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A prospective, multi-center, phase Ib/II trial of first-line cadonilimab plus axitinib in advanced non–clear cell renal cell carcinoma.
4501 Background: Non-clear cell renal cell carcinoma (nccRCC) is a rare and heterogeneous disease with limited treatment evidence. Patients with nccRCC generally respond less favorably to systemic immunotherapy than those with clear cell RCC. However,current evidence for the treatment of nccRCC remains limited,underscoring the need for new strategies. Cadonilimab,a bispecific PD-1/CTLA-4 antibody,has shown antitumor activity in various solid tumors, but its efficacy in RCC remains unknown. Here, we report initial results from a phase Ib/Il trial of cadonilimab plus axitinib in advanced nccRCC. Methods: This open-label, multi-center, single-arm, phase Ib/Il trial included patients with metastatic or unresectable treatment-naive nccRCC, regardless of PD-L1 status, to receive cadonilimab plus axitinib 5mg b.i.d. In phasel,a 3+3 dose-escalation design was adopted,starting at 10 mg/kg Q3W of cadonilimab with axitinib to evaluate safety. In phase Il, an additional 31 patients were enrolled at the recommended phase ll dose (RP2D). The primary endpoints were safety assessment in phase Ib and objective response rate (ORR) by RECIST v1.1 in phase Il. Results: As of October 1,2025, A total of 37 patients was enrolled (Phase Ib:n=6;Phase ll: n=31), with a median follow-up duration of 14.4 months. In phase Ib, no DLTs were observed. AEs were reported in 100.0% (6/6) of cases. Grade≥3 treatment-related adverse events (TRAEs) occurred in 66.7% (4/6) of cases,including proteinuria, hypertriglyceridemia, myasthenia gravis, diarrhea and alanine aminotransferase increased. The RP2D for cadolinimab was 10 mg/kg. For secondary endpoints, ORR was 50% (2/4) and DCR was 100% (6/6). In phase Il, the ORR was 51.6%(16/31). DCR was 96.8% (30/31). AEs were reported in100.0% of cases. Grade≥3 treatment-related adverse events (TRAEs) occurred in 58.1% (18/31) of cases. All AEs were expected and manageable. The median PFS was 16.7 (95%Cl,11.8-NR). The median OS was NR at the data cutoff. For the total cohort, the median PFS was 17.3(95%Cl,12.1-NR). The median OS was NR at the data cutoff. Conclusions: Cadonilimab combined with axitinib demonstrated encouraging efficacy and tolerability as first-line therapy in advanced nccRCC across subtypes in this multi-center phase Ib/II study. Clinical trial information: NCT05808608 . Summary of efficacy analysis and tumor response review per RECIST v1.1. Phase Ib Phase II Total cohort Objective response rate, n(%) 2 (50) 16 (51.6) 18 (51.4%) Disease control rate, n(%) 6 (100) 30 (96.8) 36 (97.2%) mPFS (95%CI) months NR (17.3, NR) 16.7 (11.8-NR) 17.3 (12.1-NR) mOS (95%CI), months NR (NR, NR) NR (NR, NR) NR (NR, NR)
Time toxicity in patients with advanced pancreatic cancer in Mexico.
4214 Background: Advanced pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies despite advances in systemic therapy. Beyond survival, the burden of time spent receiving health care (also known as time toxicity) has emerged as a relevant patient-centered outcome, particularly in diseases where treatment benefits may be modest. This study aimed to quantify time toxicity in patients with advanced PDAC and to analyze differences in time toxicity by demographic and clinical characteristics. Methods: We conducted a subanalysis of a single-center prospective cohort of patients with advanced solid tumors enrolled in a patient navigation program in Mexico. Patients ≥18 years diagnosed with advanced PDAC between June 2017 and August 2023 were included; patients with a second invasive malignancy or treated outside the institution were excluded. Demographic and clinical variables, baseline quality of life (FACT-G), and days with in-person healthcare encounters (clinic visits, treatments, tests, emergency visits, and hospitalizations, regardless of whether oncology-related) were collected from the diagnosis of advanced disease. Overall survival (OS) was defined as the time from diagnosis of advanced PDAC to death or loss to follow-up. Time toxicity was defined as the proportion of days involving in-person healthcare contact relative to OS. Comparisons used nonparametric tests and beta regression models were fitted to evaluate factors associated with time toxicity. Results: A total of 103 patients were included. Median age was 64 years, 65% were women, 83.5% presented with de novo advanced PDAC, and 75.7% received palliative chemotherapy. The mean baseline FACT-G score was 63.7±15.4. Median follow-up was 13.0 months, and median OS for the entire cohort was 11.5 months (95% CI, 6.2-16.7). The median time toxicity of the sample was 21.8% (IQR, 14.9-31.7). Patients with recurrent advanced PDAC experienced lower time toxicity than those with de novo disease (14.9% vs 22.8%, p = 0.003). In multivariable beta regression, disease presentation remained the only independent factor associated with increased time toxicity (β-0.51, p = 0.011). Age, sex, receipt of chemotherapy, and baseline FACT-G score were not independently associated with time toxicity. In an exploratory subgroup analysis among patients receiving palliative chemotherapy, patients ≥65 years had higher time toxicity compared to younger patients (23.4% vs. 17.9%; p = 0.041). Conclusions: In this cohort of Mexican patients with advanced PDAC, approximately one-fifth of OS time was spent in direct contact with health care system. Time toxicity was associated with disease trajectory rather than treatment or patient characteristics. Among patients receiving palliative chemotherapy, older patients experienced higher time toxicity. These findings highlight the importance of incorporating time toxicity into shared decision-making.
Carcinoma with osteoclast-like giant cells.
e16392 Background: Carcinoma with osteoclast-like giant cells (COGC) is a rare, undifferentiated malignancy composed of atypical epithelial cells and reactive multinucleated giant cells resembling osteoclasts. Although most tumors arise in the pancreas, COGC has been reported at other anatomic sites and can share features with hepatocellular and other giant-cell rich neoplasms, complicating diagnosis. Current understanding is largely limited to case reports and small institutional series, leaving its epidemiology poorly defined. We therefore analyzed the National Cancer Database (NCDB) to characterize the demographic and socioeconomic features of patients with COGC. Methods: A retrospective analysis of the 2004–2020 NCDB identified 333 cases of histologically confirmed COGC (8035). Demographic, socioeconomic, and clinical variables, including age, sex, race, ethnicity, insurance type, facility characteristics, residential setting, income, Charlson–Deyo score, and short-term mortality, were summarized using descriptive statistics. Incidence trends were analyzed using regression analysis, additional variables analyzed include survival outcomes, treatment modalities, and primary site. Results: The mean age at diagnosis was 64.9 ± 12.8 years; most patients were female (60.4%), White (85.6%), and non-Hispanic (88.9%). Tumors most commonly arose in the pancreatic head (32.7%). Patients were most often treated at academic (51.1%) or comprehensive community programs (24.6%); approximately half were insured through Medicare (50.2%). Most resided in metropolitan areas (87.0%), and 44.3% were in the highest income quartile (≥$74,063). The largest proportion presented with Stage II disease (36.6%), though 20.7% had Stage IV disease. Surgery was performed in 64.0% of cases, with margin-negative resection achieved in 53.8%. Radiation and chemotherapy were administered in 28.8% and 49.8% of patients, respectively. Overall survival was 87.3% at two years, 79.9% at five years, and 45.8% at ten years, with a mean survival of 78.8 months. Conclusions: To our knowledge, this is the first NCDB analysis of COGC. Patients were predominantly older, non-Hispanic White females, with tumors most commonly arising in the pancreatic head. Despite frequent early-stage presentation, one in five patients were diagnosed at Stage IV, indicating a substantial burden of advanced disease. Surgical resection was common, but margin-negative removal occurred in only half of cases, underscoring challenges in local control. Radiation and chemotherapy were frequently used, suggesting reliance on multimodal therapy. Although early mortality was low, long-term survival declined markedly. These findings highlight the need for improved diagnostic strategies, more effective treatments, and refined prognostic tools for this rare tumor.
INTerpath-013: A phase 2, randomized, double-blind study of intismeran autogene plus pembrolizumab and chemotherapy as first-line treatment for metastatic squamous non–small cell lung cancer.
TPS8670 Background: Non–small-cell lung cancer (NSCLC) is the leading cause of cancer mortality worldwide. The anti-PD-1 pembrolizumab plus platinum-based chemotherapy is a recommended treatment for metastatic squamous NSCLC. Despite the inclusion of anti-PD-(L)1 therapies into treatment guidelines, there remains an unmet medical need for further improving patient outcomes. Intismeran autogene (intismeran; formerly V940, mRNA-4157) is an investigational mRNA-based individualized neoantigen therapy (INT) encoding up to 34 neoantigens unique to each patient’s tumor and is designed to promote antitumor immune response. INTerpath-013 is a phase 2 study evaluating the addition of intismeran to pembrolizumab plus chemotherapy for previously untreated metastatic squamous NSCLC. Methods: This phase 2, randomized, double-blind, placebo-controlled study is enrolling patients aged ≥18 years with previously untreated histologically or cytologically confirmed stage IV squamous NSCLC (M1a, M1b, M1c1, or M1c2 per AJCC version 9) and measurable disease per RECIST v1.1 by investigator. Participants are also required to have ECOG PS 0 or 1 and provide a tumor sample for next-generation sequencing. Exclusion criteria include known active CNS metastases and/or carcinomatous meningitis, or untreated or symptomatic brain metastases. Approximately 180 participants will be randomized 2:1 to receive 1 treatment cycle comprising intravenous pembrolizumab 400 mg Q6W (1 dose) plus carboplatin AUC 6 mg/mL/min Q3W (2 doses), with either paclitaxel 200 mg/m 2 Q3W (2 doses) or nab-paclitaxel 100 mg/m 2 QW (6 doses). At week 6 (after cycle 1), tumor imaging will be performed and participants with complete response, partial response, or stable disease per RECIST v1.1 by BICR will continue 1 more treatment cycle and also receive up to 2 cycles of intismeran intramuscularly 1 mg (study arm A) or placebo (arm B) Q3W. All participants who complete the first 2 cycles of treatment will then receive up to 7 additional doses of intismeran or placebo (9 total) plus pembrolizumab up to 15 additional doses (17 total). Any participant with PD at the 6-week scan will have treatment unblinded and those in arm A may receive exploratory treatment with up to 9 doses of intismeran plus docetaxel 75 mg/m 2 Q3W until PD, unacceptable toxicity, or participant/physician decision; those in arm B will not receive further investigational treatment. Randomization will be stratified by PD-L1 tumor proportion score ( < 1% vs ≥1% to ≤49% vs ≥50%), ECOG PS (0 vs 1), and the number of metastatic sites (1 vs > 1). Primary endpoints are PFS per RECIST v1.1 by BICR and OS. Secondary endpoints include ORR and duration of response per RECIST v1.1 by BICR and safety. Enrollment began in December 2025 and is ongoing across 55 global sites. Clinical trial information: NCT07221474 .
The DUET-1 trial: Feasibility and toxicity outcomes and early oncological outcomes of <sup>177</sup> lutetium-PSMA radioligand therapy (RLT) alternated with <sup>233</sup> radium-dichloride in patients with metachronous oligorecurrent osseus hormone sensitive prostate cancer (mHSPC).
e17083 Background: Currently, no available therapy has been shown to significantly improve long-term oncological outcomes in patients with metachronous bone-oligometastatic hormone-sensitive prostate cancer (HSPCa). Combining alpha- and beta-particle treatments—specifically ²²³[Ra]Radium-dichloride and ¹⁷⁷[Lu]Lutetium-PSMA—may confer greater therapeutic benefit when initiated during earlier phases of disease such as in patients with metachronous bone-oligometastatic HSPCa. Methods: The DUET-1 trial was a prospective, single-arm, phase I–II study conducted at Amsterdam University Medical Center in the Netherlands. The study enrolled six patients with metachronous oligorecurrent bone-metastatic HSPCa following curative therapy such as radical prostatectomy or external beam radiotherapy. All participants had oligometastatic prostate cancer on PSMA PET/CT, defined as one to five bone metastases, and an ECOG performance status of 0–1. Patients received 3 cycles of ²²³Ra-dichloride (55kBq/kg) at 0,4 and 8 weeks and 2 cycles of ¹⁷⁷Lu-PSMA (7.4 GBq/cycle) at 6 and 12 weeks. The primary endpoint was feasibility of 223 Ra-dichloride and 177 Lu-PSMA radioligand therapy (RLT), toxicity, adverse events (AE) and patient reported outcomes (HRQoL and xerostomia inventory). Secondary endpoints were biochemical response (prostate-specific antigen (PSA) and alkaline phosphatase (AFP) levels) at 3 mo. post-treatment and radiological progression free survival (rPFS) at 3 mo. post-treatment. Results: Six patients were enrolled between January 2025 and October 2025 of whom 5 had reached three months of follow-up. All patients were able to complete radioligand therapy (RLT) without any interruptions or delays. No serious adverse events were reported during the treatment period. There were no hematological toxicities observed in any of the patients. Only mild adverse events occurred, specifically grade 1 xerostomia and grade 1 fatigue. Patients maintained health-related quality-of-life scores that were comparable to their baseline assessments. At three months after initiation of therapy, no PSA progression was observed in 3/5 patients and no AFP progression was observed in 5/5 patients. Stable radiological disease or a mixed response was seen in 3/5 patients. Conclusions: Dual RLT with 3 cycles of ²²³[Ra]Radium-dichloride and 2 cycles of ¹⁷⁷[Lu]Lutetium-PSMA in patients with metachronous oligorecurrent osseous mHSPC is safe, is feasible, and has hardly any impact on HRQoL. It has a promising biochemical response and provides for a mixed radiological response with stable disease in some patients on follow-up.
A head-to-head comparison of sextant-systematic biopsy versus extended-systematic biopsy for prostate cancer diagnosis in the era of MRI-targeted biopsy: Non-inferiority randomized clinical trial.
5120 Background: In recent years, combined targeted biopsy (TB) and 12-core extended systematic biopsy (SB) (TB+12SB) has been recommended for biopsy-naïve patients with prostate MRI-visible lesions. However, increasing SB cores elevates complication risks and healthcare expenditure. Retrospective data indicated noninferior PCa detection with TB + sextant-SB (TB+6SB) vs TB+12SB. This RCT aims to compare the novel TB+6SB scheme and classical TB+12SB for PCa diagnosis. Methods: In this non-inferiority RCT (NCT06684652), 506 biopsy-naïve men with solitary mpMRI lesions (PI-RADS ≥3) underwent transperineal cognitive fusion 3-core TB within the predefined mpMRI index lesion (ROI), followed by randomization to 12-core SB or 6-core sextant SB (2 peripheral+1 transitional cores/side). The primary outcome was clinically significant PCa [csPCa, grade group (GG) ≥2] detection rate. Non-inferiority was established if the lower 95% CI bound for the rate difference exceeded -15%. Results: Baseline characteristics were similar. TB+6SB demonstrated noninferior csPCa detection versus TB+12SB [54.3% (138/254) vs. 54.8% (138/252); rate difference -0.5%, 95%CI -9.2%-8.3%]. Comparable detection was also observed in PCa, high-grade PCa (GG≥3), and clinically insignificant PCa (GG=1). The concordance in GG between biopsy and radical prostatectomy whole-mount specimens was similar for both TB+12SB [52.3% (34/65), κ=0.55] and TB+6SB [51.7% (30/58), κ=0.50] groups (p=0.25). TB+6SB showed superior safety profiles, significantly relieving the procedural discomfort, reducing the post-biopsy pelvic pain, and improving the quality of life (p<0.05). The biopsy time of TB+6SB was significantly shorter than that of TB+12SB (p<0.001). Conclusions: TB+6SB achieves non-inferior diagnostic efficacy to classical TB+12SB with fewer cores and improved safety, positioning it as an effective strategy for PCa diagnosis in biopsy-naïve patients with solitary MRI-suspicious lesions. TB+6SB could improve operational efficiency, providing both clinical safety and cost-effectiveness in histopathological workflows. Clinical trial information: NCT06684652 . Clinicopathological characteristics after biopsy. Characteristics TB+12SB (n=252) TB+6SB (n=254) P value csPCa (%) 138 (54.8) 138 (54.3) 1 RD (95%CI) -0.5% (-9.2%, 8.3%) High-grade PCa (%) 72 (28.6) 74 (29.1) 1 Number of biopsy cores (per case) 15.0 9.0 Proportion of positive cores (%) (median [IQR]) 20.0 [0, 46.7] 33.3 [0, 55.6] 0.02 Procedural time (second) (median [IQR]) 234.0 [220.0, 258.3] 167.5 [154.0, 187.0] <0.001 Cost of pathological examination ($) (per case) 75.0 50.0 - Pain level (VAS) (median [IQR]) 3.0 [2.0, 4.0] 2.0 [2.0, 4.0] 0.004 Discomfort level (median [IQR]) 3.0 [3.0, 5.0] 3.0 [1.5, 4.0] 0.03 OABSS total score after biopsy (median [IQR]) 3.0 [2.0, 7.0] 3.0 [2.0, 5.0] 0.02
Health system inequities as a mediator of age-related survival differences in high-grade serous ovarian cancer: Chile as a case study for Latin America.
e17597 Background: Health system inequities are major drivers of cancer outcomes in Latin America, where rapidly ageing populations intersect with fragmented access to specialized oncologic care. In high-grade serous ovarian cancer (HGSOC), older age and treatment within resource-limited health systems are associated with worse survival. Whether these associations reflect intrinsic tumour biology or are mediated by inequities in access to optimal care remains unclear. Global assessments have demonstrated variation in HGSOC outcomes by world region and Human Development Index, underscoring the role of health system capacity in shaping survival. Chile, with its segmented public–private health system, provides a natural setting to disentangle these effects. Methods: We conducted a retrospective cohort including 450 patients with HGSOC treated within the Chilean public or private health systems, with 20th years of follow up. The primary endpoint was overall survival (OS), defined as time from diagnosis to death from any cause. For independent prognostic factors we used Cox proportional hazards models integrating age (>65 vs ≤65 years), health system (public vs private), surgical strategy, FIGO stage, lactate dehydrogenase (LDH), and BRCA/HRD status. We evaluated whether age-related survival differences were attenuated after adjustment for health system and surgical strategy, conceptualized as proxies for access to specialized oncologic care. Attenuation was interpreted as consistent with mediation by access to care; however, formal causal mediation analyses were not performed. A propensity score model and inverse probability of treatment weighting (IPTW) were applied as sensitivity analyses. Results: Median OS was 48·2 months and median PFS was 13·8 months. In unadjusted analyses, OS differed significantly by age, stage, surgical strategy, LDH, BRCA/HRD status, and health system. In multivariable models, advanced stage, absence of primary cytoreductive surgery, elevated LDH, BRCA/HRD negativity, and treatment in the public health system were independently associated with worse OS, whereas age was not independently associated with OS after adjustment. IPTW analyses confirmed a robust association between primary cytoreductive surgery and improved OS (hazard ratio 0·29). The survival benefit of primary cytoreductive surgery was preserved across age groups. Conclusions: In this cohort, age-related survival differences in HGSOC were largely explained by inequities in access to optimal surgical care and comprehensive oncologic treatment rather than by chronological age or tumor biology. In segmented health systems such as those in Chile and much of Latin America, structural barriers to specialized care represent key determinants of survival.
Hospital-acquired sepsis as a driver of failure-to-rescue in AML and MDS: A national inpatient sample analysis, 2016–2023.
e23219 Background: Sepsis is a frequent proximate cause of inpatient death in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), yet national data quantifying a hospital-acquired sepsis–linked failure-to-rescue signal are limited. This study evaluated sepsis timing phenotypes and associated mortality, ICU-level escalation, and resource utilization in AML/MDS hospitalizations. Methods: A survey-weighted analysis of the National Inpatient Sample (2016–2023) was conducted. Adult hospitalizations with AML or MDS were identified from diagnosis coding; obstetric admissions were excluded. Sepsis was classified using a length-of-stay timing proxy as early/present-on-admission (≤2 days), late/hospital-acquired (≥4 days), or indeterminate (3 days; excluded from primary analyses). Outcomes included in-hospital mortality, ICU-level care (mechanical ventilation, dialysis/CRRT, or shock), length of stay, costs/charges, and discharge disposition. Survey-weighted regression models adjusted for demographics, payer, income quartile, admission characteristics, hospital factors, year, and hospital AML/MDS volume. Results: The weighted cohort included approximately 1.05 million AML/MDS hospitalizations from 2016–2023. Hospital-acquired sepsis occurred in 14.9% of admissions, compared with 2.2% with sepsis present on admission. In-hospital mortality differed markedly by sepsis timing: 18.3% for hospital-acquired sepsis, 42.4% for present-on-admission sepsis, and 4.3% for admissions without sepsis. Among hospital-acquired sepsis admissions, ICU-level careoccurred in 20.6%, invasive mechanical ventilation in 14.9%, and dialysis/CRRT in 6.8%. In adjusted analyses, hospital-acquired sepsis was independently associated with higher in-hospital mortality compared with no sepsis (adjusted odds ratio [aOR] 5.11, 95% CI 4.89–5.34). Present-on-admission sepsis demonstrated an even higher mortality association (aOR 16.95, 95% CI 15.78–18.20). Among hospital-acquired sepsis admissions, mortality increased with age (aOR 1.01/year, 95% CI 1.01–1.01) and male sex (female vs male aOR 0.87, 95% CI 0.81–0.93). Death was more likely in urban teaching hospitals (aOR 1.59, 95% CI 1.33–1.90) and large hospitals (aOR 1.51, 95% CI 1.36–1.68), with higher failure-to-rescue also observed in high-volume AML/MDS centers (aOR 1.25, 95% CI 1.14–1.38). Conclusions: In AML/MDS hospitalizations, late hospital-acquired sepsis is common and is associated with high failure-to-rescue, frequent ICU escalation, and markedly increased mortality and resource use. Sepsis timing emerges as a scalable inpatient vulnerability and quality signal in hematologic malignancies, highlighting the need for systems-level strategies to prevent late sepsis and improve rescue.
Impact of corticosteroid and tocilizumab use on infection incidence and outcomes following CAR T-cell therapy with axicabtagene ciloleucel.
e19007 Background: Corticosteroids and tocilizumab are frequently used to manage cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS) following chimeric antigen receptor T-cell (CAR-T) therapy. However, their impact on post-infusion complications remains uncertain. We aimed to evaluate the association between corticosteroid or tocilizumab exposure and outcomes after CAR-T therapy. Methods: A retrospective multicenter analysis was performed using publicly available data from the Center for International Blood and Marrow Transplant Research (CIBMTR) registry (P-6093, Wudhikarn et al.), limited to patients who received axi-cel. Patients receiving corticosteroids and/or tocilizumab following CAR-T infusion were compared against those who did not. The primary outcome was 100-day infection incidence (overall, bacterial, viral, and fungal). Secondary outcomes included overall survival (OS), neutrophil engraftment, and infection-related mortality (IRM). Baseline characteristics were compared using chi-square and t-tests. Associations between corticosteroid/tocilizumab use and outcomes were assessed using Cox proportional hazards models adjusted for age, Karnofsky performance status (KPS), hematopoietic cell transplantation comorbidity index (HCT-CI), disease category, prior HCT, and transformed lymphoma status. Statistical significance was defined as p<0.05. Results: Among 2,749 CAR-T recipients, 1,873 (68.1%) received corticosteroids or tocilizumab. These patients were older (60.2±12.6 vs 58.1±13.4 years; p<0.001), had lower KPS (20.4% vs 15% with KPS < 80; p<0.001), and more frequently had transformed lymphoma (74% vs 64%; p<0.001) compared to those who did not. Corticosteroid/tocilizumab use was independently associated with higher 100-day overall infection incidence (HR 1.64; 95%CI 1.33–2.01; p<0.001), bacterial infections (HR 1.92; 95%CI 1.46–2.52; p<0.001), and fungal infections (HR 2.47; 95%CI 1.25–4.88; p=0.009). Viral infections were not significantly different between the two groups (HR 1.34; 95%CI 0.99–1.80; p=0.057). The use of corticosteroids/tocilizumab was also significantly associated with increased infection-related mortality (HR 4.24; 95%CI 1.29–13.94; p=0.018). However, there was no statistically significant difference in terms of overall survival (HR 1.11; 95%CI 0.96–1.27; p=0.149) or neutrophil engraftment (HR 0.92; 95%CI 0.84–1.01; p=0.089). Conclusions: Corticosteroid and tocilizumab use following CAR-T therapy is independently associated with an increased risk of bacterial and fungal infections and higher infection-related mortality, highlighting the importance of antimicrobial prophylaxis and infection surveillance.
ERBIOTAX (TTCC-2022-02): A phase II, multicenter, randomized study of cetuximab with or without weekly paclitaxel after progression on first-line pembrolizumab plus platinum/5-FU in recurrent or metastatic head and neck squamous cell carcinoma.
TPS6131 Background: Pembrolizumab, with or without platinum–5FU (PF), is the current first-line (1L) standard of care for PD-L1–positive recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN). However, no established standard of care exists after progression on immune checkpoint inhibitors (ICI). Emerging evidence suggests that cetuximab administered post-ICI achieves higher objective response rates (ORR) and longer progression-free (PFS) and overall survival (OS) compared with historical second-line (2L) cetuximab outcomes from the pre-ICI era. We hypothesize that 2L treatment with cetuximab +/- paclitaxel may be more effective after ICI failure than previously observed in the pre-ICI era. Methods: This is a multicenter, open-label, randomized, non-comparative, two-arm, investigator-initiated phase 2 trial. Patients will be randomized (2:1) to cetuximab plus paclitaxel (Arm A: ERBITAX) or cetuximab monotherapy (Arm B), administered on Days 1, 8 and 15 of 21-day cycles for 4 cycles, followed in both arms by biweekly cetuximab monotherapy until disease progression, death, unacceptable toxicity, or withdrawal of consent. A total of 65 evaluable patients will be enrolled: 41 in Arm A (H0: ORR 25%, H1: 45%, 80% power, two-sided alpha 0.05) and 24 in Arm B (H0: ORR 10%, H1: 30%, 80% power, two-sided alpha 0.05). The primary endpoint is ORR in each arm. Secondary endpoints include disease control rate (DCR), PFS, OS, health-related quality of life (EORTC QLQ-C30, EORTC QLQ-H&N35 and EuroQol EQ-5D) and safety. Baseline tumor tissue (all patients) and on-treatment samples (between cycles 2-5 in 50% of patients; optionally at progression), as well as serial plasma samples will be collected for translational exploratory studies. Patients must have histologically confirmed SCCHN of oral cavity, oropharynx (HPV-positive or HPV-negative), hypopharynx, or larynx, with confirmed progression per RECIST 1.1. on or after 1L pembro + PF. The study started enrollment in June 2025, with 7 patients enrolled by December 23, 2025. The total accrual period is 18 months. Clinical trial identifiers: NCT06856213; EUDRACT 2024-514953-31-00. Trial supported by Merck, S.L.U., Madrid, Spain, an affiliate of Merck KGaA, Darmstadt, Germany, providing study medication and financial support. Clinical trial information: NCT06856213 .
Impact of central review process on response rates in neuroblastoma clinical trials: A report from NANT Consortium.
10044 Background: Accurate and reproducible response assessment is critical for evaluating efficacy in clinical trials. Central response review is frequently used to reduce inter-site variability but is resource intensive and may delay data availability. Whether centralized review meaningfully alters response endpoints compared with remote source verification of site assessment remains unclear. Methods: We evaluated response assessments from eight NANT phase 1–2 trials conducted between February 2013 and December 2022 in relapsed/refractory high-risk neuroblastoma. Initial investigator-assessed response, remote source-verified response (remote review of radiology/bone marrow [BM] reports), and centrally-reviewed responses (review of radiographic images and BM biopsy slides) were assessed. Each patient’s best overall response (BOR) and individual component responses (BM, MIBG/bone, and soft tissue [ST]) at time of BOR as determined by these three review methods were assessed. Only patients with MIBG-avid disease were included in bone response. Results: Among 244 evaluable patients, concordance between remote source-verified response and central review response exceeded the concordance between initial investigator-assessed response and central review response (BOR: 89% vs 79%, BM: 91% vs 74%, MIBG/bone: 92% vs 83%, ST: 82% vs 74%). Concordance between initial investigator-assessed response and remote source-verified response was 86% for BOR and similar for component response (BM: 83%, MIBG/bone: 91%, ST: 86%). Remote source-verified assessment compared to central review demonstrated higher level of concordance than initial investigator assessment for complete response (CR) (90.0% vs 81.0%), partial response (PR) (85.7% vs 72.7%), minor response (MR) (80.6% vs 71.0%), and stable disease (SD) (92.1% vs 86.7%), indicating improved response classification consistency across all major BOR categories. Overall, the initial investigator-assessed response for CR, PR, and MR agreed with central review 74.0% of the time, while remote source-verified agreed 84.7%. Most discordance reflects relabeling within adjacent categories (e.g., CR vs PR or PR vs MR). A change in response from CR/PR/MR to SD/PD when compared to central review was uncommon: 9.4% for initial investigator-assessed response, and decreased with remote source verification down to 7.1%. A change from CR/PR to MR/SD/PD was more frequent but also improved with remote source verification (from 20% to 11.3%). Conclusions: Remote source verification substantially improves agreement with central review and reduces responder misclassification. These findings demonstrate that structured remote source verification improves response assessment reliability and harmonization with central review, reinforcing its role as an important quality-control mechanism in multicenter trials.
Dose-response relationship of serum iron, ferritin, and transferrin saturation with cancer-related mortality: An analysis of population-based data.
11043 Background: Altered iron homeostasis has been linked to cancer outcomes, with epidemiologic evidence suggesting that both reduced iron availability (low transferrin saturation or anemia) and elevated iron markers, particularly ferritin, may correspond to higher cancer mortality. However, population-level data quantifying dose–response relationships between continuous iron indices and cancer-related mortality remain limited. This study evaluates the dose–response association of serum iron, transferrin saturation (TSAT), and ferritin with cancer mortality using nationally representative NHANES data. Methods: NHANES laboratory data were linked to National Death Index mortality files (1999–2019). Survey-weighted Cox proportional hazards models and Fine–Gray competing-risk models were used to assess linear, quintile-based, and restricted cubic spline–modeled non-linear relationships between iron biomarkers and cancer mortality. Models were further adjusted to evaluate independent effects of each biomarker. Results: A total of 52,593 participants were included, with 6,875 recorded deaths. In survey-weighted log₂ Cox models, serum iron (HR 1.41; 95% CI 0.17–11.68) and ferritin (HR 1.14; 95% CI 0.84–1.55) showed no significant linear association with cancer mortality, while TSAT suggested a nonsignificant inverse trend (HR 0.30; 95% CI 0.02–5.43). Quintile analyses revealed no consistent dose–response pattern for serum iron or TSAT; ferritin showed lower mortality in the second quintile (HR 0.33; 95% CI 0.12–0.92) without a graded pattern across higher quintiles. In mutually adjusted models including all three biomarkers, none demonstrated independent linear associations. Fine–Gray analyses identified a statistically significant but clinically small association for ferritin, whereas serum iron and TSAT remained nonsignificant. Restricted cubic spline models showed no clear non-linear dose–response for any biomarker. Conclusions: Among the iron indices evaluated, ferritin demonstrated the strongest and most consistent association with cancer-related mortality, although no clear linear or non-linear dose–response pattern emerged. Ferritin may serve as a more informative marker for risk stratification, but further mechanistic and longitudinal studies are warranted.
Preliminary results of an open-label, single-arm phase 2/3 trial (SPARK-ALL) of calaspargase pegol in adults with newly diagnosed Philadelphia chromosome–negative acute lymphoblastic leukemia.
6529 Background: Asparaginase is an important component of many regimens for acute lymphoblastic leukemia (ALL). In patients (pts) <21 years, calaspargase pegol (Cal-PEG) provides more sustained asparagine depletion than pegaspargase. SPARK-ALL is a multicenter phase 2/3 study (NCT04817761) assessing the safety and anti-leukemic activity of Cal-PEG in pts aged ≥22 years with newly diagnosed Philadelphia chromosome-negative (Ph−) ALL. Methods: Part 1 was a dose-finding study in pts with a body mass index (BMI) ≤35 kg/m 2 aged 22–39 and 40–54 years (Cal-PEG 2000 and 1500 U/m 2 , respectively) and pts with BMI >35 kg/m 2 or aged ≥55 years (Cal-PEG 1000 U/m 2 ). Part 2 was a dose-expansion study in pts with BMI ≤35 kg/m 2 aged 22–39 years (Cal-PEG 1750 U/m 2 ) or 40–54 years (Cal-PEG 1500 U/m 2 ). Six Cal-PEG IV infusions were given as part of a multiagent chemotherapy regimen based on CALGB 10403 (Stock W, et al. Blood 2019;133(14):1548–1559). The primary objectives are assessment of safety in all pts, and anti-leukemic activity using the surrogate marker of nadir plasma asparaginase activity (NPAA) ≥0.1 U/mL 21 days after the D43 consolidation dose in all evaluable pts who were treated at the recommended dose (primary NPAA [PNPAA]) analysis set). Results: A total of 42 pts received Cal-PEG treatment: 26 and 16 in parts 1 and 2, respectively. Overall, 31 (73.8%) and 16 (38.1%) pts experienced grade 3/4 treatment-related adverse events (TRAEs) and serious TRAEs, respectively. Overall, 15 pts (35.7%) had TRAEs leading to study drug discontinuation, including hypersensitivity-type events in 6 pts (14.3%); 4 (9.5%) had nervous system events, including cerebral venous sinus thrombosis in 2 pts (4.8%). Three pts (7.1%) had a grade 3 pulmonary embolism, which, per protocol, required study drug discontinuation. The most common grade 3/4 TRAEs included hypertriglyceridemia (9 pts; 21.4%), alanine aminotransferase increase (7 pts; 16.7%), and blood fibrinogen decrease (5 pts; 11.9%). In part 1, intolerable toxicities considered related to Cal-PEG were experienced by 2/8 pts who were older and 2/8 pts with a BMI >35 kg/m 2 ; 1 (11.1%) pt aged between 22–39 years experienced an event of hypersensitivity. One Cal-PEG-related death was reported as likely related to complications from embolic stroke in a pt aged 71 years with comorbidities. Dose expansion was pursued in the first two cohorts. At 21 days after the D43 post-consolidation dose, all pts in the PNPAA set had NPAA values above the 0.1 U/mL efficacy threshold. Conclusions: Cal-PEG has a safety profile consistent with asparaginase class toxicity and, as part of multidrug chemotherapy regimen, provides sustained asparagine depletion in newly diagnosed Ph− ALL pts aged ≥22 years. In light of the observed high-grade TRAEs, future studies will evaluate different Cal-PEG doses for this pt population. Clinical trial information: NCT04817761 .
Sex differences in immune-related adverse events requiring hospitalization among patients with checkpoint inhibitor-sensitive malignancies: A national analysis.
11169 Background: Immune checkpoint inhibitors (ICIs) can cause immune-related adverse events (irAEs) with significant morbidity/mortality. Sex influences immunity, yet sex-specific irAE patterns and outcomes in hospitalized patients remain underexplored. We investigated sex differences in irAE hospitalizations and mortality in ICI-sensitive cancers. Methods: Retrospective cohort study using the National Inpatient Sample (2019-2022) identified adults with ICI-sensitive malignancies (lung, melanoma, renal cell carcinoma [RCC], bladder, hepatocellular carcinoma [HCC]) and high-specificity irAEs (colitis, pneumonitis, cardiac, hepatic, dermatologic, neurologic) at academic centers. Primary outcome was in-hospital mortality. Secondary outcome was irAE distribution by sex. Multivariable logistic regression adjusted for demographics, cancer type, comorbidities, irAE type, discharge weights for national estimates. Results: Among 203,990 weighted hospitalizations (62.8% male; mean age 68), women had lower mortality (13.7% vs 15.0%; aOR 0.91, 95% CI 0.88-0.93, p<0.0001), consistent across models. Women had higher odds of neurologic (aOR 1.76, 95% CI 1.68-1.85), dermatologic (1.24, 1.20-1.29), hepatic (1.08, 1.05-1.11), and pneumonitis (1.05, 1.01-1.08) irAEs; men had higher GI colitis (aOR 0.51 for women, 0.48-0.53) and cardiac (0.81, 0.79-0.83) risks. Within irAEs, women had lower mortality for neurologic (6.0% vs 10.0%), pneumonitis (11.5% vs 14.2%), colitis (4.7% vs 6.5%), and dermatologic (4.5% vs 6.2%). Female survival advantage persisted across cancers (e.g., lung aOR 0.91, 0.87-0.94; HCC 0.95, 0.91-1.00) and after excluding autoimmune disease (aOR 0.93, 0.91-0.96). Temporal analysis showed widening sex gap (2019 aOR 0.99 to 2022 0.86; year × sex interaction p=0.0002). Conclusions: Women experience distinct irAE patterns (more neurologic/dermatologic) but lower overall and subtype-specific mortality versus men, with differences amplifying over time. Sex-stratified irAE surveillance and personalized ICI strategies can be implemented to optimize outcomes. In-hospital mortality by sex in irAE hospitalizations. Characteristic / Subgroup N (weighted) Male In-Hospital Mortality (%) Female In-Hospital Mortality (%) Adjusted OR (Female vs Male) 95% CI p-value Overall (Fully adjusted model¹) 203990 15 13.6 0.93 0.91-0.96 <0.0001 Overall (Fully adjusted + irAE type²) 203990 15 13.6 0.91 0.88-0.93 <0.0001 Lung Cancer 93135 16.2 14.2 0.91 0.87-0.94 <0.0001 Melanoma 6725 11.2 9.6 0.72 0.60-0.87 0.0006 Bladder Cancer 16795 10.3 8.4 0.74 0.64-0.85 <0.0001 GI Colitis irAE 17610 6.5 4.7 0.65 0.56-0.74 <0.0001 Pneumonitis irAE 21075 14.2 11.5 0.76 0.70-0.83 <0.0001 Dermatologic irAE 15215 6.2 4.5 0.62 0.54-0.73 <0.0001 Neurologic irAE 8695 10 6 0.66 0.55-0.79 <0.0001
Final results from ZZFIRST: A randomized phase 2 trial of enzalutamide (EZ) and talazoparib (TALA) in metastatic hormone-naïve prostate cancer (mHNPC).
5006 Background: ADT plus AR pathway inhibition (ARPI) improves outcomes in mHNPC, yet responses remain heterogeneous. AR–PARP cotargeting has shown enhanced clinical activity in prostate cancer, but the underlying mechanisms are incompletely defined. ZZFIRST evaluated enzalutamide (EZ) plus talazoparib (TALA) in mHNPC, including the study of tumor adaptation response to ADT+ARPI through biopsies obtained on therapy. Methods: ZZFIRST (NCT04332744) is an open label, randomized academic phase 2 trial that included patients (pts) with high-volume (HV)-mHNPC (CHAARTED), ECOG PS ≤1, PSA≥4 ng/mL. All pts received standard ADT and started EZ 160 mg/day. After two 28-day cycles, pts were randomized 2:1 to EZ+TALA 0.5 mg/day or continue EZ alone until progressive disease (PD), unacceptable toxicity, or withdrawal. Randomization was stratified by DDR mutation status. Primary endpoint was confirmed PSA < 0.2 response rate (PSA < 0.2-RR) at 12 months (mo) for EZ+TALA. Key secondary endpoints included rPFS, time to PSA-PD, time to castration resistance, and safety. The study was powered (80%, one-sided α = 5%) to detect improved PSA < 0.2-RR (H0: 20%; H1≥40%) for EZ+TALA. Between-arm comparisons were exploratory. Spatial transcriptomics (Visum HD) was performed on baseline (BL) and Cycle 2-Day 1 (C2D1) on-treatment tumor biopsies. Results: 54 pts were enrolled (37 EZ+TALA, 17 EZ). 7 pts harbored HRR alterations by tumor tissue NGS (13%; 5 EZ+TALA, 2 EZ). Visceral metastases were present in 17 pts (32%); 51 pts (94%) had de novo M1 disease. Median follow-up was 3.6 years. The primary endpoint was met, with a 73% 12-mo PSA < 0.2-RR for EZ+TALA (95%CI, 55.9%-86.2%, p < 0.001); the rate was 64.7% for EZ. Median rPFS was 45.3 mo (29.4-NR) for EZ+TALA vs 31.1 mo (13.5-NR) for EZ (HR = 0.62; 95%CI, 0.28-1.37). Median time to PSA-PD was not reached (30.4-NR) for EZ+TALA vs 30.7 mo (6.6-NR) for EZ (HR = 0.47; 95%CI, 0.21-1.04). Median TTCR was 30.4 mo (23.0-NR) for EZ+TALA vs 22.8 mo (6.3-45.4) for EZ (HR = 0.62; 95%CI, 0.30-1.26). In TALA+EZ, common treatment-emergent AEs were fatigue (any grade: 83.8%; G≥3: 13.5%) and anemia (67.6%; G≥3: 40.5%). 14 (38%) pts required TALA dose reductions. Two pts on EZ+TALA developed acute myeloid leukemia (AML) 26.0 and 32.8 mo after study entry. Transcriptomics analysis on C2D1 vs BL biopsies showed induction of cell cycle arrest, with downregulation of AR and DDR signatures and upregulation of IFN-related and inflammatory response signatures upon ADT+EZ. Conclusions: EZ+TALA demonstrated promising antitumor activity in HV-mHNPC. The toxicity profile was consistent with prior AR+PARP trials, although two cases of AML were observed with prolonged TALA exposure. Paired tumor biopsies revealed mechanisms of tumor adaptation to ADT+EZ inhibition, supporting a biologically informed rationale for AR+PARP treatment intensification strategies in mHNPC. Clinical trial information: NCT04332744 .
A machine learning–enhanced analysis of temporal trends in biomarker-based eligibility restrictions in oncology clinical trials.
11019 Background: The adoption of biomarker-based eligibility criteria reflects the evolution of precision oncology, but temporal trends and predictors of biomarker restrictions are unclear. Understanding these patterns is essential for optimizing trial design and ensuring equitable patient access to investigational therapies. We used machine learning and natural language processing to analyze biomarker restriction trends across oncology trials. Methods: We analyzed all 54,985 oncology interventional trials from ClinicalTrials.gov from 2010-2024. Biomarker restrictions were identified using curated term lists plus NLP-based classification (TF-IDF vectorization with logistic regression). We developed complementary machine learning modules for emerging biomarker discovery using named entity recognition, requirement type classification (inclusion/exclusion/stratification), and eligibility complexity scoring via text feature engineering. Statistical analyses included logistic regression with Wilson score confidence intervals and Benjamini-Hochberg FDR correction. Results: Biomarker-restricted trials increased from 20.8% (2010) to 31.2% (2024), representing a 1.5-fold increase over 15 years (OR per year: 1.046, 95%CI: 1.041-1.050, p<0.001). Industry sponsorship (OR: 1.88, 95%CI: 1.80-1.97) and NIH sponsorship (OR: 1.89, 95%CI: 1.67-2.13) independently predicted higher biomarker restrictions versus academic sponsors (all p<0.001). US-based trials showed 40% higher odds of restrictions (OR: 1.40, 95%CI: 1.35-1.46). Phase II trials demonstrated the highest rates (40.9%). Among specific biomarkers, PD-1 showed the steepest adoption trajectory (0.08% to 10.59%), followed by EGFR (5.07% to 8.84%) and HER2 (5.16% to 8.17%). Our NLP-based emerging biomarker discovery identified CTLA-4, PSMA, CD19, CD137, and LAG-3 as rapidly emerging eligibility biomarkers reflecting next-generation immunotherapy targets. Cancer-specific analyses revealed dramatic increases in lung (22.8% to 50.5%) and gastric cancers (14.6% to 45.5%), while prostate cancer showed declining rates (60.5% to 52.3%). Our complexity scoring algorithm demonstrated that biomarker-restricted trials have significantly higher eligibility complexity (mean: 50.0 vs 31.0, p<0.001). All findings remained robust across multiple sensitivity analyses. Conclusions: Biomarker-based eligibility restrictions in oncology trials have increased substantially over 15 years, driven primarily by immune checkpoint and targeted therapy biomarkers. Industry-sponsored and later-phase trials show the highest adoption rates. These scalable ML findings inform precision medicine trial design and highlight considerations for patient access and trial generalizability.
Racial, socioeconomic, and geographic disparities in survival among patients with ampullary carcinoma: A population-based SEER analysis (2000–2022).
e16483 Background: Ampullary carcinomas (AC) are rare malignancies comprising ~0.2% of GI cancers with limited population-level data. Although social determinants of health (SDOH) influence outcomes in many GI cancers, their impact on AC remains unclear. We evaluated the association between SDOH and survival in a large national cohort of patients with AC. Methods: We conducted a retrospective cohort study using the SEER-17 database to identify patients with AC (ICD-O-3 site C24.1; histology codes 8140–8147, 8480, 8490, 8500) diagnosed between 2000 and 2022. Variables included sex, race, median household income, and geography. Overall survival (OS) and cancer-specific survival (CSS) were evaluated using Kaplan–Meier methods and Cox regression, with patients diagnosed through 2017 for ≥5-year follow-up. Analyses were performed in Python (v3.12) using lifelines and pandas, reporting adjusted hazard ratios (HRs) with 95% confidence intervals (CIs); p < 0.05 was considered statistically significant. Results: A total of 9,026 patients were included; 56.3% were male, and 82.5% lived in metropolitan areas. Racial distribution was 60.8% White, 18.4% Hispanic, 12.6% Asian, and 7.4% Black. Median OS was 21 months (95% CI, 20–22) and median CSS was 32 months (95% CI, 30–34). Race was significantly associated with OS and CSS on unadjusted analysis (p < 0.001), with Black patients having shorter survival than White patients (median OS: 14 vs 19 months; median CSS: 21 vs 32 months). On multivariable analysis, Black race remained independently associated with worse OS (HR 1.13, 95% CI 1.03–1.24, p = 0.010) and CSS (HR 1.16, 95% CI 1.04–1.29, p = 0.006), while sex was not associated with survival. Higher household income ( > $90,000; Q3) was associated with improved survival on unadjusted analysis, with significantly better OS (HR 0.85, 95% CI 0.79–0.92, p < 0.001) and CSS (HR 0.87, 95% CI 0.80–0.95, p = 0.002) compared with lower income( < 60,000; Q1). These associations remained significant on multivariable analysis, with Q3 demonstrating improved OS (HR 0.85, p < 0.001) and CSS (HR 0.87, p = 0.002). Patients in non-metropolitan areas had worse OS and CSS on unadjusted analysis (median OS: 18 vs 22 months; median CSS: 27 vs 34 months; both p = 0.001). However, geographic status was not independently associated with survival on multivariable analysis (OS HR 0.99; CSS HR 0.95). Conclusions: In this population-based study of ampullary carcinoma, Black race and lower household income were independently associated with worse overall and cancer-specific survival, highlighting the need for interventions to improve healthcare access and reduce structural inequities. Future research should investigate the social, biological, and healthcare factors driving these disparities to inform targeted strategies for high-risk populations.
Digital delivery of personalized cancer risk reduction: Real-world engagement with ACS CancerRisk360.
e22515 Background: Access to personalized, disease site agnostic guidance to lower cancer risk remains an unmet public health need. In response, the American Cancer Society (ACS) launched ACS CancerRisk360, a large scale publicly available dissemination tool designed to assess risk and connect users to evidence-based recommendations to reduce modifiable risks. This free web-based app uses a sophisticated decision matrix to synthesize clinical variables, family history, lifestyle factors, and evidence-based guidelines into personalized risk reduction and screening recommendations for the user. Methods: ACS CancerRisk360 was developed with input from diverse clinical specialists, patients, and caregivers, and reflects established health literacy best practices. To maximize usability and minimize data loss risk, ACS CancerRisk360 incorporates read-aloud functionality and retains only aggregate, nonidentifiable demographic information. Personal health information is not stored, but engagement metrics are captured using Matomo and Microsoft Power BI. This analysis summarizes platform utilization, engagement, and feedback from January–December 2025. Results: 161,278 page views generated 89,909 assessment starts and 71,194 completed assessments (79% completion rate). Most users were aged 30–69 years (72%); 78% were female; 83.5% of users identified their race or ethnicity as White. ZIP-code–level data demonstrated nationwide reach with users from 50 states, Puerto Rico and Guam. Users spent an average of 14 minutes engaged with the tool. Engagement with personalized outputs was high: 7719 users downloaded, 7680 emailed, 2122 printed, and 1173 texted their results to a mobile phone. Users made 17,892 visits to additional ACS educational resources. The most frequently accessed linked resources addressed body weight and cancer risk (1301 visits), radon and lung cancer (1005 visits), and genetic testing for cancer risk (978 visits). 6899 users rated the tool 4.24 of 5. Free text comments from 1162 users demonstrated high user satisfaction, particularly with screening recommendations, diet and activity guidance, and information about genetic testing. The most commonly cited limitation was the absence of a numeric risk score. Conclusions: ACS CancerRisk360 demonstrates the feasibility and impact of a large-scale, direct-to-consumer digital platform for delivery of personalized, evidence-based cancer risk-reduction guidance. High completion rates, sustained engagement with personalized outputs, and positive user feedback suggests the tool effectively supports awareness of cancer risk, screening needs, implications of family history, and modifiable lifestyle behaviors. Future development will focus on enhancing personalization, leveraging emerging scientific evidence, and expanding dissemination to reach more diverse populations and underserved communities.
A phase 1b, two-arm study of tolododekin alfa (ANK-101) in combination with an anti–PD-1/PD-L1 antibody in participants with advanced non–small cell lung cancer (NSCLC).
TPS2678 Background: Tolododekin alfa (ANK-101) is an anchored immunotherapy linking IL-12 to aluminum hydroxide through an alum-binding protein (ABP). Direct delivery to tumors results in prolonged IL-12 local retention and limited systemic absorption. A Phase 1 study in advanced solid tumors demonstrated ANK-101 was well tolerated with evidence of antitumor activity, recruitment of CD8+ T cells, and induction of local programmed cell death ligand 1 (PD-L1) expression. ANK-101 is now being evaluated in combination with PD-1/PD-L1 checkpoint blockade (ICB) in patients with non-small cell lung cancer (NSCLC). Methods: This study is a Phase 1b, two-arm, open-label study of direct injection (IT) of tolododekin alfa administered in combination with an anti-PD-1/PD-L1 antibody in participants with locally advanced or metastatic NSCLC. Cohort A will be conducted in participants who have progressed on prior standard of care treatment with ICB and platinum-based chemotherapy, either in combination or sequentially. Cohort B will enroll participants with untreated locally advanced or metastatic NSCLC with a PD-L1 tumor proportion score (TPS) ≥ 50%. Participants with targetable EGFR mutations or ALK rearrangements are excluded. In Cohort A, participants will receive tolododekin alfa at 250 µg/mL IT in combination with cetrelimab (anti-PD-1) intravenously (IV) Q3W at a dose of 360 mg for up to 8 cycles, followed by cetrelimab monotherapy for up to one year, unless they have unacceptable toxicity, clinical deterioration, confirmed tumor progression, or have withdrawn consent. In Cohort B, participants will receive tolododekin alfa at 250 µg/mL IT in combination with investigator’s choice of an FDA-approved ICB for first-line use as monotherapy in patients with TPS ≥" role="presentation" tabindex="0">≥ 50% IV Q3W at the approved dose for up to 8 cycles, followed by continued ICB according to the FDA-approved label. The primary objective is objective response rate by RECIST 1.1. Secondary endpoints include safety, duration of response, disease control rate, progression-free survival, and overall survival. In addition, lesion-level responses, serum PK analyses, and anti-drug antibody (ADA) levels will be assessed. Exploratory endpoints include measurements of selected serum cytokine levels and characterization of the composition of the tumor microenvironment before and on-treatment. This clinical trial is in progress. Clinical trial information: NCT07027514 .
Patterns of failure and outcomes in triple-negative compared to estrogen receptor–positive breast cancer.
e12760 Background: Advances in molecular classification have led to subtype-specific treatments for breast cancer, improving outcomes while revealing distinct recurrence patterns. This study compares outcomes and failure patterns between triple-negative breast cancer (TNBC) and estrogen receptor–positive (ER-positive) disease. Methods: We conducted a retrospective analysis using whole dataset of the Oncology Research Information Exchange Network (ORIEN), including women with non-metastatic breast cancer. Patients were categorized as TNBC or ER-positive. Outcomes included overall survival (OS), disease-free survival (DFS), locoregional control, and patterns of failure. Results: A total of 1,277 patients with stage I–III breast cancer were included, comprising 276 patients with TNBC and 1,001 with ER-positive disease. The median age was 52 years (interquartile range [IQR], 44–62). Most patients were White (83.3%) and non-Hispanic (84.5%). HER2 was positive in 13.4% of ER-positive disease. Compared with TNBC, ER-positive patients more frequently presented with clinical stage I (37.8% vs. 31.9%) and stage II disease (43.0% vs. 39.9%). In contrast, clinical stage III disease was more common among patients with TNBC than those with ER-positive disease (15.2% vs. 8.0%). Neoadjuvant systemic therapy was administered to 154 patients, including 62 (22.5%) with TNBC and 92 (9.2%) with ER-positive disease. Pathological complete response after neoadjuvant systemic therapy was observed in 14 (9.1%) patients (6 TNBC and 8 ER-positive). Adjuvant systemic therapy was delivered to 641 patients, including 108 (39.1%) with TNBC and 533 (53.2%) with ER-positive disease. Among the ER-positive patients who received adjuvant systemic therapy (n = 533), 498 (93.4%) received adjuvant endocrine therapy. Radiation therapy was delivered to approximately two-thirds of patients in both groups. Among those treated with radiation, 83.7% received whole-breast or chest wall irradiation with nodal coverage. Lymph node irradiation was administered in 36.8% of patients, not administered in 33.7%, and was unknown in 29.5%. With a median follow-up of 75.2 months (range, 0–393.7 months), TNBC was associated with significantly worse overall survival (hazard ratio [HR] 2.85, 95% confidence interval [CI] 2.04–3.96), disease-free survival (HR 2.10, 95% CI 1.56–2.83), and distant metastasis–free survival (HR 2.28, 95% CI 1.25–4.16) compared with ER-positive disease. No significant differences were observed in local control (HR 1.17, 95% CI 0.51–2.70) or regional control (HR 2.28, 95% CI 0.85–6.11) between the two groups. Conclusions: TNBC was associated with significantly worse survival outcomes and higher rates of distant failure compared with ER-positive disease. These results highlight distant metastasis as the dominant pattern of failure in TNBC and support the need for more effective systemic therapies.