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Machine learning for prediction of postoperative pulmonary embolism after lung cancer surgery using routine perioperative variables.
e20522 Background: Postoperative pulmonary embolism (PE) remains a potentially fatal complication after lung cancer (LC) resection. Widely used VTE risk tools (e.g., Caprini) are time-consuming and not optimized for thoracic surgical populations. We developed PEPred, a machine learning (ML)–informed model based on 8 routinely captured perioperative variables, to enable efficient and low-cost PE risk stratification. Methods: A retrospective cohort of 9,726 LC resections without chemoprophylaxis was used, including 55 PE cases. An XGBoost model selected 8 key surgical features, such as surgical approach (open vs. VATS), extent of resection, and tumor location. These features were incorporated into PEPred, a logistic regression model with L1 regularization and pairwise feature interactions. Its performance was evaluated using 5-fold cross-validation, with metrics including ROC-AUC, PR-AUC, accuracy, precision, recall, and F1 score. Decision curve analysis assessed clinical utility. Results: The PEPred model achieved a ROC-AUC of 0.853 (95% CI: 0.771–0.921) and a PR-AUC of 0.582 (95% CI: 0.447–0.711), demonstrating robust discriminative ability. Key predictive features included the extent of resection (e.g., more extensive resections increased risk), surgical approach (open vs. VATS), and tumor location (e.g., upper lobe involvement). Pairwise feature interactions, such as the combination of surgical approach and extent of resection, further enhanced model performance, with some interactions showing odds ratios as high as 6205.757 for increased PE risk. Decision curve analysis confirmed the its clinical utility, with PEPred providing a positive net benefit across threshold probabilities ranging from 0.5% to 10%. At a 1.0% threshold, the net benefit was 0.0037, outperforming both “treat-all” and “treat-none” strategies. The model’s accuracy was 0.997, precision 0.786, recall 0.600, and F1 score 0.680, highlighting its ability to reliably identify high-risk cases. Feature importance analysis revealed that the extent of resection (32.61%), surgical approach (20.74%), and lobe involvement (15.34%) were the most significant contributors to model performance. Overfitting was minimal, with training and validation ROC-AUC and PR-AUC curves showing consistent convergence. The model’s simplicity, relying solely on surgical data, makes it highly feasible for integration into clinical workflows without requiring additional laboratory tests or complex data inputs. Conclusions: PEPred is a novel ML-based tool for predicting postoperative PE in LC surgery, using only 8 routine surgical parameters. Its strong performance and simplicity make it a promising tool for improving perioperative risk stratification and guiding targeted prophylaxis. Future efforts will focus on clinical validation and real-world evidence to assess its impact on patient outcomes.
Real-world conditional survival analysis of blastic plasmacytoid dendritic cell neoplasm.
e23332 Background: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematologic cancer that often involves the skin, lymph nodes, and bone marrow with poor overall survival (OS). However, conditional survival (CS) is not well studied. Methods: This retrospective cohort study utilized 2 independent databases: the TriNetX database, a global electronic health records database, as well as the Surveillance, Epidemiology, and End Results (SEER) program. The TriNetX cohort included 110 adult patients with BPDCN after propensity-score matching who received either chemotherapy or tagraxofusp from 2000-2025. SEER data included 637 histologically confirmed BPDCN cases from 2001-2022, stratified by primary site (skin, lymph nodes, hematopoietic system). OS was determined by Kaplan-Meier analysis, and CS was calculated as survival in subsequent years conditional on prior survival. Results: After matching, mean age in the TriNetX cohort was 68.9 years, and most patients were male (82–86%). OS was higher with chemotherapy vs tagraxofusp, though not statistically significant. Three-year CS given 1-year survival was 59.2% for tagraxofusp and 62.0% for chemotherapy. A total of 637 patients diagnosed with BPDCN in the SEER 22 database were included, with the most common primary sites being lymph nodes (n = 312), the hematopoietic system (n = 163), and the skin (n = 92). OS declined steeply during the first 2 years after diagnosis with 2 year OS of 62.6% (95% CI: 58.7 – 66.6) followed by a slower decline to a 5 year OS of 54.0% (95% CI: 50.1 – 58.0). CS at 5-years improved with increasing time from diagnosis, both overall and among each primary site (see Table). Conclusions: Survival patterns in TriNetX suggest chemotherapy may show modestly improved OS compared to those treated with tagraxofusp, although sample size limits inference. Improvements were minimized when comparing CS. Across all sites in the SEER 22 analysis, BPDCN showed a pattern of high early mortality followed by markedly improved CS, suggesting that patients who survive the first 2-3 years may enter a lower risk phase with significantly better long-term prognosis. Subgroup differences were seen, with lymph node primary disease demonstrating higher survival probabilities. Our results highlight that patients with BPDCN who survive the initial high-risk period have a notably improved long-term outlook, which offers important prognostic evidence for counseling and treatment planning. 5-year conditional survival by years survived, SEER 22 (2001-2022), % (95% CI). Years Survived Overall (n = 637) Lymph Nodes (n = 312) Hematopoietic System (n = 163) Skin (n = 92) 0 54.0 (50.1 – 58.0) 60.7 (55.2 – 65.5) 44.7 (36.3 – 51.0) 34.7 (23.9 – 42.2) 1 72.8 (68.5 – 77.0) 77.3 (72.0 – 82.0) 67.4 (57.0 – 74.7) 49 (35.3 – 58.0) 2 86.3 (82.8 – 90.1) 87.9 (83.4 – 92.2) 83.2 (73.6 – 90.1) 68.5 (52.8 – 78.5) 3 92.4 (89.5 – 95.9) 95.7 (92.8 – 99.2) 87.2 (78.2 – 93.8) 72.0 (56.3 – 82.0)
Assessing the efficacy of cognitive behavioral therapy on anxiety, depression, and distress in people with cancer.
12100 Background: Patients with cancer frequently experience psychological impairments, including anxiety, depression, and emotional distress, which may significantly affect quality of life and overall well-being. Third-generation cognitive-behavioral interventions such as Mindfulness-Based Cognitive Therapy-Cancer (MBCT-Ca), Acceptance and Commitment Therapy (ACT) and Compassion Focused Therapy (CFT) have shown potential benefits in reducing psychological burden, although evidence of their efficacy remains limited. This study aimed to evaluate the efficacy of a structured third-generation cognitive behavioral therapy (CBT) intervention in reducing psychological symptoms in patients (pts) with cancer undergoing active cancer treatment. Methods: A third-generation CBT intervention was delivered twice a month. The eight individual 45-minute sessions included psychoeducation, behavioral activation, relaxation and breathing techniques, present-moment awareness, self-compassion, problem-solving, and assertiveness training. Psychological outcomes were assessed using the Hospital Anxiety and Depression Scale (HADS) and Distress Thermometer (DT) at baseline (T0) and post- psychological intervention (T1). Descriptive statistics, Student t-test and Chi-square test were performed. Results: Overall 341 pts were recruited. The mean age was 65.8 years ( SD = 11.80); 60% (n = 204) were women. Most patients were married or partnered 82% (n = 279). Regarding education level, 65% (n = 221) had higher education, 29% (n = 100) secondary education, and 6% (n = 20) primary education.. At baseline psychological assessment, 4.4% of patients (n = 15) had early-stage disease (stage I–II), 50.7% (n = 173) had locally advanced disease (stage III), and 44.9% (n = 153) had advanced-stage disease (stage IV). The most represented cancer sites were gastrointestinal cancer 55.7% (n = 190), followed by lung 11.7% (n = 41) and breast cancer 10.6% (n = 36). Chemotherapy was the most frequently administrated treatment 74% (n = 254), followed by targeted therapy 10% (n = 35) and immunotherapy 10% (n = 34). At T0, clinically significant levels of anxiety, depression, and distress were reported in 33.2%, 31.3%, and 86,9% of patients, respectively. A total of 313 patients completed the intervention (dropout rate 8.2%, mainly due to disease progression), resulting in an adherence rate of 91.8%. At three-months follow up (T1), significant reductions in clinically relevant symptoms were observed for anxiety (-24.6%, p < 0.001), depression (-24.0%, p < 0.001), and distress (-30.0%, p < 0.001). Conclusions: These findings support the routine use of validated psychological screening tools in oncology and highlight the clinical value of structured CBT-based psycho-oncological interventions delivered by trained professionals to improve psychological well-being in patients with cancer.
Benchmarking the KEYNOTE-811 standard of care using AI-reconstructed external control arms in advanced gastric cancer.
4021 Background: Randomized controlled trials in rare cancers and biomarker-enriched populations face significant recruitment burdens. External control arms (ECA) derived from historical Individual Patient Data (IPD) can mitigate these challenges, yet cross-trial heterogeneity often confounds comparisons. This study evaluates the feasibility of an AI-powered pipeline to reconstruct IPD from historical HER2+ advanced gastroesophageal adenocarcinoma trials and validates the cohort against a modern standard-of-care benchmark (KEYNOTE-811). Methods: An LLM-computer vision pipeline digitized KM curves from 10 historical trials (2011–2022) and the KEYNOTE-811 control arm (2023). IPD was reconstructed using a modified Guyot algorithm with risk-table guidance and least-squares optimization. Accuracy was validated against published HR and median survival. A propensity score matched (PSM) analysis (1:1 nearest-neighbor) compared the KEYNOTE-811 control arm (n=348) to historical controls (n=395). Sensitivity analyses addressed geographic imbalance (34% vs. 95% Asian) and early-period confounding via 3- and 6-month landmarking. Results: Technical validation demonstrated high fidelity: median OS concordance was 100%, with a reconstructed-to-published OS HR delta of only 0.01 (0.85 vs 0.84). The initial PSM suggested significantly worse outcomes for the KEYNOTE-811 control (OS HR 1.69, p<0.0001). However, this discrepancy was primarily driven by regional heterogeneity. After region-specific matching, OS HR stabilized at 1.13 (p=0.40). A 6-month landmark analysis further resolved early-period bias, achieving statistical equivalence for OS (HR 1.26, p=0.057) and PFS (HR 0.97, p=0.84). Residual imbalances in ECOG (SMD 0.25) and primary site (SMD 0.32) persisted but did not negate the trend toward equivalence. Conclusions: AI-powered IPD reconstruction achieves high fidelity to original trial data. While naive pooled ECAs may display era-specific survival artifacts, rigorous causal inference frameworks can resolve cross-trial heterogeneity. This study confirms that AI-reconstructed ECAs are viable tools for benchmarking novel therapies when paired with robust methodological guardrails for regional and baseline covariate alignment. PSM sensitivity analyses with covariate balance. Analysis OS HR (95% CI) PFS HR (95% CI) Pairs Key Imbalances (SMD >0.2) Main PSM 1.69 (1.37–2.08)*** 1.30 (1.05–1.61)* 217 Age (0.86), ECOG (0.42), Primary site (0.49), Region (0.65) + Geographic matching 1.13 (0.85–1.50) 0.87 (0.66–1.16) 119 ECOG (0.25), Primary site (0.32) + 3-month landmark 1.16 (0.93–1.45) 1.17 (0.93–1.48) 194/177 ECOG (0.25), Primary site (0.32) + 6-month landmark 1.26 (0.99–1.60) 0.97 (0.73–1.30) 174/115 ECOG (0.25), Primary site (0.32) ***p<0.001, *p<0.05; SMD = standardized mean difference; All other covariates SMD <0.2.
Comparative efficacy and safety of ROS1 tyrosine kinase inhibitors for advanced ROS1-positive non–small cell lung cancer: A systematic review and network meta-analysis.
e20733 Background: ROS1 rearrangements occur in approximately 1–2% of non–small cell lung cancers and define a clinically distinct subset responsive to tyrosine kinase inhibitors. Multiple ROS1 inhibitors are available; the recent 2025 approval of taletrectinib expands treatment options beyond crizotinib, repotrectinib, and entrectinib, yet the absence of head-to-head trials complicates selection. Methods: Databases and trial registries were systematically searched, followed by Bayesian network meta-analysis using R NetMeta and risk of bias assessment with RoB 2.0. Results: Ten studies comprising 1,246 patients with advanced ROS1-positive NSCLC were included. Patient numbers by treatment were crizotinib (n = 275), entrectinib (n = 247), repotrectinib (n = 127), and taletrectinib (n = 597). For overall response rate, taletrectinib showed superior efficacy (RR 1.24, 95% CI 1.14–1.35; SUCRA 92%), followed by repotrectinib (RR 1.10, 95% CI 1.01–1.20; SUCRA 71%), while entrectinib was comparable to crizotinib (SUCRA 41%). For progression-free survival, taletrectinib ranked highest (HR 0.45, 95% CI 0.32–0.63; SUCRA 95%), followed by repotrectinib (HR 0.54, 95% CI 0.40–0.74; SUCRA 82%), with entrectinib showing no benefit (SUCRA 29%). Regarding safety, taletrectinib demonstrated the most favorable profile, with a significantly lower risk of treatment discontinuation due to adverse events (HR 0.70, 95% CI 0.50–0.98; SUCRA 90%) and reduced neurologic toxicity. In contrast, repotrectinib showed a comparable risk of treatment discontinuation (HR 1.10, 95% CI 0.85–1.40; SUCRA 48%), alongside a higher incidence of neurologic adverse events, while entrectinib was associated with an increased risk of treatment discontinuation (HR 1.25, 95% CI 1.00–1.56; SUCRA 22%) and greater overall adverse-event burden. Conclusions: Taletrectinib demonstrated the most favorable overall efficacy and safety profile, repotrectinib showed strong efficacy with higher toxicity, and entrectinib provided comparable efficacy with less favorable safety; overall risk of bias across included studies was low.
A multicenter analysis of CAR T-cell toxicities, target antigens, and dosing in solid and hematological malignancies.
e14513 Background: Chimeric antigen receptor T-cell (CAR-T) therapy has showed remarkable efficacy in haematological malignancies and is increasingly investigated in solid tumours. Comprehensive safety data from real world study remain sparse. Understanding toxicity patterns across tumour types is essential for optimising patient selection and management protocols in diverse clinical environments. Methods: We retrospectively analysed the characteristics, treatment parameters, and safety outcomes of consecutive adult patients receiving CAR-T therapy across our institutions between Sept 2024 and Jan 2025, with institutional ethics approval. Data on patient demographics, CAR-T target antigens, dosing, and adverse events were collected. Toxicities were graded per CTCAE v5.0 and ASTCT criteria for CRS/ICANS. Descriptive statistics were used to summarise the findings. Results: 14 patients received CAR-T infusions: 8 solid tumours (Gastric Carcinoma (Ca) n = 2, Parotid Ca n = 1, Rectal Adenocarcinoma n = 1,Pancreatic Ca n = 1, ovarian Ca n = 1, Glioblastoma n = 1, Ewing Sarcoma n = 1)) and 6 haematological malignancies (DLBCL n = 3, B-ALL n = 1, Multiple Myeloma n = 2). Median age was 47.5 years (range 17-68), with 71% males and 64% ECOG PS 1. Five patients (35.7%) had significant comorbidities including hypertension, diabetes mellitus, hypertriglyceridemia, ulcerative colitis, and mixed hyperlipidemia. CAR-T antigen targets were HER2 (n = 2), BCMA (n = 2), B7H3 (n = 3), claudin18.2 (n = 2), mesothelin (n = 1), and CD19 (n = 4), with median dose of 8.2 million cells/kg (range 2.75-10 million/kg). While most infusions were intravenous, one patient with glioblastoma received intracranial delivery via an Ommaya reservoir. Grade 2-3 cytokine release syndrome (CRS) was observed in five patients (35.7%), occurring more frequently in haematological (50%) than solid tumour (25%) cohorts. These events, associated with CD19, B7H3, and Claudin 18.2 targets, were resolved using standard management with tocilizumab and corticosteroids. Immune effector cell-associated neurotoxicity syndrome (ICANS) was limited to a single grade 1 event (7.1%) in the patient receiving intracranial CAR-T. Haematologic toxicities were frequent but manageable, including predominantly grade 1-3 anaemia (50%), leucopenia (50%), and thrombocytopenia (42.9%). One instance of capillary leak syndrome and three cases of transient grade 1-3 hepatotoxicity were noted. Importantly, no nephrotoxicity, endocrine dysfunction, or treatment-related deaths occurred. Conclusions: This early Indian experience demonstrates that CAR-T therapy exhibits manageable toxicity across both solid and haematologicalmalignancies, with CRS rates comparable to international data in haematological tumours but lower in solid tumours. These real world data support expansion of CAR-T with appropriate safety monitoring in oncology setting.
Dose-dense weekly versus standard three-weekly paclitaxel in combination with carboplatin for resectable stage II-IV epithelial ovarian carcinoma: A retrospective cohort study.
5568 Background: Dose-dense weekly paclitaxel combined with carboplatin has demonstrated variable efficacy in first-line treatment of resectable epithelial ovarian cancer across different populations. While Japanese and selected real-world studies suggest improved outcomes, large Western trials have failed to confirm a survival advantage. Data from South Asian populations remains limited. This study compared progression-free survival (PFS), overall survival (OS), and toxicity profiles of dose-dense versus standard three-weekly paclitaxel plus carboplatin in a real-world, resource-constrained setting. Methods: This single-center retrospective cohort study included women aged ≥20 years with resectable, FIGO stage II–IV epithelial ovarian, fallopian tube, or primary peritoneal carcinoma treated between January 2015 and December 2018. Patients received first-line carboplatin at an AUC of 5 (Area Under Curve 5) with either dose-dense weekly paclitaxel (80 mg/m² on days 1, 8, and 15) or standard three-weekly paclitaxel (175 mg/m²). Kaplan–Meier methods were used to estimate PFS and OS, and comparisons were performed using the log-rank test. Cox proportional hazards models were applied for univariate and multivariate analyses. Results: Seventy-two patients were included, 36 in each arm. The majority presented with stage III disease (63.9% in the dose-dense arm vs. 52.8% in the standard arm). High-grade serous carcinoma was the predominant histology in both groups (83% vs. 75%). The distribution of primary versus interval debulking surgery and rates of residual disease were similar between the two arms. The dose-dense regimen was associated with significantly improved PFS compared with the standard schedule (mean PFS 25 vs. 18 months; 95% CI: 23.1-28.4; log-rank p = 0.01); median PFS was 32 months in the dose-dense arm, whereas it could not be estimated in the standard arm. OS favoured the dose-dense group (mean OS of 56 vs. 50 months), although this difference was not statistically significant (p = 0.27). In the multivariate analysis of the dose-dense cohort, elevated baseline Ca-125 (HR = 6.80; 95% CI: 1.38–34.20; p = 0.01) and cytoreduction type (HR = 13.30; 95% CI: 1.90–90.20; p = 0.008) were independent predictors of PFS but not for OS. Rates of grade ≥3 treatment-related adverse events were comparable between arms, while sensory neuropathy occurred more frequently with dose-dense therapy (39% vs. 28%). Conclusions: This real-world analysis supports the use of dose-dense weekly paclitaxel combined with carboplatin for improved PFS, findings consistent with some regional studies. While OS data showed a non-significant trend favouring the dose-dense regimen with some risk of neuropathy, they highlight the need for larger prospective regional studies to better define patient populations most likely to benefit.
A phase 3 study of olverembatinib (HQP1351) in patients with chronic-phase chronic myeloid leukemia: POLARIS-2 trial in progress.
TPS6608 Background: Chronic myeloid leukemia (CML) is driven by the BCR::ABL1 oncogenic fusion protein. Although tyrosine kinase inhibitors (TKIs) have transformed CML management, normalizing life expectancy for many patients, treatment resistance and intolerance remain significant clinical challenges. Olverembatinib is a novel third-generation BCR::ABL1 TKI with activity against wild-type BCR::ABL1, multiple resistance-conferring mutations including T315I, and challenging compound mutations. The POLARIS-2 study evaluates olverembatinib efficacy and safety in patients with relapsed/refractory chronic phase CML (CP-CML). Methods: This global, multicenter, open-label, randomized phase 3 registrational study includes two patient cohorts based on T315I mutation status (ClinicalTrials.gov identifier: NCT06423911; internal study number: HQP1351CG301). Part A randomly allocates patients with CP-CML previously treated with at least two approved TKIs to receive either olverembatinib or bosutinib (2:1 randomization). The primary endpoint is major molecular response (MMR) rate at 24 weeks. Part B is a single-arm study evaluating olverembatinib in patients with CP-CML with the T315I mutation at screening, and the primary endpoint is MMR rate by 24 weeks. Key inclusion criteria include age ≥18 years, diagnosis of CP-CML, Eastern Cooperative Oncology Group performance status ≤ 2, and adequate organ function. Key exclusion criteria include prior hypersensitivity to study drugs and pregnancy or lactation. Patients in Part A receiving bosutinib who do not achieve MMR by 24 weeks are eligible to cross over to olverembatinib. The study hypothesis posits that olverembatinib will demonstrate superior MMR compared to bosutinib in Part A and provide clinical benefit in T315I-positive patients in Part B. Clinical trial information: NCT06423911 .
Phase 3 study to assess the safety and efficacy of <sup>177</sup> Lu-girentuximab in advanced, relapsed, or recurrent ccRCC (LUTEON).
TPS4631 Background: A high unmet need remains for treatments that provide durable disease control while preserving quality of life in patients with advanced clear-cell renal cell carcinoma (ccRCC). Girentuximab is a monoclonal antibody targeting carbonic anhydrase IX (CAIX), which is expressed on >95% of ccRCC cells with limited expression in healthy tissues. Radiolabeling girentuximab with β emitting luteium-177 ( 177 Lu-girentuximab) enables targeted delivery to CAIX-expressing tumor cells. Phase 1 - 2 data of 177 Lu-girentuximab in patients with metastatic ccRCC suggest favorable safety, tolerability, and efficacy profile. 1,2,3 LUTEON is a Phase 3 study designed to assess safety and efficacy of 177 Lu-girentuximab in patients with advanced, relapsed or recurrent ccRCC. Methods: LUTEON is a 2-part, randomized, open-label, multicenter study to determine the optimal activity and schedule of 177 Lu-girentuximab (Part 1), and evaluate efficacy and safety of 177 Lu-girentuximab versus an approved monotherapy standard-of-care (SOC) comparator (Part 2). Eligible patients are aged ≥18 years, have relapsed or recurrent, locally advanced or metastatic, histologically or cytologically confirmed ccRCC, and have received 2-3 prior lines of systemic therapies (including a PD-1/PD-L1 inhibitor and a VEGF/VEGFR-targeting agent) for locally advanced or metastatic ccRCC. Patients must have CAIX-positive cancer as determined by 89 Zr-girentuximab PET (performed during screening). In Part 1, patients will be randomized 1:1 (≤20/arm) to receive either 3 IV infusions of 1887 MBq 177 Lu-girentuximab every 8 weeks or 6 infusions of 1258 MBq 177 Lu-girentuximab every 4 weeks. Unacceptable toxicity is managed with predefined, clinically appropriate measures. In Part 2, patients will be randomized 1:1 to receive 177 Lu-girentuximab at the optimal regimen identified in Part 1 or an SOC comparator. In both parts, the end of treatment (EOT) visit occurs 3 ±1 week after the last infusion or within 30 days of discontinuing treatment. After EOT, efficacy assessments occur every 8 ±2 weeks for 6 months; patients will undergo tumor assessments according to RECIST 1.1 and will receive a contrast-enhanced CT and/or MRI of the chest, abdomen, and pelvis. In Part 2, after the first 6-month follow-up visits, patients continue follow-up every 12 ±2 weeks for up to 24 months after the EOT visit or until progression of disease, death, or the initiation of new systemic anticancer therapies, whichever occurs first. The primary endpoints of Part 1 are incidence and severity of TEAEs, patient discontinuation due to TEAEs, and dosing delays due to TEAEs. The primary endpoint of Part 2 is progression-free survival, defined as time from randomization to first disease progression according to RECIST 1.1 or death due to any cause. This study is sponsored by Telix Pharmaceuticals. Clinical trial information: NCT07197580 .
Project IOTA (input optimization for tissue-based assays): Improving turnaround time (TAT) of mutation profiling for non-small cell lung cancer (NSCLC).
e23142 Background: Next-generation sequencing (NGS)–based biomarker testing is essential for guiding therapy in NSCLC, but limited tissue availability and reliance on formalin-fixed paraffin-embedded (FFPE) specimens can result in test failure and long turnaround times. To address these challenges, we developed Project IOTA, an agile, multidisciplinary workflow that streamlines specimen processing at the time of biopsy in parallel for both diagnostic and molecular pathology. This study aimed to evaluate the concordance and TAT of the NGS results obtained by IOTA workflow process versus standard of care (SOC) commercial NGS testing. Methods: This IRB-approved prospective study, funded by the National Comprehensive Cancer Network (NCCN), enrolled patients with known or suspected lung cancer at Roswell Park who were undergoing routine tissue biopsy for biomarker testing and/or histologic confirmation or disease staging. During the biopsy procedure, upon diagnosis of NSCLC from rapid on-site cytology evaluation for tissue adequacy, one of the fresh tissue needle passes that would have been otherwise incorporated into SOC FFPE processing was instead sent directly for mutation profiling using a custom Thermo Fisher NGS panel. The primary endpoint was an assessment of concordance of IOTA-based NGS testing results for genes with therapeutic relevance in NSCLC genes (ALK, BRAF, EGFR, HER2, KRAS, MET, NTRK, RET, ROS1) with SOC NGS. Secondary endpoints included a comparison of test failure rates and differences in TAT. Results: 80 biopsies were performed in 72 patients (7 patients underwent at least 1 repeat biopsy either due to disease progression or initial biopsies being negative for malignancy but with high index of suspicion for cancer). NSCLC was identified in 64 biopsies (remaining were small cell lung cancer n = 4, non-malignant pathology n = 12), all sent for SOC NGS. SOC NGS was successfully completed in 53 biopsies (83%), of which 34 (64%) yielded sufficient tissue for IOTA-based NGS testing. All 34 biopsies demonstrated 100% concordance between SOC and IOTA NGS results. Nineteen biopsies did not undergo parallel IOTA NGS testing, primarily due to inadequate tissue from the final needle pass. Of the 11 biopsies that failed SOC NGS due to insufficient tissue, 4 produced adequate material for IOTA NGS testing; results of which were concordant with either subsequent liquid biopsy or prior archival tissue NGS results. Turnaround time (TAT) for SOC NGS ranged from 2 to 33 days (median, 12 days), vs. 1 to 6 days (median, 1 day) for IOTA-based NGS testing. Conclusions: Custom NGS testing using the IOTA workflow has median TAT of 1 day and demonstrated 100% concordance with SOC NGS. Further studies are needed to improve specimen adequacy rate at the time of biopsy for IOTA workflow without compromising tissue adequacy for standard pathology and biomarker testing.
Efficacy, safety, and cytokine profiling with addition of the toll-like receptor (TLR) 7/8 dual agonist EIK1001 to standard of care (SOC) first-line (1L) therapy: The phase 2 TeLuRide-005 trial in stage 4 NSCLC.
8568 Background: EIK1001 a TLR 7/8 dual agonist activates dendritic cells via both innate and adaptive pathways. This mechanism of action (MOA) associated with cytokine (CK) release and T-cell differentiation is complementary to immune checkpoint inhibitors (ICIs) that enhance anti-tumor T-cell activity. It provides rationale to add EIK1001 to SOC chemotherapy (chemo) + ICI in Stage 4 NSCLC, a disease with unmet therapeutic needs. Methods: TeLuRide-005 (NCT#06246110) is an ongoing multicenter, open-label study of intravenous weekly (wk) EIK1001 combined with SOC q3-wk pembro + chemo in treatment-naïve patients (pts) with Stage 4 NSCLC. The nonsquamous (NSQ) and squamous (SQ) cohorts completed accrual in May ’25 and Jan ’26, respectively. CK were sampled pre- and post EIK1001 treatment (PT) on Day 1 of Cycle (C) 1 and C4. Results: 71 pts (median age: 68, male:73%) were treated. An ORR of 61% and DCR of 90% were observed for the pooled study population. Cytokine release syndrome (CRS) events were of low grade: 4 pts with Grade 1 and 3 pts with Grade 2. For safety, and efficacy by histology, see Table. 71% of NSQ remain progression free at 8 months and despite over 11 months of follow-up, median PFS is not yet accurately estimable. Type 1 and 2 interferons (IFN) and Interleukin 6/8 (IL6/8) increased PT on C1. By C4, baseline IP-10, an IFN inducible protein that is a T-cell chemotactant, was upregulated by a median of 1.6- fold increase from baseline C1D1. Conversely, CRS-associated IL6 and IL8 were reduced or less inducible on C4D1 than on C1D1, consistent with our observation of only one pt. experiencing CRS after C4. Conclusions: 1L EIK1001 + SOC demonstrates encouraging efficacy in Stage 4 NSCLC with evidence of durable effect. AEs were similar to SOC alone and CRS events were low-grade. Cytokine data support the MOA of the TLR 7/8 dual agonist, EIK1001, and reduced inducibility of IL6/IL8 PT by C4 may suggest CRS likelihood diminishes with time. Clinical trial information: NCT#06246110 . Safety Results At least 1 ≥ Grade 3 TEAE % (n/N) 76.1% (54/71) Serious adverse event (SAE) % (n/N) 46.5% (33/71) Efficacy Results NSQ (n=39) SQ (n=32) Months of follow up (f/u), median (range) 11.2 (5.5-23.0) 6.5 (0.5-19.1) Progression-Free Survival at 8 months* (95% CI) 70.7% (56.9-87.8%) NA Objective Response Rate** (ORR), % (95% CI) 55.6% (38.1-72.1%) 68.0% (46.5-85.1%) Disease Control Rate (DCR), % (95% CI) 83.3% (67.2-93.6%) 100% (86.3-100%) Duration of Response (DOR), Range in Months 2.1+ - 15.1+ 1.0 - 13.2+ NA: Not Analyzed due to short duration of follow-up; *4 scan opportunities at 8 months; **Response evaluable.
Correlative analysis between external and internal lymphedema in head and neck cancer survivors.
12120 Background: More than 75% of head and neck cancer (HNC) survivors develop lymphedema following cancer treatment. Lymphedema can affect both external (e.g., soft tissue of the face and neck) and internal (e.g., pharynx and larynx) structures. Early identification and timely referral are essential for maintaining functionality and minimizing symptom burden. Understanding the relationship between external and internal lymphedema may inform assessment and treatment strategies. However, data describing the association between external and internal lymphedema remains limited. The purpose of this report is to fill this gap. Methods: A prospective, longitudinal descriptive study included 117 patients with oral cavity and oropharyngeal cancer. External lymphedema was evaluated through physical examination using the validated Head and Neck External Lymphedema and Fibrosis Assessment Criteria. Internal lymphedema was evaluated using an endoscopic examination scored with the Modified Patterson Scale. Examinations were performed at baseline and every three months for 12 months post-treatment. Somers’d correlation coefficients were calculated to test associations between external and internal lymphedema measures. Results: Both the total number of sites with external lymphedema and the total external lymphedema severity score correlated with the presence of at least one site of internal lymphedema (both d = 0.31). The total number of external sites of lymphedema moderately correlated with internal lymphedema involving the following structures: epiglottis (d = 0.31), pharyngoepiglottic folds (d = 0.35), aryepiglottic folds (d = 0.34), and anterior commissure (d = 0.32). The total external lymphedema severity score correlated with internal lymphedema involving the following structures: the epiglottis (d = 0.32), pharyngoepiglottic folds (d = 0.35), and aryepiglottic folds (d = 0.34). External submental lymphedema correlated with internal lymphedema involving the buccal mucosa (d = 0.27), epiglottis (d = 0.28), pharyngoepiglottic folds (d = 0.28), and pyriform sinus (d = 0.28). External lymphedema of the neck correlated with internal lymphedema in the pharyngoepiglottic folds (d = 0.28), arytenoids (d = 0.27), and anterior commissure (d = 0.29). External cheek lymphedema failed to correlate significantly with internal lymphedema. Conclusions: HNC survivors with external lymphedema are likely to have concurrent internal lymphedema. The presence of external lymphedema should initiate evaluation for internal lymphedema, particularly in patients with dysphagia or shortness of breath. The site of external lymphedema correlates with the sites of internal lymphedema: this may help inform assessment and management.
Development and validation of a clinical-pathological tool for RS prediction: A practical alternative for resource-limited settings.
e13637 Background: International guidelines recommend the 21-gene Recurrence Score (RS) to guide adjuvant chemotherapy decisions in early-stage luminal breast cancer. However, high costs and limited availability create significant barriers to access in countries like Mexico, where only a minority of patients can afford genomic testing. We developed a multivariable linear regression equation based on standard clinico-pathological features to predict RS, aiming to provide a practical tool for treatment optimization in resource-constrained environments. Methods: We analyzed 90 Mexican patients with HR+/HER2- early breast cancer (Stages IA-IIB, pT1b-c, pN0-1) . Clinicopathological variables were correlated with RS results using SPSS v31 . RS was analyzed as a continuous and a dichotomous variable (Low-Intermediate: 0-25; High: > = 26). A multivariable regression model was constructed using an interaction term between SBR grade and Ki67 . The model's performance was compared against actual RS results and the Magee Score (Equation 1) using 2x2 contingency tables to calculate sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Results: Median age was 57 years; 32% were premenopausal, 37% were node-positive (1-3 nodes), and median Ki67 was 13% . Univariate analysis showed that Progesterone Receptor (PR) intensity, Nottingham (SBR) score/grade, and Ki67 significantly correlated with RS (p < 0.006), while age, tumor size, and nodal status did not . The multivariable model (R = 0.630, R^2 = 0.396, p < 0.001) yielded the equation: RS = 2.512 - 3.979(PR) + 3.009(SBR\Sum) - 9.094(G3) - 0.252(G1\times Ki67) + 0.150(G2\times Ki67) + 0.487(G3\times Ki67). When dichotomized, the model achieved a sensitivity of 46.7%, a specificity of 98.7%, a PPV of 87.5%, and an NPV of 90.2% (p< 0.001). Conclusions: The proposed Mexican regression equation is a highly specific tool for predicting RS risk groups. This model demonstrates strong alignment with established benchmarks such as the Magee Score, while offering particularly robust specificity (98.7%) and PPV (87.5%) within our specific population . These results suggest a reliable and cost-effective strategy to identify patients who are unlikely to require genomic testing, serving as a practical alternative to expand the reach of precision medicine and optimize resource allocation in oncology settings with limited access to commercial platforms . Performance and predictive accuracy. Actual Recurrence Score (Oncotype DX) Mexican Multivariate Regression Model High Risk (>=26) Low-Intermediate Risk (0-25) Total High Risk 7 (87.5% PPV) 1 (46.7% Sensitivity) 8 Low-Intermediate Risk 8 (90.2% NPV) 74 ( 98.7% Specificity) 82 Total 15 75 90
Novel accelerated partial breast irradiation simultaneous integrated boost technique: Rush experience.
e12536 Background: Breast cancer is the most common malignancy among U.S. women. Radiation therapy after lumpectomy reduces recurrence but requires multiple sessions, creating barriers related to time, access, and cost. Newer approaches of shorter fractionation schedules aim to maintain efficacy while minimizing treatment burden and side effects. Accelerated partial breast irradiation (APBI) with simultaneous integrated boost (SIB) delivers higher doses to the tumor bed in fewer treatments, improving convenience without compromising local control. However, guidelines of the American Society for Radiation Oncology (ASTRO) are limited by underrepresentation of patients with higher-risk clinical or pathologic features in major trials. Real-world data are needed to better define APBI candidacy for these groups. Methods: This retrospective cohort study evaluates patients treated with 5-fraction APBI with SIB at Rush University Medical Center between March 2023 and July 2025. Eligible patients are aged ≥18 years with stage I–II invasive ductal carcinoma (IDC) or ductal carcinoma in situ (DCIS) who underwent breast-conserving surgery followed by a 5-fraction regimen. Exclusions are metastatic disease at diagnosis, or incomplete records. Patients are grouped per ASTRO APBI categories (“recommended,” “conditionally recommended,” and “conditionally not recommended”). Collected variables include tumor features, surgical details, systemic therapy, radiation parameters, and acute toxicity. Results: Current evidence shows APBI provides comparable toxicity across diverse patient subgroups while reducing overall treatment time and maintaining local control. SIB delivery appears feasible and safe, with potential benefit for patients with higher-risk features. As of December 2025, our cohort includes 87 patients with a median follow-up of 327 days. Of these, 54 patients had IDC and 33 had DCIS. According to ASTRO criteria, 54 patients were “recommended,” 31 “conditionally recommended,” and 2 “conditionally not recommended.” Two local recurrences occurred, both in the “recommended” category. No significant differences in acute toxicities were observed among risk groups, though longer follow-up is needed. Conclusions: This study provides real-world evidence on outcomes of 5-fraction APBI with SIB, particularly among patients historically underrepresented in clinical trials. Findings will help refine selection criteria, clarify safety in higher-risk groups, and support more individualized and accessible radiation therapy strategies for early-stage breast cancer.
Modified soluble interleukin-2 receptor to ferritin ratio for diagnosis of lymphoma-associated hemophagocytic lymphohistiocytosis.
e19115 Background: Lymphoma-associated hemophagocytic lymphohistiocytosis (L-HLH) has higher mortality than HLH due to other causes. Soluble IL-2 to ferritin ratio is thought to have diagnostic value in lymphoma-associated hemophagocytic lymphohistiocytosis with prior studies suggesting that high values are more suggestive of lymphoma as the underlying cause. However, its use is limited as it lacks generalizability. This is due to the heterogeneity of assays including differences in units and reference ranges. Methods: We used PUBMED, and Clinical Key for the literature search using keywords including HLH, and hemophagocytic lymphohistiocytosis for adult HLH cases that reported absolute sIL-2R and ferritin values with reference ranges with individual patient data. We introduced a modified soluble IL-2 to ferritin ratio, defined as multiples of sIL-2R above the upper limit of normal divided by multiples of ferritin above the upper limit of normal. We used receiver operating characteristic curve analysis to determine sensitivities and specificities. Results: Eighty-one studies with 97 patients met inclusion criteria, including 22 patients with L-HLH. The area under the ROC curve (AUC) for the modified ratio was 0.74 (95% CI, 0.62–0.87). An optimal cutoff value of 0.47 yielded a sensitivity of 59.09% and specificity of 81.33%. A higher cutoff (>1.68) demonstrated high specificity (90.67%) for L-HLH. The modified ratio performed better than sIL-2r or ferritin considered independently. Conclusions: The modified soluble IL-2 to ferritin ratio improves identification of L-HLH. Specificity is high at higher cutoff values. However, all included studies were case reports or case series, which limit clinical utility due to bias from case-based data. Prospective studies using standardized assays are needed to improve diagnostic accuracy. Distribution of ferritin and soluble IL-2 receptor values (expressed as multiples of the upper limit of normal) by etiology of hemophagocytic lymphohistiocytosis; values are shown as ranges. Pathology Ferritin / ULN (range) sIL-2R / ULN (range) Modified Ratio (range) Hodgkin lymphoma 21.7–127.1 2.3–24.5 0.02–0.38 T-cell lymphoma 1.7–1025.0 1.4–52.6 0.01–0.49 Diffuse large B-cell lymphoma 5.2–8.1 5.4–29.4 1.03–3.65 B-cell lymphoma (other) 4.3–11.6 8.1–10.3 0.89–1.90 Intravascular B-cell lymphoma 0.27–11.2 4.9–27.1 1.03–62.6 Chronic lymphocytic leukemia 83.2–492.4 1.3–5.7 0.00–0.03 Idiopathic HLH 7.6–320.0 1.0–29.4 0.01–2.99 Epstein–Barr virus 2.5–87.1 2.0–85.5 0.02–7.23 Cytomegalovirus 17.1–1004.0 4.1–4.3 0.00–0.24 Herpes simplex virus 11.7–886.7 5.1–17.9 0.01–0.44 Parvovirus B19 5.6–550.3 1.1–11.7 0.02–0.20 Tuberculosis 14.3–56.7 2.4–13.6 0.10–0.40 Histoplasmosis 106.7–134.2 6.3–25.6 0.06–0.19 Systemic lupus erythematosus 25.2–182.2 3.5–8.0 0.04–0.14 Still’s disease 32.9–234.3 2.2–25.7 0.05–0.11
Metabotyping using early body weight velocity in lung cancer patients treated with pembrolizumab.
e20527 Background: PD-L1 tumor proportion score guides immune checkpoint inhibitor therapy in advanced non-small cell lung cancer, yet outcomes remain heterogeneous. We assessed whether early on-treatment body weight velocity after pembrolizumab initiation is associated with overall survival (OS). Methods: Using the nference nSights federated platform across multiple medical centers, we retrospectively studied adults with lung cancer (ICD-10 C34.x) treated with pembrolizumab. Baseline weight was the closest measurement within 90 days pre-initiation. Percent weight change from baseline was computed at 1–6 months post-initiation (nearest weight within ±15 days). Landmark Cox models were fit independently at each timepoint for OS, adjusting for age, sex, baseline weight, baseline BMI when available, and time from diagnosis to treatment initiation. Model discrimination was assessed with the concordance index. Results: A total of 5,748 patients met inclusion criteria. Baseline demographic and clinical characteristics, including age at treatment initiation, body weight, body mass index, and time from diagnosis to treatment, were captured for all patients. Across all evaluated timepoints, percent weight gain following pembrolizumab initiation was significantly associated with improved overall survival after adjustment (hazard ratio per 1% weight change range: 0.954–0.961; all p < 0.0001). Effect estimates were similar across 1–6 month landmarks. Model discrimination increased modestly with longer follow-up (C-index 0.582 at 1 month; 0.613 at 6 months). At the 6-month landmark, 2,158 deaths were observed among 3,970 patients and each 1% weight gain was associated with lower mortality risk (HR 0.961; 95% CI 0.956–0.966). A 5% increase in body weight corresponded to an estimated 18–21% lower mortality hazard, whereas a 5% decrease corresponded to an estimated 22–27% higher mortality hazard, holding covariates constant. Conclusions: Early on-treatment body weight velocity is a low-burden routinely collected measure consistently associated with OS during pembrolizumab therapy. Weight-velocity metabotyping may complement tumor and host biomarkers for pragmatic risk stratification and supportive-care assessment, supporting scalable value-conscious care. Association between weight change and overall survival in lung cancer patients treated with pembrolizumab. HR <1 indicates weight gain is associated with reduced mortality risk. Timepoint Patients Events C-index Weight Change HR 95% CI p-value 1 month 5548 3172 0.582 0.958 0.949-0.966 <0.0001 2 months 5339 3094 0.601 0.954 0.947-0.96 <0.0001 3 months 5034 2868 0.608 0.958 0.952-0.963 <0.0001 4 months 4624 2609 0.61 0.957 0.952-0.963 <0.0001 5 months 4199 2370 0.612 0.959 0.954-0.965 <0.0001 6 months 3970 2158 0.613 0.961 0.956-0.966 <0.0001
Survival outcomes of young patients with non-small cell lung cancer in Latin America: A real-world cohort study.
8067 Background: Young patients with non-small cell lung cancer (NSCLC) represent a distinct biological subgroup, frequently enriched with actionable oncogenic drivers. However, real-world survival data from Latin America are limited. We evaluated survival outcomes and prognostic factors in young versus older patients with NSCLC treated in Peru. Methods: We conducted a retrospective cohort study including patients with histologically confirmed NSCLC treated between 2018and 2024 at a national reference cancer center. Patients were stratified by age at diagnosis (<45 vs ≥45 years). Overallsurvival (OS) was estimated using the Kaplan–Meier method. Multivariable Cox regression was performed adjusting for sex,ECOG performance status, smoking history, clinical stage, histology, molecular alterations and first-line treatment. Results: A total of 317 patients were included; 19.9% were younger than 45 years. The cohort was predominantly female (59.3%),never-smokers (85.5%) and had adenocarcinoma histology (95.6%). Advanced disease (stage III–IV) was present in 94.0% ofcases. Actionable molecular alterations were identified in 69.4% of patients, most commonly EGFR mutations (48.3%).Younger patients showed a higher frequency of actionable mutations compared with older patients (70% vs 56%, p=0.038).After a median follow-up of 40.9 months, 92 deaths (29.0%) were recorded. In adjusted analysis, young age was notassociated with worse OS (adjusted HR 1.32; 95% CI 0.79–2.21; p=0.29). Former smoking history was the only independentpredictor of inferior OS (adjusted HR 2.38; 95% CI 1.16–4.91; p=0.018). Conclusions: Young age at NSCLC diagnosis was not associated with inferior survival. Despite advanced-stage presentation, youngerpatients exhibited a high prevalence of actionable oncogenic drivers, supporting routine comprehensive molecularprofiling. These results provide robust regional evidence and reinforce the importance of precision oncology inunderrepresented populations.
Real-world access to molecular diagnostics and immunotherapy for advanced melanoma in Syria.
e13635 Background: Melanoma is an aggressive skin malignancy with rising global incidence, for which checkpoint inhibitors (CPI) and BRAF-targeted therapies are standard of care in advanced disease. However, access to molecular diagnostics and CPI remains limited in conflict-affected regions such as Syria. Real-world data describing melanoma management in this setting are scarce. Methods: We conducted a retrospective study of all patients diagnosed with melanoma between 2022 and 2024 at Al-Bairouni University Hospital (ABUH), Syria’s primary oncology referral center. Demographic and clinical characteristics were analyzed for the entire cohort, and patients with advanced disease were evaluated for molecular testing and treatment patterns. Semi-structured interviews were conducted in a mixed advanced cancer subset (N = 35) to explore barriers to immunotherapy access. Results: Among 115 patients with melanoma, the median age at diagnosis was 57 years (IQR 44.5–67), and 54.7% were male. At presentation, 18.3% had stage I disease, 1.7% stage II, 2.6% stage III, and 40.9% stage IV disease; staging was unavailable in 36.5%. Among patients with advanced melanoma (n = 47), BRAF testing was performed in 17 (36.2%), with targeted therapy administered to 5/16 BRAF-positive patients. Only 7/47 patients (14.9%) received CPI, primarily as monotherapy. In the qualitative subset (predominantly lung cancer), five major barriers to immunotherapy access emerged: financial toxicity (n = 22), limited drug availability (n = 9), limited patient awareness (n = 8), geographic/logistical challenges (n = 5), and system delays (n = 4). Conclusions: Despite a substantial burden of advanced melanoma, access to molecular testing, targeted therapy and CPI in Syria remains limited. Qualitative findings highlight financial and structural barriers as primary drivers of limited access, underscoring the need for improved drug availability, diagnostic infrastructure, and patient education in conflict-affected settings.
Elacestrant in combination with capivasertib in patients with ER+/HER2− advanced breast cancer: Update from ELEVATE, a phase 1b/2, open-label, umbrella study.
1098 Background: Disease progression in patients (pts) with ER+/HER2- ABC on 1L ET+CDK4/6i is associated with several mechanisms of resistance, including intrinsic alterations in the PI3K/AKT/mTOR or cell cycle pathways, and/or ESR1 mutations, a type of acquired resistance that emerges in up to 50% of pts. Elacestrant is the only single-agent oral SERD to significantly improve PFS vs SOC ET in all pts (HR 0.70; 95% CI 0.55-0.88; P=0.0018) and in those with ESR1m tumors (HR 0.55; 95% CI 0.39-0.77; P=0.0005) with manageable safety in EMERALD, a trial that required prior ET+CDK4/6i [Bidard 2022]. In CAPItello-291, capivasertib + fulvestrant showed a mPFS of 7.3 mo (AKT-pathway altered) and 5.5 mo (prior CDK4/6i exposure) [Turner 2023]. In ER+ BC MCF7 CDX and CTG-2308 PDX models ( ESR1 wt/ PIK3CAm ), elacestrant + capivasertib showed superior antitumor activity compared with single-agent treatment, including an improvement in activity vs fulvestrant + capivasertib, further supporting the rationale to combine elacestrant with an AKT inhibitor in ER+ BC [Data on file]. This analysis reports updated Ph 1b safety and preliminary efficacy for elacestrant + capivasertib. Methods: ELEVATE is evaluating elacestrant in combination with everolimus, alpelisib, capivasertib, abemaciclib, ribociclib, or palbociclib to address different resistance mechanisms. Pts with ER+/HER2- ABC and 1-2L of prior ET±CDK4/6i are eligible regardless of ESR1m status; no prior chemo allowed in the ABC setting. Objectives are to identify the RP2D (Ph 1b) and evaluate PFS (Ph 2). Results: As of Dec 2025, 31 pts have been enrolled in the Ph 1b elacestrant (258-345 mg) + capivasertib (320-400 mg) cohorts. Key baseline characteristics include pts with visceral mets (90%), primary endocrine resistance (23%), ESR1m (45%), prior CDK4/6i (94%), and prior fulvestrant (45%). The most common (≥35%) TEAEs were diarrhea (81%; 6% Gr 3), nausea (74%; 0% Gr 3), rash (61%; 13% Gr 3), fatigue (58%; 3% Gr 3), vomiting (42%; 0% Gr 3); observed hyperglycemia was 29% (10% Gr 3). Elacestrant 345 mg QD + capivasertib 320 BID [4 days on/3 days off] was determined as the RP2D based on the safety profile and PK analysis; no DLTs were observed. In RP2D response-evaluable pts (n=9), preliminary efficacy showed an ORR of 22%, CBR24 wk at 67% (1 CR, 1 PR, and 6 SD), and a mPFS of 11.3 mo. Median follow-up is 10.2 mo [1.8-12.0]. Updated results and additional data will be reported. Conclusions: Elacestrant + capivasertib shows a manageable safety profile, consistent with known capivasertib + fulvestrant Gr 3 AEs, and clinically important efficacy in pts with AKT-pathway altered ER+/HER2- ABC with progressive disease. Enrollment in Ph 2 is ongoing. Elacestrant + capivasertib combination therapy offers pts the benefit of receiving both drugs with manageable safety and potential extended clinical benefit as an all-oral treatment option. Clinical trial information: NCT05563220 .