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TPS11585 Background: Soft tissue sarcomas (STS) with genomic complexity are often aggressive but may be sensitive to further genotoxic stress. Leiomyosarcoma (LMS), a common STS, frequently harbors genomic complexity and DNA damage response (DDR) dysregulation. Preclinical data showed hyper-dependency on DNA-PK-mediated non-homologous end joining (NHEJ) DDR, and low-dose liposomal doxorubicin (LD-LPD) synergized with the DNA-PK inhibitor peposertib to inhibit tumor growth in LMS models. We hypothesize that a low, sensitizing dose of LPD enhances DNA damage and safely synergizes with peposertib in LMS and other genomically complex STS. Methods: This phase 1, open label, multicenter dose escalation and dose expansion study (NCT05711615) evaluates LD-LPD given intravenously (IV) on day 1 of 28-day cycles with peposertib given orally (PO) twice daily (BID) continuously (Table). Up to 18 patients (pts) over 18 years-old with advanced or unresectable LMS, undifferentiated pleomorphic sarcoma, myxofibrosarcoma, dedifferentiated liposarcoma, and synovial sarcoma, ECOG performance status ≤2, who received ≥1 prior line of systemic therapy (including anthracycline ≤300 mg/m 2 ) are eligible for dose escalation. Dose expansion will include 12 pts with LMS. The primary objective is to determine the recommended phase 2 dose of LPD+peposertib based on the dose limiting toxicity rate. The Bayesian Optimal Interval (BOIN) design will inform dose escalation decisions. Secondary endpoints for the expansion cohort include adverse event rate, progression-free survival, and objective response rate per RECIST v1.1. Potential predictive biomarkers and changes in DDR biomarkers will be evaluated on biopsies during screening and at cycle 1 day 7. Circulating tumor DNA (ctDNA) collected at baseline (dose escalation and dose expansion), on treatment and at progression (dose expansion) will be correlated with disease activity and response. This trial activated on 8-May-2023 through the Experimental Therapeutics Clinical Trials Network (ETCTN) and is enrolling at select sites in the United States. Dose escalation is ongoing as of January 2025. Clinical trial information: NCT05711615 . Planned dose levels for dose escalation. Dose Escalation Schedule Dose Level Dose Liposomal doxorubicin Peposertib (tablet) -1 10 mg/m 2 IV 50 mg PO BID 0* 10 mg/m 2 IV 100 mg PO BID +1 10 mg/m 2 IV 150 mg PO BID +2 10 mg/m 2 IV 200 mg PO BID +3 15 mg/m 2 IV 200 mg PO BID +4 20 mg/m 2 IV 200 mg PO BID *Starting dose.

TPS11580 Background: Gastrointestinal stromal tumor (GIST) is the most common sarcoma of the gastrointestinal tract. KIT and platelet-derived growth factor receptor α ( PDGFRA ) mutations remain the key oncogenic drivers in the majority of patients with advanced GIST, with acquired secondary drug-resistant mutations contributing to the heterogeneity and complexity of the disease. The diversity of these resistance mutations allows escape from standard-of-care tyrosine kinase inhibitor (TKI) therapy, creating an unmet need for novel therapies that inhibit all clinically relevant GIST-driving mutations. DCC-3009 is an investigational, highly potent, and selective switch-control KIT and PDGFRA inhibitor designed to act against known clinically relevant primary and secondary GIST-driving mutations while limiting off-target effects. Preclinical data showed that DCC-3009 has strong antitumor effects in xenograft models driven by resistant KIT mutations, optimized solubility and oral bioavailability, and low risk of cytochrome P450 inhibition. Here, we describe an ongoing phase 1/2 study evaluating DCC-3009 as a monotherapy in patients with advanced GIST. Methods: This study is a multicohort, open-label, phase 1/2 trial evaluating the safety, tolerability, and efficacy of DCC-3009 in patients with advanced GIST (NCT06630234). This trial uses a modular approach, with each module defined according to the therapy (DCC-3009 alone or in combination with other anticancer agents) and divided into 2 parts (dose escalation and dose expansion). For inclusion in the DCC-3009 monotherapy dose escalation, adult patients (≥18 years) must have histologically or cytologically confirmed advanced GIST with documented KIT or PDGFRA mutation and progression on or intolerance to at least 1 approved TKI regimen in the advanced setting (imatinib if KIT -mutant). Patients must have at least 1 measurable lesion per modified Response Evaluation Criteria in Solid Tumors version 1.1 (mRECIST v1.1) and an Eastern Cooperative Oncology Group Performance Status of 0 or 1 at screening. Exclusion criteria include receiving systemic anticancer therapy (encompassing investigational agents) within 14 days or less than 5 half-lives, radiotherapy within 14 days prior to first dose of study drug, prior or concurrent malignancy requiring treatment or expected to need treatment for active cancer, known allergy or hypersensitivity to the study drug components or any of its excipients, and impaired oral absorption or malabsorption syndrome. Enrolled patients across monotherapy dose escalation will receive DCC-3009 orally in 28-day cycles. The primary outcome measures for monotherapy dose escalation include safety assessment. Secondary outcome measures include objective response rate, duration of response, and progression-free survival by mRECIST v1.1, as well as overall survival and pharmacokinetics. Clinical trial information: NCT06630234 .

TPS11579 Background: Gastrointestinal stromal tumors (GIST) are commonly driven by mutations in the receptor tyrosine kinase KIT . Resistance to approved tyrosine kinase inhibitors (TKIs) arises from additional KIT mutations in the ATP-binding pocket (AP) and activation loop (AL). No single approved TKI broadly suppresses all resistant clones, and overlapping VEGFR inhibition and toxicity limits TKI combinations. The type I TKI bezuclastinib (“BEZ,” CGT9486) inhibits KIT AL resistance mutations, does not inhibit VEGFR, and has complimentary activity with sunitinib (“SUN,” inhibitor of KIT AP resistance mutations). The first-in-human study (PLX121-01) and ongoing Peak trial (NCT05208047) evaluated BEZ+SUN showing promising safety and efficacy in GIST. SARC044 investigates BEZ+SUN in patients (pts) with SUN-resistant, KIT-mutant GIST, and correlatives aim to determine mechanisms of response and resistance (NCT06208748). Methods: SARC044 is a multi-center, open label, single-arm phase II trial enrolling up to 40 adult pts with KIT exon 9 or 11-mutant GIST resistant to imatinib and SUN. After TKI washout (baseline, “b/l”), pts initiate BEZ 600 mg daily for 2 weeks, then add SUN 37.5 mg daily, taking both drugs continuously (28-day cycles) until mRECISTv1.1 progression or unmanageable toxicity. Response evaluations (RE) are performed every 8 weeks (wk) through 15 months (mo) on study, then every 12 wk. Circulating tumor DNA (ctDNA) is collected at b/l, cycle 1 day 15 (C1D15), C2D1, C3D1, and progression. Targeted exome sequencing (TES) of ctDNA will track primary/resistant KIT mutation dynamics across therapy. 18 FDG PET/CTs are performed in 20 pts at b/l, C1D15, and C2D1, which guide a biopsy of a resistant tumor. TES, allele-specific and long-read PCR (to detect AP+AL mutation phasing), and immunoblotting (evaluating KIT pathway activation) will be performed on tissue. EORTC QLQ-C30 surveys collect pt-reported outcomes (PRO) at b/l, on treatment, and at progression. The primary endpoint is median progression-free survival (mPFS) and secondary endpoints include overall survival at 1 and 2 years, clinical benefit rate at 16 wk, adverse event rate, PRO, and KIT mutation profile in ctDNA and tissue. 35 evaluable pts achieves 83% power (p<0.05, one-sided) in a one-sample log-rank test to detect a mPFS of 6.5 mo vs 4 mo (historic control). Expected accrual is 12 mo across 4 sites in the United States with ~36 mo to study completion. Clinical trial information: NCT06208748 .

6008 Background: ATC patients present with advanced, often surgically unresectable disease with historically dismal prognosis. Median PFS and OS of DT without pembrolizumab were 6.7 and 13.5 months, respectively, in the ROAR trial. Neoadjuvant DTP achieved locoregional control without radical surgery in a retrospective series of BRAF m-ATC patients, providing rationale to evaluate efficacy and safety in a phase 2 prospective trial. Methods: In this single-arm multicenter phase 2 trial, patients with BRAF m-ATC stage IVB/IVC were enrolled in 5 US centers. Following a 3-6 week run-in with D (150 mg BID) and T (2 mg daily), P (200 mg Q3W) was added, with restaging every three (21-day) cycles. Post-operatively, patients continued P (or DTP) with radiotherapy or transitioned directly to adjuvant DTP (up to 26 cycles). Primary endpoints included R0/R1 resection rate (historically 5%) and overall survival (OS). Secondary endpoints included RECIST 1.1 response after DTP and progression-free survival (PFS). Results: Between 9/2021-1/2025, 42 patients were enrolled; 36 are included in the current analysis (3 not evaluable, 3 pending surgery) (Table). Patients received median 4 (range: 2-7) neoadjuvant DTP cycles, with 26 (72%) achieving radiographic PR/CR. 30 patients (83%) had surgery after neoadjuvant DTP, achieving R0/R1 resection in 29/30 (97%). Mean surgical morbidity score (0-4 scale, 4=unresectable) improved from 3.3 to 1.6 after DTP (p<0.01). Complete ATC pathologic response occurred in 20/30 patients (67%), while 10/30 (33%) had residual ATC in the surgical specimen. Postoperatively, 11/30 (37%) received adjuvant neck radiation, and 28/36 (78%) completed a median of 11 (range: 1-26) adjuvant DTP cycles. With median follow up 18 months, 15/36 (42%) patients died. Median OS was 20 months (95% CI: 12.6-NR); 1- and 2-year OS were 71% and 48%. Complete pathologic responders had better 2-year OS than those with residual ATC (69% vs. 22%, p=0.02). Median PFS was 13.9 months (95% CI, 7.5-NR); 1- and 2-year PFS were 57% and 36%. Grade 5 adverse events occurred in 8 patients (22%), including one possible (duodenal perforation), one probable (kidney injury with sepsis), and 6 unlikely/unrelated treatment-related deaths. Conclusions: Neoadjuvant DTP enables surgical resection in BRAF m-ATC compared with historical controls, and leads to improved PFS and OS. This approach should now be considered a standard of care for BRAF m-ATC. Clinical trial information: NCT04675710 . Total N=36 Age (y), median (range) 67 (46-86) Stage IVB/IVC, n (%) 15 (42%)/21 (58%) Best RECIST response neoadjuvant phase, n (%) CR 2 (6%) PR 24 (67%) SD 6 (17%) PD 4 (11%) Percent change target lesion diameter, mean (95% CI) -44% (-54%, -34%) Surgical morbidity score change, mean (95% CI) -1.7 (-2.1, -1.3)

3520 Background: Recent analyses highlight nonhierarchical outcomes using the 8 th Edition AJCC staging system for CC. For instance, the 5-year survival rate for stages I and IIIa patients (pts) closely align. Additionally, tumor deposits (TDs) have been established as significant prognostic indicators. The AJCCCCEP commissioned this study to develop an updated pathological staging system for CC focused specifically on pts without distant metastasis (M0), while retaining the existing stage IV classification. Methods: Individual patient data (IPD) from pts diagnosed with cc (2010- 2017) in the NCDB were divided into training (70%) and internal validation (30%) datasets. External validation used IPD from clinical trials. The primary endpoint was overall survival (OS). Risk classification development for M0 pts incorporated ungrouped data on pathologic T categories, the number of involved regional lymph nodes (LN+), and TD counts. Recursive partitioning and regression tree analyses were applied to construct hierarchical staging levels. Pre-specified criteria required survival probabilities to be consecutive and show clear separations using Kaplan-Meier (KM) estimates with pairwise log-rank test P of < 0.005 for the training and < 0.05 for validation analyses. Results: Data from 281,997 pts (median age 67 years, 50% male, 81% white, 55% T3, 19% T4, 44% N+, 26% M+, and 11% with ≥1 TD) were analyzed, with a median follow-up of 7.3 years. The updated staging system (Table) met pre-specified criteria, with all observed pairwise P < 0.0001 in the development and internal validation sets. KM OS curves displayed a hierarchical separation across all sub-levels after the 1 st year of diagnosis. Consistent results were seen in pts treated with adjuvant chemotherapy in 4 trials (all pair-wise P < 0.0001). Conclusions: The proposed pathological staging system for M0 pts fulfills pre-specified criteria for hierarchical risk stratification, validated both internally and externally, and provides an evidence-based update. Pending review process, the AJCCCCEP will recommend that these changes be made to the Version 9 staging protocol for colon cancer to improve prognostication for CC pts. Stage T, # of LN+, # of TD M % of pts 1y OS (CI), % 3y OS (CI), % 5y OS (CI), % I T1, 0, 0 0 5 96 (95-97) 91 (90-92) 84 (83-86) IIa T2, 0, 0 0 10 95 (94-95) 88 (88-89) 80 (79-81) IIb T1, 0, 1+T1, 1+, 0T2, 0, 1+T2, 1-4, 0T3, 0, 0 0 27 93 (92-93) 84 (84-85) 75 (75-76) IIIa T1, 1+, 1+T2, 1-4, 1+T2, 5+, 0T3, 0, 1+T3, 1-4, 0 0 14 92 (91-92) 80 (80-81) 71 (70-72) IIIb T2, 5+, 1+T3, 1-4, 1+T3, 5+, 0T4a, 0-4, 0T4b, 0-2, 0 0 13 86 (86-87) 69 (68-70) 58 (57-59) IIIc T3, 5+, 1+T4a, 0-4, 1+T4a, 5+, anyT4b, 0-2, 1+T4b, 3+, any 0 5 78 (77-80) 53 (51-54) 40 (38-41) IVa Any 1a 19 59 (58-60) 28 (28-29) 17 (16-18) IVb Any 1b 7 43 (42-44) 14 (13-14) 6 (6-7) CI: 95% confidence internal; Peritoneum involvement data were not available before 2018 in NCDB. Thus, IVa/b were based on 7 th Edition.

3504 Background: Among patients with resected node-positive colon cancer, nearly 30% will relapse despite standard adjuvant chemotherapy. Analysis of molecular residual disease (MRD) using circulating tumor DNA (ctDNA) may enable risk stratification for tumor recurrence and inform adjuvant treatment decisions. Methods: Postsurgical ctDNA was analyzed in patients with stage III colon carcinoma who participated in a phase 3 trial of adjuvant FOLFOX alone or combined with cetuximab (n = 3084) [NCCTG N0147]. We utilized a tissue-free epigenomic assay for ctDNA detection (Guardant Reveal) with sampling prior to start of adjuvant therapy. Among ctDNA positives, epigenomic tumor fraction (TF) was estimated and ctDNA genotyping was done with Guardant360 (panel of 739 genes). Median follow-up was 6.1 years (yr). Study endpoints included time-to-recurrence (TTR), disease-free survival (DFS) and overall survival (OS) analyzed by Kaplan–Meier method. Multivariable Cox proportional hazards models were used to assess prognostic utility of ctDNA status adjusting for confounders. Interaction between ctDNA and clinicopathological features were assessed. Results: Among 2260 patients with evaluable ctDNA data, 461 (20.4%) were ctDNA positive.Tumors were significantly associated with higher T, N stage, BRAF V600E , high grade, obstruction/perforation, and worse performance status. Positive vs negative ctDNA was significantly associated with shorter TTR (hazard ratio [HR] 4.33, 95% confidence interval [CI] 3.65-5.13, P < 0.0001), poorer DFS (HR 3.74, CI 3.18-4.39, P < 0.0001] and OS (HR 3.17, CI 2.63-3.83, P < 0.0001), adjusting for covariates and tissue MMR, KRAS and BRAF V600E . ctDNA positive vs negative patients had 3y DFS of 36.4% (95%CI 32.2-41.2%) vs 82.5% (95% CI 80.0-84.4%), respectively. Adverse prognosis was consistent across subgroups (all P < 0.05), with stronger detrimental effects for positive ctDNA in N1 (vs. N2), T1/2 (vs T3 or 4), and mismatch repair deficient tumors [interaction P = 0.0002 to 0.041). Among patients with positive ctDNA, TF in those who recurred/died within 3 yr was double of those who remained recurrence-free ( P = 0.0001). High vs. low ctDNA TF ( > vs ≤ median) further stratified TTR (HR 1.48, CI 1.17-1.88, P = 0.0011), DFS (HR 1.52, CI 1.21-1.92, P = 0.0004) and OS (HR 1.58, CI 1.21-2.07, P = 0.0009), adjusting for confounders. ctDNA positive cases, . Analyses of ctDNA detection by site of recurrence, ctDNA clearance, and genomic variant detection are ongoing. Conclusions: In the largest study evaluating tissue-free epigenomic-based MRD detection, we demonstrate a robust prognostic utility of postsurgical ctDNA. Tumor fraction provided further patient stratification and analysis is ongoing to identify a subgroup based on TF that may be unlikely to clear ctDNA despite adjuvant chemotherapy.

TPS3648 Background: Indoleamine 2,3-dioxygenase 1 (IDO1) metabolizes tryptophan along the kynurenine pathway and is recognized as a potent suppressor of tumor reactive immunity. Epacadostat is an orally active, potent and selective inhibitor of IDO1. In preclinical studies, IDO1 was found to promote resistance to radiation in rectal cancer, irrespective of microsatellite instability (MSI) status. IDO1 inhibition with epacadostat improved tumor radiosensitivity by relieving immune suppression and augmenting radiation-induced apoptosis while protecting the normal intestine from radiation damage. In a phase 1 trial, 17 patients were enrolled from 4/2019 to 8/2023. Epacadostat in combination with short-course radiation therapy (SCRT) and CAPOX was well-tolerated and the recommended phase 2 dose (RP2D) of epacadostat was determined to be 400 mg BID. An NCI supported Phase 2 trial is ongoing to further evaluate the promising disease responses reported in the dose escalation phase. Methods: This phase 2 multicenter, open-label trial includes treatment and biomarker cohorts. In the treatment cohort, epacadostat at 400 mg BID will be administered concurrently with SCRT followed by epacadostat monotherapy until 1 day prior to neoadjuvant chemotherapy, followed by standard-of-care (SOC) neoadjuvant chemotherapy and, ultimately, surgical resection or non-operative management (NOM). Biomarker cohort enrollment will commence at completion of treatment cohort accrual. Enrolled patients will be treated with SOC SCRT followed by SOC neoadjuvant chemotherapy and surgical resection or NOM. Eligible patients must be a treatment-naïve, newly diagnosed, pathologically confirmed, locally advanced rectal cancer (defined by 8 th edition AJCC stage 2 or 3, or stage 1 not eligible for sphincter-sparing surgery) with plans to proceed with neoadjuvant SCRT and chemotherapy. The primary endpoint is the neoadjuvant rectal (NAR) score. Secondary endpoints are pathologic complete response (pCR) rate, complete clinical response (cCR) rate and progression-free survival (PFS). Exploratory endpoints are pharmacodynamics, PDX and organoid generation, identification of molecular predictors of response and resistance, correlation of radiographic and pathologic response and effect of treatment on patient quality of life. We aim to enroll 27 patients in the treatment cohort and 10 in the biomarker cohort. Clinical Trial Registration: NCT03516708 .

11506 Background: Catequentinib Hydrochloride (AL3818, Anlotinib, Catequentinib) is a novel, orally administered, small molecule tyrosine kinase inhibitor. There remains an unmet need for effective, well tolerated therapies for patients (pts) with advanced/ metastatic leiomyosarcoma (LMS). We performed a randomized, double blind trial of Catequentinib monotherapy versus placebo in advanced/metastatic LMS. Methods: Patients with a diagnosis of LMS requiring third or further line treatment were eligible. Catequentinib was administered in a 21-day cycle with 14 days on and 7 days off regimen. In this double blind phase 3 trial, patients were randomized 2:1 to Catequentinib or placebo, with the option of crossover to Catequentinib after confirmed Progression Disease (PD) on placebo. Progression-free survival (PFS) with Log Rank test was the primary endpoint and the trial was conducted at multiple sites in the US, UK and EU. Results: Total N = 111 patients were enrolled, and N = 110 were treated and evaluated, 74 randomized to Catequentinib (C), and 36 to placebo (P). In arms (C)/(P) median ages were 59.0/60.5 (range: 33-91) years respectively and 59/29 (79.7%/80.6%) were female. Median PFS by Blinded Independent Central Review (BICR) met the primary endpoint at 3.42 months (95% CI: 2.60, 6.83) for (C) and 1.41 months (95% CI: 1.35, 4.86) for (P) with a p-value of 0.0265 and a HR of 0.536 (95% CI: 0.307, 0.936). Median PFS for patients stratified at ≤ 3 prior lines was 4.86 months (95% CI: 2.04, 8.94) for (C) and 1.41 months (95% CI: 1.31, 4.86) for (P) with a p-value of 0.0046 and a HR of 0.386 (95% CI: 0.196, 0.760). The 6-month progression-free rate was 42.37% for (C) and 20.71% for (P). OS was 17.45 months (95% CI: 13.57, 19.32) for (C) and 16.33 months (95% CI: 11.27, NE) for crossover patients in the (P) arm. 30 (40.5%) of patients have experienced grade 3 treatment-related adverse events in the (C) arm compared to 3 (8.3%) of patients in the (P) arm. The most common TEAE for (C) vs (P) were diarrhea (50.0% vs 22.2%), stomatitis (31.1% vs 8.3%), fatigue (64.9% vs 41.7%), and hypertension (47.3% vs 19.4%). Conclusions: This phase 3 trial met the primary PFS endpoint and demonstrates superior PFS for Catequentinib vs placebo in metastatic/advanced LMS. This study confirms the acceptable benefit-risk profile of Catequentinib in LMS. Catequentinib is an effective and well tolerated treatment option for patients with LMS. Clinical trial information: NCT03016819 .

Abstract Inotuzumab ozogamicin (InO) is an antibody-calicheamicin conjugate with high efficacy in lymphoid malignancies. It targets the B-cell surface protein CD22, which is expressed in most B-cell acute lymphoblastic leukemia (B-ALL) cases, albeit with variable intensity. However, factors governing CD22 expression and thus leukemia sensitivity to InO remain incompletely understood. Using multiomic characterization of 196 human B-ALL samples, coupled with ex vivo InO sensitivity profiling, we showed that early leukemia differentiation arrest at the pre–pro-B stage is associated with resistance to InO. Screening of 1639 transcription factor genes identified early B-cell factor 1 (EBF1) as a key regulator of CD22 expression (false discovery rate of 7.1 × 10−4). When comparing the assay for transposase-accessible chromatin with sequencing profiling results of the most InO-sensitive and -resistant cases (50% lethal concentration &lt;10th vs &gt;90th percentile, n = 18), the binding motif for EBF1 was strikingly enriched in regions with differential open chromatin status (P = 8 × 10−174). CRISPR interference targeting EBF1 binding sites at the CD22 locus led to an ∼50-fold reduction in cell surface CD22 expression and, consequently, an ∼22-fold increase in InO resistance in ALL cell lines. Interestingly, within BCR::ABL1 ALL, we observed intrasubtype heterogeneity linked to EBF1 transcriptional downregulation (P = 1.1 × 10−15) and/or somatic alteration (P = .004), which led to reduced CD22 expression (P = 8.3 × 10−11) and ex vivo and in vivo resistance to InO. Collectively, these findings point to the direct impact of EBF1 on CD22 expression during B-cell development, which, in turn, contributes to interpatient variability in InO response, even within the same subtype of B-ALL.

e13551 Background: The landscape of cancer care is evolving rapidly. In 2023, there were 83 new FDA oncology approvals, and 145 interventional treatment (tx) studies opened across Mayo Clinic. We are exploring novel precision outreach approaches utilizing an LLM-integrated chatbot application to “ping” patients (pts) with specific clinical or genomic characteristics about newly available drugs or clinical trials. As novel outreach methods are considered, we surveyed a patient (pt) support group to understand communication preferences and awareness of adjuvant CDK4/6 inhibitors in tx of breast cancer (BC). Methods: On October 7, 2024, we administered a cross-sectional survey to 41 members of the Breast Cancer Support Network (BCSN) in Rochester, MN as a part of an IRB exempt quality improvement project. Leaders of the BCSN shared information to all participants, noting that the survey’s intent was to represent the pt voice and participation was voluntary. Anonymous survey data were collected with descriptive results reported. Results: 34/41 participants in the BCSN shared demographic information. The majority (83%) were > 50 years of age. 47% reported stage I BC, 12% stage II, 6% stage III, and 35% were unsure of their stage. Most participants (26/34, 76%) reported that their BC was hormone receptor positive (HR+), 2 HER-2 positive, and 6 unsure of their BC receptor status. 24/26 (92%) of pts with HR+ BC were taking or planning to start adjuvant endocrine therapy. 10/34 (29%) were aware that adjuvant CDK 4/6 inhibitors were approved. Of these 10 participants, 2 learned of it from online health resources, 6 from their clinician, 1 from social media, and 1 from a support group. The majority (66%) were unsure if they qualified for these drugs. Regarding receipt of information on new drug approvals/tx options, the highest ranked communication preference was to receive this information in person at an upcoming visit (ranked 1st by 50% of participants), followed by EHR-based message (28%), email (10%), phone call (6%), letter (4%), or an interactive chatbot (0%). Most respondents noted that communication from their healthcare provider was very important (30/37, 81%), with others stating that this was somewhat important (5/37, 14%) or neutral (2/37, 5%). Most noted that receiving information about tx options via video or visual aid before a visit would be very helpful (33/41, 80%). When asked about follow up after learning of a new drug approval, 17/32 (53%) of pts preferred an appointment, 9/32 (28%) a phone call, 3/32 (9%) a decision aid tool, and 3/32 (9%) a questionnaire to assess their understanding. Conclusions: Providing personalized, timely communication about new FDA approved tx options is important for BC survivors and critical for improving care delivery. While technological solutions could broaden awareness, this requires balancing pt preferences for direct communication with clinicians.