Study Enrollment Research Articles

FURVENT: Phase 3 trial of furmonertinib vs chemotherapy as first-line treatment for advanced NSCLC with EGFR exon 20 insertion mutations (FURMO-004).

TPS8668 Background: EGFR exon 20 insertion mutations (ex20ins) occur in approximately 2% of non-small cell lung cancer (NSCLC) and overall account for approximately 9% of all the EGFR mutations in NSCLC (Robichaux et al., 2021). Current first-line standard of care for NSCLC patients with these mutations is platinum-based chemotherapy (NCCN NSCLC, 2023). Furmonertinib is an oral, highly brain penetrant, broadly active mutant-selective EGFR inhibitor that targets EGFR exon 20 insertions and other EGFR mutations (1). Furmonertinib recently obtained FDA Breakthrough Therapy Designation for the first line treatment of patients with advanced NSCLC with EGFR ex20ins based on the data from the FAVOUR study. In FAVOUR, treatment naïve patients with locally advanced or metastatic NSCLC with EGFR ex20ins mutations showed preliminary clinical activity with a confirmed overall response rate (ORR) of 78.6% (n=28) by blinded independent central review (BICR) with a preliminary median DOR of 15.2 months when treated with 240 mg daily [QD] of furmonertinib (2). In previously treated patients both the 240 mg and 160 mg QD dose levels were active with confirmed ORR of 46.2% (n=26) and 38.5% (n=26) respectively and included patients harboring near and far loop mutations. Furmonertinib showed a generally well-tolerated safety profile with expected EGFR-TKI class toxicities. Methods: The FURVENT (FURMO-004) study is a registrational global, phase 3, randomized, multicenter, open-label study. Eligible patients have treatment-naïve, locally advanced or metastatic non-squamous NSCLC with EGFR exon 20 insertion mutations. Key inclusion criteria include documented EGFR ex20ins mutation and measurable disease per RECIST 1.1. Key exclusion criteria include prior systemic anticancer therapy in the locally advanced or metastatic setting or any prior EGFR TKI therapy. Approximately 375 patients will be randomized 1:1:1 to receive furmonertinib 160 mg QD, furmonertinib 240 mg QD, or platinum-based chemotherapy (cisplatin or carboplatin plus pemetrexed for 4 cycles followed by pemetrexed maintenance therapy). Stratification factors include the history or presence of central nervous system metastases at baseline, geographic region, and sex at birth. Patients from the platinum-based chemotherapy arm with documented disease progression can crossover to furmonertinib cohort. The primary endpoint is progression-free survival comparing between the treatment arms (furmonertinib 160 mg or 240 mg vs chemotherapy) based on BICR assessment. The key secondary endpoint is overall survival. Study enrollment is ongoing. 1. Musib et al., NACLC 2022. 2. Han et al., WCLC 2023. Clinical trial information: NCT05607550 .

Phase 1 study of ASP1002, a bispecific antibody targeting claudin 4 (CLDN4) and CD137, in patients with locally advanced (LA) or metastatic solid tumors that express CLDN4.

TPS2670 Background: The lack of benefit for many cancers from newer-generation combination chemotherapies has stimulated research into targeted agents. CLDN4, a claudin protein family member that regulates tight junction formation, is highly expressed in multiple tumor types including non-small cell lung cancer (NSCLC), urothelial carcinoma (UC), colorectal cancer (CRC), prostate adenocarcinoma (PA), ovarian cancer (OC), and triple-negative breast cancer (TNBC). Following primary T cell activation, CD137 provides a costimulatory signal that enhances T cell proliferation and cytokine production. Together CLDN4 and CD137 represent promising therapeutic targets for solid tumors. ASP1002 is a bispecific antibody designed to target CLDN4 and CD137, thereby enhancing the antitumor response of T cells against CLDN4-expressing tumor cells. Methods: This phase 1 first-in-human, open-label, multicenter study (NCT05719558) is evaluating the safety and tolerability, maximum tolerated dose (MTD), and/or recommended phase 2 dose (RP2D) of ASP1002 in adult patients with LA or metastatic solid tumors that express CLDN4. The primary endpoint is safety and tolerability, as assessed by dose-limiting toxicities (DLTs), adverse events (AEs), serious AEs, laboratory tests, vital signs, ECGs, PEs, and ECOG performance status. Secondary endpoints are pharmacokinetic characteristics; confirmed objective response rate (ORR), duration of response, and disease control rate per iRECIST and RECIST 1.1; and incidence rate and expression levels of CLDN4 by immunohistochemistry. Dose escalation will include patients with LA or metastatic NSCLC, UC, CRC, PA, OC, or TNBC. ASP1002 will be administered at escalating doses Q1W IV on days 1, 8, 15 in a 21-day cycle until discontinuation to determine MTD and/or candidate RP2D regimens. At doses ≥10 mg, multi-participant cohorts will be included. Safety follow-up visits will occur within 7 days posttreatment, and on 30 and 90 days posttreatment. Next, dose expansion will enroll patients with LA or metastatic NSCLC, UC, CRC, and other tumor types with confirmed complete response (CR) or partial response (PR) in dose escalation. Candidate RP2D regimens based on dose escalation data will be evaluated in ≤40 patients per dose level, per tumor type in dose expansion. ORR (confirmed CR or PR) per iRECIST will be evaluated in tumor-specific expansion cohorts. The minimum number of responders needed to establish activity is 4 (NSCLC), 3 (CRC), and 7 (UC). Study enrollment is currently ongoing in the United States. Clinical trial information: NCT05719558 .

SABA prescriptions and asthma management practices in Singapore: results from a cross-sectional, observational SABINA III study

ObjectivesTo evaluate asthma characteristics and treatment patterns, including short-acting β2-agonist (SABA) prescriptions, in primary and specialist care in the Singapore cohort of the SABA use IN Asthma (SABINA III) study.DesignCross-sectional,...

Developing behavioral intervention to support molecular testing of patients with biliary tract cancer.

TPS1641 Background: Biliary tract cancer (BTC) represents 7% of gastrointestinal malignancies in the United States, with an incidence of 0.5 to 2.0 cases per 100,000 individuals. Standard care involves systemic chemotherapy, predominantly gemcitabine and cisplatin. Recent advancements in immunotherapy, as evidenced by the TOPAZ-1 trial and KN966, support the use of durvalumab, and pembrolizumab as treatment options. Genetic tumor testing identifies up to 40% of BTC patients with targetable mutations, leading to recent FDA approvals for FGFR2 inhibitors - pemigatinib, infigratinib, futibatinib, and IDH1 inhibitor ivosidenib. The emerging data on inhibitors targeting the BRAF mutation, together with HER2 amplification, underscore the importance of understanding the tumor's molecular profile. Navigating this evolving treatment landscape emphasizes an unmet need for patients to comprehend the pivotal significance of tumor molecular profiling in formulating effective and personalized treatment plans. Identifying knowledge gaps among BTC patients concerning tumor genetic testing and precision medicine, along with strategies to address these gaps, holds promise for improving the management and the outcome of patients with BTC. Methods: This is a behavioral intervention study where participants will undergo two in-person survey interviews before and after an educational intervention. The initial survey aims to establish baseline knowledge about the BTC diagnosis and treatment and ascertain preferences for various educational interventions. Patients’ knowledge gap will be determined by comparing their responses to the initial survey and medical history documented by their treating physicians. They will then be provided with a 10-minute educational video. Participants will have the flexibility to access the video multiple times. Within 6 weeks from enrollment, they will have a post-education survey to determine the effectiveness of the education intervention. Following completion of baseline surveys, collaboration with key stakeholders including medical oncology and community perspectives will be initiated to identify knowledge gaps and inform the design of an educational intervention. The study enrollment will be targeted at BTC patients receiving systemic therapy at Georgetown University Hospital, Fox Chase Cancer Center, and Hackensack Meridian Health. Ten participants are enrolled and have completed the first survey and intervention. This study is currently enrolling participants: GUIRB: STUDY00007119.

Camrelizumab combined with apatinib as neoadjuvant therapy for locally advanced esophageal squamous cell carcinoma: A phase 2 trial.

e16087 Background: Increasing evidences prove the encouraging efficacy of neoadjuvant immunochemotherapy for esophageal squamous cell carcinoma (ESCC). However, the safety of chemotherapy is still unsatisfactory. Previous studies have confirmed the good efficacy and tolerance of PD-1 inhibitors combined with angiogenesis inhibitors in advanced ESCC. This trial is to assess the effectiveness and safety of camrelizumab (PD-1 inhibitor) plus chemotherapy or apatinib (angiogenesis inhibitor) as neoadjuvant therapy for locally advanced ESCC. Methods: This was an open-label, non-randomized phase 2 trial of patients with stage cT2-4aN0-3M0 ESCC. Eligible patients were 18-75 years old, had ECOG PS score of 0-1. Patients received 2 cycles (1 cycle per 4 weeks) of camrelizumab (200 mg Q2W) and apatinib (250 mg QD). Surgery was performed within 4-6 weeks after neoadjuvant therapy. The primary endpoint was major pathological response (MPR) rate. Secondary endpoints included pathological complete response (pCR) rate, R0 resection rate, disease-free survival (DFS), overall survival (OS), and safety. Results: Between Feb 2022 and Dec 2023, 24 patients (19 males and 5 females) with a median age of 67 years were enrolled in the study. Twenty-one patients completed neoadjuvant therapy, the ORR was 50% and the DCR was 95%. Nineteen patients completed surgery and all patients (100%) reached R0 resection, 3 patients (3/19, 10.5%) reached pCR, 8 patients (8/19, 42.1%) reached MPR, and 13 patients (13/19, 68.4%) had TNM downstaging. The median follow-up was 11.9 months, and the median DFS had not yet reached. Any grade and grade ≥3 adverse events occurred in 87.5% and 8.3% of 24 patients, respectively. The most common AEs were increased alanine aminotransferase (8/24, 33.3%), increased alanine aminotransferase (7/24, 29.2%) and thrombocytopenia(7/24, 29.2%). No new safety signals or treatment-related deaths were observed. Conclusions: Neoadjuvant camrelizumab in combination with apatinib in patients with locally advanced ESCC showed promising pathological response and downstaging effect with acceptable security. The study enrollment is ongoing, and further survival and safety data will be reported in the future. Clinical trial information: NCT03917966 .

Factors associated with PrEP-era HIV seroconversion in a 4-year U.S. national cohort of n = 6059 sexual and gender minority individuals who have sex with men, 2017-2022.

Community-based cohort studies of HIV seroconversion can identify important avenues for enhancing HIV prevention efforts in the era of pre-exposure prophylaxis (PrEP). Within individuals, one can assess exposure and outcome variables repeatedly and with increased certainty regarding temporal ordering. This cohort study examined the association of several risk factors with subsequent HIV seroconversion. We report data from a 4-year study (2017-2022) of 6059 HIV seronegative sexual and gender minority individuals who have sex with men who had indications for-, but were not using-, PrEP at enrolment. Participants completed repeat exposure assessments and self-collection of biospecimens for HIV testing. We examined the roles of race and ethnicity, socio-economic status, methamphetamine use and PrEP uptake over the course of follow-up in relation to HIV seroconversion. Over 4 years, 303 of the participants seroconverted across 18,421 person-years (incidence rate = 1.64 [95% CI: 1.59-1.70] per 100 person-years). In multivariable discrete-time survival analysis, factors independently associated with elevated HIV seroconversion risk included being Black/African American (adjusted risk ratio [aRR]: 2.44, 1.79-3.28), Hispanic/Latinx (1.53, 1.19-1.96), housing instability (1.58, 1.22-2.05) and past year methamphetamine use (3.82, 2.74-5.33). Conversely, time since study enrolment (24 vs. 12 months, 0.67, 0.51-0.87; 36 months, 0.60, 0.45-0.80; 48 months, 0.48, 0.35-0.66) and higher education (master's degree or higher vs. less than or equal to high school, 0.36, 0.17-0.66) were associated with reduced seroconversion risk. Compared to non-PrEP users in the past 2 years without a current clinical indication, those who started PrEP but then discontinued had higher seroconversion risk, irrespective of clinical indication (3.23, 1.74-6.46) or lack thereof (4.30, 1.85-9.88). However, those who initiated PrEP in the past year (0.14, 0.04-0.39) or persistently used PrEP in the past 2 years (0.33, 0.14-0.74) had a lower risk of seroconversion. Of all HIV seroconversions observed during follow-up assessments (12, 24, 36 and 48 months), methamphetamine was reported in the 12 months prior 128 (42.2%) times (overall). Interventions that acknowledge race and ethnicity, economic variables such as education and housing instability, and methamphetamine use are critically needed. Not only are interventions to engage individuals in PrEP care needed, but those that retain them, and re-engage those who may fall out of care are essential, given the exceptionally high risk of seroconversion in these groups.

Molecularly matched therapies identified by comprehensive genomic profiling before the first-line setting to provide alternative treatment outcomes in patients with solid tumors: 1-year follow-up of the prospective FIRST-Dx study.

3137 Background: Comprehensive genomic profiling (CGP) test by next-generation sequencing has been reimbursed in Japan since 2019. However, only 9.4% of patients (pts) had received molecularly-matched treatment because CGP test in Japan is only indicated after standard of care (SoC). To determine the clinical utility of a CGP test (FoundationOne CDx) in the first-line setting for pts with advanced solid tumors, we previously reported the results of the FIRST-Dx study, in which the molecular tumor board identified molecular-based recommended therapy (MBRT) for 61% of pts (105/172) (Matsubara J, et al. JAMA Netw Open 2023). In this 1-year follow-up of the FIRST-Dx study, we investigated the clinical benefits provided by the upfront CGP test. Methods: The FIRST-Dx study was a multi-institutional, prospective study in 6 hospitals in Japan. Chemotherapy-naïve adult pts with advanced solid tumor (GI, Lung, Breast, GYN, Melanoma) and ECOG performance status of 0-1 were enrolled. This follow-up study was planned for 3 years and an interim analysis was prespecified at 1 year after the final patient enrollment in the FIRST-Dx study. Primary endpoint was overall survival (OS). Secondary endpoints were the proportion of pts who received MBRT, overall response rate, progression-free survival (PFS), and a PFS ratio (PFS on MBRT/PFS on prior therapy). Results: Data from 172 pts with a median follow-up of 15.1 months were available. Median OS was not reached (95% CI: 18.4 months to not reached). Thirty-nine pts (22.7%) had received MBRT. The total number of pts treated with MBRT were 21 in 1st-line, 20 in 2nd-line, 4 in 3rd-line, and 1 in 4th-line, respectively. Overall response rate was 56.3% [95% CI: 29.9-80.2%] in 1st-line MBRT group vs 42.3% [95% CI: 33.9-51.1%] in 1st-line SoC (N=137), and 26.3% [95% CI: 9.1-51.2%] in 2nd-line MBRT group vs 17.1% [95% CI: 9.7-27.0%] in 2nd-line SoC (N=82), respectively. Median PFS was 12.9 months [95% CI: 7.4 months to not reached] in 1st-line MBRT group vs 11.3 months [95% CI: 8.6-14.1 months] in 1st-line SoC, and 6.9 months [95% CI: 2.8 months to not reached] in 2nd-line MBRT group vs 5.7 months [95% CI: 3.7-7.4 months] in 2nd-line SoC, respectively. Regarding the PFS ratio of 2nd-line MBRT (N=15) (PFS on MBRT in 2nd-line/PFS on 1st-line therapy), median PFS ratio was 1.0 (range: 0.1-14.6) and 4 pts (27%) had the PFS ratio of >1.3, indicating that MBRT might be effective in changing the clinical outcome (Von Hoff DD, et al. J Clin Oncol 2010). Conclusions: We showed that MBRT identified by CGP test before the first-line setting provides better treatment outcomes than SoC in pts with solid tumors early in their disease course. Our data suggested that the timing of CGP test in Japan for pts with advanced solid tumors should be indicated before starting SoC. Clinical trial information: jRCT1050220041 .

A phase IV trial to confirm the efficacy of olaparib in combination with bevacizumab as maintenance frontline treatment of HRD-positive ovarian tumours (IOlanTHe).

TPS5628 Background: PAOLA-1/ENGOT-ov25 trial demonstrated that Olaparib (O) plus Bevacizumab (B) determined a significant survival benefit in patients (pts) with advanced, high-grade, epithelial ovarian, peritoneal and/or fallopian-tube cancer (HEOC) presenting defects of homologous recombination repair system (HRD+) in clinical response after first-line platinum-based chemotherapy (CT) plus B. Methods: IOLANTHE is a multicenter Italian phase IV trial (sponsored by the MaNGO group, Protocol Number IRFMN-OVA-8542) aiming to confirm in a setting close to clinical practice the efficacy of this combination in pts with HRD+HEOC. As the study includes a consistent translational component, all suspicious advanced cases will be considered for study enrollment. Pts with a confirmed pathological diagnosis of HEOC will be included in the step 1 of the trial which main inclusion criteria are the following: -availability of formalin-fixed, paraffin-embedded samples for the central testing of HRD status (performed by Myriad Mychoice CDx Plus assay) - suitability to receive CT + B. Only HRD+ pts responding to first line CT plus at least one cycle of B will be enrolled in the step 2 of the trial and will be treated with B 15 mg/kg every 3 weeks plus O 300 mg twice daily. Considering the PAOLA-1 median progression free survival (PFS) of 37.2 months (mo) in the B-O arm, with a sample size of 90 pts followed for 24 months and setting a one-side error of 5%, we will have a statistical power of 80% to demonstrate a PFS-24mo≥64% with an upper critical value of 61%. In order to have 90 patients eligible for the step 2 of the study, 190 pts are needed to be enrolled in the step 1 of the clinical study (as approximately 80% of pts with HEOC will respond to CT and out of these, 60% will be HRD+). The translational subproject 1 will consist of the analysis of circulating-tumor (ctDNA), using whole genome sequencing aiming - to correlate residual tumour after surgery and ctDNA levels - to anticipate the diagnosis of progression - to monitor the mutational status of HR-related genes and other genes such as Tp53BP1, POLQ, REV7 probably involved in PARPi resistance during the maintenance therapy. The translational subproject 2 will be developed to compare pts’ response to therapy with that of cancer cells, tested by organotypic model treated with the combination. These models will be generated using fresh tumor tissue and ascitic fluid for the isolation of the tumor cells and macroscopically healthy omentum for the isolation of the mesothelial cells and fibroblasts. Eight centers have been activated and other 6 are waiting for the activation with 19 patients registered and 3 screening failures. The enrollment is continuing, according to protocol timeline (12 months for enrollment, 6 months for surgery and CT and 24 months for maintenance treatment). Clinical trial information: NCT06121401 .

Orthorexia nervosa in breast cancer survivors: The role of disease characteristics and psychological aspects (GOIRC 02-2019).

e24092 Background: Orthorexia Nervosa (ON), although not yet considered as a full-blown psychopathological disorder, is defined as altered thoughts and behaviours related to healthy eating and its prevalence is increasing in general population. Surviving cancer is a condition that may affect patients behaviour and mental status leading to beliefs that may affect everyday life to avoid cancer recurrence. Among these, eating behaviour is mostly represented in cancer survivors. The aim of the present study is to evaluate the prevalence and characteristics of ON among breast cancer (BC) survivors. Methods: This observational study enrols adult patients attending the outpatient clinic at the Oncology Division of Modena University Hospital. Patients with a BC diagnosis that have concluded the surgical, radiotherapy and chemo and/or targeted therapy treatment phase were considered eligible. Ongoing hormonal adjuvant therapy was permitted. Socio-demographic, clinical variables (stage, year of diagnosis, hormone receptor status, HER2 status, proliferation index, treatment) were collected on an anonymized database. Moreover, three psychometric measurements were administered to patients: the Hospital Anxiety-Depression Scale (HADS), the Personality Inventory for DSM-5 Brief Form (PID-5-BIF) and the ORTO-R, a 6-item self-administered tool that is the most used scale to measure ON. Results: Data were collected from 137 patients. Mean age was 62.4 years and (± 10.3) and the mean BMI was 26.3 (± 5.2). Sixty-six percent of patients were diagnosed with stage I disease, 28% with stage II and 6% with stage III disease. Thirty percent of patients received adjuvant chemotherapy, 89% hormonal therapy and 15.5% anti-HER2 targeted therapy. The ORTO-R mean score was 12.2 ± 3.8. The prevalence of psychiatric symptoms at the HADS was 36.5%. The ORTO-R score was found to correlate negatively to age of patients (the older, the less the score at ORTO-R, p = 0.001) and positively to 3 of the constructs of personality at the PID-5-BF, disinhibition, psychoticism and negative affect. Interestingly, ORTO-R was poorly associated to cancer variables, such as stage, hormone receptors, treatments, phenotype (luminal, HER2 positive, triple negative), lifestyle and psychiatric symptomatology. Conclusions: Eating behaviours among cancer patients may be influenced by psychological aspects and need to be addressed during follow-up. Further investigations are needed to evaluate correlation with BC specific characteristics.[Table: see text]

Phase 2 open label, multicenter study evaluating CRG-022, a CD22-directed autologous CAR T-cell therapy, in patients (pts) with relapsed/refractory (R/R) large B-cell lymphoma (LBCL) after CD19-directed CAR T-cell therapy.

TPS7085 Background: Autologous (auto) CD19-directed CAR T-cell therapy can induce long-term remissions for pts with R/R LBCL but approximately 60% will experience disease progression resulting in poor outcomes (Neelapu, 2023; Zurko, 2023). CRG-022 is a novel CAR T-cell product targeting CD22, a common B-cell antigen widely expressed in LBCL. Key features of CRG-022 include a fully human scFv derived from the m971 monoclonal antibody and 4-1BB/CD3z intracellular signaling domains (Singh, 2021). This CD22 CAR construct was developed at the National Cancer Institute and was investigated in phase (ph) 1 studies of pediatric/young adult pts with R/R CD22+ malignancies (Shah, 2020; NCT02315612) and at Stanford University in adults with R/R LBCL (Baird, 2021; NCT04088890) primarily in pts who received prior CD19-directed CAR-T therapy. The Stanford ph 1b study reported an overall response rate (ORR) and complete response rates of 66% and 52%, respectively in 29 pts treated at the recommended Phase 2 dose (RP2D) of 1x106 CAR+ T cells/kg (Frank, 2023). After a median follow-up of 27.3 months, the median overall survival had not been reached at the RP2D (Su, 2023). At the RP2D, no grade >3 cytokine release syndrome (CRS), immune-effector cell associated neurotoxicity syndrome (ICANS), or immune effector cell associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS) occurred; two pts (7%) developed grade 2 IEC-HS (Su, 2023; Srinagesh, 2023). Based on these notable results, this potentially pivotal ph 2 trial has been initiated. Methods: This Phase 2 study will evaluate the safety/efficacy of CRG-022 at 1x106 CAR+ T cells/kg in pts with R/R LBCL whose disease has progressed after CD19-directed CAR T-cell therapy. The primary endpoint is ORR according to Lugano response criteria (Cheson, 2014) by blinded independent review. Adverse events (AEs) are graded per CTCAE v5 except with CRS, ICANS, and IEC-HS graded per ASTCT guidelines. Pts with diffuse large B-cell lymphoma (DLBCL), high grade B-cell lymphoma, DLBCL transformed from follicular or marginal zone lymphoma, follicular large B-cell lymphoma (FLBL)/FL Grade 3B, and primary mediastinal B-cell lymphoma are eligible. Other eligibility criteria include adequate hematologic and organ function, and no prior allogeneic stem cell transplant. Pts with prior treatment to both a CD19-directed auto CAR-T and a bispecific T-cell engaging antibody are also eligible within a separate cohort. Lymphodepletion with fludarabine 30 mg/m2/day and cyclophosphamide 500 mg/m2/day for 3 days will be administered ahead of a single infusion of CRG-022. The study is designed to enroll approximately 123 pts. Study enrollment commenced in the US in August 2023, with 9 pt infused as of 08 JAN 2024. Clinical trial information: NCT05972720 .

Scoping review of the use of mesenchymal stem and stromal cell products in cats, Part 1: current logistics and safety.

Despite a pressing need for new therapies to address unmet veterinary medical need, no approved stem cell products are available for use in cats in the US. To evaluate the current state of mesenchymal stem or stromal cell (MSC) research in cats, a scoping review of published literature was performed, which identified 108 publications related to feline MSCs. Twenty-six of the articles described administration of MSC products to a total of 215 cats. Twelve of the studies included a control group. These experimental and clinical trials used 7 cell sources, 9 administration routes, 12 delivery vehicles, and a 300-fold range in dosages for initial studies in healthy cats and cats with 12 naturally occurring and induced diseases. The majority of studies administered 2 doses of allogeneic, adipose-derived MSC IV and monitored a median of 6.5 treated cats for a median of 90 days. The majority (150/215 [69.8%]) of cats had no reported adverse events associated with treatment. Although an increase in feline MSC publications in the past 10 years indicates progress, the wide variety and small number of studies using MSCs and MSC products in cats demonstrates that current evaluations are mostly still in the discovery phase, and several issues remain related to larger scale trials using MSC products in cats. The current available publications provide information to direct further clinical study development and informed owner consent for study enrollment.

Evaluation of a novel university-based testing platform to increase access to SARS-CoV-2 testing during the COVID-19 pandemic in a cohort study

ObjectiveWe aimed to evaluate the feasibility and utility of an unsupervised testing mechanism, in which participants pick up a swab kit, self-test (unsupervised) and return the kit to an on-campus...

Pooled analysis on characteristics of nausea and vomiting in patients receiving trastuzumab deruxtecan (T-DXd) in clinical studies.

12118 Background: The efficacy and safety profile of T-DXd has been established in patients (pts) with various tumor types, and nausea and vomiting are the most common treatment-emergent adverse events (TEAEs). T-DXd study protocols were refined over time to recommend prophylaxis (eg, neurokinin or serotonin receptor antagonists and/or steroids) before T-DXd treatment, in line with antiemetic and institutional guidelines. We conducted a pooled, post hoc analysis capturing safety information across tumor types; we report results on nausea and vomiting. While this analysis was not designed to assess antiemetic effectiveness, it reveals the incidence of nausea and vomiting in clinical trials of T-DXd 5.4 mg/kg in more detail across a large dataset. Methods: 1449 pts treated with ≥1 dose of 5.4 mg/kg T-DXd (every 3 wks) were included from 7 phase 1-3 clinical trials in metastatic HER2+ and HER2-low breast cancer, HER2+ gastric cancer, and HER2-mutant non–small cell lung cancer (DESTINY-Breast01, -Breast02, -Breast03, -Breast04, -Lung01, -Lung02, and the first-in-human phase 1 study J101 in multiple tumor types; study enrollment starting 2015-2021). Regardless of antiemetic use (including prophylaxis), the incidence, severity, time to onset, and duration of nausea and vomiting TEAEs were assessed along with event outcomes. Results: Of 1449 pts receiving T-DXd 5.4 mg/kg (median [range] number of 3-wk treatment cycles: 13 [1-60]), 74.6% (n=1081) experienced nausea, and 41.6% (n=603) reported vomiting. Most pts had grade 1/2 nausea (41.2%/27.6%) and/or vomiting (26.2%/12.8%). Grade 3 TEAEs of nausea were reported in 5.8% of pts, with grade ≥3 TEAEs of vomiting observed in 2.6% of pts. By the data cutoff for each trial, 66.9% of pts with nausea and 87.6% with vomiting had their symptoms resolve. Most pts who experienced nausea and vomiting did so during the initial 21 days (cycle 1; n=879 [81.3%] and 336 [55.7%], respectively; 35.8% of all pts received antiemetic prophylaxis at cycle 1); both TEAEs declined notably in subsequent cycles. Rates of drug discontinuation, dose reduction, and drug interruption due to nausea and vomiting were generally low (Table). Conclusions: Most nausea and vomiting events were reported during the first 3 wks of treatment and resolved. Appropriate prophylaxis of nausea and vomiting is a key management strategy and allows pts to benefit from longer treatment durations with T-DXd. Ongoing studies are exploring the implementation and impact of prophylaxis for T-DXd–related emesis. Clinical trial information: NCT03248492 , NCT03523585 , NCT03529110 , NCT03734029 , NCT03505710 , NCT04644237 , NCT02564900 . [Table: see text]

Impact of early phase study enrollment for pediatric oncology patients on symptom burden and quality of life (QOL): Early report of trial-in-progress results.

e23195 Background: Pediatric patients with relapsed or refractory malignancy have few options. The quality of life (QoL) impact for enrolling in a phase I or II trial compared to those not participating is unknown. This information is invaluable to the consenting process as well as to clinical trial design. The primary aim was to determine if those enrolled on a phase I or II trial had lower scores on the Symptom Screening in Pediatrics Tool (SSPedi) total score compared to those not enrolled on a trial. Methods: This Canadian multi-site study had nine sites open for accrual. SSPedi was calculated based on patient reports for 8-18 years and parent-proxy reports for all children. The total score is the sum of 15 items’ 4 Likert scale scores, score ranges from 0 to 60 (worst possible). Scores from baseline, 4 weeks and 8 weeks of those enrolled on an early phase trial were compared to those who did not enroll in such trials. Results: Of the 54 49 patients, 21 (43%) patients were enrolled on an early phase trial and 28 (57%) patients were not enrolled in a study. For those enrolled on the study at enrollment time, 4 weeks and 8 weeks time points, the total SSPedi score for the participant mean was 11.1 (SD 8.1), 9.2 (SD 6.3) and 10.1 (8.3) respectively compared to those not enrolled on a study with mean scores at the same time points of 13.8 (SD 8.6), 13.5 (SD 9.4), and 15.4 (SD 12.6). Conclusions: These results suggest that it is feasible to evaluate patients enrolled and not enrolled on early phase trials, and to compare their symptom experience. Further efforts will focus on more recruitment and using the PedsQL 3.0 Acute Cancer Module to further define differences in QoL. The results suggest that those enrolled in an early phase trial had an improved quality of life compared to those non-enrolled. This research is supported through granting from the C17 Council and Kindred Foundation. [Table: see text]

Standardized In-Bed Mobility Protocol to Increase Functional Outcomes in Pediatric Intensive Care Unit: A Pilot Randomized Controlled Trial

AbstractThe primary aim of this study is to determine whether a standardized in-bed mobility protocol involving an in-bed cycle ergometer in critically ill children increases functional outcomes as measured by the Functional Status Scale (FSS) and dynamometer measurements compared with patients participating in standard rehabilitation care. The secondary aim was to compare hospital length of stay (HLOS) between the two groups. This pilot randomized controlled trial (RCT) was conducted between April 2021 and December 2022. Eligible patients were randomized to the intervention group (up to 30 minutes of daily in-bed cycle ergometer use) or the control group (standardized rehabilitation care). During the study duration, 30 patients were randomized (13 in the control group and 17 in the intervention group). The difference in whole-body muscle strength measurements (enrollment vs. completion of study) was higher in the experimental group (3.68 lbs.) compared with the control group (1.5 lbs.). However, the difference between groups was not statistically significant (p = 0.18). Both the intervention group and the control group showed similar significant improvements in the FSS scores throughout the therapy, with no difference between the two groups. There was a significant positive correlation between exercise time and change in muscle strength (r = 0.75, p = 0.002). No difference in HLOS was detected in the study. Results from this pilot RCT suggest a trend toward benefits from using in-bed cycle ergometers. These devices may be an additional modality for preserving muscle function in critically ill children. Larger multicentric studies are needed for more conclusive evidence.

A comparison of two weaning strategies for non-invasive ventilation in chronic obstructive pulmonary disease patients with acute respiratory failure.

Non-Invasive Ventilation (NIV) is a crucial therapy for managing acute exacerbations of Chronic Obstructive Pulmonary Disease (COPD) with hypercapnic respiratory failure. Research has shown that NIV can decrease the rate of endotracheal intubation, length of hospital and Intensive Care Unit stays, and mortality. There are three main strategies for weaning patients off NIV: gradual reduction of NIV duration, gradual reduction of NIV pressure support, and immediate cessation of NIV. To compare the rate of successful withdrawal of COPD patients with acute hypercapnic respiratory failure, one group will use a stepwise reduction of duration of NIV, while the other group will use a stepwise reduction of pressure support. This study was a prospective observational study conducted at the Department of Pulmonary Medicine, Institute of Chest Diseases, Government Medical College, Kozhikode, over a period of 15months. The study population consisted of all COPD patients admitted to the Pulmonary Medicine ward or ICU with acute hypercapnic respiratory failure who were managed with non-invasive ventilation (NIV) without the need for invasive mechanical ventilation. Exclusions included patients requiring NIV for respiratory diseases other than COPD, those with significant comorbiditieslike acute left ventricular failure or fluid overload states as in chronic kidney disease, COVID-19 positive patients, patients on home NIV, patients who needed intubation early in treatment, and patients unwilling to participate in the study. The sample size was 140. Initial NIV settings and other management decisions prior to enrolment in the study were made by the treating physician according to standard protocols. Once weaning criteria were met (i.e., arterial pH > 7.35, SpO2 ≥ 90% at an FiO2 ≤ 50%, respiratory rate ≤ 25 breaths per minute, heart rate ≤ 120 beats per minute, systolic BP > 90mm Hg, and no signs of respiratory distress), patients were assigned to either group 1 or group 2 by purposive sampling. Group 1: stepwise reduction of duration of NIV use, with a reduction to 16h per day on day 1 of enrolment, 12h on day 2 (including 6-8h of nocturnal NIV), 6-8h on day 3, and NIV withdrawal on day 4. Group 2: stepwise reduction of pressure support, with pressure support reduced by 2-4cm every 4-6h until Inspiratory Positive Airway Pressure is < 8cm H2O and Expiratory Positive Airway Pressure is < 4cm H2O, followed by NIV withdrawal. The clinical outcome was classified as either improved or weaning failure. Improved was defined as an objective or subjective sense of improvement. Weaning failure was defined as the presence of any of the following: respiratory rate ≥ 25/minute or increase of ≥ 50% from baseline, heart rate ≥ 140/minute or increase of ≥ 20% from baseline, SpO2 ≤ 90% on FiO2 ≥ 50%, arterial pH ≤ 7.35, or respiratory distress. Data was collected using a pro forma that included demographic details, smoking status, GOLD COPD category, comorbidities, and vital signs. ABG parameters, NIV settings at the time of hospital admission, at the time of study enrolment, and 48h after weaning were also recorded. Independent sample t-test was used to test the statistical significance of the difference between means of variables between the two groups. Pearson Chi square test and Fisher's exact test were used to compare categorical variables between the groups. A p-value of < 0.05 was considered statistically significant. NIV was successfully withdrawn in 56/70 (80%) and 50/70 (71.4%) patients in Groups 1 and 2, respectively. This difference was not statistically significant. The length of hospital stay was longer in the stepwise reduction of duration group (Group 1), but this was not statistically significant. On comparison of two methods of NIV withdrawal, it was found that neither method is superior to the other in terms of weaning failure, intubation rates, and average length of hospital stay.

Oral flecainide therapy and myocardial pacing: preliminary data from a prospective multicenter registry

Abstract Background Antiarrhythmic drugs, class I are widely used for prevention of atrial fibrillation recurrence. However, previous studies found that these drugs could affect pacing thresholds among pacemaker recipients. Aim of the study: evaluate short -term effect on myocardial pacing following therapy with oral flecainide (200 mg/daily). Methods 45 consecutive pacemaker recipients were prospectively enrolled in a multicenter registry. These patients had preserved left ventricular ejection fraction, a dual chamber pacemaker with symptomatic sustained high-rate atrial fibrillation episodes and stable output atrial and ventricular thresholds. Patients were followed with ambulatory and/or remote monitoring. Results mean age was 74±1 years, 48% pts were male and AF burden was 8±16%. Pacemaker implantation was performed 3.9±0.3 year before study enrollment. Three (6%) out of 45 patients were excluded due to drug sided effects including dyspnea (n=1), diplopia (n=1) and toxicity during acute renal insufficiency (n=1). Flecainide treatment was associated with a significant reduction of atrial fibrillation burden (from 8±16% to 5±12%, p&amp;lt;0.01). At 30 days follow-up since Flecainide starting therapy both atrial and ventricular sensing significantly decreased (3.6 ± 2.2 vs 3.4 ± 2.1mV p=0.01; 12.5±6.6 vs 11.8±6.3 mV p=0.01), while there was a slight increase of both atrial and ventricular capture thresholds (0.77±0.61V@0.4ms vs 0.80±0.42V@0.4ms p=0.01; 0.80±0.53V @0.4ms vs 0.83±0.33V @0.4ms p=0.01). No patient required pacemaker parameters reprogramming. Conclusions oral flecainide therapy among pacemaker recipients at 30 days follow-up seems to be safe and do not affect device function. Further studies with additional follow-up data are warranted.

Impact of industry funding on atrial fibrillation clinical trials: insights and implications

Abstract Background/Introduction Commercial industry is an important source of funding for atrial fibrillation clinical trials, the implications of which have not been analyzed. Purpose The purpose of this study is to describe the characteristics of contemporary AF clinical trials and to evaluate their association with funding source. Methods We systematically assessed all completed atrial fibrillation trials registered in ClinicalTrials.gov between conception to September 1, 2022, and extracted publicly available information including funding source, trial size, race, ethnicity, sex, intervention, location, and publication status. Trial characteristics were compared using the Wilcoxon rank sum test and Fisher’s exact test for continuous and categorical variables, respectively. Results Of the 253 clinical trials assessed, 171 (68%) reported industry funding. Industry funding was associated with a greater median total enrollment (172 vs. 80; P &amp;lt; 0.001), publication rate (56.7% vs. 42.7%; P = 0.04), participation in device trials (48.0% vs. 24.4%; P &amp;lt; 0.001), and multicontinental recruitment location (25.2% vs. 2.4%; P &amp;lt; 0.001) when compared to non-industry funded clinical trials. However, industry funding was not associated with a significant difference in median impact factor (7.7 vs. 7.7; P = 0.723) or median number of citations (60.0 vs. 29.0; P = 0.09). The overall proportion of industry funded trials did not change over time (P = 1.00) since inception of the ClinicalTrials.gov database. Participant demographics remained relatively uniform over time across both industry-funded and non-industry-funded trials. Conclusion(s). Industry funded clinical trials in atrial fibrillation are often larger, more frequently published, multicontinental, and device-focused. Industry funding was found to be associated with significant differences in study enrollment, publication metrics, and study interventions. Insights from this study inform trial design, regulation, and policy considerations in the evolving landscape of AF research.TableFigure

Medical care services interplay between individual and Medicaid managed care markets in expansion versus non‐expansion states

AbstractWe study enrollment, medical service utilization, and incurred expenses of individual comprehensive and Medicaid managed care plans in states with or without Medicaid expansion adopted at the Affordable Care Act (ACA) early stage 2014–2016. To make healthcare services more accessible, 27 states expanded Medicaid eligibility to cover nearly‐poor non‐elderly adults who have had incomes between 100% and 138% of federal poverty level in 2014. In non‐expansion states, early enrollees in this income cohort had to choose individual market plans rather than Medicaid. Early enrollees' enrollment choices and their health status have had a great impact on the individual market premiums and Medicaid spending. We examined health insurers' annual regulatory filings with the National Association of Insurance Commissioners for 2013–2016 and found that: First, individual comprehensive insurance enrollment grew much faster in states not expanding Medicaid eligibility. Second, after incorporating early enrollees, per member per month (PMPM) medical service utilization and expenses of individual comprehensive insurance grew much faster in non‐expansion states. Third, among major types of medical utilization and expense measures, PMPM hospital inpatient days and PMPM prescription drug expenses increased substantially since 2014. Finally, Medicaid beneficiaries generated more PMPM medical utilization and expenses in expansion states.

#1458 Adverse muscle composition predicts all-cause mortality in CKD

Abstract Background and Aims Sarcopenia is common in CKD and associates with morbidity and mortality. A rapid and standardized MRI (Magnetic Resonance Imaging) scan protocol allows an accurate muscle composition analysis by quantification of skeletal muscle volume and muscle fat infiltration (MFI). The combined observation of low muscle volume and high muscle fat infiltration, i.e. adverse muscle composition (AMC), is a prevalent muscle composition phenotype within CKD and associates to poor function, high prevalence of comorbidity, and an increased risk for coronary heart disease (CHD). It has also been shown that AMC is an independent predictor of all-cause mortality in patients with non-alcoholic fatty liver disease and in general population. In this study we aimed to investigate muscle composition as predictor of all-cause mortality within participants with CKD in the UK Biobank imaging study (UKB). Method This is a prospective study including UKB participants with CKD defined as having an eGFR cystatin C &amp;lt; 60 ml/min/1, 73 m2. A control group was created by matching each participant with CKD for sex, age, and BMI to four participants with normal eGFR. Cystatin C was analyzed based on blood samples at time of study enrolment 7-9 years prior to the MRI. Fat-tissue free thigh muscle volume and MFI were quantified using a rapid neck-to-knee water and fat separated MRI protocol and automated image analysis (AMRA® Researcher). For each participant, a personalized muscle volume z-score (sex- and body size-specific) was calculated and combined with MFI to divide the participants into four muscle composition phenotype groups; 1) normal muscle composition, 2) only low muscle volume, 3) only high MFI and 4) AMC, using previously published thresholds based on the whole UKB cohort. The thresholds were the 25th percentile (&amp;lt; -0.68 SD) for muscle volume z-score and the 75th percentile (men &amp;gt;7.69%; women &amp;gt;8.82%) for MFI. The mortality data were obtained through the UKB´s linkage to national death registries. All-cause mortality was investigated using Kaplan-Meier curves and Cox regression. Models within participants with CKD were crude and subsequently adjusted for sex, age, BMI, low hand grip strength (&amp;lt;16/27 kg for females/males), physical activity, smoking, alcohol, and previous diagnosis of cancer, prevalent CHD and type 2 diabetes, all assessed at the time of imaging. Results Conclusion AMC, determined by standardized MRI, was a strong predictor of all-cause mortality in CKD. The study results indicate that CKD patients with poor muscle health, identified as having both low muscle volume z-score and high MFI, have a significantly higher mortality risk. This vulnerable group would potentially benefit from targeted interventions and is also of specific interest when evaluating new treatments for CKD.