic veins, likely related to chronic indwelling pacemaker leads. Case Report A 73-year-old woman with bileaflet mitral valve prolapse with mild-to-moderate regurgitation, sinus node dysfunction status post pacemaker placement in 2014, atrial fibrillation and an unprovoked extensive right upper extremity deep venous thrombosis (DVT) managed on chronic apixaban therapy presented to clinic for evaluation of bilateral pleural effusions. One year prior to presentation, she developed facial and supraclavicular edema with positional dyspnea. A CT head and neck did not explain her abrupt facial edema though showed a left-sided pleural effusion, which was addressed locally with serial thoracenteses followed by tunneled pleural catheter placement. This ultimately led to discomfort without improvement in dyspnea, prompting catheter removal. She later developed a right-sided pleural effusion and underwent thoracentesis with the fluid analysis shown in Table 1. Physical exam was notable for collateral vessels along the chest wall and abdomen. The collateral vessels, unexplained pleural effusions, prior extensive right upper extremity DVT, and history of now resolved facial edema prompted CT venogram; this revealed occlusion of the right and left brachiocephalic veins and severe narrowing of the SVC with venous collaterals noted. PET-CT showed no evidence of malignancy. Electrophysiology consultation attributed the SVC stenosis to the indwelling pacemaker leads. The patient underwent SVC cavogram with successful angioplasty across right internal jugular vein down to the SVC with improvement in pressure gradient. After recanalization, there was no significant reaccumulation of pleural effusions on follow up and patient’s dyspnea improved. Discussion Pleural effusions in the setting of SVC syndrome have been described, most commonly due to thrombosis, device-related complications, or malignancy. This case highlights the importance of considering device-related vascular complications in patients with unexplained pleural effusions, particularly those with a history of intrathoracic devices or procedures. Management should target the underlying cause of the effusion; however long-term data on outcomes and optimal management strategies for pacemaker-related SVC syndrome remain limited. This abstract is funded by: None