Fairfax Neonatal Associates

Abstract Background: HER3-targeted antibody-drug conjugates (ADCs) have shown benefits in breast cancer (BC). DB-1310 is a novel ADC comprised of a humanized anti-HER3 IgG1 monoclonal antibody with a highly internalizing unique Domain I epitope, a cleavable peptide linker, and a potent DNA topoisomerase I inhibitor P1021. Initial clinical data demonstrated a manageable safety profile and encouraging anti-tumor activity, particularly in patients with EGFR-mutant NSCLC (Lisberg ASCO 2025). Here, we present the efficacy and safety results of DB-1310 in pretreated hormone receptor-positive (HR+), HER2-negative (HER2-) BC patients. Methods: In the Phase 1 part of this trial (NCT05785741), patients with advanced solid tumors, including HR+/HER2- BC, received DB-1310 monotherapy intravenously every three weeks (Q3W). Safety was the primary endpoint, with efficacy endpoints including objective response rate (ORR), duration of response (DoR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) as secondary endpoints. Results: As of July 04, 2025, a total of 207 patients with solid tumors were enrolled and treated with DB-1310 monotherapy (1.5-6.5 mg/kg, Q3W) in Phase 1 (ECOG PS 1, 84.1%; White, 26.1%; Asian, 69.1%). Among these, 16 HR+/HER2- BC patients were enrolled (3.0-5.5 mg/kg, Q3W), with 15 of them being efficacy-evaluable, and a median prior line of systemic therapy was 2 (range, 1-7). Efficacy Results (N=15 HR+/HER2- BC patients from Phase 1): nine achieved a partial response (one pending confirmation), and four achieved stable disease, resulting in a confirmed ORR of 53.3% (95%CI: 26.59, 78.73) and a DCR of 86.7% (95%CI: 59.54, 98.34). Notably, all partial responses occurred in patients treated with 5-5.5 mg/kg (N=13), yielding an unconfirmed ORR of 69.2%, a confirmed ORR of 61.5%, and a DCR of 92.3% for this dose range. The median DoR is not reached. Median PFS is 14.78 months (95% CI: 11.60, not evaluable) and median OS is 14.69 months (95% CI: 11.89, not evaluable). Safety Results (N=207, all enrolled patients from Phase 1): The safety profile was assessed in the entire Phase 1 part. Treatment-related adverse events (TRAEs) of Grade (G) ≥ 3 occurred in 89 (43.0%) patients, and 25 patients (12.1%) had treatment-related serious adverse events. TRAEs led to dose reduction in 38 (18.4%) and discontinuation in 9 (4.3%) patients. No TRAE-related deaths were reported. Most common TRAEs (any grade/≥G3; >20% overall) were neutrophile count decreased (49.3%/ 26.1%), anemia (47.8%/ 6.8%), platelet count decreased (45.4%/ 15.9%), white blood cell count decreased (43.5%/ 11.1%), nausea (40.6%/ 1.0%), decreased appetite (29.5%/ 0.5%), aspartate aminotransferase increased (26.6%/ 0), alopecia (26.1%/ 0), vomiting (24.6%/ 0), and hypoalbuminemia (21.7%/ 0). Interstitial lung disease/pneumonitis occurred in 10 pts (4.8%; one Grade 2, all others G1). The safety profile in the 16 HR+/HER- BC patients was consistent with the overall Phase 1 part. Conclusion: DB-1310 showed promising anti-tumor activity in heavily pretreated HR+/HER2- BC patients. The manageable safety profile observed in the larger Phase 1 part, involving 207 patients, is consistent with that of the BC subpopulation, supporting its further development. Citation Format: Y. Yin, A. Spira, H. Lan, M. Zhao, Y. Mao, W. Yao, Y. Sun, J. Wu, X. Sun, S. Liu, H. Mu, K. Wang, Y. Qiu, E. Hamilton. First clinical data of DB-1310 (HER3-targeted antibody-drug-conjugate), in patients with pretreated hormone receptor-positive/HER2-negative breast cancer: efficacy and safety data from a phase 1/2a trial [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS4-06-17.

<title>Abstract</title> Purpose To evaluate whether N-terminal pro-brain natriuretic peptide (NT-proBNP) measured at 48–72 hours of life predict moderate-to-severe bronchopulmonary dysplasia (msBPD) using a competing risk framework. Methods We conducted a prospective cohort study including infants ≤ 32 weeks of gestation admitted between 2013–2023 to a level III neonatal unit. NT-proBNP was routinely measured at 48–72 hours. Primary outcomes were msBPD (2001 NIH definition) and death before 36 weeks postmenstrual age, analyzed using Fine and Gray competing risk regression. Secondary analyses included cumulative incidence of successful extubation by day 28 and sensitivity analyses restricted to infants surviving beyond 14 days. Models were adjusted for gestational age (GA) and other clinically relevant covariates. Results Among 264 included infants with a median (IQR) gestational age and birth weight of 30 [27.5–31.5] weeks and 1230 [981–1568] g) respectively, 38 (14.4%) developed msBPD and 18 (6.8%) died. NT-proBNP was not associated with msBPD in univariate [subdistribution hazard ratio (SHR) 1.03, 95% confidence interval (CI) 0.79–1.34; p = 0.84] or adjusted models. Conversely, NT-proBNP independently predicted death [adjusted SHR 2 (95% CI 1.2–3.2); p = 0.008). NT-proBNP was also associated with a reduced chance of successful extubation [adjusted SHR 0.88, (95% CI 0.8–0.98); p = 0.027). In infants surviving &gt; 14 days, NT-proBNP showed a modest association with msBPD [adjusted SHR 1.3 (95% CI 1.01–1.73); p = 0.042). Conclusion Early NT-proBNP is primarily a marker of early mortality risk rather than a specific predictor of msBPD. Competing risk methods are essential to avoid overestimating biomarker utility in bronchopulmonary dysplasia (BPD) prediction.

ABSTRACTIn this design‐based research study, in‐service educators participated in a grant‐funded professional development (PD) project to increase district capacity for multilingual learner instruction. Initial data indicated teacher comfort with technology but difficulty tailoring it to the unique multiliterate practices of culturally and linguistically diverse students. Based on teachers' needs and a departmental goal, a modification of a digital escape room (the JEDI Library Escape) was designed and implemented to teach principles of culturally sustaining pedagogies (CSPs) and multiliteracies. Results indicate that infusing CSP and multiliteracies into a digital escape room as PD enacted critical reflection, increased multiliteracies awareness, and created an overall enjoyable experience while shifting teachers' holistic impressions of multilinguals and their caregivers. Future iterations of the JEDI escape will include more opportunities for applying multiliteracies and JEDI principles to classroom settings, followed by opportunities for peer reflection through coursework.

In this study, we analyse the influence of nutrition during the early neonatal period on the development and prevention of atopic dermatitis (AD) in children with a history of very low birth weight (VLBW). A retrospective cohort study was performed of VLBW preterm infants to assess the risk of their developing AD during childhood, according to nutrition with breastmilk and/or probiotic supplementation during the neonatal period. The analysis focused on nutritional and early childhood follow-up data for 437 newborns, of whom 184 received probiotics up to 36 weeks postmenstrual age. AD was present in 23.5% of the study sample. Of the children who did not develop AD, 44.9% had received probiotics from birth to 36 weeks of gestational age. Therefore, the administration of probiotics to infants at less than 36 weeks postmenstrual age is associated with a protective effect against the development of AD (odds ratio (OR) 0.57; 95% confidence interval (CI) 0.34-0.93). Moreover, a protective interaction was observed between probiotic administration and breastmilk (OR 0.46; 95% CI 0.25-0.82). The adjusted data in the regression model allow us to observe a statistically significant association with the protective effect of Lacticaseibacillus rhamnosus with the development of AD at school age (OR 0.55; 95% CI 0.30-0.99). Probiotic supplementation in VLBW newborns is associated with a decreased risk of subsequent development of AD. Breastmilk strengthens the protective effect of probiotics against the development of AD.

Heterozygous SNVs or CNV deletions involving the FOXF1 gene, or its distant enhancer, are causative for 80–90% of cases of alveolar capillary dysplasia with misalignment of pulmonary veins. Recently, we proposed bimodal structure and parental functional dimorphism of the lung-specific FOXF1 enhancer, with Unit 1 having higher activity on the paternal chr16 and Unit 2 on the maternal chr16. Here, we describe a novel unusually sized pathogenic de novo copy-number variant deletion involving a portion of the FOXF1 enhancer on maternal chr16 that implies narrowing Unit 2 to an essential ~ 9-kb segment. Using a restrictase-based assay, we found that this enhancer segment is weakly methylated at ApT adenine, with about twice the frequency of methylation on the maternal versus paternal chr16. Our data provide further insight into the FOXF1 enhancer structure and function.