Target Lesion Research Articles

Research Progress of Drug Delivery Systems Targeting the Kidneys.

Chronic kidney disease (CKD) affects more than 10% of the global population, and its incidence is increasing, partially due to an increase in the prevalence of disease risk factors. Acute kidney injury (AKI) is an independent risk factor for CKD and end-stage renal disease (ESRD). The pathogenic mechanisms of CKD provide several potential targets for its treatment. However, due to off-target effects, conventional drugs for CKD typically require high doses to achieve adequate therapeutic effects, leading to long-term organ toxicity. Therefore, ideal treatments that completely cure the different types of kidney disease are rarely available. Several approaches for the drug targeting of the kidneys have been explored in drug delivery system research. Nanotechnology-based drug delivery systems have multiple merits, including good biocompatibility, suitable degradability, the ability to target lesion sites, and fewer non-specific systemic effects. In this review, the development, potential, and limitations of low-molecular-weight protein-lysozymes, polymer nanomaterials, and lipid-based nanocarriers as drug delivery platforms for treating AKI and CKD are summarized.

Deep Learning-Based Detect-Then-Track Pipeline for Treatment Outcome Assessments in Immunotherapy-Treated Liver Cancer.

Accurate treatment outcome assessment is crucial in clinical trials. However, due to the image-reading subjectivity, there exist discrepancies among different radiologists. The situation is common in liver cancer due to the complexity of abdominal scans and the heterogeneity of radiological imaging manifestations in liver subtypes. Therefore, we developed a deep learning-based detect-then-track pipeline that can automatically identify liver lesions from 3D CT scans then longitudinally track target lesions, thereby providing the evaluation of RECIST treatment outcomes in liver cancer. We constructed and validated the pipeline on 173 multi-national patients (344 venous-phase CT scans) consisting of a public dataset and two in-house cohorts of 28 centers. The proposed pipeline achieved a mean average precision of 0.806 and 0.726 of lesion detection on the validation and test sets. The model's diameter measurement reliability and consistency are significantly higher than that of clinicians (p = 1.6 × 10-4). The pipeline can make precise lesion tracking with accuracies of 85.7% and 90.8% then finally yield the RECIST accuracies of 82.1% and 81.4% on the validation and test sets. Our proposed pipeline can provide precise and convenient RECIST outcome assessments and has the potential to aid clinicians with more efficient therapeutic decisions.

The efficacy and safety of adding PD-1 blockade to induction chemotherapy and concurrent chemoradiotherapy (IC-CCRT) for locoregionally advanced nasopharyngeal carcinoma: an observational, propensity score-matched analysis

BackgroundDespite the success of PD-1 blockade in recurrent/metastatic nasopharyngeal carcinoma (NPC), its effect for locoregionally advanced NPC (LANPC) remains unclear. This study aimed to evaluate the benefit of adding PD-1 blockade to the current standard treatment (gemcitabine and cisplatin IC <induction chemotherapy> plus cisplatin CCRT <concurrent chemoradiotherapy>) for LANPC patients.MethodsFrom January 2020 to November 2022, 347 patients with non-metastatic high-risk LANPC (stage III-IVA, excluding T3-4N0) were included. Of the 347 patients, 268 patients were treated with standard treatment (IC-CCRT), and 79 received PD-1 blockade plus IC-CCRT (PD-1 group). For the PD-1 group, PD-1 blockade was given intravenously once every 3 weeks for up to 9 cycles (3 induction and 6 adjuvant). The primary endpoint was disease-free survival (DFS) (i.e. freedom from local/regional/distant failure or death). The propensity score matching (PSM) with the ratio of 1:2 was performed to control confounding factors.ResultsAfter PSM analysis, 150 patients receiving standard treatment and 75 patients receiving additional PD-1 blockade remained in the current analysis. After three cycles of IC, the PD-1 group had significantly higher rates of complete response (defined as disappearance of all target lesions; 24% vs. 9%; P = 0.006) and complete biological response (defined as undetectable cell-free Epstein-Barr virus DNA, cfEBV DNA; 79% vs. 65%; P = 0.046) than that in the standard group. And the incidence of grade 3–4 toxicity during IC was 47% in the PD-1 group and 41% in the standard group, with no significant difference (P = 0.396). During follow-up period, additional PD-1 blockade to standard treatment improved 3-year DFS from 84 to 95%, with marginal statistical significance (HR, 0.28; 95%CI, 0.06-1.19; P = 0.064).ConclusionAdditiaonl PD-1 blockade to gemcitabine and cisplatin IC and adjuvant treatment results in significant improvement in tumor regression, cfEBV DNA clearance, superior DFS, and comparable toxicity profiles in high-risk LANPC patients.

Speeding Up and Improving Image Quality in Glioblastoma MRI Protocol by Deep Learning Image Reconstruction.

A fully diagnostic MRI glioma protocol is key to monitoring therapy assessment but is time-consuming and especially challenging in critically ill and uncooperative patients. Artificial intelligence demonstrated promise in reducing scan time and improving image quality simultaneously. The purpose of this study was to investigate the diagnostic performance, the impact on acquisition acceleration, and the image quality of a deep learning optimized glioma protocol of the brain. Thirty-three patients with histologically confirmed glioblastoma underwent standardized brain tumor imaging according to the glioma consensus recommendations on a 3-Tesla MRI scanner. Conventional and deep learning-reconstructed (DLR) fluid-attenuated inversion recovery, and T2- and T1-weighted contrast-enhanced Turbo spin echo images with an improved in-plane resolution, i.e., super-resolution, were acquired. Two experienced neuroradiologists independently evaluated the image datasets for subjective image quality, diagnostic confidence, tumor conspicuity, noise levels, artifacts, and sharpness. In addition, the tumor volume was measured in the image datasets according to Response Assessment in Neuro-Oncology (RANO) 2.0, as well as compared between both imaging techniques, and various clinical-pathological parameters were determined. The average time saving of DLR sequences was 30% per MRI sequence. Simultaneously, DLR sequences showed superior overall image quality (all p < 0.001), improved tumor conspicuity and image sharpness (all p < 0.001, respectively), and less image noise (all p < 0.001), while maintaining diagnostic confidence (all p > 0.05), compared to conventional images. Regarding RANO 2.0, the volume of non-enhancing non-target lesions (p = 0.963), enhancing target lesions (p = 0.993), and enhancing non-target lesions (p = 0.951) did not differ between reconstruction types. The feasibility of the deep learning-optimized glioma protocol was demonstrated with a 30% reduction in acquisition time on average and an increased in-plane resolution. The evaluated DLR sequences improved subjective image quality and maintained diagnostic accuracy in tumor detection and tumor classification according to RANO 2.0.

Cardiogenic shock following ST-segment elevation myocardial infarction in women: complications and outcomes

Abstract Funding Acknowledgements None. Background Differences in women’s prognosis have been described for both ST-segment elevation myocardial infarction (STEMI) and cardiogenic shock (CS). These might reflect asymmetries in clinical management, but also gender-specific comorbidities and pathologic mechanisms. Purpose We aimed to evaluate the risk of in-hospital complications and mid-term outcomes of women with CS following STEMI. Methods We retrospectively studied STEMI patients treated by primary percutaneous coronary intervention (PCI) from 2008 to 2017 in a tertiary care centre, presenting or evolving in Killip class IV (defined as cardiogenic shock or hypotension and organ hypoperfusion). Clinical and demographic characteristics, as well as complications and outcomes, were collected. Major adverse cardio-cerebrovascular events (MACCE) at 1-year follow-up was a composite of death, cerebrovascular accident, new myocardial infarction in any vessel, or target lesion revascularization. Results Among 1131 patients presenting with STEMI, our study included 117 (10.3%) patients in CS, of which 40 (34.2%) were women. Women were older [71.8(±13.4) vs 64.6(±11.72) years, p=0.002] and less frequently smokers (25.0% vs 50.7%, p=0.008). Prevalence of classic cardiovascular risk factors, namely diabetes (34,1% vs 39.2%, p=0.860), hypertension (71.5% vs 60.8%, p=0.212), and dyslipidaemia (47.5% vs 70.0%, p=0.799), was the same for both groups. Body mass index was also similar [26.6(±5.2) vs 26.1(±3.4) kg/m2, p=0.539]. Women had lower haemoglobin [12.4(±1.9) vs 13.8(±1.9) g/dl, p&amp;lt;0.001] and lower creatinine clearance at admission [52.4(±30.6) vs 67.3(±29.4) ml/min, p=0.017]. Door-to-balloon times [80(59-180) vs 68(48-105) min, p=0.302], total ischemic time [210(120-360) vs 203(120-476) min, p=0.302] and prevalence of anterior STEMI (35.0% vs 50.0%, p=0.123) were not significantly different between sexes. The prevalence of in-hospital complications was generally similar for both sexes (Table 1), except for the risk of advanced atrioventricular (AV) block that was higher in women (32.5% vs 10.7%, p=0.004). Also, haemoglobin nadir was lower in women [10.6(±2.1) vs 11.7(±2.1) g/dl, p=0.023]. In a 1-year follow-up, the occurrence of MACCE was similar for both sexes (60.0% vs 59.7%, log-rank P 0.734) (Figure 1). Conclusion Women with STEMI complicated by CS submitted to PCI had a similar prevalence of in-hospital complications as men. Also, mid-term outcomes, assessed by MACCE at 1 year, did not differ between groups.

Drug-Eluting Balloons in Calcified Coronary Lesions: A Meta-Analysis of Clinical and Angiographic Outcomes.

Background: The usefulness of drug-eluting balloons (DEBs) has not been fully elucidated in calcified coronary lesions (CCLs). This meta-analysis aimed to evaluate the efficacy of DEBs compared to a drug-eluting stent (DES) in this setting. Methods: PubMed, EMBASE and Cochrane were searched through December 2023. The primary endpoint was 12 months major adverse cardiac events (MACE). Secondary endpoints included clinical outcomes and angiographic results after PCI and at a 12-month follow-up. Results: Five studies and a total of 1141 patients with 1176 coronary lesions were included. Overall, the DEB was comparable to DES in MACE (RR = 0.86, 95% CI: 0.62-1.19, p = 0.36), cardiac death (RR = 0.59, 95% CI: 0.23-1.53, p = 0.28), myocardial infarction (RR = 0.89, 95% CI: 0.25-3.24, p = 0.87) and target lesion revascularization (RR = 1.1, 95% CI: 0.68-1.77, p = 0.70). Although the DEB was associated with worse acute angiographic outcomes (acute gain; MD = -0.65, 95% CI: -0.73, -0.56 and minimal lumen diameter; MD = -0.75, 95% CI: -0.89, -0.61), it showed better results at 12 months follow-up (late lumen loss; MD = -0.34, 95% CI: -0.62, -0.07). Conclusions: This meta-analysis showed that the DEB strategy is comparable to DES in the treatment of CCLs in terms of clinical outcomes. Although the DEB strategy had inferior acute angiographic results, it may offer better angiographic results at follow-up.

Sex disparities in mid-term outcomes of ST-segment elevation myocardial infarction across age

Abstract Funding Acknowledgements None. Background Women with ST-segment elevation myocardial infarction (STEMI) have been reported to have higher short-term mortality than men, especially in younger patients. However, data on long-term outcomes did not corroborate this association. Purpose We aimed to evaluate if sex was an independent predictor of major adverse cardio-cerebrovascular events (MACCE) at 1-year follow-up. A sub-analysis across different age subgroups was performed. Methods We retrospectively studied consecutive STEMI patients treated by primary percutaneous coronary intervention (PCI) from January 2008 to December 2017. Cox proportional hazard models were used to identify predictors of MACCE at 1-year follow-up (death, cerebrovascular accident, new myocardial infarction in any vessel, or target lesion revascularization). Patients were divided into four age groups, according to quartiles, for subgroup analysis (≤50, 51-60, 61-70, &amp;gt;71 years). Results Of the 1131 patients included in the study, 291 (25.7%) were women. Women were older [68.2 (±14.2) vs 60.6 (±12.2) years, p&amp;lt;0.001], more often non-smokers (21.5% vs 60.2%, p&amp;lt;0.001), and had a higher prevalence of diabetes (34,8% vs 20.9%, p&amp;lt;0.001) and hypertension (71.6% vs 50.2%, p&amp;lt;0.001). They also had lower haemoglobin [12.8 (±1.6) vs 14.5 (±1.7) g/dl, p&amp;lt;0.001] and lower creatinine clearance at admission [73.8 (±35.3) vs 92.6 (±35.2) ml/min, p&amp;lt;0.001], as well as longer door-to-balloon times [90 (60-166) vs 75(50-120) min, p=0.005]. However, total ischemic time was not significantly different between groups [250(175-480) vs 224(150-440) min, p=0.054]. Overall, women had a higher occurrence of MACCE (22.1% vs 15.4%; log-rank P = 0.008, Figure 1). On multivariate analysis, sex was not found to be an independent predictor of MACCE (HR 1.12; 95% CI, 0.77–1.65; P = 0.547). The risk of unfavourable outcomes was mainly driven by other comorbidities (namely, age, presence of peripheral arterial disease, lower haemoglobin concentration, lower systolic blood pressure on admission, a higher peak CK activity, and the utilization of a femoral approach). When MACCE was stratified by age, sex was not an independent predictor of MACCE in any age group (Figure 2). Conclusion Women with STEMI submitted to PCI had a higher rate of MACCE at 1-year follow-up compared with men, however, sex was not an independent predictor of these events on multivariate analysis, regardless of the age subgroups considered.

The efficacy of atherectomy combined with percutaneous transluminal angioplasty (PTA)/drug-coated balloon (DCB) compared with PTA/DCB for infrapopliteal arterial diseases: A systematic review and meta-analysis.

With the development of endovascular therapies, some studies have indicated a therapeutic potential for infrapopliteal arterial revascularization with atherectomy (AT). This study was designed to perform a meta-analysis to investigate the efficacy of AT combined with percutaneous transluminal angioplasty (PTA) or drug-coated balloon (DCB) compared with PTA or DCB for infrapopliteal arterial diseases. This is a systematic review and meta-analysis. The Pubmed, Web of Science, and Cochrane Library were systematically searched for articles published up to November 2022, reporting using atherectomy devices for infrapopliteal arterial patients. Randomized controlled trials and retrospective studies were included, and clinical characteristic outcomes were extracted and pooled. Then, we analyzed the efficacies of the AT (AT + PTA or DCB) group and the non-AT (DCB or PTA) group for infrapopliteal arterial patients. We identified 6 studies with 1269 patients included in this meta-analysis. The risk ratios (RRs) of primary patency for patients treated with atherectomy group compared to non-atherectomy group at 6months was 1.03 (95% confidence intervals (CIs) 0.86-1.23, p = .74), at 12months was 1.05 (95% CIs 0.84-1.30, p = .66), in the subgroup analysis between AT combined with DCB and DCB alone, the RRs of primary patency was 1.56 (95% CIs 1.02-2.39, p = .04). The RRs of freedom from target lesion revascularization (TLR) at 6 months was 1.04 (95% CIs 0.93-1.17, p = .45), at 12 months was 1.20 (95% CIs 0.83-1.75, p = .33). The RRs of mortality at 6 months was 0.57 (95% CIs 0.29-1.11, p = .10), and at 12 months was 0.79 (95% CI 0.50-1.25, p = .31). The RRs of limb salvage at 12 months was 0.99 (95% CIs 0.92-1.07, p = .87). The standardized mean difference (SMD) of (Ankle-brachial index) ABI at 12months was 0.16 (95% CIs 0.06-0.26, p = .001). According to this systematic review and meta-analysis, no significant advantages were found with the addition of atherectomy to balloon angioplasty in the below-the-knee segment. Only in the analysis of a small subgroup of atherectomy + DCB versus DCB alone was the primary patency rate at six months significantly higher when adding atherectomy. No further significant differences were found related to 12months of primary patency, TLR, limb salvage, and mortality among groups.

Patient-specific temperature distribution prediction in laser interstitial thermal therapy: single-irradiation data-driven method

Laser interstitial thermal therapy (LITT) is popular for treating brain tumours and epilepsy. The strict control of tissue thermal damage extent is crucial for LITT. Temperature prediction is useful for predicting thermal damage extent. Accurately predicting in vivo brain tissue temperature is challenging due to the temperature dependence and the individual variations in tissue properties. Considering these factors is essential for improving the temperature prediction accuracy. Objective. To present a method for predicting patient-specific tissue temperature distribution within a target lesion area in the brain during LITT. Approach. A magnetic resonance temperature imaging (MRTI) data-driven estimation model was constructed and combined with a modified Pennes bioheat transfer equation (PBHE) to predict patient-specific temperature distribution. In the PBHE for temperature prediction, the individual specificity and temperature dependence of thermal tissue properties and blood perfusion, as well as the individual specificity of optical tissue properties were considered. Only MRTI data during one laser irradiation were required in the method. This enables the prediction of patient-specific temperature distribution and the resulting thermal damage region for subsequent ablations. Main results. Patient-specific temperature prediction was evaluated based on clinical data acquired during LITT in the brain, using intraoperative MRTI data as the reference standard. Our method significantly improved the prediction performance of temperature distribution and thermal damage region. The average root mean square error was decreased by 69.54%, the average intraclass correlation coefficient was increased by 37.5%, the average Dice similarity coefficient was increased by 43.14% for thermal damage region prediction. Significance. The proposed method can predict temperature distribution and thermal damage region at an individual patient level during LITT, providing a promising approach to assist in patient-specific treatment planning for LITT in the brain.

One-year Outcomes of Biodegradable Polymer-coated Sirolimus-eluting Coronary Stent in Acute Coronary Syndrome - A Patient-level Pooled Analysis from Two Indian Registries.

This pooled analysis was conducted to assess the clinical safety and performance of the Supra family (Sahajanand Medical Technologies Ltd., Surat, India) of sirolimus-eluting stents (SES) in patients with acute coronary syndromes (ACS) including ST segment elevation myocardial infarction (STEMI) from two real-world all-comers Indian registries at one-year. We evaluated 1824 patients with ACS who underwent percutaneous coronary intervention with the Supra family of SES from two real-world Indian registries (891 patients from T-Flex registry and 933 patients from Tetriflex real-world registry). The primary endpoint was the incidence of target lesion failure (TLF) defined as a composite of cardiac death, target vessel myocardial infarction (TV-MI), and target lesion revascularization (TLR) at one-year follow-up. The safety endpoint was stent thrombosis at one-year follow-up. Among a total of 1824 patients with ACS, 689 (37.8%) patients presented with STEMI. In ACS and STEMI groups, 47.6% and 41.8% patients had multi-vessel disease, respectively. Of 2128 lesions in ACS group, 76.7% lesions were type B2/C and 16.2% lesions were totally occluded. In the STEMI group, out of 784 treated lesions, 76.7% were type B2/C lesions and 21.9% were totally occluded. At one-year follow-up, incidence of TLF was 5.3% (cardiac death: 0.9%, TV-MI: 2.5%, TLR: 1.9%) in patients with ACS and 6.2% (cardiac death: 1.4%, TV-MI: 2.1%, TLR: 2.7%) in patients with STEMI. The one-year rate of definite/probable stent thrombosis were 0.3% and 0.7% in patients with ACS and STEMI, respectively. This patient-level pooled analysis provides evidence for the safe and effective use of the Supra family of SES in complex patient populations such as ACS and even in STEMI with favourable rates of TLF and stent thrombosis at one-year follow-up.

A data augmentation approach that ensures the reliability of foregrounds in medical image segmentation

Medical image segmentation is an important task in medical imaging and diagnosis. Data augmentation can substantially improve the accuracy of medical image segmentation when the dataset has a small amount of medical images. However, the data augmentation methods for medical image are usually based on big models that require extensive search space. Furthermore, excessively complex models often have a heavy burden for the general healthcare organization or researcher. To address this problem, we propose a method of data augmentation that is simple to implement even for the general researcher and simple to transplant across various models. Here we introduce our new methods called KeepMask and KeepMix, which can be simply ported to a variety of models and provide high performance. These methods allow data augmentation without any effect on the target organ or lesion and can also be adapted to multi-class segmentation. KeepMask and KeepMix can not only perturb the background of an existing medical image but also add target organs that are not present to it and generate new images based on the image. In this paper, we performed our methods on both binary class datasets and multi-class datasets and obtained better performance. We conducted numerous experiments showing the predicted segmentation images using our proposed methods obtained more accurate boundaries.

Final 5-year report of BIONYX comparing the thin-composite wire-strut zotarolimus-eluting stent versus ultrathin-strut sirolimus-eluting stent.

The BIONYX randomized trial is the first study to evaluate the Resolute Onyx durable polymer-coated zotarolimus-eluting stent (ZES) in all-comers. Furthermore, it is the first trial to assess safety and efficacy of this stent versus the Orsiro biodegradable-polymer sirolimus-eluting stent (SES) in all-comers, paying particular attention to patients with diabetes. It has previously shown promising results until 3 years of follow-up. We aimed to assess long-term clinical outcome after percutaneous coronary intervention (PCI) with Onyx ZES versus Orsiro SES at 5-year follow-up. The main composite endpoint was target vessel failure (TVF): cardiac death, target vessel myocardial infarction,or target vessel revascularization. Time to primary and secondary endpoints was assessed using Kaplan-Meier methods, applying the log-rank test for between-group comparison. Follow-up was available in 2414/2488 (97.0%) patients. After 5 years, TVF showed no significant difference between Onyx ZES and Orsiro SES (12.7% vs. 13.7%, hazard ratio [HR]0.94, 95%confidence interval [CI][0.75-1.17], plog-rank = 0.55). Landmark analysis between 3- and 5-year follow-up found a lower target lesion revascularization rate for Onyx ZES (1.1% vs. 2.4%, HR 0.47, 95%CI[0.24-0.93], plog-rank = 0.026). A prespecified subgroup analysis showed no significant between-stent difference in clinical outcome among patients with diabetes. After treatment with Onyx ZES, patients aged ≥75 years had significantly lower rates of TVF (13.8% vs. 21.9%, HR 0.60, 95%CI[0.39-0.93], plog-rank = 0.023). The final 5-year analysis of the randomized BIONYX trial showed favorable and similar long-term outcomes of safety and efficacy for Onyx ZES and Orsiro SES in both all-comers and patients with diabetes.

The Transorbital Approach: A Comprehensive Review of Targets, Surgical Techniques, and Multiportal Variants.

The transorbital approach (TOA) is gaining popularity in skull base surgery scenarios. This approach represents a valuable surgical corridor to access various compartments and safely address several intracranial pathologies, both intradurally and extradurally, including tumors of the olfactory groove in the anterior cranial fossa (ACF), cavernous sinus in the middle cranial fossa (MCF), and the cerebellopontine angle in the posterior cranial fossa (PCF). The TOA exists in many variants, both from the point of view of invasiveness and from that of the entry point to the orbit, corresponding to the four orbital quadrants: the superior eyelid crease (SLC), the precaruncular (PC), the lateral retrocanthal (LRC), and the preseptal lower eyelid (PS). Moreover, multiportal variants, consisting of the combination of the transorbital approach with others, exist and are relevant to reach peculiar surgical territories. The significance of the TOA in neurosurgery, coupled with the dearth of thorough studies assessing its various applications and adaptations, underscores the necessity for this research. This extensive review delineates the multitude of target lesions reachable through the transorbital route, categorizing them based on surgical complexity. Furthermore, it provides an overview of the different transorbital variations, both standalone and in conjunction with other techniques. By offering a comprehensive understanding, this study aims to enhance awareness and knowledge regarding the current utility of the transorbital approach in neurosurgery. Additionally, it aims to steer future investigations toward deeper exploration, refinement, and exploration of additional perspectives concerning this surgical method.

One-Year Outcomes of Long Coronary Drug-Eluting Stents (≥40 MM) in Patients With Diffuse Coronary Artery Disease: Findings From a Tertiary Care Hospital in North India.

Background and objective Diffuse coronary artery disease (CAD) is associated with extensive involvement of coronary arteries, necessitating the useof long (≥40 mm) drug-elutingstents (DES) based on the lesion length. However, these long DES can lead to complications such as in-stent restenosis (ISR) and stent thrombosis. This study aimed to assess the safety, efficacy, and one-year clinical outcomes of using long DESin patients with diffuse CAD undergoing PCI at a tertiary care hospital in north India. Methodology Patients with diffuse CAD undergoingPCI with longDESbetween January 2017 and June 2022 were included in the study. Baseline characteristics were recorded, and patients were followed up telephonically or in the outpatient department (OPD) at one, three, six, and 12 months following the PCI. The primary endpointwas the target lesion failure (TLF) rate, with secondary endpoints constituting all-cause mortality, major adverse cardiovascular events (MACE), subacute stent thrombosis, and ISR. Results A total of 200 patients were recruited and followed up for one year. The median age of the patients was 58 years (range: 48.25-63 years), and 82% were men. The most frequently stented artery was the left anterior descending (LAD, 48%), followed by the right coronary artery (RCA, 36%). A total of 388 stents (mean: 1.94 ±0.79) were implanted, including both long and short stents. The mean length and diameter of long stents were 43.64 ±3.58 mm and 3 ±0.37 mm, respectively. At the one-year follow-up, patients undergoing PCI with long DES ≥40 mm had an overall TLF rate of 5%, all-cause mortality of 6% (12 patients), MACE of 6% (12 patients), subacute stent thrombosis of 4% (eight patients), and ISR of 1% (two patients).A large proportion of patients (90%) had an uneventful follow-up of up to a year. At the one-year follow-up, all 10 (5%)patients with a primary outcomehad a smallerstent diameterthan those without a primary outcome (2.5 ±0.25 mm vs. 3.03 ±0.35 mm, p=0.015). Conclusions Our results suggest that using extremely long stents (>40 mm) for diffuse coronary lesions is safe, efficacious, and associated with relatively low event rates. In addition, the stent diameter has a substantial correlation with the primary outcome. Further studies with larger sample sizes as well as longer follow-up periods are required to validate our findings.

Abstract PO2-27-01: TFX06, a next-generation oral CERAN/SERD, shows favorable safety and PK profile, extracranial and intracranial efficacy in patients with ER+/HER2- breast cancer: Preliminary results from a phase 1/2 first-in-human trial

Abstract Aims: TFX06 is an investigational oral complete estrogen receptor (ER) antagonist (CERAN) and selective ER degrader (SERD) (Wu J, et al., 2023 AACR annual meeting). A Phase 1/2, multicenter, open-label dose-escalation and dose-expansion study (CTR20230789) was initiated in China to evaluate TFX06 in previously heavily treated patients with ER+/HER2- locally advanced and/or metastatic breast cancer. The primary objectives were to assess safety and tolerability, recommended Phase 2 dose (RP2D), and pharmacokinetics (PK). Methods: A 3+3 dose-escalation design was implemented. TFX06 tablets were orally administered at 60 mg/100 mg daily for 28 days of treatment cycle until disease progression or intolerant to TFX06. As of the cut-off date (Sept. 15, 2023), the Phase 1 study enrolled five patients with Stage IV diseases with distant metastases. Three were treated with TFX06 at 60 mg, the starting dose and two at the next dose level of 100 mg. Median age of patients were 50 years (39-65) with a ECOG score of 0-1. Two out of five patients carried estrogen receptor 1 (ESR1) mutations (ctDNA). Prior anticancer treatments included one or two lines of endocrine therapies, including fulvestrant, and/or one or two lines of chemotherapies. Clinical responses by investigator according to RECIST v1.1 were performed every two cycles to explore preliminary efficacy. Results: Three patients in 60 mg and one in 100 mg dose cohorts completed dose-limiting toxicity (DLT) observation period. No DLT observed. All treatment related adverse events (TRAEs) were grade 1-2 in severity, including nausea, drowsiness, decreases in WBC and neutrophils, and anemia. Analyses of plasma concentrations of TFX06 in all three patients receiving 60 mg revealed a similar PK profile with small variations in Cmax. The average steady-state Cmax and Cmin of TFX06 were 101 ng/mL and 65 ng/mL, respectively, and the Cmax of TFX06 was approximately 4-fold higher than that of fulvestrant administered intramuscularly at 500 mg in clinic (28 ng/mL). Two patients in the 60 mg cohort were evaluable for response assessment. One patient discontinued due to progressive disease (PD) after two cycles of treatment. This patient experienced a 17.1% decrease in target lesions in the lung; however, new metastases to bone observed. The other patient who carried ESR1 D538G mutation showed a decrease of 91% in ESR1 mutation burden 8 days after treatment, and a decrease of 34.2% in target lesions (partial response, PR), including a substantial shrinkage of 78.6% in the brain lesion (target lesion), as well as complete responses (CR) of non-target lesions in lung after 4 cycles of treatment. This patient remains on the study as of the cut-off date. Conclusions: Based on the preliminary results, oral administration of TFX06 at 60 or 100 mg once daily had favorable safety and PK profiles. TRAEs, such as gastrointestinal toxicities, bradycardia, and visual disturbances were not observed. Pleasingly, TFX06 demonstrated early extracranial and intracranial antitumor activity (PR) in a patient with a brain metastasis. Citation Format: Zhaojian Fu, Zhiye Zhang, Jia Song, Yang Chen, Douglas Fang, Wei Sha, Jian Zhang, Charles Ding. TFX06, a next-generation oral CERAN/SERD, shows favorable safety and PK profile, extracranial and intracranial efficacy in patients with ER+/HER2- breast cancer: Preliminary results from a phase 1/2 first-in-human trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-27-01.

Abstract PO3-20-07: Five years and counting: A case of a 47-year-old female with De Novo Metastatic HER2 positive disease on multiple lines of treatment

Abstract HER2-positive breast cancer refers to a specific subtype of breast cancer characterized by the overexpression or amplification of the human epidermal growth factor receptor 2 (HER2) protein on the surface of cancer cells. The overexpression of HER2 leads to increased signaling pathways that promote cell growth and division, making HER2-positive breast cancer inherently more aggressive compared to other subtypes. The aggressive behaviour of HER2-positive disease may be attributed to its rapid cell growth, high metastatic potential, and increased risk of recurrence. Fortunately, there are targeted therapies that specifically inhibit the HER2 protein. These targeted treatments help to block HER2 signaling, slow down tumor growth, and reduce the risk of recurrence. We report a case 47 year old premenoapausal Filipino female diagnosed with de-novo metastatic HER2-positive breast cancer with liver and lung metastasis in 2018. Advised Pertuzumab Trastuzumab and Taxane therapy but due to financial constraints was amenable only to Trastuzumab and Paclitaxel. During treatment noted symptomatic cardiac decline, hence shifted to Lapatinib &amp; Capecitabine, tolerated well with stable disease for 1 year. Disease then progressed to the contralateral breast, given 6 cycles of Ado Trastuzumab Emtansine with partial response followed by modified radical mastectomy of the right and toilet total mastectomy of the left breast. She was lost to follow up. Her cancer recurred 1 year later as skin lesions on chest wall. She was given 6 cycles of Ado Trastuzumab Emtansine, however still with progression as skin lesions on the chest. Patient was then given 5 cycles of Trastuzumab with Eribulin. Despite treatment, there was progression with symptomatic brain metastasis and further increase in size and number of skin metastasis of the chest wall. Lesions were noted to be ulcerating and bleeding. Hence patient underwent 5 of 5 sessions of Fractionated stereotactic radiation therapy and 10 of 10 sessions of palliative radiotherapy to the chest wall. Patient was then given Pertuzumab &amp; Trastuzumab with note of improvement of chest wall lesions. However, after 7 cycles of treatment, noted progression again as skin metastasis on the chest wall. Hence patient was shifted to Trastuzumab Deruxtecan. At the time of writing, the patient has had a good response with Fam-Trastuzumab Deruxtecan-nxki with partial resolution of her skin metastases on the chest with stable disease of lung and brain target lesions. No bleeding or ulcerations of the lesions and no recurrence of dizziness or imbalance reported. The patient will continue to receive Fam-Trastuzumab Deruxtecan-nxki until disease progression and/or unacceptable toxicity. Here we have a case of patient with extended survival after being fortunate to have received multiple lines of treatment for the disease. In this case we were able to apply the advances of research in HER2-positive breast cancer and see it in the clinical setting. Thus, ultimately translating to extended overall survival for the patient. We see the importance of continuous research on HER2-positive breast cancer disease and how these studies have helped us in overcoming treatment resistance, understanding disease progression, tailoring of therapies to individual patients, optimizing treatment outcomes, developing new therapies, and enhancing the quality of life for patient. Ongoing research continues to explore new therapeutic approaches and strategies to further improve outcomes for individuals with metastatic HER2-positive breast cancer. This is truly an exciting time for cancer research because what used to be a very deadly disease is now becoming something that we are able manage. Citation Format: Sofia Dominique Unson, Rubi Li. Five years and counting: A case of a 47-year-old female with De Novo Metastatic HER2 positive disease on multiple lines of treatment [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-20-07.

Abstract PO3-05-12: Randomized Phase 2 of Bria-IMT, an Allogenic Human Cell Line with Antigen Presenting Activity, in Heavily Pretreated Metastatic Breast Cancer

Abstract Introduction Despite progress in MBC, too many continue to succumb due to treatment resistance or intolerance. SV-BR-1-GM is an allogenic human breast cancer cell line with antigen presenting cell activity designed to overcome the immune-suppressive tumor microenvironment while being acceptable to extensively pretreated contemporary MBC patients. We report interim exploratory analysis of the ongoing RCT of the Bria-IMT regimens. Methods An interim exploratory analysis using preliminary partially available evaluable data of the ongoing prospective, randomized phase 2 (NCT03328026; 2018-present) of Bria-IMT (irradiated SV-BR-1-GM) with a PD-1check point inhibitor (CPI) every 3 weeks (25 patients dosed to date). Both regimens include cyclophosphamide 300 mg/m2 48-72 hours prior to intradermal Bria-IMT (~20 x 106 cells) followed by interferon-alpha at the inoculation sites 2 days later. The control arm used the original sequence with simultaneous start of Bria-IMT and CPI in cycle 1. The experimental arm started CPI in cycle 2 after the 2nd inoculation. Candida skin test was performed before cycle 1 to determine anergy status while delayed-type hypersensitivity skin test (DTH), defined as &amp;gt;5mm erythema &amp; induration, was done at every cycle by intradermal injection of a small test dose of Bria-IMT prior to full dose inoculation. Results Median age: 58 (range 37-81); median prior therapies: 8 lines (range 4-18); 89% were grade 2/3 (n=18); 68% hormone receptor positive; 61% HER2 negative, 33% HER2 low, and 6% HER2 high; 33% triple negative. Overall, 53% of subjects had a clinical benefit as best response by BICR, PI or target lesion measurement. The two treatment arms were similar with a trend showing longer median durations on therapy (mDOT) of 3.7 mo in the experimental delayed CPI arm compared with mDOT = 2.9 for original sequence control arm. 47% of patients were anergic to candida. Among all anergic subjects, the mDOT was 3.5 compared to 2.5 mo for non-anergic patients. However, among anergic subjects, the alternative treatment arm had a lower risk of treatment discontinuation (improved HR) with mDOT of 3.7 compared to the 3.3 mo mDOT of the original treatment. 50% of anergic subjects eventually developed DTH to SV-BR-1-GM. mDOT was 4.0 mo for DTH+ pts vs 3.0 mo for those who did not mount DTH. Median OS was not yet reached; mean OS was higher in non-anergic vs anergic pts. Among those who developed an inoculation site reaction to Bria-IMT, OS was greater than for those who did not. Time on the Bria-IMT regimen exceeded the time on penultimate treatment in 22% of subjects while 33% of subjects with prior CPI use exceeded last therapy. AEs were mild with 28% of subjects (n=7) having &amp;gt; grade 3 events. The most common grade 3+ AE was lipase increase (n=3). One subject with encouraging changes in peripheral blood tumor markers and CTCs completed a PET study using Zr-89 crefmirlimab berdoxam, a zirconium-89 labelled truncated antibody specific to human CD8α (CD8 Immuno-PET) and demonstrated increased uptake in some metastatic lesions and draining lymph nodes. Updated results will be provided at the meeting. Conclusion Sequencing of CPI with Bria-IMT is associated with differential clinical outcome trends but not statistically significant in this interim preliminary exploratory analysis regardless of prior CPI use. Bria-IMT is immunogenic with clinical benefit demonstrated for both treatment schedules among patients with inducible DTH reactions. Patients who develop an immune response to Bria-IMT had an increase in OS compared to those who did not. The nodal localization of CD8+ cells on PET may indicate a systemic activation of CD8 positive lymphoid cells. It also provides support that the Bria-IMT + CPI combination immune-based therapy can result in an increase of CD8+ tumor infiltrating lymphocytes in breast cancer metastatic sites. These preliminary results will be evaluated in the ongoing randomized phase 3 pivotal registrational trial. Citation Format: Carmen Calfa, Chaitali Nangia, Minal Barve, John Knecht, Jarrod Holmes, Kendrith Roland, Ralph Boccia, Frances Valdes-Albini, Zach Gostout, Mingjin Chang, William Williams, Charles Wiseman, Bonnie Guerin, Shaker Dakhil, Giuseppe Del Priore, Saranya Chumsri. Randomized Phase 2 of Bria-IMT, an Allogenic Human Cell Line with Antigen Presenting Activity, in Heavily Pretreated Metastatic Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-05-12.

Abstract PS08-06: A Phase Ib/II Study to Assess the Safety and Efficacy of PM8002 (Anti-PD-L1 x VEGF-A Bispecific Antibody) in Combination with Nab-Paclitaxel for First Line Treatment of Locally Advanced or Metastatic Triple-Negative Breast Cancer

Abstract Background: PD-L1 and VEGF play important roles in immune evasion and pro-tumor angiogenesis promoting cancer growth and metastasis. PM8002 is a bispecific antibody targeting PD-L1 and VEGF-A for treating cancer. Here, we present results from a Phase Ib/II study of PM8002 in combination with nab-paclitaxel in patients with locally-advanced or metastatic triple-negative breast cancer (TNBC). Methods: 42 patients with locally-advanced or metastatic TNBC (without prior systemic treatment) were enrolled in this Phase Ib/II study to test the safety and efficacy of PM8002 in combination with nab-paclitaxel. The first 6 patients were enrolled during Phase Ib with safety as the primary endpoint, and the remaining patients were enrolled during Phase II with objective response rate (ORR) as the primary endpoint. Each treatment cycle lasts 28 days. All patients received PM8002 at 20 mg/kg (Q2W) and nab-paclitaxel at 100 mg/m2 on the 1st, 8th, and 15th days of each cycle until unacceptable toxicity or disease progression were observed. Tumor responses were evaluated every 8 weeks according to RECIST 1.1. Safety was evaluated according to CTCAE 5.0. Nab-paclitaxel dose was reduced according to toxicity, while PM8002 dose was kept consistent according to body weight. PD-L1 expression in tumors was tested, and subgroup analysis of ORR data stratified by PD-L1 expression was also included. Results: As of June 30, 2023, 42 patients were treated and evaluated at least once for treatment efficacy. The median duration of drug exposure was 4.6 months (min, max: 2.0, 7.6). The best overall ORR was 76.2% (32/42), including 1 complete response (CR) and 31 partial responses (PRs) with 29 objective responses occurring at the patient's first evaluation. The confirmed ORR was 57.2% (24/42) and the overall disease control rate (DCR) was 95.2% (40/42). The median time to response (TTR) was 1.9 months (95% CI:1.8~2.0) and the median best percentage change from baseline for target lesions was -47.2% (Q1, Q3: -56.9%, -33.5%). Among 13 patients with PD-L1 combined positive scores (CPS) &amp;lt; 1, the best ORR and DCR were 69.2% (9/13) and 100.0% (13/13), respectively. Among 25 patients with PD-L1 CPS ≥1, the best ORR and DCR were 80.0% (20/25) and 96.0% (24/25), respectively. Among 9 patients with PD-L1 CPS ≥10, the best ORR and DCR were both 100.0% (9/9). At the cut-off date of data analysis, 38 patients were still on treatment with a median progression-free survival (mPFS) of 7.4 months (95% CI: 7.4~NA); 38 patients were censored due to no disease progression or death. The incidence of treatment-related adverse events (TRAEs) was 95.2%, of which 26.2% were Grade 3 or 4; no Grade 5 TRAEs were observed. The incidence of drug-related TRAEs related to PM8002 was 92.9%, of which 23.8% were Grade 3 or 4. The incidence of drug-related TRAEs related to nab-paclitaxel was 95.2%, of which 26.2% were Grade 3 or 4. 1 patient (2.4%) reduced nab-paclitaxel dose due to diarrhea. 1 patient (2.4%) discontinued PM8002 and nab-paclitaxel treatment due to diarrhea. The most common TRAEs related to PM8002 and nab-paclitaxel included neutropenia (69.0%), leukocytopenia (59.5%), anemia (52.4%) and proteinuria (26.2%). The incidence of immune-related adverse events (irAEs) was 11.9%, which included hyperthyroidism, hypothyroidism, and rash. No ≥ Grade 3 irAEs were observed. AEs related to targeting VEGF were also analyzed, including hypertension 19.0% (4.8% at Grade 1, 11.9% at Grade 2, and 2.4% at Grade 3) and proteinuria 26.2% (9.5% at Grade 1, and 16.7% at Grade 2). Conclusions: Rapid, deep, and durable tumor responses were observed for the combination of PM8002 and nab-paclitaxel in patients with first line TNBC. PM8002 did not enhance toxicity that is typically observed for nab-paclitaxel. This Phase II study is still ongoing with plans for entering late-stage clinical development for solid tumors. Citation Format: Jiong Wu, Jian Zhang, Zhongsheng Tong, Qingyuan Zhang, Yong-Sheng Wang, Qiao Cheng, Xin Chen, Zhihua Li, Yongmei Yin. A Phase Ib/II Study to Assess the Safety and Efficacy of PM8002 (Anti-PD-L1 x VEGF-A Bispecific Antibody) in Combination with Nab-Paclitaxel for First Line Treatment of Locally Advanced or Metastatic Triple-Negative Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS08-06.

Abstract PO4-18-12: MELODY: A prospective non-interventional multicenter cohort study to evaluate different imaging-guided methods for localization of malignant breast lesions (EUBREAST-4/iBRA-NET, NCT 05559411)

Abstract Background: In the last decades, the proportion of breast cancer patients receiving breast-conserving surgery has increased, reaching 70-80% in developed countries. In case of non-palpable lesions, surgical excision requires some form of breast localization. While wire-guided localization has long been considered gold standard, it carries several limitations, including logistical difficulties, the potential for displacement and patient discomfort, and re-excision rates reaching 21%. Other techniques (radioactive seed or radio-occult lesion localization, intraoperative ultrasound, magnetic, radiofrequency and radar localization) have been developed with the aim of overcoming these disadvantages. However, comparative data on the rates of successful lesion removal, negative margins and re-operations are limited. In the majority of studies, the patient’s perspective with regard to discomfort and pain level has not been evaluated. The aim of MELODY (MEthods for LOcalization of Different types of breast lesions) is to evaluate different imaging-guided localization methods with regard to oncological safety, patient-reported outcomes, and surgeon and radiologist satisfaction. Methods: The EUBREAST and the iBRA-NET have initiated the MELODY study to assess breast localization techniques and devices from several perspectives (NCT05559411, http://melody.eubreast.com). MELODY is a prospective intergroup cohort study which enrolls female and male pts. requiring breast-conserving surgery and imaging-guided localization for invasive breast cancer or DCIS. Multiple or bilateral lesions and neoadjuvant chemotherapy are allowed. Primary outcomes are: 1) Intended target lesion and/or marker removal, independent of margin status on final histopathology, and 2) Negative resection margin rates at first surgery. Secondary outcomes are, among others: rates of second surgery and secondary mastectomy, Resection Ratio (defined as actual resection volume divided by the calculated optimum specimen volume), duration of surgery, marker dislocation rates, rates of marker placement or localization failure, comparison of patient-reported outcomes, rates of “lost markers” and diagnostician/radiologist’s and surgeon’s satisfaction as well as the health economic evaluation of the different techniques. Target accrual: 7,416 patients. Enrollment started in January 2023. The study will be conducted in 30 countries and is supported by the Oncoplastic Breast Consortium (OPBC), AWOgyn, AGO-B and SENATURK. Financial support will be provided by Endomag, Merit Medical, Sirius Medical and Hologic. Citation Format: Maggie Banys-Paluchowski, Thorsten Kühn, Yazan Masannat, Nina Ditsch, Antonio Esgueva, Neslihan Cabıoğlu, Dawid Murawa, Nuh Zafer Canturk, Isabel Rubio, Jana de Boniface, Andreas Karakatsanis, Rajiv Dave, Shelley Potter, Ashutosh Kothari, Oreste Davide Gentilini, Walter Weber, Natalia Krawczyk, Steffi Hartmann, Guldeniz Karadeniz Cakmak, Markus Hahn, Michael P. Lux, Tove Tvedskov, Lina Pankratjevaite, Michalis Kontos, Florentia Peintinger, Aoife Lowery, Marjolein Smidt, Lia Rebaza, Maria Vasconcelos, Bahadir M. Gulluoglu, Bilge Aktas Sezen, Rosa Di Micco, Sarah Nietz, Francois Malherbe, Maria Luisa Gasparri, Séverine Alran, SVS Deo, Mah Muneer Khan, James Harvey. MELODY: A prospective non-interventional multicenter cohort study to evaluate different imaging-guided methods for localization of malignant breast lesions (EUBREAST-4/iBRA-NET, NCT 05559411) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-18-12.

Abstract PO1-04-01: Phase 1 dose escalation study of ARX788, a next-generation anti-HER2 antibody drug conjugate, in heavily pretreated breast cancer patients

Abstract Introduction: ARX788 is a next-generation anti-HER2 antibody-drug conjugate (ADC) conjugated to amberstatin269 (AS269), a potent cytotoxic tubulin inhibitor. ARX788 is highly stable with nearly identical PK profiles for the total ADC and the total antibody due to proprietary site-specific oxime conjugation chemistry. The stability of ARX788 results in limited systemic toxicity and increased targeted delivery of payload to tumor cells. Clinical benefit of ARX788 has been observed in patients (pts) with HER2-positive (HER2-pos) breast cancer (BC) in multiple clinical trials and recently in a randomized, controlled, phase 3 registrational trial conducted in China. Methods: ARX788-1711 (NCT03255070)was a phase 1 dose-escalation study of ARX788 monotherapy in pts with advanced solid tumors with HER2 expression. There was no limit to the number of prior therapies. An objective of the trial was investigating the safety and tolerability of ARX788 in pts with BC. Results: Between August 2020 and June 2023, 42 pts with HER2-pos and HER2-low BC with a median of 6 prior lines of therapy received intravenous ARX788 at either 1.5, 1.6, or 1.7 mg/kg every 21 days (Q3W) or every 28 days (Q4W). Treatment regimens were combined for these analyses. ARX788 was generally well tolerated. Most adverse events (AEs) were grade (Gr) 1 or 2, the most common being ocular, alopecia, nausea, and fatigue. Gr3 treatment-related AEs (TRAEs) occurred in 23.8% of pts and included nausea, ocular, AST and ALP increase (4.8% each); one pt (2.4%) had Gr3 pneumonitis/interstitial lung disease. A Gr3 ocular SAE occurred 48 days after the pt’s last study dose and was resolving 9 days after onset. There were no Gr4 or Gr5 events. Treatment discontinuation due to drug-related AEs occurred in 7.1% of pts. Overall response rate (ORR) per RECIST v1.1 was analyzed in groups by HER2-low or HER2-pos tumor status. In pts with HER2-pos BC (n=11) the ORR was 54.5% (4 confirmed, 2 unconfirmed); in pts with HER2-low BC (n=30) the ORR was 23.3% (5 confirmed, 2 unconfirmed). The disease control rate (confirmed complete or partial response + stable disease) was 81.8% and 76.7%, for HER2-pos and HER2-low BC, respectively. Six of 9 pts with confirmed responses had a duration of response greater than 5 months. Six of eight pts with prior trastuzumab deruxtecan (T-DXd) exposure also had prior trastuzumab emtansine (T-DM1). Two pts with prior T-DM1 and T-DXd had significant target lesion reductions of 55% and 32%; these were a HER2-low pt with 6 prior cancer therapy regimens and a HER2-pos pt with 9 prior cancer therapy regimens, respectively. Both pts came off treatment before response confirmation. As of the data cut-off (19 Jun 2023), 4 of 9 confirmed responders remain on treatment and continue to experience clinical benefit including one pt with prior T-DM1 exposure with a durable response of 15.8 months. Importantly, significant target lesion reductions were observed in heavily pretreated pts who also received prior T-DXd and T-DM1. Discussion: Based on the promising safety and antitumor activity of ARX788 in this heavily pretreated pt population, a phase 2 study is open (NCT04829604) and enrolling pts with HER2-pos BC who have been previously treated with T-DXd. Citation Format: Sophia Frentzas, Haesong Park, George Budd, Vinod Ganju, Catherine Shannon, Sara Hurvitz, Katharine Cuff, Peter Lau, Richard Eek, Joyce O'Shaughnessy, Fran Boyle, Sandra Aung, Colin Hessel, Janice Lu. Phase 1 dose escalation study of ARX788, a next-generation anti-HER2 antibody drug conjugate, in heavily pretreated breast cancer patients [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-04-01.