Background Asthmatics and COPD patients have more severe outcomes with viral infections than people without obstructive disease. Objective To evaluate if obstructive diseases are risk factors for ICU stay and death due to COVID19. Methods We collected data from the electronic medical record from 596 adult patients hospitalized in University hospital of Liege between 18 th of March and 17th of April 2020 for SARS-CoV2 infection. We classified patients in three groups according to the underlying respiratory disease, present prior to COVID19 pandemics. Results Among patients requiring hospitalization for COVID19, asthma and COPD accounted for 9.6% and 7.7% respectively. The proportions of asthmatics, COPD and patients without obstructive airway disease hospitalized in ICU were 17.5%, 19.6% and 14% respectively. One third of COPD patients died during hospitalization while only 7.0% of asthmatics and 13.6% of patients without airway obstruction died due to SARS-CoV2. The multivariate analysis showed that asthma, COPD, ICS treatment and OCS treatment were not independent risk factors for ICU admission or death. Male gender (OR:1.9; 95%CI: 1.1 to 3.2) and obesity (OR:8.5; 95%CI: 5.1 to 14.1) were predictors of ICU admission while male gender (OR1.9; 95%CI: 1.1-3.2), older age (OR:1.9; 95%CI: 1.6-2.3), cardiopathy (OR: 1.8; 95%CI: 1.1-3.1) and immunosuppressive diseases (OR: 3.6; 95%CI: 1.5-8.4) were independent predictors of death. Conclusion Asthma and COPD are not risk factors for ICU admission and death related to SARS-CoV2 infection.

BackgroundBintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of the TGF-βRII receptor (a TGF-β ”trap”) fused to a human IgG1 mAb blocking PD-L1. Here we report cumulative safety and pharmacokinetic (PK) results from the global, phase 1b/2 INTR@PID LUNG 024 study (NCT03840915), which evaluated bintrafusp alfa in combination with chemotherapy (CT) in patients with stage IV NSCLC.MethodsAdult patients with stage IV nonsquamous or squamous NSCLC and an ECOG PS ≤1 were included. Cohorts A, B, and C included patients with no prior systemic therapy; patients in cohort D had disease that progressed with previous anti–PD-(L)1 therapy. Cohorts received bintrafusp alfa 2400 mg every 3 weeks intravenously in combination with CT for 4 cycles (A [nonsquamous only]: cisplatin or carboplatin + pemetrexed; B: carboplatin + nab-paclitaxel or paclitaxel; C: cisplatin or carboplatin + gemcitabine; D: docetaxel) followed by bintrafusp alfa maintenance (monotherapy or in combination with pemetrexed in cohort A) for up to 31 cycles. The primary objective of this study was to evaluate the safety of bintrafusp alfa in combination with CT. Dose-limiting toxicities (DLTs) were assessed during a 3-week observation period. Serial samples were drawn to assess serum concentration and calculate PK parameters by noncompartmental analysis.ResultsAs of the May 5, 2021, data cutoff, 70 patients received bintrafusp alfa in combination with CT. Of 35 patients included in the DLT analysis, 4 experienced 1 DLT according to a safety monitoring committee (data cutoff May 5, 2021; A: n=1/8; B: n=1/8; C: n=0/8; D: n=2/11). Cumulative safety data are reported in table 1. PK data were available for 67 patients (A: n=38; B: n=9; C: n=8; D: n=12). PK profiles were similar across cohorts and between patients who did and did not experience a DLT. Observed bintrafusp alfa first-cycle exposures (Cmax, AUC, and Ctrough) were consistent with the published population PK (popPK) model.1Abstract 465 Table 1Safety results from the INTR@PID LUNG 024 studyConclusionsThe safety profile of bintrafusp alfa in combination with CT was manageable and similar to that reported for ICIs in combination with CT, with the exception of TGF-β–related skin lesions known to occur with TGF-β inhibition. No new safety signals were identified and there were no treatment-related deaths. The PK profile was consistent with the predicted monotherapy popPK model, suggesting no victim DDI potential for bintrafusp alfa with CT.AcknowledgementsThe authors thank the patients and their families, investigators, co-investigators, and the study teams at each of the participating centers, at the healthcare business of Merck KGaA, Darmstadt, Germany, and at EMD Serono, Billerica, Massachusetts, USA.Trial RegistrationNCT03840915ReferenceWilkins JJ, Vugmeyster Y, Dussault I. Population pharmacokinetic analysis of bintrafusp alfa in different cancer types. Adv Ther 2019;36:2414–2433.Ethics ApprovalThe trial was approved by each site’s independent ethics committee.

9020 Background: Interleukin-1 Receptor Accessory Protein (IL1RAP) is expressed by cancer and stromal cells of many solid tumors. The IL-1 pathway is active in tumors and upregulated in response to chemotherapy. IL1RAP interacts with IL-1R1 and modulates downstream factors (e.g. IL-6, IL-8) and CRP level. Nadunolimab (CAN04), a fully humanized ADCC-enhanced IgG1 antibody, targets IL1RAP and blocks IL-1α and IL-1β signaling. Here, results are reported from the phase 1/2a clinical trial CANFOUR evaluating nadunolimab combined with CG in NSCLC. Methods: Patients (pts) with unresectable, locally advanced or metastatic NSCLC, progressed on pembrolizumab or in first line for advanced disease, were eligible. Pts received 1 (n =17), 2.5 (n = 3) or 5 mg/kg (= 13) nadunolimab given Q1W in Cycle 1 and Q2W from Cycle 2, combined with standard CG. Due to risk of infusion-related reactions, a priming dose of 0.5 mg/kg nadunolimab was given one week before CG. Primary objective was safety; secondary objectives included ORR, PFS and OS, and exploratory objectives included effects on serum and tumor tissue biomarkers. Results: Thirty-three pts were enrolled: median age 64 years (39-77), 30% female, 42% ECOG 0, 55% non-squamous histology, 82% stage IV, 45% received previous pembrolizumab monotherapy. Treatment-related adverse events of grade≥3 were observed in 73% of pts, including neutropenia (58%), febrile neutropenia (9%), thrombocytopenia (30%) and anemia (18%). Neutropenia could be managed by G-CSF. Thirty pts received combination therapy and were included in the efficacy analysis. Three pts did not receive chemotherapy due to clinical deterioration (n = 2) or consent withdrawal (n = 1). ORR was 53% (95% CI 34-72%), disease control rate 80% (61-92%) and median duration of response 5.5 months (3.7-7.0) with 23% of pts still on treatment. The lower limit of the 95% CI for the observed ORR excludes the pre-specified 30%. ORR in pts with squamous histology was 46% and non-squamous 56%. Median PFS was 6.7 months (5.5-7.3) and median OS 13.7 months. The neutrophil-lymphocyte ratio was reduced throughout the trial and was driven by the reduction in circulating neutrophil numbers. IL1RAP expression on both cancer and stromal cells was confirmed in tumor biopsies. Conclusions: Nadunolimab combined with CG shows manageable safety and promising efficacy with a response rate of 53% in NSCLC pts. Nadunolimab is currently evaluated in several clinical trials investigating chemotherapy or IO combinations, including carboplatin and pemetrexed in non-squamous NSCLC. Clinical trial information: NCT03267316.

Abstract. Neurotrophins (NTs) modulate the growth of human malignancies, including lung cancers. Our prospective study evaluated the accuracy of pleural NTs [nerve growth factor, brain-derived neurotrophic factor (BDNF), neurotrophin 3 (nT3) and 4 (nT4)] levels for differentiating benign from malignant pleural exudates. Levels of NTs were measured by ELISA in 170 patients with non-neutrophilic (<50%) exudative benign or malignant pleurisies diagnosed by pleuroscopy. Fifty-nine benign (9 infections and 50 inflammatory diseases) and 111 malignant (50 extrathoracic tumors, 51 lung cancers and 10 mesotheliomas) pleural exudates were diagnosed by thoracoscopy. Levels of BDNF were significantly higher in malignant than in benign effusions [17 pg/ml (0-367) vs. 8 pg/ml (0-51), p<0.05]. ROC analysis showed an area under the curve of 0.609 (p=0.012; best threshold 44 pg/ml). Pleural BDNF levels were significantly higher in pleural metastasis of pulmonary tumors and in mesothelioma than in pleural benign effusions. Finally, a higher proportion of pleural nT3 was detected in squamous cell lung carcinoma in comparison to that in nonsquamous cell lung carcinoma (72.7 vs. 10%, p<0.0001). NTs and particularly BDNF may play a role in the pathogenesis of malignant pleural effusions.

Background: The impact of coronavirus disease 2019 (COVID-19) on cancer patients is still unknown. We aimed to describe the clinical characteristics and 28-day mortality among patients with solid cancers (SC) and COVID-19.Methods: This single-center retrospective study included all adult patients with SC and RT-PCR confirmed COVID-19 between March 12, 2020 and April 30, 2020. Both oncological and COVID-19-related clinical data were collected. COVID-19 severity was defined according to Chinese CDC criteria. In-hospital and 28-day mortality were estimated. Multivariate analysis was adjusted for age, sex and COVID-19 severity. Results: We included 58 (2.7%) of 2130 patients with COVID-19 diagnosed in our hospital; 37 (63.8%) were males. Median age was 68.5 years (IQR, 61-75). Main comorbidities were hypertension (28 [48.3%]) and overweight/obesity (23 [39.7%]). Most common SC were prostate (12 [20.7%]), lung (10 [17.2%]) and breast (10 [17.2%]). Overall, 48 (82.8%) patients had previous ECOG PS of 0-1; 26 (44.8%) were stage IV and 32 (57.1%) were undergoing cancer treatment. Fifty-six (96.5%) patients were admitted. Most frequent COVID-19 symptoms were fever (40 [69.0%]), cough (35 [62.5%]) and dyspnea (27 [48.2%]). Hydroxychloroquine and azithromycin were used in 40 (69.0%) and 38 (65.5%) patients, respectively; only 3 (5.2%) patients received tocilizumab. Eighteen patients (32.1%) had severe/critical COVID-19. Major complications were respiratory failure (33 [57.9%]), sepsis (14 [24.6%]) and acute kidney injury (13 [22.4%]). Four (6.9%) patients were admitted to ICU. In-hospital and 28-day mortality were 17.2% (10/58) and 24.1% (14/58), respectively. In the multivariate analysis, only dyspnea at diagnosis (hazard ratio [HR]: 6.71, 95% CI 1.40-32.25, p¼0.017) and ECOG PS of 2-3 (HR: 4.17; 95% CI: 1.13-15.30, p¼0.031) were independent risk factors for 28-day mortality.Conclusions: In our patients with SC and COVID-19, 32.1% had a severe/critical disease and 24.1% died within 28 days from diagnosis. Dyspnea at diagnosis and previous ECOG PS of 2-3 were the major predictors for 28-day mortality. Cancer treatment and stage were not associated with mortality.Legal entity responsible for the study: The authors.