ABSTRACTThe role of perioperative immunotherapy as a chemotherapy-free option for patients with resectable mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) colon cancer is evolving, with early-phase neoadjuvant studies reporting favorable long-term outcomes. AZUR-2 is an ongoing global, Phase III, open-label, randomized study evaluating the efficacy of perioperative dostarlimab monotherapy compared with standard of care (SoC) (adjuvant chemotherapy or surveillance) in adult patients with previously untreated, pathologically confirmed, radiologically evaluable T4N0 or Stage III resectable dMMR/MSIH colon adenocarcinoma. Patients will be randomized 2:1 to receive neoadjuvant dostarlimab 500 mg every 3 weeks (4 cycles), followed by surgery, then adjuvant dostarlimab 1000 mg every 6 weeks (6 cycles), or to receive immediate surgery followed by SoC. The primary endpoint is event-free survival assessed by blinded independent central review. The key secondary endpoint is overall survival; additional secondary endpoints include pathological response assessed by residual viable tumor determined by local assessment, safety, and tolerability.Clinical trial registration: NCT05855200 (www.clinicaltrials.gov).

ABSTRACTAimTo evaluate the real-world incidence of cardiovascular adverse events (CVAE) and clinical outcomes among patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) treated with covalent Bruton’s Tyrosine Kinase inhibitors (cBTKis).MethodsPatients initiating cBTKi treatment from 1 January 2020 to 1 January 2023 were identified using claims data. Demographics, first-line (1L) and second-line or later (2L+) therapy, incident CVAEs, and clinical outcomes were assessed.ResultsIn total, 2,163 patients (81.4% in 1L and 18.6% in 2L+) were identified with a mean age of 73.8 9.2 years and 40.6% female. The most common incident CVAEs were hypertension (23.4%), atrial fibrillation (10.2%), ventricular arrhythmias (10.1%), heart failure (8.5%), and atrial flutter (4.2%). Those with CVAEs experienced higher switching to next treatment + death and worse overall survival than those without CVAEs. Incidence rates were ~2–3 fold lower with acalabrutinib than ibrutinib for hypertension, atrial fibrillation, and atrial flutter. Kaplan-Meier estimates for the likelihood of not experiencing a CVAE were 83% (acalabrutinib) and 72% (ibrutinib) at 12-months.ConclusionsDespite improvements in 2nd-generation cBTKi cardiotoxicity, patients with CLL/SLL receiving cBTKis have a considerable cardiovascular disease burden. These findings highlight the unmet need for CLL/SLL treatment options with improved efficacy and safety profiles.

ABSTRACTAimsImmune checkpoint inhibitors (ICIs) have improved outcomes in several malignancies, but survival remains poor for patients with unresectable advanced or recurrent esophageal or gastric cancer. Recent evidence suggests that modulation of the intestinal microbiota may influence the therapeutic response to ICIs. This study aims to evaluate the safety and preliminary efficacy of fecal microbiota transplantation following antibiotic pretreatment (A-FMT) in patients scheduled to receive ICI-containing regimens.MethodsThis phase I – II, single-institution clinical trial enrolls patients with unresectable advanced or recurrent esophageal or gastric cancer. Participants receive a 1-week course of oral antibiotics (amoxicillin, fosfomycin, and metronidazole) prior to transplantation. A single dose of donor-derived intestinal microbiota solution is administered via colonoscopy, followed by initiation of ICI-based therapy on the next day. The primary endpoint is the incidence of dose-limiting toxicity. Secondary endpoints include response rate, disease control rate, progression-free survival, overall survival, and adverse events. Comprehensive translational research is conducted using stool, blood, and tissue samples to characterize immune responses and identify biomarkers associated with A-FMT and ICI efficacy.Trial registration: jRCTs031240170.The study is ongoing, and patients are currently being enrolled. Enrollment started in June 2024. A total of 7 patients have been enrolled as of August 2025. This protocol is version 3.2.

ABSTRACTAimsLack of diversity in clinical trial populations often results in healthcare inequity. This retrospective analysis presents the impact of implementing inclusive research practices on the diversity of the MyTACTIC trial population.Patients & methodsAdult patients with advanced solid tumors were enrolled from large academic centers or community cancer clinics and a number of inclusive research practices were implemented to diversify patient recruitment. We summarized race/ethnicity data of the study population related to the sites’ catchment area.ResultsOverall, 252 patients were enrolled (83% White). Community clinics represented 95% of screening sites (enrolled 249/252 patients). The proportion of patients from racial/ethnic minorities was generally higher in study centers from ethnically diverse catchment areas. Streamlining the protocol and implementing a free transport scheme to improve patient recruitment yielded positive feedback from site staff; 14 patients (5.5%) used the transportation service.ConclusionFindings from the MyTACTIC trial suggest that running trials at community oncology sites does not, by itself, increase patient diversity; other efforts are also necessary. NCT04632992.

ABSTRACTBackgroundThere is limited real-world evidence regarding patients with intermediate/poor-risk advanced renal cell carcinoma (aRCC) receiving nivolumab plus ipilimumab (NIVO+IPI) in England. This study aimed to describe characteristics, treatment patterns, and efficacy outcomes in these patients.MethodsA retrospective chart review of medical records in patients with aRCC receiving NIVO+IPI at any line of therapy between 5 April 2019 and 1 April 2022 in five sites across England was conducted. Data were analyzed descriptively overall, in patients with and without NIVO maintenance after NIVO+IPI initiation, and by prior nephrectomy status.ResultsIn total, 128 patients (mean age 60.7 years [standard deviation 10.1], 71.1% male) were eligible; most received first-line (1L) NIVO+IPI (n = 122, 95.3%). Median follow-up was 13.6 months (interquartile range [IQR] 7.1–25.0). Median progression-free survival and overall survival (OS) were 7.6 months (95% confidence interval [CI]: 5.6, 13.1) and 30.7 months (95% CI: 22.5, not reached), respectively. Median OS was not reached in patients who received NIVO+IPI plus NIVO maintenance and patients with prior nephrectomy.ConclusionPatients who received NIVO+IPI with NIVO maintenance and patients who had undergone prior nephrectomy experienced the most favorable survival outcomes, aligning with results from previous studies.

ABSTRACTAimsUp to 40% of patients with diffuse large B-cell lymphoma (DLBCL) have relapsed or refractory (R/R) disease after first-line treatment with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone, and outcomes are poor after hematopoietic stem cell transplantation failure. CheckMate 436 (NCT02581631) was a phase 1/2 study to evaluate the efficacy and safety of nivolumab, a PD-1/PD-L1 inhibitor, plus brentuximab vedotin (BV) for the treatment of R/R non-Hodgkin lymphoma.Materials and methodsAdult patients received nivolumab plus BV in 3-week cycles. The primary endpoint was overall response rate (ORR). Here, we report the results from the R/R DLBCL cohort (n = 42).ResultsWith a median follow-up of 7.7 months, the ORR was 28.6% (n = 12), and 7.1% (n = 3) of patients achieved a complete response. Median duration of response (95% CI) was 3.6 (1.2–36.5) months. All patients experienced an adverse event (AE), most commonly diarrhea (n = 20, 47.6%). Grade 3/4 and 5 AEs occurred in 24 (57.1%) and 4 (9.5%) patients, respectively. Any-grade treatment-related AEs occurred in 35 (83.3%) patients. No new safety signals were identified.ConclusionsOverall, the efficacy data from CheckMate 436 do not support the use of nivolumab plus BV for the treatment of R/R DLBCL.