Multicenter Trial Research Articles

HEalth-Related Quality of Life-Intervention in Survivors of Breast and Other Cancers Experiencing Cancer-Related Fatigue and Associated Cognitive Symptoms Using TraditionAL Chinese Medicine: The 'HERBAL' Trial.

As pharmacological strategies remain limited for relieving fatigue and associated cognitive symptoms, integrative modalities such as traditional Chinese medicine (TCM) could be explored as therapeutic strategies in cancer survivors. Here, we evaluate and report the efficacy and safety of a TCM concoction, modified Xiang Bei Yang Rong Tang (XBYRT), on quality of life (QOL), cancer-related fatigue (CRF), and cognitive symptoms, compared to placebo. In a single-centered, randomized, double-blinded, placebo-controlled pilot trial conducted from 2019 to 2022, fatigued cancer survivors ≥21 years old were recruited to receive the XBYRT intervention or placebo (5% diluted) once daily for the duration of 8 weeks. Patient-reported outcomes for QOL, CRF, cognition, blood samples for biomarker testing, and adverse events were collected at baseline (T0), 4 weeks (T1), 8 weeks (T2), and 10 weeks (T3) after baseline. Linear regression was performed to evaluate differences between groups at T2 and T3. A total of 1502 patients were screened, with 672 patients considered eligible. Of the eligible, 15 XBYRT and 13 placebo subjects with similar mean ages (58.5 vs 58.4) were recruited. Both groups were predominantly Chinese (93% vs 62%), breast cancer patients (87% vs 62%), and diagnosed with stage 2 cancer (60% vs 46%). Although no significant difference was found in QOL between groups, the XBYRT group exhibited improved emotional fatigue at T3 (P = .045) and higher BDNF levels at T2 (P = .047) and T3 (P = .029). After baseline adjustment, XBYRT was associated with better perceived cognitive impairment at T2 (P = .011) and T3 (P = .017), as well as overall perceived cognitive function at T3 (P = .028). XBYRT is well tolerated, with grade 3 adverse events reported in three XBYRT (20%) and two placebo (15%) subjects. In this pilot study, XBYRT as an integrative therapy is safe and generates encouraging improvements in cognitive and fatigue symptoms. Difficulties with recruitment limited the generalizability of trial findings, thus findings should be verified through a larger, multi-centered trial.

Neoadjuvant Clinical Trials in Adults with Newly Diagnosed High-Grade Glioma: A Systematic Review.

High-grade gliomas are devastating cancers that remain incurable with standard surgical resection and radiochemotherapy. Although beneficial against neoplasms, radiation lowers lymphocyte counts, weakens immune activation, and recruits suppressive myeloid cells impairing immune responses. Tumor environments treated with radiation experience long-term immunosuppression, reducing immunotherapy effectiveness and contributing to recurrence. Investigating pre-radiation treatments in newly diagnosed patients could identify active agents, assess immunotherapy impact, and enable multiomic analyses without radiation-induced confounding factors. This literature review was conducted to describe the feasibility, safety, and outcomes of postsurgical, pre-radiation clinical trials for adults with newly diagnosed high-grade glioma. A systematic review was performed of the English-language literature reporting results of clinical trials for adults with newly diagnosed high-grade glioma administered postsurgical treatment prior to radiation therapy. A search was conducted in PubMed and references cited in research and review articles were also considered. From 1991 to 2024, 52 clinical trials were identified: 3 phase I, 38 phase II, 4 phase III, and 7 of unknown phase. Nine trials were randomized, 24 were multicenter trials, 21 investigated temozolomide-containing regimens, and 12 focused on inoperable tumors, involving a total of 2,737 patients. Pre-radiation neoadjuvant studies are feasible and may identify active drugs. This is particularly relevant in the era of personalized medicine with brain-penetrant drugs, targeted therapy, and immuno-oncology advancements. Investigating pre-radiation treatments in newly diagnosed high-grade glioma is a viable approach to rapidly identify active and inactive regimens while the immune system and tumor microenvironment remain intact.

Non-contrast MRI as a surveillance tool for recurrent hepatocellular carcinoma after curative treatment: A prospective multicenter intra-individual comparison trial.

530 Background: Hepatocellular carcinoma (HCC) often recurs following curative treatment, significantly impacting long-term survival. Contrast-enhanced multiphasic computed tomography (CECT) is widely utilized for HCC recurrence surveillance but carries risks such as radiation exposure and adverse reactions to contrast agents. This prospective multicenter trial aimed to compare the accuracy of non-contrast abbreviated magnetic resonance imaging (NC-MRI) with CECT in detecting late recurrent HCC. Methods: This prospective multicenter intra-individual head-to-head comparison trial (study identifier: NCT05690451, KCT0006395) enrolled participants who had undergone curative treatment for HCC and remained recurrence-free for over two years. Participants underwent three rounds of surveillance at 2–6-month intervals using both CECT and NC-MRI. The primary outcome was the detection accuracy of each modality, compared using the McNemar test. Secondary outcomes included detection sensitivity and specificity. Results: A total of 203 participants underwent 528 rounds of paired CECT and NC-MRI, detecting recurrent HCC in 22 participants (10.8%). Among these cases, 21 showed intrahepatic recurrent HCC with a median tumor size of 1.3 cm, and one exhibited aortocaval lymph node metastasis. NC-MRI demonstrated a detection accuracy of 96.6% (196/203), significantly higher than CECT's 91.6% (186/203) (P=0.006). NC-MRI also exhibited significantly higher sensitivity in detecting recurrent HCC compared to CECT (77.3% [17/22] vs. 36.4% [8/22]; P=0.012), while specificity did not differ significantly between NC-MRI and CECT (98.9% [179/181] vs. 98.3% [178/181]; P=0.999). Conclusions: NC-MRI showed significantly higher sensitivity and accuracy in detecting recurrent HCC among patients who had been disease-free for more than two years after curative treatment, establishing it as the preferred surveillance modality for late recurrence. Clinical trial information: NCT05690451 . Contrast enhanced CT Non-contrast MRI Difference, % (95% CI) P-value Estimates, % (n/N) 95% CI, % Estimates, % (n/N) 95% CI, % Accuracy 91.6% (186/203) 87.8-95.5 96.6% (196/203) 94.0-99.1 4.9 (1.7, 8.2) 0.006 Sensitivity 36.4% (8/22) 14.5-58.2 77.3% (17/22) 58.3-96.3 40.9 (16.8, 65.0) 0.012 Specificity 98.3% (178/181) 96.5-100 98.9% (179/181) 97.4-100 0.6 (-0.5, 1.6) 0.999

A phase 1/2 study to evaluate CHM-2101, an autologous cadherin 17 (CDH17) chimeric antigen receptor (CAR) T cell therapy for the treatment of relapsed or refractory gastrointestinal cancers.

TPS844 Background: Patients with advanced gastrointestinal (GI) malignancies have poor prognoses and limited treatment options. Cadherin 17 (CDH17) is a cell membrane-associated protein important for GI cell-cell interactions that is expressed in proximity to epithelial tight junctions. In some GI malignancies, CDH17 expression is also expressed diffusely across the cancer cell membrane, thus providing access to CDH17 directed CAR T-cells. CHM CDH17 is a third generation autologous CAR T-cell product candidate that was designed to target and eradicate CDH17+ solid tumors. Notably, expression of CDH17 varies across indications in the cancer setting CDH17– TABLE 1. Methods: Clinical Trial NCT06055439 is a seamless Phase 1/2 clinical trial of autologous CHM CDH17 CAR T-cells for patients with advanced gastric cancer (GC), colorectal (CRC) cancer or neuroendocrine tumors (NETs) of the midgut or hindgut. As CDH17 expression in GC is heterogenous, GC subjects will be screened for CDH17 expression. In preparation for receiving CDH17 CAR T-cells, subjects receive 3-days of lymphodepleting intravenous (IV) chemotherapy (fludarabine and cyclophosphamide). The Phase 1 portion of the clinical trial uses a 3+3 dose escalation and a starting dose of 50 million CAR-T cells in a single IV infusion. Decisions regarding dose escalation/de-escalation are based on real-time dose-limiting toxicity evaluation during the first 28 days of treatment during dose escalation. After establishing a recommended Phase 2 dose, three indication-specific Simon 2-Stage cohorts will be initiated in (1) GC (2) CRC and (3) NETs of the midgut or hindgut to further characterize the safety and assess the efficacy of CHM CDH17 CAR T-cells. This is an ongoing first-in-human multi-center clinical trial of CHM CDH17, a CDH17 directed autologous CAR T-cell product candidate, enrolling subjects with advanced GI cancers that express CDH17. Clinical trial information: NCT06055439 . Expression of CDH17 in selected gastrointestinal cancer indications. Indication Sample size CDH17Expression %* Colorectal cancer 821 96% Neuroendocrine tumors of the midgut and hindgut 119 97% Gastric cancer 1,409 64% *Expression of total tumors tested for CDH17 by immunohistochemistry (CHM data on file).

The Abdominal Drain after Gastrectomy (ADiGe) Trial: a multicenter non-inferiority randomized trial investigating the role of prophylactic drain in the management of post-operative collections.

The Abdominal Drain after Gastrectomy (ADiGe) Trial: a multicenter non-inferiority randomized trial investigating the role of prophylactic drain in the management of post-operative collections.

Randomized, multicenter, active-controlled open-label study of NPC-25, zinc histidine hydrate, (non-inferiority to NOBELZINTM, zinc acetate dihydrate) for patients with hypozincemia

ObjectiveThis study evaluated the efficacy and safety of NPC-25, zinc histidine hydrate, in patients with hypozincemia. This randomized multicenter active-controlled open-label trial aimed to verify the non-inferiority of NPC-25 to NOBELZINTM, zinc acetate dihydrate. MethodsParticipants whose serum zinc concentrations were <70 μg/dL at two points within 8 weeks before the start of treatment were randomized 1:1 into the NPC-25 (active drug) administration group and the NOBELZINTM (control drug) administration group, using dynamic allocation. The initial daily doses were 50mg or 100mg as the baseline serum zinc levels, and administration periods were set at maximum of 24 weeks with the goal of maintaining the target serum zinc concentration (≥80 and <200 μg/dL) for 8 weeks, with extension up to 52 weeks as needed in the NPC-25 group, but not the NOBELZIN group. The primary efficacy endpoint was the proportion of participants who maintained the target serum zinc concentration for 8 weeks at the same dosage within 24 weeks after the start of administration. The key secondary endpoints were the cumulative achievement percentage for target serum zinc concentration at each observation time point, the cumulative achievement percentage for maintenance of target concentration for 8 weeks at the same dosage at each observation time point, change in mean serum zinc concentration, and comparison of dosage amount. Safety assessments included the incidence of adverse events and adverse drug reactions, as well as changes in clinical laboratory and physical measurements. ResultsFor the primary endpoint for full analysis (FAS) set (n=103, NPC-25 group; n=107, NOBELZIN group), the proportion of participants who maintained the target serum zinc concentration for 8 weeks at the same dose was 86.4% (89/103) in the NPC-25 group and 80.4% (86/107) in the NOBELZIN group, which confirmed the non-inferiority of NPC-25 to NOBELZINTM. For the secondary endpoint for FAS, at each observation point, although there was no significant difference between the two groups in the proportion of participants who achieved the target serum zinc concentration, there was a tendency that the maintenance of the target concentration for 8 weeks was achieved earlier with NPC-25.There was also a tendency to achieve maintenance with a lower daily dose in the NPC-25 group. Furthermore, at each observation point, there was no significant difference between the two groups in terms of the mean serum zinc concentration or the average change in serum zinc concentration from baseline. In the safety assessment for safety population (SP), the incidence of nausea and vomiting was lower with NPC-25 than with NOBELZIN (2.8% and 6.4% with nausea, 0.9% and 2.8% with vomiting), but there were no significant differences in other adverse drug reactions. ConclusionIn this study, non-inferiority of NPC-25 to NOBELZINTM was confirmed in terms of efficacy and safety. Furthermore, regarding safety, NPC-25 resulted in a lower frequency of digestive symptoms, such as nausea and vomiting.

Analysis of lipogenic and metabolic subtypes and survival outcome in patients with pancreatic adenocarcinoma.

775 Background: Delayed diagnosis and rapid progression are major drivers of poor survival outcomes for Pancreatic Ductal Adenocarcinoma (PDAC). In previous studies, molecular profiling in tumor tissue has identified Cholesterogenic, Classical, or Exocrine-Like pathological subtypes associated with improved prognosis. Herein, in a clinical trial called Project Survival, we molecularly and clinically characterized a prospective PDAC biomarker cohort. This multicenter (n=6) clinical trial (NCT 02781012) of PDAC combined with high-fidelity longitudinal phenotypic characterization and multi-omic profiling was utilized to identify biomarkers with diagnostic and therapeutic utility. The study included assessment of plasma, serum, buffy coat, urine, saliva, and tumor tissue samples and followed 269 PDAC subjects for up to 7 years (Median survival was 700 days, with IQR of 822 days). Methods: We assessed plasma samples to identify circulating biomarkers using proteomics, metabolomics, and lipidomics profiling. Multi-omic comparison of patients with Overall Survival (OS) above the 75th percentile (improved survival) against those with OS below the 25th percentile (poor survival) was performed. Results: We identified distinct panels of proteins, metabolites, and lipids that were associated with patient survival outcomes. Protein biomarkers that were increased in improved survival outcomes were associated with cholesterol metabolism (7/14, p-value = 0.00085) and glycolysis/gluconeogenesis (5/12, p-value = 0.00089), however, protein markers associated with immune surveillance and inflammation were associated with poorer survival. For metabolite biomarkers, 19 metabolites were increased in poorer survivors of which 13/19 were carnitine metabolites, and 42 metabolites were increased in patients with improved survival. Interestingly, only two lipid molecular species of the diacylglyceride family were increased in patients with poorer survival. Conclusions: Project Survival, a prospective biomarker-driven clinical trial identified distinct metabolic and molecular subtypes of patients which characterize survival outcome in PDAC. These subtypes go beyond tumor genomic characterization and align with distinct cholesterogenic and glucogenic phenotypes associated with survival outcomes, which can potentially be leveraged for therapeutic intervention strategies.

Second-line therapy with Nal-IRI/5-FU/FA after failure of gemcitabine/nab-paclitaxel in advanced pancreatic cancer (PC): Predictive role of 1st-line therapy (PREDICT) and impact of quality of life (QoL).

707 Background: Metastatic PC has the lowest survival rate of all malignant diseases and is the fourth most common cancer. QoL remains an unresolved issue in PC for patients (pts) after treatment failure of 1 st -line CTx (TTF1). Nanoliposomal irinotecan (Nal-IRI) with 5-FU/folinic acid (FA) increased survival of PC pts from 4.2 months (mo) to 6.1 mo as compared to 5-FU/FA alone, with a rate of toxicities that may impact QoL. PREDICT is an open label, single arm, multicenter Phase IIIb trial (NCT03468335) and examined 2 nd -line Nal/IRI/5-FU/FA for PC. Here we report on QoL during 2 nd -line Nal-IRI after failure of 1 st -line gemcitabine/nab-Paclitaxel (gem/nab-Pac). Methods: In this prospective trial, 151 patients with locally advanced or metastatic PC were treated with biweekly Nal-IRI/5-FU/FA (70 mg/m², 2400 mg/m², 400 mg/m²) after failure of gem/nab-pac (TTF1). Primary end point (EP) was the time to treatment failure of 2 nd -line therapy (TTF2) and has been reported elsewhere. Secondary EP were QoL and Health related quality of life (HR-QoL) which were evaluated using questionnaires (EORTC QLQC30, QLQ-PAN26, EQ-5D-5L). Evaluation of time to definitive deterioration of QoL (TDD) during 2 nd -line therapy, defined as the time from screening/baseline until loss of ≥10 points in the EORTC QLQ-C30 was compared to baseline. Results: QoL analyses were performed with all QoL evaluable subjects set (QAS). The QAS included 143 pts, of which 48 pts were included in TTF1 high (TTF of 1 st -line ≥213 d) and 49 pts in the TTF1 low (TTF ≤119 d) cohort, with 79 (54.1%) female and 67 (45.9%) male pts. Mean age was 68.2±8.9 years. Overall, a low global health status / QoL mean score was observed at baseline for TTF1 high and low cohorts (about 48 points), which slightly improved during the study for TTF1 high (3.5±23.7) and slightly worsened for TTF1 low cohort (-0.7±22.5). Substantial improvements were observed for both cohorts in emotional functioning scale at certain study time points (TTF1 high: up to 9.1±25.7, TTF1 low: up to 6.6±17.0). A relatively high mean score was observed for cognitive function scale for both cohorts at baseline (TTF1 high: 70.1±30.2; TTF1 low: 72.5±21.4). Pts in the TTF1 low vs. high cohort showed more pronounced worsening of cognitive function. Median TDD was numerically longer (about one month) for TTF1 high (5,3 mo) compared to TTF1 low cohort (3,9 mo). The probability to maintain QoL after six months was similar between the two cohorts. Conclusions: QoL showed similar global and HR-QoL scores with only slight changes during the study. Median TDD was numerically longer for high TTF1 pts, but similar after six months between pts still on 2 nd line Nal/IRI/5-FU regardless of duration of TTF in 1 st -line. Clinical trial information: NCT03468335 .

The efficacy of high load-volume exercise versus low load-volume exercise for rotator cuff tendinopathy: A pilot and feasibility trial.

The most effective exercise variables for rotator cuff tendinopathy are unknown. Determine feasibility of a fully powered trial comparing high load-volume versus low load-volume exercise for adults with rotator cuff tendinopathy. Two arm, multi-centre pilot and feasibility randomised controlled trial. Participants aged over 18 were recruited via social media and randomised into 12 weeks of either high load-volume exercise (i.e. with dumbbell resistance) or low load-volume exercise (i.e. without added resistance). Feasibility outcomes were rates of recruitment, retention, questionnaire completion, adverse events and adherence to prescribed exercise. Fifteen participants were randomised to high load-volume and 16 to low load-volume (18/31 were female). Retention rate was 84% at 6 weeks, and 81% at 12 and 26 weeks. Five participants withdrew and one participant was lost to follow up. Questionnaire completion rate was 78%. Adherence to the prescribed exercise sets was 77%. Recruitment, conversion and retention rates were above the pre-defined success criterion. There were no serious adverse events. A fully powered multi-centre randomised trial is feasible with minor amendments addressing exercise adherence and questionnaire response rate. Future trials should utilise outcomes that consider participants baseline physical activity levels and adequately measure pain disparate from performance.

Prognosis of patients with liver single-organ metastases: Updated survival results of BBCAPX-II.

157 Background: Although immunotherapy has changed the treatment strategy for many cancers with great success, patients with microsatellite stable (MSS) and RAS-mutant metastatic colorectal cancer (mCRC) especially with liver metastases have a low response rate to immunotherapy. Sintilimab plus bevacizumab and CapeOX (BBCAPX) has proved its efficacy and safety in above unresectable mCRC patients (1). Here, we report subgroup analysis of updated survival results of this single arm, open-label, phase 2 trial. Methods: Eligible patients were histologically confirmed unresectable metastatic colorectal adenocarcinoma by multidisciplinary team, and had RAS gene mutation and confirmed MSS status. All patients received treatment with sintilimab plus bevacizumab, oxaliplatin and capecitabine of each 21-day cycle. ORR, DCR, PFS, OS, and subgroup analyses based on metastasis site were performed. Results: From April 2021 to December 2021, 25 patients were enrolled. The ORR was 84% and the DCR was 100%. Six (24%) patients including 5 patients with liver single organ metastases underwent surgical treatment and unexpectedly achieved no evidence of disease status. At the data cut-off day (September 13, 2024), patients with liver single organ metastases presented better prognosis. Median PFS was 25.3 months (95% CI, 4.8-NA) in the patients with liver single organ metastases and 11.5 months (95% CI, 4.83-24.3) in the patients with other metastasis. Median OS was not reached in the patients with liver single organ metastases and 35.5 months (95% CI, 9.36-NA) in the patients with other metastasis. The OS rate at 24 months was 72% (95% CI, 56.4-91.9) in FAS. Median OS was not reached in FAS and 35.5 months (95% CI, 11.4-NA) in PPS. 32% patients had at least one grade 3 or 4 TRAEs. No grade 5 adverse events occurred during the study. Conclusions: This study provides a highly promising regimen for patients with RAS-mutant, MSS, unresectable mCRC, especially those with liver single organ metastases. Furthermore, we are launching a phase III, randomized, open-label, multicentric clinical trial (NCT05171660) to further analyze the effects, safety, and prognostic biomarkers of this regimen. 1. Xuefeng Fang et al. ASCO 2022. Clinical trial information: NCT04194359 . PFS and OS results of BBCAPX-II study. Median PFS 6m PFS rate (%) 12m PFS rate (%) Median OS 12m OS rate (%) 24m OS rate (%) Full analysis set (FAS), n = 25 17.9 (95% CI, 8.84-27) 84 (70.8-99.7) 56 (39.6-79.3) NA 76 (61-94.7) 72 (56.4-91.9) Per-protocol set (PPS), n = 19 9.79 (95% CI, 6.44-27.9) 78.9 (62.6-99.6) 42.1 (24.9-71.3) 35.5 (95% CI, 11.4-NA) 68.4 (50.4-92.9) 63.2 (44.8-89) Classified by metastatic organs (FAS, n = 25) Liver single organ metastases, n = 10 25.3 (95% CI, 4.8-NA) 90 (73.2-100) 70 (46.7-100) NA (11.4-NA) 90 (73.2-100) 80 (58.7-100) Other metastases, n = 15 11.5 (95% CI, 4.83-24.3) 80 (62.1-100) 46.7 (27.2-80.2) 35.5 (9.36-NA) 66.7 (46.6-95.3) 66.7 (46.6-95.3)

Repetitive transcranial magnetic stimulation for fibromyalgia: are we there yet?

Repetitive transcranial magnetic stimulation (rTMS) has increasingly been used to modify cortical maladaptive plastic changes shown to occur in fibromyalgia (FM) and to correlate with symptoms. Evidence for its efficacy is currently inconclusive, mainly due to heterogeneity of stimulation parameters used in trials available to date. Here, we reviewed the current evidence on the use of rTMS for FM control in the format of a narrative review, in which a systematic dissection of the different stimulation parameters would be possible. We conducted a search in Medline and Embase for controlled trials on rTMS in people with FM with at least 10 participants in each treatment arm, and treatment/follow-up of at least 3 weeks. The search identified 482 abstracts, of which 45 were screened to full review, and 11 met inclusion criteria. Six out of 11 trials were positive. The dorsolateral prefrontal cortex was the target in 218 patients (49.2%), and the primary motor cortex (M1) in 225 (50.8%). Studies targeting M1 at 10 Hz, with stimulation current delivered in the posterior-anterior, were systematically positive, frequently showing that maintenance sessions delivered weekly, and biweekly were able to maintain the analgesic effects seen after daily induction sessions. Studies assessing the effects of rTMS for FM are still marked by heterogeneity in stimulation petameters, choice of primary outcomes, and inclusion criteria. The selection of the stimulation parameters associated with significant analgesic effects is likely to benefit following larger multicenter trials and improve the overall management of pain and associated symptoms in people with FM.

First-in-human, phase 1a, dose escalation study of BGB-B167, a CEA x 4-1BB bispecific antibody, as monotherapy or combined with tislelizumab (anti-PD-1), in patients with selected advanced or metastatic solid tumors.

123 Background: BGB-B167 is potentially a first-in-class IgG-based bispecific antibody that targets CEA, a tumor-associated antigen overexpressed in many cancers, and 4-1BB, a key T-cell co-stimulatory receptor expressed on activated CD4+/CD8+ T lymphocytes. Preclinical data suggest BGB-B167 binds to these target proteins with high specificity/affinity, inducing T-cell activation and antitumor activity, with potential for mitigating strong AEs, eg CRS and hepatoxicity. We present results of a first-in-human, phase 1a, open-label, multicenter trial of BGB-B167 given as monotherapy (Part A [A]) or with tislelizumab (TIS) (Part B [B]) (NCT05494762). Methods: Eligibility: ≥18 y with unresectable/metastatic CRC, CEA+ GC or CEA+ NSCLC previously treated with standard systemic therapy or for whom treatment is unavailable; pts with CRC and known MSI-H/dMMR status must have received prior ICI, if available. Primary objectives: safety/tolerability; MTD and RP2D for BGB-B167 ± TIS; key secondary objective: antitumor activity (RECIST v1.1). Results: As of July 7, 2024, 54 pts were enrolled (31 in A, 23 in B) with BGB-B167 dose ranges of 5–1200 mg IV QW assessed in A and 50–600 mg IV QW in B. In A and B, respectively, 29/31 (93.5%) and 18/23 (78.3%) had CRC, 2/31 (6.5%) and 3/23 (13%) had GC, 0/31 (0%) and 2/23 (8.7%) had NSCLC; 19/31 (61.3%) and 18/23 (78.3%) had liver metastases; 20/31 (64.5%) and 14/23 (60.9%) received ≥3 lines of prior therapy. TEAEs occurred in all pts (Table). Most common treatment-related TEAEs were nausea (4/31; 12.9%) and fatigue (3/31; 9.7%) in A and pruritus (5/23; 21.7%) and diarrhea (4/23; 17.4%) in B; there were no treatment-related TEAEs indicative of hepatotoxicity or CRS. There was a single DLT (gr 3 SJS) in a pt who received 600 mg BGB-B167 + TIS (resolved after treatment discontinuation). MTD was not reached. 3 pts (1 with CRC [A]; 1 with CRC and 1 with GC [B]) had confirmed PRs. DoR was ≥5.6 mo for the pt in A and ≥5.6 mo and ≥6.9 mo for the pts in B; all remained on treatment with ongoing responses as of the data cutoff date. DCR (95% CI) was 33.3% (17.3–52.8) in A and 40.9% (20.7–63.6) in B. Serum exposure of BGB-B167 increased dose dependently from 150 to 1200 mg. Conclusions: Overall, BGB-B167 ± TIS was well tolerated and has demonstrated limited antitumor activity in pts with advanced/metastatic CEA+ solid tumors. Clinical trial information: NCT05494762 . Safety. Part ABGB-B167 monotherapy(N=31) Part BBGB-B167 + TIS(N=23) Any TEAE 31 (100.0) 23 (100.0) Any treatment-related TEAE 17 (54.8) 15 (65.2) Gr ≥3 4 (12.9) 1 (4.3) Serious 0 (0) 2 (8.7) Leading to death 0 (0) 0 (0) Leading to treatment discontinuation 0 (0) 1 (4.3) Any imAE 2 (6.5) 5 (21.7) IRRs 4 (12.9) 6 (26.1) Patients with multiple adverse events (AEs) are counted once. All AEs are listed as n (%). imAE, immune-mediated AE; IRR, infusion-related reaction; TEAE, treatment-emergent AE.

Digital Home-Based Self-Monitoring System for People with Heart Failure: Protocol for Development of SmartHeart and Evaluation of Feasibility and Acceptability.

Heart failure (HF) is a chronic, progressive condition where the heart cannot pump enough blood to meet the body's needs. In addition to the daily challenges that HF poses, acute exacerbations can lead to costly hospitalizations and increased mortality. High health care costs and the burden of HF have led to the emerging application of new technologies to support people living with HF to stay well while living in the community. However, many digital solutions have not involved consumers and health care professionals in their design, leading to poor adoption. The SmartHeart project aimed to codevelop a smart health ecosystem to support the early detection of HF deterioration and encourage self-care, potentially preventing hospitalizations. This study aims to provide an overview of the SmartHeart project by describing our approach to designing the SmartHeart system, outlining its features, and describing the planned pilot study to determine the feasibility of the system. We used the Integrate, Design, Assess, and Share (IDEAS) framework to guide the development of the SmartHeart system, involving users (people with HF and their caregivers) and stakeholders (health care providers involved in the management of HF) in its design. SmartHeart is a complete remote heart health monitoring and automated feedback delivery system. It includes 2 user interfaces for patients: an Amazon Alexa conversational agent and a smartphone app. The system collects physiological, symptom, and behavioral data through wireless sensors and self-reports from users. These data are processed and analyzed to provide personalized health insights, self-care support, and alerts in case of health deterioration. The system also includes a web-based user interface for health care professionals, allowing them to access data, send messages to users, and receive notifications about potential health deterioration. A single-arm, multicenter pilot trial (N=20) is planned to determine the feasibility and acceptability of SmartHeart before evaluation through a randomized controlled trial. The primary outcome will be a description of the study's feasibility (recruitment, attrition, engagement, and changes in self-care). The SmartHeart study started in January 2021 on procurement of funding. Recruitment for the pilot trial started in August 2024 and will be completed by March 2025. We have currently enrolled 12 participants. Follow-up of all participants will be completed by the end of May 2025. We have co-designed and developed a complete remote heart health monitoring and automated feedback delivery system for the early detection of HF deterioration and prevention of HF-related hospitalizations. The next step is a pilot study, which will provide valuable information on feasibility and preliminary effects to inform a larger evaluation trial. SmartHeart has the potential to augment existing health services and help people with HF stay well while living in the community. DERR1-10.2196/62964.

Continuous risk monitoring and management of heart failure: Rationale and design of the ALLEVIATE-HF trial.

Early identification and management of worsening heart failure (HF) is necessary to prevent disease progression and hospitalizations. The ALLEVIATE-HF (Algorithm Using LINQ Sensors for Evaluation and Treatment of Heart Failure) trial is a prospective, randomized, controlled, double-blind, multicentre trial that aims to assess the safety and efficacy of using the Reveal LINQ™ insertable cardiac monitor (ICM) in patients with HF to continuously monitor and evaluate HF risk status and guide timely interventions. The ICM algorithm uses parameters derived from electrocardiogram (atrial fibrillation [AF], ventricular rate during AF, heart rate variability, and night heart rate), three-axis accelerometer (patient activity duration), and subcutaneous bioimpedance (fluid volume, respiration rate). The trial will enroll ~760 patients with New York Heart Association class II or III HF with recent hospitalization for HF or needing intravenous diuretics in the outpatient setting or elevated natriuretic peptide levels, who do not have an implanted cardiac implantable electronic device or haemodynamic monitor. Patients are randomized to an observation or an intervention arm, where the latter will receive an intervention pathway with remote nurses implementing individualized pro re nata (PRN or 'as needed') 4-day medication interventions for acute volume management upon high risk. After 13 months of randomized follow-up, all patients enter an unblinded prolonged follow-up phase with PRN interventions upon high risk. The primary hierarchical composite endpoint for the study includes cardiovascular death, HF events, Kansas City Cardiomyopathy Questionnaire score, and 6-min walk test distance. ALLEVIATE-HF will evaluate how ICM-based HF management can impact the outcomes of patients with HF regardless of ejection fraction.

Abstract IA08: Theragnostics &amp; external beam radiation dose absorbed - Similarities, differences and thoughts for the future

Abstract External Beam Radiotherapy (EBRT) and theragnostics share a key core characteristic – the use of radiation to exert its therapeutic benefit. However, the role radiation dose absorbed plays is significantly different between these two modalities in clinical practice. On the one hand it is a critical element of EBRT prescriptions (e.g. cGy), while on the other it is not even a requirement to document in theragnostic practices, where prescriptions are expressed as administered activities (e.g. GBq). Radiation dose absorbed by tumor and normal tissues is recognized to be variable across patients. It is acknowledged to be a critical metric in the safe use of radiopharmaceuticals and is required for all first in human studies and a priority for the development of any novel radiopharmaceutical. The process of individualized dosimetry is well described, enabling radiation dose absorbed estimates to regions of interest. There is an active debate currently as to when, in whom and how individualized dosimetry should be incorporated into clinical practice. The lack of high quality evidence to support radiation dose absorbed to patient outcomes, the lack of standardized methodologies to enable comparability of dose absorbed data across institutions, the burden on patients to return for dosimetry scans post treatment, the burden on the health care system to incorporate individualized dosimetry into treatment workflows and the lack of reimbursement codes for these activities are the main barriers cited against routine clinical use. In this session, we will review some of the theoretical and logistic considerations as well as evidence behind this debate. We will also take a broader view, of theragnostics as a rapidly growing modality, that patients and their oncology teams would need radiation absorbed dose information when considering “re-irradiation”, be it re-challenge with theragnostics, or to provide safety estimates when using different forms of radiation along patients’ cancer journey in the real world. Through a recently completed multi-center trial as a case study, we will review the processes involved in setting up individualized dosimetry across four academic institutions and our subsequent transition into standard of care. We will discuss the value of radiation dose information for our patients, at the systems and academic levels. Finally, we will consider radiation dose absorbed in the future of theragnostics - as a prognostic factor for response and toxicity, as a factor in understanding the mechanism of treatment resistance, as a strategy to create novel dosing approaches and as part of combined modality to strive for superior patient outcomes. We propose that we are at a critical time, where a collaborative strategy across theragnostic practices is critical. The adoption of the reporting of radiation dose absorbed as a quality metric, blending lessons learned across theragnostics and EBRT will set the stage for the future with excellent quality of care and accelerated discoveries for our patients. (458 words). Citation Format: Rebecca K.S. Theragnostics &amp; external beam radiation dose absorbed - Similarities, differences and thoughts for the future. [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Targeted Therapies in Combination with Radiotherapy; 2025 Jan 26-29; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(2_Suppl):Abstract nr IA08

Efficacy of Prostate Biopsies via Transperineal and Transrectal Routes for Significant Prostate Cancer Detection: A Multicenter Paired–Matched Study

Background: A transperineal approach to prostate biopsy is now recommended to reduce the risk of infectious complications associated with the transrectal route. Our aim is to compare the efficacy of transrectal- and transperineal-guided biopsies involving the magnetic resonance imaging (MRI) of index lesions in detecting significant prostate cancer (sPCas), and to evaluate the role of systematic biopsies. Methods: In a prospective and multicenter trial conducted in an opportunistic early detection program for sPCa in Catalonia (Spain), between 2021 and 2023, 4029 men suspected of having PCa underwent multiparametric MRI followed by guided and systematic biopsies. From this cohort, we retrospectively selected 1376 men with reports of the size and localization of their index lesions. A matched group of 325 pairs of men subjected to transrectal and transperineal biopsy were chosen to account for confounding variables. We compared sPCa detection rates determined via index lesions and systematic biopsies, as well as by lesion localization. Results: Transperineal and transrectal biopsies detected sPCa in 49.5% vs. 40.6% overall (p = 0.027), 44.6% vs. 30.8% from index lesions (p = 0.001), and 24.3% vs. 35.1% from systematic biopsies (p = 0.003). SPCa detection rates were higher in transperineal biopsies across all index lesion localizations, with significant increases in the anterior zone (47.8% vs. 20.8% at the mid-base, p = 0.039, and 52.9% vs. 24.2% at the apex, p = 0.024) and central zone (33.3% vs. 5.9%, p = 0.003). With regards to SPCa detected only in systematic biopsies, 10.5% of cases were detected in transrectal biopsies and 4.9% of cases were detected in transperineal biopsies (p = 0.012). Conclusions: Targeted biopsies conducted via the transperineal route showed higher sPCa detection rates than transrectal biopsies, particularly for anterior and apical lesions, with systematic biopsies showing reduced utility.

Dual anti-CTLA-4 and anti-PD-1 blockade in metastatic basal cell carcinoma

We report the basal cell cancer (BCC) cohort of the SWOG/NCI 1609 Dual Anti-CTLA-4 & Anti-PD-1 blockade in Rare Tumors (DART), a phase II prospective, multicenter basket trial of nivolumab and ipilimumab. The primary endpoint was objective response rate (ORR) (RECIST v1.1). Overall survival (OS), progression-free survival (PFS), and toxicity were secondary endpoints. Sixteen patients with advanced/metastatic BCC were evaluable. The ORR was 31% (95% CI, 19–50%), and the 12-month OS, 75% (95% CI, 57–100%). Median PFS was 9.3 months (95% CI, 3.3–NA). Of 15 patients evaluable for clinical benefit, five partial responses (PRs) and five stable disease >6 months (total = 10/15 (66.7%)) were seen. The most common toxicities included fatigue (37.5%), pruritis (31.3%), and diarrhea (25%). In patients with advanced/metastatic BCC, ipilimumab and nivolumab produced an ORR of 31% and prolonged (>6 months) PFS in 73% of patients, with seven PFS/iPFS of >1 year, including one with prior anti-PD-1. ClinicalTrials.gov ID: NCT02834013 (Registered 7/15/2016; https://clinicaltrials.gov/ct2/show/NCT02834013).

The STROGHAT study protocol: An intervention study to evaluate safety, effectiveness and feasibility of treating gambiense HAT seropositive subjects with acoziborole.

Background Coordinated efforts in the control of gambiense human African trypanosomiasis (gHAT) have significantly reduced its endemicity. WHO targets interruption of transmission by 2030. However, challenges remain, including low sensitivity of the current parasitological confirmation tests, leaving a potential human reservoir untreated. Acoziborole, a single-dose oral treatment, effective in both disease stages with a good safety profile, offers the potential of treatment of parasitologically negative gHAT seropositive subjects, which could improve diagnostic sensitivity. The STROGHAT study aims to evaluate whether this approach can lead to elimination of T.b. gambiense from its human reservoir, and to provide further safety data on acoziborole. It also includes a costing analysis and a prospective evaluation of the performance of the screening and diagnostic tests used. Methods STROGHAT is a one-arm epidemiological study, with a nested phase IIIb, one-arm, open label, non-randomized, multicentre clinical trial. It will be implemented over four years in the endemic region of the Equateur North, in the Democratic Republic of Congo. For the first three years, parasitologically negative gHAT seropositive subjects will be treated with acoziborole, while parasitologically confirmed cases will receive standard of care. Individual follow-up needs and accurate prevalence estimate will be based on immunological and molecular tests performed for all gHAT screening test seropositive subjects at a reference laboratory. In the fourth year, standard procedures will resume, and a prevalence survey will assess whether interruption of transmission has been achieved. Discussion The manuscript outlines the study background, objectives and methods while discussing its strengths and challenges. If successful, the STROGHAT study will provide critical evidence on the effectiveness, safety and feasibility of the new strategy, and inform future elimination strategies. Clinical trial registration NCT06356974. Date of registration: April 4, 2024.

The proof of the pudding is in the eating: real-life intra- and extrapulmonary impact of elexacaftor/tezacaftor/ivacaftor.

Elexacaftor/tezacaftor/ivacaftor (ETI) has shown significant improvements in pulmonary and nutritional status in persons with cystic fibrosis (pwCF). Less is known about the extrapulmonary impact of ETI and effects on airway microbiology, lung clearance index (LCI) and fraction of exhaled nitric oxide (FeNO). A multicentre prospective observational trial, including 79 pwCF ≥ 18 years eligible for ETI. Assessments were done at the initiation of, and 3 and 6 months into treatment with ETI. Outcomes included forced expiratory volume in 1 second (FEV1), LCI, FeNO, sputum or cough swab culture, body mass index (BMI), cystic fibrosis questionnaire-revised respiratory domain (CFQ-R RD), sinonasal outcome test-22 (SNOT-22), general anxiety disorder-7 (GAD-7), patient health questionnaire-9 (PHQ-9), fecal elastase-1 (FE-1), adherence to baseline therapies, exacerbation rate and adverse events. Our cohort included 79 pwCF (31±11(SD) years) with a baseline ppFEV1 of 68±23. Forty-two (53%) pwCF were previously treated with a CFTR modulator. In the entire study group, there were significant improvements from baseline in ppFEV1, LCI, FeNO, annualized exacerbation rate, BMI, CFQ-R RD and SNOT-22 (p<0.05 for all). Airway culture positivity for methicillin-susceptible Staphylococcus aureus and Pseudomonas aeruginosa also decreased during the study period. There was no significant change in FE-1, GAD-7 or PHQ-9. Adherence to dornase alfa and hypertonic saline decreased. ETI treatment led to significant improvements in respiratory and nutritional status, alongside a decrease in adherence to chronic supportive therapies. We did not observe any significant changes in exocrine pancreas function or in questionnaire scores for depression and anxiety.

Efficacy of butylphthalide in preventing cognitive decline in ischaemic stroke survivors: a 12-month prospective following-up study

BackgroundCognitive decline is a significant concern for stroke survivors, affecting their quality of life and increasing their burden on the healthcare system. DL-3-n-butylphthalide (butylphthalide) has shown efficacy in the short-term...