Challenging the myths of subcutaneous delivery: An industry expert perspective.

107th AATS Annual Meeting - Save The Date

Bioarchaeological research in the Roman period: proceedings of the 1st and 2nd annual meetings of the International Congress on Roman Bioarchaeology

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Chronic itch is the most burdensome symptom of atopic dermatitis (AD), yet its routine assessment and measurement remain inconsistent. This study aimed to characterise current practices for evaluating itch in AD among UK dermatologists and, through a narrative review,to summarise available itch assessment tools and inform practical recommendations for routine practice. This was a cross-sectional clinician survey and narrative literature review. A total of 394 dermatologists participated in the survey of itch and its assessment in AD during the 2024 British Association of Dermatologists Annual Meeting. Dermatologists reported itch as the most bothersome symptom in atopic dermatitis (78.68%, n = 310), and nearly half identified itch as the strongest predictor of disease severity (47.97%, n = 189). Only 28.68% of respondents (n = 113) reported assessing itch often or always using the peak pruritus numerical scale (PP-NRS) or visual analogue scale (VAS), while 45.18% (n = 178) assessed itch sometimes and 26.14% (n = 103) never assessed itch. Reduction of itch was selected as the most important treatment goal by 56.35% of respondents (n = 222). In addition, 94.16% (n = 371) agreed or strongly agreed that they routinely try to understand the impact of itch on their patients, and 74.11% (n = 292) agreed or strongly agreed that there is currently a lack of effective treatment options for itch relief. The narrative review identified validated unidimensional itch measures (numerical rating scale (NRS), VAS, verbal rating scale (VRS)) and multidimensional instruments (Patient-Oriented Scoring of Atopic Dermatitis (PO-SCORAD), Patient-Oriented Eczema Measure (POEM), 5-D itch scale, ItchyQOL), with clinical studies reporting that reductions of approximately 3-4 points on the itch NRS correspond to patient-perceived meaningful improvement. This large UK-based survey among dermatologists highlighted a gap between recognition of itch burden in atopic dermatitis and its systematic measurement in routine practice. The accompanying narrative review identified simple patient-reported measures, including the numerical rating scale (NRS), as feasible options to support more consistent itch assessment in routine care.

Objective Academic conferences provide opportunities for research presentation, networking, and career advancement. However, travelling for conferences can pose challenges for those with childcare responsibilities. To explore childcare support at conferences, the 83rd Annual Meeting of the Japanese Society of Public Health conducted a survey among in-person attendees.Methods An online survey was conducted among in-person attendees of the meeting in November 2024. The participants were recruited via email invitations sent to pre-registered attendees and members of the Japanese Society of Public Health. The respondents provided demographic information and shared their opinions on attending conferences with their children. Those with elementary school-aged children or younger were asked about the age of their youngest child, childcare arrangements during the conference, and perceived usefulness of various childcare support measures. Data were analyzed based on the presence or absence of children in this age group and sex. Free-text responses were analyzed using content analysis and quantitative text analysis with the KH Coder software.Results Of 856 respondents, 615 (71.8%) rated attending conferences with children as "favorable" or "very favorable." The proportion of women with elementary school-aged children or younger (15.3%) was significantly lower than that of men (31.0%) (P < 0.01). Furthermore, there were significantly fewer women with children aged 0-2 years (15.9%) than men (31.3%) (P = 0.03). Participants with elementary school-aged children or younger valued a "welcoming atmosphere for attendees bringing children to the conference venue" (men; 83.8%, women; 82.9%), "kids' space within the conference venue" (men; 80.8%, women; 84.1%), and "free childcare room at the conference venue" (men; 80.8%, women; 79.3%). Free-text responses highlighted a desire for expanded childcare capacity, parent-priority seating, weekend conference scheduling, on-demand streaming, and welcoming atmosphere for attending conferences with children.Conclusion The meeting initiative to support conference attendance of participants with children received positive feedback. However, the attendance remained low among women with very young children. Future efforts should continue on-demand streaming and expand childcare capacity while introducing new initiatives, such as parent-priority seating and children's spaces. These measures foster "a welcoming atmosphere for attendees bringing children to the conference venue," thereby making conferences more accessible to participants with childcare responsibilities.

The author discusses, at the Clinical Orthopaedic Society Annual Meeting 2025, acute weight-bearing protocols in ankle fracture management.

Original Abstracts from the 22nd Annual Meeting of ISMPP

Abstract Patients (pts) with metastatic (met) MSS CRC are treated with sequential lines of chemotherapy (chemo), but most experience progression and prolonged toxicities during their disease course. BOT is a 2nd-gen Fc modified anti-CTLA-4 agent, exhibiting enhanced antibody dependent cell mediated cytotoxicity of Tregs and Fc-receptor mediated myeloid activation. A phase I/II study with BOT/BAL (an anti-PD-1 antibody) in pretreated patients with MSS CRC achieved a 73% disease control rate (DCR) in pts without liver mets. We tested the hypothesis that anatomically selected pts with met MSS CRC would benefit from BOT/BAL in the 1L, delaying or negating the need for chemo.We enrolled 15 untreated Stage IV MSS CRC pts who did not have liver, bone, or brain mets (NCT06268015). Pts received BOT (75 mg q6 weeks (w) up to 4 doses)/BAL (240 mg q2w) 1L, followed by staging CT scans and iRECIST measurements q6w. If iCPD was observed, standard-of-care chemo (SOC: FOLFOX + bevacizumab or panitumumab) was added to BAL. Tissue biopsies were taken prior to treatment and at the time of progression. Primary objectives included safety, feasibility, and DCR to BOT/BAL. Secondary objectives included best overall response to BOT/BAL alone and at chemo crossover (ORR1, iRECIST; ORR2/DCR2, RECIST), overall and progression-free survival (OS, PFS1; PFS2). Exploratory objectives include spatial studies on tumor tissue biopsies taken prior to treatment and at the time of progression to predict response and resistance. As of 1/5/2026, one pt withdrew from treatment (BRAF mut); 13 pts were evaluable for response and 14 pts for irAEs (6 Gr 1-2; 7 Gr 3; no Gr 4), with a median follow up of 4.3 mo (95% CI, 1.6-Not Estimable, NE). Pts were a median age of 50 (Q1:40, Q3:62) at time of consent, with 10 (66.7%) males. Distribution of sites of mets included lymph nodes (3; 20%), other (3; 20%), peritoneum (4; 26.7%), and lungs (5; 33.3%). A median of 3 cycles of BOT were given. Gr 3 toxicity was primarily colitis (5), which we managed with short course prednisone that patients were given to take home before starting therapy, followed by infliximab within 48 hours. Categories of all grades of irAEs experienced by &amp;gt;1 pt included diarrhea/colitis (7), fatigue (7), rash (5), AST/ALT (3), fever (3), hypothyroidism (2), and arthritis (2), which was effectively managed with naproxen or ibuprofen. Median freedom from crossover to chemo was 8.7 mo (95% CI, 6.2-NE). There was 1 confirmed iPR to BOT/BAL alone in a pt with lung mets and TMB of 1 mut/mb, and 4 iSD at 24w of follow-up, resulting in a 71% DCR. Five BOT/BAL only pts are too early to assess at cutoff. Of 4 pts crossing over to SOC at a median of 6.3 mo (95% CI, 3.7-NE) from BOT/BAL start, 3 were evaluable for response to chemo by RECIST with a 67% DCR. No deaths occurred. Initial analysis of multiplex IHC demonstrated an increase in cDC1s in responders to BOT/BAL compared to non-responders, who exhibited an increase in Spp1/CXCL9 macrophage ratios.Our study is the first to demonstrate the safety and feasibility of 1L BOT/BAL in MSS CRC pts without liver, bone, or brain mets. 1L BOT/BAL has durable activity in some pts and can delay the need for chemo, which was added safely in pts who do progress. Further studies including the development of biomarkers are warranted in PhII studies to establish this approach in 1L MSS CRC. Citation Format: Nicholas C. Devito, Emily Bolch, Aman Opneja, Hope Uronis, Lisa Vlastelica, Gerard C. Blobe, John W. Hickey, Yuexi Kylee Li, Kevin S. Tanager, Cheryl H. Chang, Jingchen Chai, Kara Bonneau, Niharika B. Mettu, Michael A. Morse, Tucker W. Coston, Shiaowen David Hsu, Carol A. Wiggs, Donna Niedzwiecki, Dana A. Warren, John H. Strickler. Preliminary results of first-line botensilimab (BOT) and balstilimab (BAL) optimization in microsatellite stable colorectal cancer (MSS CRC) without liver, bone, or brain metastasis (BBOpCo) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr CT184.

Abstract Background: PARP inhibitors (PARPi) selectively kill tumor cells harboring genetic mutations in critical DNA repair genes (e.g., BRCA1/2). Approved nonselective PARPi have demonstrated robust antitumor activity, but are associated with significant hematologic toxicities that limit dose intensity and clinical benefit. Drugs that selectively inhibit PARP1, but spare PARP2, may improve the risk-benefit profile by retaining antitumor activity while avoiding PARP2-related toxicities. Furthermore, current PARPi have variable brain penetrance, limiting their utility for targeting CNS tumors or brain metastases. EIK1004 (IMP1707) is a potent, CNS-penetrant, PARP1-selective inhibitor that demonstrates tumor growth inhibition in preclinical brain metastasis models. Methods: Study EIK1004-001 (IMP1707-101) is a FIH, global, multi-center, Phase 1/2 study evaluating the safety and potential antitumor activity of EIK1004 monotherapy in patients with advanced ovarian, breast, prostate, or pancreatic cancer, with or without brain metastases (NCT06907043). The study consists of Part 1 (Dose Escalation; using the Bayesian optimal interval [BOIN] design) and Part 2 (Dose Optimization). All participants must have a deleterious or suspected deleterious mutation in select homologous recombination repair genes and received no more than one prior line of PARPi treatment. Eligible participants must be ≥ 18 years, have histologically or cytologically confirmed tumors and received appropriate prior antitumor therapies, and have evaluable disease (eg, at least 1 measurable lesion by RECIST 1.1 [or RANO-BM for brain metastases] and/or serum tumor markers). Primary endpoints include safety and tolerability including identifying the maximum tolerated dose or maximum achievable dose, and recommended dose(s) for expansion (RDE). Secondary endpoints include evaluation of EIK1004 pharmacokinetics and preliminary antitumor activity including overall response, duration of response, and progression-free survival. Part 2 will open once the RDE is determined from Part 1. This study opened on 23-Jan-2025 and is actively enrolling participants. Citation Format: Timothy A. Yap, Jian Zhang, Yanhua Xu, Sanum Chaudry, Kevin H. Eng, Yawei Zhang, Viola J. Chen, Gerald Falchook. A first-in-human (FIH), Phase 1/2, dose-escalation and dose-optimization study of central nervous system (CNS)-penetrant, PARP1-selective inhibitor EIK1004 in patients with advanced solid tumors with or without brain metastases [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr CT287.

Abstract Background: Platinum-resistant ovarian cancer (PROC) and clear cell gynecologic cancer (CCGC) are associated with poor prognoses and have limited effective treatment options. PROC has a recurrence rate of approximately 70%, while CCGC, a rare histologic subtype, demonstrates resistance to most standard therapies. These unmet clinical needs underscore the importance of developing novel therapeutics to improve patient outcomes. Immune checkpoint inhibitors have shown promising preliminary antitumor activity in PROC and CCGC, although they are not currently approved for either indication. Lorigerlimab is an investigational bispecific (PD-1 x CTLA-4), tetravalent DART® molecule. It is engineered to enhance CTLA-4 blockade in a PD-1-binding-dependent manner, intended to improve activity in the tumor microenvironment while minimizing off-tumor toxicity. Preclinical and early-phase clinical data support lorigerlimab immunomodulatory activity and tolerability. This study investigates the efficacy and safety of lorigerlimab monotherapy in patients with PROC and CCGC. Methods: This open-label, multicohort, multi-institutional, phase 2 study (NCT06730347) evaluates lorigerlimab monotherapy in participants with PROC (cohort A) or CCGC (cohort B). Cohort A utilizes a Simon’s two-stage design to enroll up to 40 participants and cohort B will enroll up to 20 participants. Participants receive lorigerlimab intravenously every 3 weeks for up to 35 cycles or until disease progression, unacceptable toxicity, or withdrawal. The primary objective is to evaluate the antitumor activity as measured by objective tumor response. Secondary objectives include characterization of safety, tolerability, and evaluation of efficacy by duration of response, disease control rate, progression-free survival, and change in tumor size from baseline. Eligible participants must have persistent or recurrent high-grade serous ovarian carcinoma or clear cell gynecologic cancers with at least 50% clear cell histomorphology. Participants with PROC must have received at least one and up to three prior lines of systemic therapy, which may include prior bevacizumab. Individuals with a germline or somatic BRCA mutation must have received PARP inhibitor therapy. Participants with CCGC must have received at least one prior line. All participants must have good functional status, measurable disease, adequate organ function, and no contraindications to immunotherapy. Individuals with primary platinum-refractory disease are excluded. Prior use of checkpoint inhibitor therapy is permitted for participants with clear cell endometrial or clear cell cervical cancer. Tumor assessments occur every 9 weeks for the first 54 weeks, then every 12 weeks until treatment discontinuation. Enrollment commenced in May 2025 and is ongoing. Citation Format: Helen D. Clark, Kelly M. Rangel, Shawana N. Richard, Jichao Sun, Pepi Pencheva, Chad Hamilton, Amir A. Jazaeri. A phase 2 multicohort study to evaluate lorigerlimab (PD-1 x CTLA-4) in participants with advanced solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr CT279.

Abstract The ability of tumor cells to tolerate DNA damage through a robust DNA damage response (DDR) limits the efficacy of many anticancer therapies, including genotoxic agents; however, the epigenetic mechanisms that sustain DDR gene expression remain poorly understood. Here, we identify Class I histone deacetylases (HDACs) as critical regulators of the DDR in pancreatic ductal adenocarcinoma (PDAC). HDAC1/2 maintain a proper genome-wide distribution of H3K27 acetylation, ensuring efficient recruitment of BRD4 and RNA polymerase II to DDR gene promoters. Pharmacological HDAC inhibition with entinostat preferentially enriches H3K27 acetylation at intergenic regions, diverting transcriptional machinery away from promoters and suppressing DDR gene expression. Consequently, HDAC inhibition increases DNA damage and sensitizes PDAC to diverse DNA-damaging (e.g., platinum agents, topoisomerase inhibitors) and DDR-targeting therapies (e.g., PARP inhibitors). To overcome the systemic toxicity that has limited the clinical translation of HDAC inhibitors, we developed a bottlebrush prodrug (BPD) nanoparticle platform for tumor-selective entinostat delivery. Entinostat-BPD enables tumor-specific HDAC inhibition, reduces system toxicity, and achieves tumor suppression comparable to free entinostat with only one-seventh of the cumulative drug exposure, demonstrating enhanced translational potential of this platform. Together, these findings uncover an HDAC-directed epigenetic mechanism that drives resistance to DNA damage-inducing agents and further establish combinatorial and precision-targeting strategies to improve PDAC outcomes. Given the central role of the DDR across cancer types and the widespread use of DNA-damaging therapies, this work may have broad therapeutic relevance beyond pancreatic cancer. Citation Format: Gaoyang Liang, Hung V. Nguyen, Jonathan Zhu, Hervé Tiriac, Hadiqa Zafar, Daniel Y. Cao, Gabriela Estepa, Dylan C. Nelson, Yang Dai, Tae Gyu Oh, Christopher Liddle, Ruth T. Yu, Andrew M. Lowy, Weiwei Fan, Morgan L. Truitt, Annette R. Atkins, Jeremiah A. Johnson, Michael Downes, Ronald M. Evans. HDAC inhibition sensitizes pancreatic cancer to DNA-damaging therapies via genome-wide redistribution of transcriptional machinery [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr LB097.

Abstract Patient-derived tumor organoids have emerged as a promising translational model for oncology drug development. However, its utility has been limited by restricted access to patient-derived materials and insufficient donor-related data such as clinical records. Here, we report the establishment of the Samsung Organoids, a GxP-based, standardized patient-derived organoid designed to support data-driven cancer drug development. All organoids were generated and processed by GxP-qualified personnel under rigorously controlled and fully documented procedures, ensuring reproducibility, traceability, and regulatory readiness. Each organoid line is linked to clinical information of the corresponding donor and multi-omics data both original tumor tissues and derived organoids. Comparative analyses demonstrated high concordance of mutational profiles and gene expression patterns between tumor tissues and matched organoids, confirming preservation of the patient-specific characteristics. To examine the responsiveness of organoids to various drugs including small molecules and ADCs, we performed high-throughput drug screening combined with high-content imaging. Drug responsiveness data revealed substantial inter-patient heterogeneity, enabling classification of organoids into distinct groups. Further, we identified particular gene expression signatures by cross-group comparison, demonstrating explanation of different drug sensitivity between organoids. Conclusively, by integrating patient clinical information with genomic/genetic alterations, transcriptomic signatures, and functional drug response data, the Samsung Organoids provides translational insights into determinants of therapeutic sensitivity and resistance, helping successful cancer drug development such as drug candidate selection, biomarker discovery, and preclinical decision-making. Citation Format: Minhyung Lee, Sekyu Oh, Seongju Jeong, Sung Min Ha, Chihah Moon, Nayoun Choi, Yoonhyeok Kwon, Seahee Kim, Sangmyung Lee, Brian Hosung Min. Samsung Organoids: A GxP-based drug screening leveraging patient-derived tumor organoids platform accompanied with clinical records and multi-omics data [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr LB397.

Abstract Background: Postoperative driver gene-specific circulating tumor DNA (ctDNA) monitoring stratifies recurrence risk in resectable stage III driver-mutant NSCLC (NCT06443684). Whether driver-specific ctDNA MRD can evaluate neoadjuvant response and predict recurrence in stage III driver-mutant NSCLC remains to be defined. Methods: From 2022 to 2025, 203 resectable stage III NSCLC patients with tissue-confirmed driver mutations were prospectively enrolled at 14 centers in China (NCT06443684). Peripheral blood was collected before neoadjuvant therapy, preoperatively, 3 days and 1 month after surgery, and every 3 months until investigator-confirmed recurrence. ctDNA was analyzed using a 10-gene driver panel (LC10). This analysis focused on peri-neoadjuvant ctDNA dynamics and clinical outcomes among 82 patients who received neoadjuvant therapy followed by surgery. Results: Among the 82 neoadjuvant-treated patients, regimens included chemo-immunotherapy (57.3%), TKI (3rd-EGFR TKI/2nd or 3rd-ALK TKI, 39.0%), and chemotherapy alone (3.7%). Post-neoadjuvant ctDNA positivity was associated with a significantly lower MPR rate versus ctDNA negativity (0% vs 42.3%, p=0.004), whereas baseline ctDNA status was not associated with MPR (16.7% vs 21.2%). Post-neoadjuvant ctDNA molecular residual level (hGE/mL) positively correlated with residual viable tumor cells (R=0.332, p=0.009). Post-neoadjuvant ctDNA-positive patients had significantly shorter event-free survival (median EFS 11.4 vs 23.8 months; HR=8.82; p=0.009). For non-MPR patients, post-neoadjuvant negative ctDNA status also indicated favorable prognosis (median EFS 23.8 vs 4.7 months; HR=5.80; p=0.054). Compared with other regimens, neoadjuvant TKI was associated with a lower post-treatment ctDNA residual rate (0% vs 15.3%; p=0.05). Patients with persistent ctDNA positivity (baseline→post-neoadjuvant) had the shortest EFS (median 4.7 months), followed by negative→positive (23.8 months), while positive to negative and persistent negative ctDNA indicated disease free status(log-rank p&amp;lt;0.001). Conclusions: A driver-specific ctDNA MRD strategy provides a practical tool for neoadjuvant efficacy assessment and postoperative recurrence risk stratification for stage III driver-mutant NSCLC patients. Citation Format: Jian Hu, Xiao Teng, Ziming Li, Yu Qi, Feng Li, Qixun Chen, Changbin Zhu, Xing Li, Shun Lu. Driver-specific MRD strategy associated with pathological response and predicted recurrence in stage III driver-mutant NSCLC receiving neoadjuvant treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr LB120.

Securing a faculty position is the final milestone for many individuals completing their PhD or postdoctoral training. However, navigating the academic job market can feel like a full-time endeavor, which often has to be balanced alongside tasks like manuscript preparation, dissertation completion, or grant applications. Despite extensive training in researchand teaching, many candidates report feeling underprepared for the multifaceted and often hidden nature of the faculty interview process. Furthermore, seeking guidance about this process can be intimidating for some, as individuals may lack access to a career development mentoring team. As part of the 2024 American Society of Biomechanics Annual Meeting's Career Development roundtables, the authors, drawing from their experiences as both applicants and interviewers, compiledkey considerations to support aspiring faculty members. This resource aims to: (1) offer a structured approach to initiating the faculty application process and (2) highlight departmental expectations during interviews to help candidates prepare effectively and present themselves confidently. By sharing practical strategies and insights, we hope to empower future faculty to successfully identify, apply for, interview for, negotiate, and accept academic positions.

Abstract Introduction: V-domain Ig Suppressor of T-cell Activation (VISTA) is an immune checkpoint regulator found on tumor, myeloid, and other immune cells. Its presence has been shown to enhance tumor growth, create an immunosuppressive microenvironment and may potentially contribute to resistance to anti-CTLA-4 and anti-PD-1/PD-L1 therapies. Therefore, VISTA represents a promising therapeutic target. HMBD-002, a non-depleting, high-affinity IgG4 monoclonal antibody against VISTA, has demonstrated significant inhibition of tumor growth in preclinical studies, both as a monotherapy and in combination with pembrolizumab. HMBD-002 is intended to increase T-cell activity and reprogram the suppressive tumor microenvironment to a proinflammatory antitumor phenotype. Cancer types including triple-negative breast cancer (TNBC) and non-small cell lung cancer (NSCLC) exhibit high expression levels of VISTA in the TME providing a rational basis for exploring these solid tumor indications. Methods: Phase 1, first-in-human, open-label, study evaluating multiple repeat doses of intravenously (IV) administered HMBD-002, with or without pembrolizumab, in participants with advanced solid tumors (i.e., locally advanced and unresectable, or metastatic). A standard 3+3 design was utilized. Dose escalation was initiated with single-agent HMBD-002. After completion of the first 4 cohorts as monotherapy HMBD-002 dose escalation, HMBD-002 was dose escalated in combination with fixed dose pembrolizumab (200 mg IV Q3W). HMBD-002 was administered as a single weekly dose, with or without pembrolizumab, in 21-day treatment cycles. Primary endpoints were safety and tolerability, maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D). Secondary endpoints included pharmacokinetics and preliminary antitumor activity. Results: A total of 48 subjects were enrolled, 28 receiving HMBD-002 as monotherapy at doses ranging from 20mg to 1400mg. Dose escalation in combination with pembrolizumab (20 subjects) ranged from 180mg to 1400mg. 18 subjects (37.5%) experienced a treatment related AE with 3 subjects having a grade 3 or greater TRAE. The most common TRAEs were fatigue, rash and nausea. 1 dose limiting toxicity, immune related hepatitis, was seen at 360mg monotherapy and resolved with corticosteroids after drug was held. No cytokine release syndrome (CRS) was observed. No MTD was declared. PK data indicates a RP2D of 720mg QW. Best observed response was stable disease (SD) in 5/28 (18%) monotherapy subjects and 5/20 (25%) combination therapy subjects. A subset of subjects experienced SD for 6 cycles or greater, including subjects with NSCLC and TNBC. Conclusions: HMBD-002 demonstrated preliminary safety and tolerability in this phase 1 study. A RP2D of 720mg QW was determined. Further investigation in tumor specific phase 2 cohorts is warranted and planned for 2026. Citation Format: Jordi Ahnert Rodon, Joshua J. Gruber, Melinda L. Telli, Andrew Hendifar, Joseph W. Kim, Sharonlin Bhardwaj, Padmanee Sharma, Dipti Thakkar, Jerome Boyd-Kirkup, Eugene Kennedy. Results of phase 1 first-in-human clinical trial of HMBD-002, an IgG4 monoclonal antibody targeting VISTA, in advanced solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr CT126.

Abstract Cancer arises within a complex cellular milieu, where the extent and composition of tumor-infiltrating immune cells strongly influence tumor progression and patient prognosis. Emerging research highlights the therapeutic potential of fasting mimicking diets (FMDs) in delaying cancer onset, providing cellular protection and regulating immunity. My project investigates immune profiles, before and after the transfer of donor-derived immune cells previously exposed to fasting, either independently or combined with therapeutic drugs. We aim to identify immune populations, enhanced by this combined treatment, and to recognize their impact on tumor advancement and immune activation. Using the syngeneic 4T1, triple negative breast cancer mouse model, we evaluated how fasting and chemotherapy affect tumor growth and immune competence. Flow cytometry and immunohistochemistry were used to characterize immune cells, recruited at tumors, spleens and bone marrows of treated hosts. A subpopulation of preconditioned splenocytes and tumor-infiltrating lymphocytes, recognized through immunophenotyping, were transplanted into tumor-bearing recipients to assess tumor control, immune priming and cytotoxicity. We observed reduced tumor volume, delayed progression and increased survival rate in the transplants exposed to FMD and doxorubicin. The treatment preserved the size, morphology, and cellularity of healthy, primary and secondary lymphoid organs, while expanded beneficial, antitumor immune signatures. Integrating FMD with standard therapeutic strategies could enhance antitumor immunity and broaden the spectrum of malignancies that respond effectively. Exploring the underlying mechanisms may reveal immune pathways that can be therapeutically leveraged to eradicate tumors, in a field that currently remains unexplored. Citation Format: Evangelia Pavlou, Olga Blazevits, Giulia Salvadori, Sara Martone, Valter Longo. Integrating a fasting mimicking diet to augment antitumor immunity following adoptive cell transfer in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr LB146.

A Nationwide Workforce Characterization of Neurosurgical Care in Postwar Vietnam.

CAR-T therapy is rapidly reshaping the treatment paradigm of multiple myeloma (MM). At the 2025 ASH Annual Meeting, pivotal trials demonstrated marked efficacy across both relapsed/refractory and newly diagnosed settings. In KarMMa-3, a subgroup analysis of older patients (≥ 70 years) showed idecabtagene vicleucel significantly improved outcomes versus standard care: overall response rate (ORR) 81.6% vs. 48.1%, median progression-free survival (PFS) 18.9 vs. 5.7 months, with median overall survival (OS) not reached in either arm. CARTITUDE-4 showed superior 30-month PFS (71.0% vs. 43.2%), while iMMagine-1 reported an ORR of 97% with 93% minimal residual disease negativity. Notably, frontline CAR-T studies achieved unprecedented outcomes, including 100% ORR, stringent complete response rates approaching 94-97%, and 30-month PFS and OS rates of 88-92%. Together, these data support a paradigm shift toward earlier integration of CAR-T therapy in MM management.