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Abstract Objectives Carbapenem resistance is a growing public health crisis with regional variability in incidence. We characterized the susceptibility of carbapenem-resistant Gram-negative rods (CR-GNRs) from the Pacific Northwest to five reserve beta-lactam agents including cefiderocol and aztreonam-avibactam. Methods A panel of 162 CR-GNRs from unique patients were tested against cefiderocol, aztreonam-avibactam, ceftazidime-avibactam, meropenem-vaborbactam and ceftolozane-tazobactam, with a subset of isolates derived from patients with bacteraemia (n = 55). Whole-genome sequencing (WGS) was performed on representative Stenotrophomonas maltophilia isolates displaying a range of cefiderocol MICs (n = 9). Results Among all isolates, the MIC50 and MIC90 to cefiderocol was 0.25 and 4 mg/L, respectively, compared with 4 and >64 mg/L for aztreonam-avibactam. Overall, 98.3% of S. maltophilia (n = 60), 91.2% of Enterobacterales (n = 34) and 88.5% of Pseudomonas aeruginosa (n = 26) isolates were susceptible to cefiderocol, while 78.6% of other non-fermenters had MICs ≤4 mg/L. Aztreonam-avibactam and cefiderocol exhibited similar activity against Enterobacterales and S. maltophilia, but aztreonam-avibactam was less active against other organisms. WGS of S. maltophilia isolates with elevated cefiderocol MICs identified disruptive mutations in PBP-encoding genes (mrcB/PBP1b and pbpC/PBP1c) that were not observed in highly susceptible isolates. The bacteraemia cohort had many comorbidities and a 29% 30 day all-cause mortality. In this cohort, cefiderocol demonstrated the highest in vitro activity as extrapolated from MICs, followed by ceftazidime-avibactam, aztreonam-avibactam, meropenem-vaborbactam and ceftolozane-tazobactam, respectively. Conclusions Cefiderocol exhibited the greatest in vitro activity against various CR-GNRs species in a Pacific Northwest population enriched for severely ill patients. Susceptibility to other agents was more variable among tested organisms.

7532 Background: BsAbs are highly effective, off-the-shelf T-cell engagers recently approved for relapsed/refractory multiple myeloma (MM) but remain underutilized in real-world settings. In partnership with the Florida Society of Clinical Oncology (FLASCO), a statewide initiative was launched to expand BsAb access through peer-led regional discussions focused on operational barriers, care transitions, and therapy management strategies. This study assessed the real-world impact of these interventions on BsAb utilization in FL. Methods: Multidisciplinary discussion forums were held in 4 FL metropolitan areas (Jan-Apr 2024). We conducted single and controlled interrupted time series (ITS) analyses using IQVIA eLAAD claims data (Apr 2023 - Sep 2025) including adult patients with a diagnosis of MM, evidence of claim activity, and provider state information. Fifth line or later (5L+) status was estimated as 3.3% of MM prevalence (Nikolaou et al.) BsAb utilization (% of MM 5L+ patients receiving a BsAb) was evaluated using segmented regression to estimate pre- and post-intervention trends, excluding the intervention period. We reported BsAb utilization by comparing FL with all other states, between community versus academic settings, and assessing the number of sites administering BsAb. Results: Before the intervention, BsAb utilization among MM 5L+ patients in FL rose from 8.2% (Apr 2023) to 11.2% (Dec 2023) (0.3 pp/mo; p=0.23), compared with a rise from 6.7% to 16.3% (1.3 pp/mo; p<0.0001) across all other states over the same time period. Post-intervention, BsAb utilization in FL increased from 22.8% (May 2024) to 35.9% (Sep 2025), reflecting a 7.0% immediate increase and 0.8 pp/mo sustained growth, exceeding the post-intervention trend observed across all other states (23.5% to 30.3%; 0.5 pp/mo). Overall, although pre-intervention BsAb utilization in FL was lower than all other states, FL demonstrated a 1.2 pp/month higher post-intervention utilization trend (p<0.001; Table). Post-intervention, FL community sites showed a 0.13 pp/mo higher BsAb utilization trend than academic sites, and the number of community sites administrating BsAb increased from 5 to 9, with no change among academic sites. Conclusions: This study suggests that the FLASCO-led, collaborative model increased BsAb utilization in FL community oncology sites and offers a framework for broader community adoption across other states. Parameter estimates from ITS model(s). FL (%) p-value Other US States (%) p-value Difference CITS:FL - Other US States (%) p-value Intercept (Apr 2023) 8.6 <.0001 7.7 <.0001 0.9 0.52 Monthly change pre-intervention 0.3 0.23 1.3 <.0001 -0.9 0.002 (Apr - Dec 2023) Immediate change post-intervention 7 0.01 0.2 0.87 6.8 0.01 (May 2024) Monthly change post-intervention 0.8 <.0001 0.5 <.0001 1.2 0.0003 (May 2024 – Sep 2025)

7516 Background: With the growing use of anti-CD38 therapies in early multiple myeloma (MM) management, there is a need for data in patients previously exposed to anti-CD38 therapy to guide decision making. In the Phase 3 IRAKLIA trial (NCT05405166), patients with relapsed/refractory MM (RRMM) received the anti-CD38 monoclonal antibody isatuximab (Isa) subcutaneously (SC) delivered via an innovative on-body injector (OBI) or intravenously (IV), with pomalidomide and dexamethasone (Pd). In this post hoc analysis, we examined outcomes in IRAKLIA patients with vs without prior anti-CD38 exposure. Methods: RRMM patients ≥18 years with ≥1 prior line of therapy including lenalidomide and a proteasome inhibitor were randomized to receive Isa SC (n=263) or IV (n=268) weekly in Cycle 1, then every 2 weeks, with Pd. Patients with prior anti-CD38 exposure <9 months (mos) before randomization or intolerance to anti-CD38 were excluded. Refractory patients were defined as those who failed to achieve minimal response on treatment or had progression within 60 days after last dose. Patients receiving Isa SC or IV were pooled. Results: Overall, 67 patients (12.6%) had prior anti-CD38 exposure with a median washout period of 20.2 mos, of which 26 (38.8%) were anti-CD38 refractory. Baseline characteristics were largely consistent between patients with or without prior anti-CD38 exposure; the median follow-up for the overall population was 12 mos. Patients with prior anti-CD38 exposure had an overall response rate (ORR) of 52.2%, 12-mo progression-free survival (PFS) rate of 40.6%, and median PFS of 8.5 mos. In patients without prior exposure, an ORR of 73.5%, 12-mo PFS of 68.8%, and non-estimable (NE) median PFS were reported. Anti-CD38 non-refractory vs refractory patients had an ORR of 48.8% vs 57.7%, 12-mo PFS of 38.9% vs 42.2%, and median PFS of 9.0 vs 7.5 mos. Patients with a longer washout period (>median of 20.2 mos) had an ORR of 63.6%, 12-mo PFS of 61.8% and NE median PFS, whereas patients whose prior anti-CD38 therapy ended more recently (≤median of 20.2 mos) had an ORR of 41.2%, 12-mo PFS of 19.2%, and median PFS of 6.7 mos. The safety profile of Isa + Pd was similar in patients with vs without prior anti-CD38 exposure. Conclusions: Isa + Pd demonstrated clinical benefit across anti-CD38–naïve, anti-CD38–exposed, and anti-CD38–refractory patients. A washout period >median of 20.2 mos resulted in outcomes comparable to those in anti-CD38–naïve patients, and outcomes were consistent between anti-CD38–exposed and anti-CD38–refractory patients after a >9-mo washout period. Efficacy of Isa + Pd in patients with prior anti-CD38 exposure from the IRAKLIA trial presents an opportunity to address an unmet need in a difficult-to-treat patient population. Clinical trial information: NCT05405166 .

625 Background: I-SPY 2 is a multicenter phase II adaptive platform trial evaluating novel agents for stage II-III high-risk breast cancer using response-predictive subtypes (RPS) and a sequential neoadjuvant treatment design of up to three blocks (A/B/C). Investigational regimens are given in Block A, followed by response-guided escalation to standard-of-care (SOC) therapy (tx) in subsequent blocks or early surgery for responders. Topoisomerase I (TOPO1) inhibition plus PARP inhibition may enhance DNA damage and tumor response. DAN-222 is a tumor-targeted polymeric camptothecin conjugate designed to improve the therapeutic index of TOPO1 inhibition. Based on favorable phase 1 safety and preliminary activity in metastatic breast cancer, DAN-222 plus niraparib was evaluated as Block A tx in HER2− disease. Notably, the neoadjuvant regimen used a higher dose of niraparib (200 mg daily) than the prior phase 1 metastatic study. Methods: Patients (pts) with HER2− breast cancer were randomized to DAN-222 plus niraparib for up to 12 weeks in Block A. Response was assessed by serial MRI and biopsy. Inadequate responders escalated early to SOC tx in Blocks B/C. Primary endpoint was pathologic complete response (pCR). Secondary endpoints included residual cancer burden, safety, early discontinuation, and treatment-strategy performance versus subtype-specific SOC tx controls. Given established PARPi sensitivity in BRCA mut disease, the key objective was to assess clinically meaningful activity of DAN-222 plus niraparib in BRCA wt pts. Accordingly, a prespecified Bayesian interim futility analysis focused on BRCA wt and tested the probability of the true pCR rate after Block A alone exceeded 15% after 50 pts. Results: Fifty pts enrolled from Sep to Dec 2024. In BRCA wt (n=47), estimated Block A pCR was 3%, with posterior probability of 0.02 that that true pCR exceeded 15%, meeting futility criteria and prompting arm closure. Across all blocks, pCR rate was 57% (8/14) for HR-HER2−; 11% (4/36) for HR+ HER2−, largely after SOC tx. 2/3 BRCA mut pts achieved pCR. Treatment strategies initiating with DAN-222 plus niraparib underperformed subtype-specific controls. 68% discontinued Block A early, mainly due to toxicity. Grade ≥3 cytopenias were common: neutropenia (n=25; 50%), anemia (24%), and thrombocytopenia (18%). Cystitis occurred in 36% (1 grade ≥3). Conclusions: Neoadjuvant DAN-222 plus niraparib showed insufficient activity and no treatment-strategy benefit in BRCA wt HER2− breast cancer, underscoring challenges for TOPO1–PARP inhibitor combinations. Although not supported for further development in this setting, these results highlight the strength of I-SPY 2 in rapidly enrolling patients and quickly distinguishing ineffective from promising therapeutic strategies to accelerate progress toward improved outcomes for patients with curable breast cancer. Clinical trial information: NCT01042379 .

5004 Background: Patients (pts) with metastatic hormone-sensitive prostate cancer (mHSPC) treated continuously with testosterone suppression (TS) plus an androgen receptor pathway inhibitor (ARPI) can experience cumulative toxicity. We conducted this single-arm phase 2 trial (NCT05241860) to test the hypothesis that pts who achieve favorable response to TS + ARPI can have prolonged treatment-free interval with testosterone recovery after treatment interruption (TI). Here we report on the primary endpoint. Methods: Eligible pts had mHSPC by conventional imaging with prostate-specific antigen (PSA) ≥ 5 ng/ml and testosterone ≥ 150 ng/dl prior to starting TS+ARPI, with PSA < 0.2 ng/ml and testosterone < 50 ng/dl at the time of enrollment after having received TS for 540-750 days and ARPI for ≥ 360 days. Prior local therapy, radiation to metastases and docetaxel were permitted. After enrollment, pts discontinued TS and ARPI and were followed with PSA and testosterone levels every 3 months (mo), CT/MRI and bone scan at least every 6 mo, and FACT-P questionnaire for patient-reported outcomes (PROs) every 6 mo. Treatment was resumed for PSA ≥ 5 ng/ml, radiographic change (progressive disease [PD] per RECIST 1.1 on CT/MRI or unconfirmed PD per PCWG3 on bone scan), or prostate cancer-related symptoms. The primary endpoint was proportion of men remaining treatment-free 18 mo after TI with eugonadal testosterone ( > 150 ng/dl). Target enrollment was 75 pts to differentiate 18-mo treatment-free rates of 0.30 (H 0 ) and 0.45 (H a ). Results: Of 79 pts enrolled between 07/2022 and 03/2024, 78 were eligible and underwent TI. Among these 78, median PSA prior to starting TS+ARPI was 19 (range 5-6759), 27 (35%) had high volume disease, 31 (40%) never received local therapy, and 55 (71%) did not receive radiation to metastases. By 18 mo after TI, 67% (52/78) recovered testosterone and 58% (45/78) remained treatment-free; 41% (32/78) remained treatment-free with testosterone recovery (80% CI 33.5-48.9%, one-sided p 0.0249). At median follow-up of 21.2 mo, 35% (27/78) resumed initial TS+ARPI after meeting re-initiation criteria (of whom 1 required treatment switch for PD 9 mo later); 5% (4/78) resumed prior to meeting criteria; 9% (7/78) pursued alternative therapy instead of resuming TS+ARPI per protocol; 5% (4/78) withdrew; 1 died of myocardial infarction prior to resuming treatment. 4 pts died, 1 of prostate cancer. Conclusions: The primary objective was achieved with 41% of favorable responders to TS+ARPI remaining treatment-free with testosterone recovery at 18 mo after TI. Analyses of biomarkers and PROs are in progress, and pts will be followed for long-term outcomes. Support: U10CA180821, U10CA180882, UG1CA189823, https://acknowledgments.alliancefound.org, Veracyte Inc. Clinical trial information: NCT05241860 .

4219 Background: Pancreatic ductal adenocarcinoma (PDAC) remains a notoriously difficult-to-treat malignancy, with limited therapy options for patients with advanced disease. While KRAS mutations are the dominant oncogenic driver in PDAC, next-generation sequencing has enabled the identification of rare, targetable alterations such as the BRAF V600E mutation, which occurs in approximately 2-3% of cases. BRAF mutant cell lines are responsive to MEK and RAF inhibitors. This study evaluates the efficacy of the combination of encorafenib and binimetinib as ≥ 2nd line therapy in this specific molecular subgroup of pancreatic cancer patients. Methods: This study used a planned two-stage design. Seven patients were pre-registered; one did not meet eligibility criteria and was excluded. Six patients were enrolled in Stage 1, which required an objective response (OR) in 40% of patients to proceed to Stage 2. Stage 2 was planned to enroll an additional 16 patients, contingent on meeting this efficacy threshold. Enrolled patients received treatment in 28-day cycles until disease progression or for a maximum of 36 cycles. Patients self-administered encorafenib (450 mg orally once daily) and binimetinib (45 mg orally twice daily) starting on Day 1 of each cycle. Objective responses were assessed using RECIST version 1.1 over 24 weeks. Results: The median number of cycles was 8. The objective response rate at 24 weeks was 33.33%. The overall objective response rate was 50%. The median time to response for progression-free survival, overall survival, duration of response, and time to response was 7.1, 15.0, 9.9, and 3.9 months respectively, with 95% CI in all categories. 50% of patients experienced at least one Grade ≥3 adverse event, including anemia, thromboembolic events, and acute kidney injury. Conclusions: The six BRAF-V600E-mutated PDAC patients in our cohort demonstrated meaningful antitumor activity with a manageable safety profile after treatment with encorafenib and binimetinib. Although the study was prematurely terminated due to limited accrual, observed objective responses and survival outcomes suggest that dual RAF/MEK inhibition may represent a feasible therapeutic strategy in this rare molecular subgroup. Larger studies are warranted to further define the efficacy and safety of this treatment combination in BRAF-V600E-mutated pancreatic cancer. Clinical trial information: NCI-2020-02972 .

4213 Background: Elraglusib (9-ING-41), a glycogen synthase kinase-3β (GSK-3β) inhibitor, has multimodal antitumor activity. In the international, open-label, randomized phase 2 1801 Part 3B study, elraglusib plus gemcitabine/nab-paclitaxel (GnP) was evaluated in previously untreated metastatic pancreatic ductal adenocarcinoma (mPDAC), with patients randomized 2:1 to weekly elraglusib/GnP or GnP alone. Primary endpoints were median overall survival (mOS) and 1-year survival. The GnP control arm demonstrated shorter mOS than contemporary randomized trials (7.2 months vs 9.2 months in NAPOLI-3 and 9.7 months in PASS-01), driven by higher early mortality (0–2 months: 23.1% vs 10.1% in NAPOLI-3). Given balanced randomization, similar early mortality was inferred in the elraglusib/GnP arm, prompting post-hoc analyses to contextualize efficacy and identify factors associated with early death. Methods: Efficacy and safety were summarized descriptively. Time-to-event endpoints were analyzed using Kaplan–Meier estimates, log-rank testing, and Cox proportional hazards models. Response rates were compared using the Cochran–Mantel–Haenszel test. Post-hoc subgroup, sensitivity, and machine-learning–based multivariate analyses explored clinical, demographic, and biomarker correlates of survival and early mortality. Results: In the full randomized population (elraglusib/GnP n=155; GnP n=78), elraglusib/GnP improved mOS by 2.9 months versus GnP (10.1 vs 7.2 months; HR 0.62; 95% CI 0.46–0.84; p=0.01), with 1-year survival rates of 44.1% versus 22.3%. Among patients receiving ≥1 full treatment cycle, mOS was 12.5 months with elraglusib/GnP and 8.5 months with GnP, comparable to contemporary registrational trials. Across multiple post-hoc sensitivity analyses—including evaluable patients, those matched to NAPOLI-3 baseline tumor burden, patients treated in the EU (early mortality 4%), and those achieving ≥20% CA19-9 decline within the first 1–2 cycles—elraglusib/GnP consistently demonstrated a ≥4-month OS advantage. Early death was associated with low baseline albumin (<3 g/dL), high CA19-9 (>800 U/mL), high tumor burden, and KRAS, TP53, and CDKN2A co-mutations. Conclusions: The elevated early mortality in the GnP control arm reflects enrollment of a heterogeneous, real-world mPDAC population with less restrictive eligibility than recent registrational trials. Post-hoc analyses identify key clinical and molecular drivers of early death and confirm a consistent survival benefit with elraglusib/GnP. These hypothesis-generating findings directly inform eligibility criteria, stratification, and endpoint assumptions for the planned phase 3 trial. Clinical trial information: NCT03678883 .

2090 Background: A subset of meningiomas has an aggressive clinical course requiring multimodal therapies. Yet, treatment options beyond surgery and radiation are limited. Somatostatin receptor 2 (SSTR2) is uniformly expressed in meningiomas and can be targeted by the radiopharmaceutical agent [ 177 Lu]Lu-DOTA-TATE ( 177 Lu-Dotatate). [ 68 Ga]Ga-DOTA-TATE ( 68 Ga-Dotatate) PET is emerging as a promising imaging modality to assess treatment response in SSTR2-expressing tumors. However, prospective clinical data supporting the use of 177 Lu-Dotatate and 68 Ga-Dotatate in treatment-refractory meningiomas is limited. Methods: In this multicenter, open-label, phase 2 clinical study (NCT03971461), adult patients with progressive intracranial meningiomas received 177 Lu-Dotatate at 7.4 GBq (200 mCi) every 8 weeks for 4 doses. The primary endpoint was 6-month progression-free survival (PFS-6). Up to 5 meningioma lesions per patient were assessed by gadolinium-enhanced T1 MRI every 12 weeks. 68 Ga-Dotatate PET was obtained before/after 177 Lu-Dotatate treatments. Lesional 68 Ga-Dotatate PET activity was assessed relative to liver/spleen or superior sagittal sinus (SSS). Results: 32 patients (female = 21, male = 11) with progressive meningiomas (WHO grade 1 = 7, grade 2 = 24, grade 3 = 1) were enrolled. Median age was 65.5 (range 41-78) years. All patients had at least one prior tumor surgery and at least one course of radiation. Overall, 177 Lu-Dotatate was well tolerated and the most common grade 3/4 adverse events were transient cytopenia in 15 patients (47%). One patient (3%) discontinued treatment due to grade 4 thrombocytopenia. PFS-6 was reached in 22 patients (69%), which includes 5 of 7 (71%) with grade 1 and 17 of 24 (71%) with grade 2 meningiomas. Best radiographic response by MRI was partial response (PR) in 5 (16%) and stable disease (SD) in 20 (63%) patients. Eight patients (16 lesions) were evaluable by paired MRI and 68 Ga-Dotatate PET pre- and post-treatment. Referenced to SSS, 68 Ga-Dotatate avidity reduced by ≥50% in 2 lesions (PR), 25-49% (minor response, MR) in 3 lesions and remained stable ( < 25% reduction and < 25% increase) in 11 lesions. Using liver/spleen as a reference (6 patients, 14 lesions), 68 Ga-Dotatate uptake was reduced in 9 lesions and stable in 5 lesions. 68 Ga-Dotatate PET assessments were generally concordant with MRI-based treatment response assessments. Conclusions: The primary endpoint (PFS-6) was met in this phase 2 study with 69% of patients achieving PFS-6, thereby surpassing established historical benchmarks. 177 Lu-Dotatate was generally well tolerated and deserves further study in patients with advanced meningiomas. Exploratory 68 Ga-DOTATATE PET studies showed decreased uptake in a subset of lesions and bears promise as an imaging biomarker to assess treatment response. Clinical trial information: NCT03971461 .

11502 Background: To report results from the open-label alveolar soft part sarcoma (ASPS) cohort of the phase III APROMISS trial (NCT03016819) evaluating Catequentinib hydrochloride (AL3818), an oral multitargeted receptor tyrosine kinase inhibitor, in adults with advanced or metastatic ASPS. Methods: Adult patients with pathologic and molecularly confirmed advanced ASPS, either treatment-naive or previously treated (excluding cediranib), were enrolled in the open-label, non-randomized ASPS cohort of the phase III APROMISS trial conducted across the United States, Asia, and Europe. Catequentinib hydrochloride was administered orally at 12 mg once daily in 21-day cycles (14 days on/7 days off) until disease progression, toxicity, or death. The primary endpoint was objective response rate (ORR) assessed per RECIST by Blinded Independent Central Review (BICR) (predefined threshold: 31%). Secondary endpoints included duration of response (DOR) with a predefined target of =/>6 months, progression free survival (PFS) and overall survival (OS). Results: From July 2017 to August 2022, a total of 56 patients entered the trial; 56 patients were evaluable for the primary endpoint. Median (m-) age was 29.5 years (range: 18 – 66), with 24 female and 32 male. Best overall response included 1/56 complete response (1.8%), 14/56 partial responses (25.0%), 36/56 stable disease (64.3%), and 3/56 (5.4%) progressive disease. RECIST ORR by BICR was 26.8% (95% CI, 15.8–40.3); m-DOR was 22.57 months (95%CI: 10.38-NE). The study data was collected close to 8 years for all patients. mPFS was 18.33 months (95% CI, 14.19–23.13), with 6- and 12-month progression-free rates of 88.77% (95% CI, 76.68–94.79) and 65.54% (95% CI, 50.42–77.06), respectively. mOS was 59.27 months (95% CI, 44.09–NE), with 6- and 12-month overall survival rates of 94.64% (95% CI, 84.30–98.24) and 90.81% (95% CI, 79.30–96.08), respectively. Overall, 27/56 (48.2%) patients experienced grade ≥3 treatment-related adverse events, most commonly diarrhea (50.0%), hypertension (44.6%), fatigue (37.5%), nausea (35.7%), and palmar-plantar erythrodysesthesia syndrome (30.4%); one patient (1.8%) had a grade 5 event (respiratory failure). Conclusions: Catequentinib hydrochloride demonstrated meaningful antitumor activity and durable responses in adults with advanced ASPS. Despite the ORR of 26.8% slightly below the predefined 31% threshold, disease control was prolonged, with a m-DOR exceeding 22 months. Favorable PFS and OS outcomes, together with a manageable safety profile, support its clinical benefit in this ultra-rare sarcoma. Clinical trial information: NCT03016819 .

10610 Background: The role for genetic testing (GT) for prostate cancer (PCa) patients (pts) has expanded to find pts with germline pathogenic variants (PV) for therapeutic opportunities given FDA-approvals for PARP inhibitors in metastatic PCa as well as understanding familial cancer risk and opportunities for tailored screening and risk reduction. The PROMISE Registry (NCT04995198) was set up as a genetic registry to partner with PCa pts for rapid access to a new standard of care given insurance coverage and clinical implementation were initially major barriers. A second goal is to characterize disease features and treatment outcomes to inform management and provide updates about novel therapeutic clinical trials, both of which remain important to rare genetic variant carriers. Methods: PROMISE is a US decentralized prospective PCa genetic registry initiated in 2021 with initial phase to enroll and provide clinical-grade germline genetic testing (30 gene cancer-specific panel) to 5,000 PCa pts to identify ~500 PCa pts with variants of interest (pathogenic variants, PV, and variants of uncertain significance, VUS) in DNA repair genes for long-term clinical follow-up of 15 years (LTFU). Here, we report the initial phase testing results and identification of the LTFU cohort. Study design and enrollment strategy have been reported separately. Results: Between 2021-2026, 7,275 pts with any stage PCa across 50 US states self-consented to PROMISE, of which 5,674 (78%) of pts completed genetic testing, indicating feasibility of patient-directed, decentralized enrollment. We have identified 495 (8.7%) pts for LTFU. Baseline data is reported for n=367 (Table 1, will be updated at time of presentation). The most frequently observed PV/LPV variants being in CHEK2 (25%) , BRCA2 (23%) , ATM (12%) , and BRCA1 (4.6%). At the time of PCa diagnosis, the majority of LTFU pts had non-metastatic disease, with 47% of pts with Gleason>7, median PSA of 5 ng/mL, and median time from diagnosis to PROMISE GT of 25 months. Conclusions: PROMISE is a nationwide decentralized PCa genetic registry that has completed initial goal to recruit 5,000 PCa pts to offer germline genetic testing and recruit a cohort of 500 for LTFU. Data about diagnosis characteristics are reported, and analysis of ongoing disease course, treatment response/outcomes and overall survival is being collected. Clinical trial information: NCT04995198 . Long-term follow-up participant demographics. Characteristic Overall, N = 367 Age at Diagnosis (yrs) 63 (57, 69) Race N = 361 (6, nr) Asian, American Indian or Alaska Native, Multiracial, Other 22 (6.0%) Black or African American 22 (6.0%) White 317 (86%) Disease State at Diagnosis N = 348 (19, nr) Metastatic 46 (13%) Non-metastatic 302 (87%) Time from Diagnosis to PROMISE GT (months) 25 (4, 82) Gleason Score N = 280 (87, nr) </= 7 148 (53%) >7 132 (47%) PSA At Diagnosis (ng/mL) 5 (0, 10) (88, nr) Subjects with baseline data entered. nr=not reported. Median (Q1, Q3); n (%).