Abstract Introduction: Simultaneous measurement of protein expression and chromosomal alterations within the same FFPE section enables direct analysis of clonal selection and disease progression from normal epithelium through precancerous to cancerous states. We developed a unified workflow based on the one-shot Orion multiplexed imaging platform (Lin et al., Nature Cancer 2023) that integrates high-dimensional protein imaging with a conventional DNA-FISH assay for in situ detection of chromosomal copy number alterations (CNAs). Traditional DNA-FISH, although widely used in diagnostic practice, requires protease digestion and permeabilization steps that destroy antigen epitopes and distort nuclear morphology, preventing reliable protein detection and limiting integration with immunofluorescence. The challenge spans both normal precursor and malignant tissues, where densely packed or overlapping nuclei complicate single-cell CNA scoring - an issue that is now particularly relevant, given the growing recognition that aneuploidy can arise even in morphologically normal epithelia. Method: Recent advances in multiplexed imaging now enable phenotypic characterization of individual cells harboring CNAs, a capability previously unattainable with conventional immunofluorescence. To realize this potential, we optimized fixation, hybridization, and imaging parameters to preserve both antigenicity and nuclear architecture while maintaining robust CNA detection. The resulting ORION-FISH workflow enables simultaneous visualization and quantification of protein states and chromosomal alterations within the same section. Results: We have found that normal fallopian tube epithelium harbors MYC and/or CCNE1, both of which are common CNAs in High Grade Serous Ovarian Cancer (HGSOC) and its precursor lesion, Serous Tubal Intraepithelial Carcinoma (STIC). We have also found that these aneuploid cells may have been under strong negative selection pressure, partially due to strong immune surveillance. Currently, we are analyzing in depth precursor samples and HGSOC specimens that will be presented at the meeting. Conclusion: We applied ORION-FISH approach to HGSOC and its precursors to generate spatial maps of aneuploidy and cell states across the normal-precancer-cancer continuum, establishing a foundation for our studies in the HGSOC Pre-Cancer Atlas 2.0. Citation Format: Tanjina Kader, Yu-An Chen, Clemens Hug, Jia-Ren Lin, Jeremy Muhlich, Euihye Jung, Charles Drescher, Ronny I. Drapkin, Peter Karl Sorger, Sandro Santagata. Integrative spatial profiling of protein and chromosomal alterations across normal, precancer, and cancer revealed the presence of aneuploidy in the normal fallopian tube [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 3533.

e22539 Background: Lynch syndrome (LS) is a genetic predisposition associated with germline alterations in the DNA mismatch repair pathway that increases the risk of endometrial cancer (EC) up to 10-fold among other cancer risks. Hysterectomy (H) is a definitive strategy for risk reduction offered after childbearing. Screening for EC with an endometrial biopsy (EMB) is a strategy for those who are not ready for surgery. However, the uptake and utility of EMB are unknown. We present data from a large retrospective cohort aiming to provide insight into these questions. Methods: We reviewed the EC risk management behaviors for 75 assigned females at birth with LS between 2006 and 2024 at a large tertiary community cancer center in Seattle, WA. Data collected include age, pathogenic variant (PV), personal and family history of cancer, gynecologic surgical history, EMB, and pathology findings at EMB and/or surgery. Results: Median age of the cohort at LS diagnosis was 44 years (21-87), and 42 and 33 patients were pre- and post-menopausal, respectively. Reasons for genetic testing included: diagnosis of LS-related cancer (n = 37), familial testing (n = 17), and family history of cancer (n = 21). 18 patients had a PV in MLH1, 21 in MSH2 , 21 in MSH6 , and 15 in PMS2 . Of the 75 patients, 44 (59%) had either H + bilateral salpingectomy (H-BS) or H + bilateral salpingo-oophorectomy (H-BSO) before (n = 14) or at LS diagnosis (n = 30); 19/44 had EC and all had H-BSO. Longitudinal follow-up information was available for the remaining 31 patients with a median follow-up time of 5.48 years (0.03, 18.62). 27/31 patients were older than 30 at some point during follow-up and were considered eligible for EMB. Nine patients underwent EMB (33%), including 2 patients who had the procedure immediately prior to surgery. One patient was found to have a precursor lesion on EMB and EC was found on subsequent H-BS. At the time of LS diagnosis, 45 patients had both a uterus and no diagnosis of EC. 25/45 patients (56%) underwent risk reducing surgery, 3 chose a H-BS and 22 H-BSO. No ovarian abnormalities were noted. There was trend favoring ovarian conservation in women aged < 45 (p = 0.1, Fisher’s exact test). No differences were observed based on the gene involved. Of the 19 patients that chose to forego surgery,15 were eligible for screening, but only 4 (27%) patients underwent EMB. Conclusions: H-BSO is the most common EC risk reduction strategy in patients with LS. Receipt of a BSO is common and similar across mismatch repair genes. Uptake of EMB is low and a substantial fraction of at-risk patients don’t receive any EC risk management strategies. Further research is needed to identify patient and provider-specific factors contributing to the observed variation in risk management.

Systematic whole-protein screening and comprehensive profiling of antigen-specific CD4+ T cells are crucial for advancing vaccine design and cancer immunotherapies, yet remain technically challenging. Here, we present a high-throughput platform that utilizes large-scale class II single-chain trimer libraries to detect antigen-specific CD4+ T cells, while simultaneously profiling their antigen specificity, TCRα/β sequences, MHC restriction, whole transcriptomes, and patient/timepoint origins at single-cell resolution. Upon rigorous platform validation, we screened the full SARS-CoV-2 spike receptor binding domain in a longitudinal cohort of 22 participants, identifying 2,188 antigen-specific CD4+ T cells and showing key metrics defining the immunogenicity of class II-restricted viral antigens. We further extended the platform to whole-protein screening of HPV-16 E6/E7 in a cohort of precancerous patients, indicating HPV-specific CD4 TCRs that, upon extensive characterization, demonstrate strong therapeutic potential. By integrating high-throughput antigen screening with high-dimensional, multi-modal cellular characterization, our approach provides detailed insight into CD4+ T cell immunity, potentially guiding vaccine design and next-generation TCR-based cancer immunotherapies.

3102 Background: EZH2 inhibition antitumor activity occurs through various mechanistic pathways in multiple tumor types, including via synthetic lethality in advanced ARID1A -mutated ovarian clear cell carcinoma (OCCC) and endometrial carcinoma (EC). Oral, next-generation, dual EZH2/EZH1 inhibitor tulmimetostat is in Phase II evaluation in multiple disease cohorts (NCT04104776; Oaknin et al. ASCO 2024, ESMO 2024). We report updated efficacy and safety data from the ARID1A -mutated OCCC/EC cohorts, including dose optimization and expansion arms. Methods: Phase II Stage 1 evaluated tulmimetostat 350 mg once daily (QD). Stage 2 dose-optimization design randomizes further patients with OCCC (M2) or EC (M3) to 200 mg or 300 mg tulmimetostat QD in Stage 2a, with an efficacy gateway for each arm to open Stage 2b. Primary endpoint is objective response rate (complete response [CR] + partial response [PR]), and secondary objectives include safety. Results: As of October 15, 2024, enrollment into the M2/M3 200 mg, 300 mg, and 350 mg arms included 20/10, 21/21 and 14/11 patients, respectively. A total of 56.4% M2 and 61.9% M3 patients received ≥3 prior lines of therapy. Most responses were seen in the M2 200 mg arm and in the M3 350 mg arm (n=4 each; Table). The safety profile across arms was consistent with the EZH1/2 drug class. In M2/M3 cohorts, treatment-emergent adverse events (TEAEs) leading to dose modifications were reported in 55.0%/60.0%, 71.4%/85.7%, and 92.9%/90.9% of patients at 200 mg, 300 mg, and 350 mg, respectively. TEAEs leading to treatment discontinuation were reported in 5.0%/20.0%, 4.8%/4.8%, and 14.3%/9.1%, respectively. Serious TEAEs considered at least possibly related (TRAEs) to tulmimetostat treatment were reported in 5.0%/0%, 9.5%/14.3%, and 21.4%/27.3%, respectively. Grade ≥3 TRAEs were mainly hematologic (Table); no TRAEs leading to death were reported. Conclusions: Tulmimetostat showed an improved and acceptable safety profile in OCCC and EC at 200 mg and 300 mg doses (versus 350 mg) with promising antitumor activity, supporting further clinical investigation. Clinical trial information: NCT04104776 . Best confirmed responses and most common grade ≥3 related TEAEs. Cohort M2: OCCC M3: EC Dose, mg 200 300 350 200 300 350 Efficacy evaluable*, N 20 20 14 10 15 11 Best confirmed response † , n CRPRStable disease 0410 0210 0 17 008 115 042 Progressive diseaseNo post-baseline response assessment 51 71 60 11 71 41 Safety evaluable, N 20 21 14 10 21 11 Grade ≥3 related TEAEs ‡ , n (%) Thrombocytopenia 1 (5) 3 (14) 4 (29) 0 4 (19) 2 (18) Anemia 3 (15) 0 7 (50) 0 5 (24) 1 (9) Neutropenia 0 0 2 (14) 0 0 4 (36) Diarrhea 0 4 (19) 0 0 0 2 (18) Data cut off: October 15, 2024. *Patients who received ≥1 dose, had ≥1 post-baseline response assessment, or discontinued treatment prior to first post-baseline assessment for any reason. † RECIST 1.1. ‡ >10% in any M2/M3 arm.

BACKGROUND:Poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitors (PARPis) are indicated for treatment of tumors with breast cancer susceptibility genes BRCA1/2 mutations and homologous recombination deficiency (HRD). Little is known about differences in care by BRCA1/2 and HRD status for breast and ovarian cancers. METHODS:We investigated clinical characteristics, treatment, clinical outcomes, and health-care resource utilization by BRCA1/2 or HRD status among patients diagnosed between 2018-2020 with HER2-negative metastatic breast (mBC) and advanced epithelial ovarian cancer (aEOC) in the United States community healthcare setting. RESULTS:The study included 314 patients with mBC and 465 with aEOC. Patients with mBC carrying a BRCA1/2 mutation were younger and had a higher proportion of triple negative cancer than non-carriers (50% vs 38%). Only 8% of eligible patients received a PARPi in first-line (1L) and 18% in second-line (2L) of treatment for mBC. In aEOC, patients with HRD were younger and a higher proportion received 1L maintenance treatment with a PARPi than patients with non-HRD tumors (95% vs 66%). In aEOC, patients without HRD had greater healthcare resource use. Patients with BRCA-mutated tumors had poorer overall survival (OS); there were no differences in OS by HRD status in aEOC. CONCLUSION:This study demonstrated differences in treatment by BRCA1/2 and HRD status. There was low PARPi uptake among patients with BRCA-mutated mBC but not among patients with aEOC. In aEOC, the cost to "treat all" may outweigh benefits; identifying patients without HRD likely to benefit from PARPis is needed.

High-grade serous ovarian cancer (HGSOC) originates from fallopian tube (FT) precursors. However, the molecular changes that occur as precancerous lesions progress to HGSOC are not well understood. To address this, we integrated high-plex imaging and spatial transcriptomics to analyze human tissue samples at different stages of HGSOC development, including p53 signatures, serous tubal intraepithelial carcinomas (STIC), and invasive HGSOC. Our findings reveal immune modulating mechanisms within precursor epithelium, characterized by chromosomal instability, persistent IFN signaling, and dysregulated innate and adaptive immunity. FT precursors display elevated expression of MHC class I, including HLA-E, and IFN-stimulated genes, typically linked to later-stage tumorigenesis. These molecular alterations coincide with progressive shifts in the tumor microenvironment, transitioning from immune surveillance in early STICs to immune suppression in advanced STICs and cancer. These insights identify potential biomarkers and therapeutic targets for HGSOC interception and clarify the molecular transitions from precancer to cancer. SIGNIFICANCE:This study maps the immune response in FT precursors of HGSOC, highlighting localized IFN signaling, chromosomal instability, and competing immune surveillance and suppression along the progression axis. It provides an explorable public spatial profiling atlas for investigating precancer mechanisms, biomarkers, and early detection and interception strategies. See related commentary by Recouvreux and Orsulic, p. 1093.

The human Fallopian tube (FT) is an important organ in the female reproductive system and has been implicated as a site of origin for pelvic serous cancers, including high-grade serous tubo-ovarian carcinoma (HGSC). We have generated comprehensive whole-genome bisulfite sequencing, RNA-seq, and proteomic data of over 100 human FTs, with detailed clinical covariate annotations. Our results challenge existing paradigms that extensive epigenetic, transcriptomic and proteomic alterations exist in the FTs from women carrying heterozygous germline BRCA1/2 pathogenic variants. We find minimal differences between BRCA1/2 carriers and non-carriers prior to loss of heterozygosity. Covariates such as age and surgical indication can confound BRCA1/2-related differences reported in the literature, mainly through their impact on cell composition. We systematically document and highlight the degree of variations across normal human FT, defining five groups capturing major cellular and molecular changes across various reproductive stages, pregnancy, and aging. We are able to associate gene, protein, and epigenetic changes with these and other clinical covariates, but not heterozygous BRCA1/2 mutation status. This sheds new light into prevention and early detection of tumorigenesis in populations at high-risk for ovarian cancer.

3097 Background: Phase I dose-finding recommended a Phase II dose of 350 mg for the investigational oral, next-generation, dual EZH2/EZH1 inhibitor tulmimetostat (1), with preliminary Phase II results previously reported (2). To find an optimal dose, design of the ongoing Phase II part was later updated under the FDA’s dose-optimization paradigm (NCT04104776). Here we report updated preliminary findings including dose expansions. Methods: Phase II is evaluating tulmimetostat ≤350 mg once daily (QD) in 28-day cycles in 6 disease-based cohorts. The dose-optimization design randomizes further pts with ovarian clear cell carcinoma (OCCC; M2)/endometrial carcinoma (EC; M3) to 200/300 mg tulmimetostat QD. Primary endpoint is objective response rate (complete response [CR]/partial response [PR]); secondary objectives include pharmacokinetics/pharmacodynamics and safety. Results: As of Oct 15, 2023, 117 pts received ≥1 dose (safety set); 111 had ≥1 post-baseline tumor assessment or discontinued prior to it (efficacy set). Median time since diagnosis was 2.8 years (0–19.6); 86.3% of pts had ≥2 prior lines of therapy. At cut-off, best responses of ≥1 CR/PR were seen in 5 cohorts (Table). 74.4% had dose modifications due to treatment-emergent adverse events (TEAEs), 41.9% had ≥1 serious TEAE, and 9.4% discontinued therapy due to TEAEs. Most frequent TEAEs (≥35% of pts; any grade/Grade ≥3) considered possibly related to treatment were diarrhea (49.6%/10.3%), thrombocytopenia (48.7%/24.8%), anemia (39.3%/16.2%), and nausea (35.9%/2.6%). Phase I/II data showed a direct correlation between increasing doses (50–375 mg) or exposure (area under the curve 0–24 hours or maximum concentration) and larger changes in gene expression, which plateau at higher doses (≥225–≤375 mg). Conclusions: The evolving Phase II data, including early data from lower doses, continue to show signs of antitumor activity/disease stabilization. The safety profile is consistent with EZH2 inhibition. These preliminary findings in heavily pretreated pts with multiple tumor types and evolving dose-optimization data support ongoing investigation of tulmimetostat. 1. Lakhani et al. ASCO 2021. 2. Drescher et al. ASCO 2023. Clinical trial information: NCT04104776 . [Table: see text]

Abstract Introduction: Despite the clear genetic evidence linking serous tubal intraepithelial carcinoma (STIC) and high-grade serous ovarian carcinoma (HGSOC), the specific conditions and events that promote the progression of STIC lesions into invasive disease remain poorly understood. Method: As a critical initial step, we have assembled a cohort of incidental p53 signatures, STIC lesions, and STIC with concurrent HGSOC. We have performed extensive multi-modal analysis using multiplexed tissue imaging and spatial transcriptomics that identify features of the immune system that play a vital role in the early steps of HGSOC development. We have processed 43 specimens using highly multiplexed tissue imaging at single-cell resolution (cyclic immunofluorescence, CyCIF), and 35 specimens for micro-regional spatial transcriptomics using the GeoMx (Whole Transcriptome, Nanostring) on over 450 pathologist-annotated regions of interest. Results: Our data suggests an immune-cold environment and T-cell dysfunction in STIC lesions, including incidental STIC. One of the significant immune populations identified was CD103+ tissue-resident memory T cells (TRM). In incidental p53 signatures, activation of TRM was rare, similar to FT, which may indicate the absence of sensing “tumor antigen” by these TRM. CyCIF analysis also revealed that most incidental STIC lesions (7/9 cases) overexpress major histocompatibility complex (MHC) class I compared to the normal epithelium, especially both HLA complex, HLA-A and HLA-E. Most STICs showed extensive intra-lesion heterogeneity, with some STICs remaining HLA-A and HLA-E negative. Incidental p53 signatures, on the other hand, were mostly HLA-A and HLA-E negative and, when positive, had only a few cells expressing HLA. We hypothesized that there might be a natural selection of HLA-E-positive clones as STICs progress to HGSOC. Consistent with this, HGSOC showed further overexpression of HLA-E. However, HLA-E heterogeneity was still observed in the invasive tumor, with both positive and negative clones co-existing. Geomx data suggested that the interferon signaling pathway is upregulated in the epithelial of HLA-E positive STIC and cancer clones compared to HLA-E negative clones. In turn, both HLA-A and HLA-E might be overexpressed in the epithelial of HLA-E-positive STICs. Overall, we showed that the response in interferon (IFN) α and γ, NF-KB, and IL-6-induced STAT-3 pathways were upregulated in both STIC lesions and carcinoma. The role of these pathways, especially STAT-3 pathway, has been shown in other aneuploid cancers in promoting immune escape, cell proliferation and migration, chemoresistance and inhibiting apoptosis. We have shown the co-localization of cGAS and BAF, a marker for micronuclei rupture, by super-resolution 3D imaging to confirm one of the mechanisms of IFN activation. Conclusion: Taken together, these data may indicate chromosomal instability is one of the mechanisms that is driving the IFN-signaling pathway and, hence, a potential selective advantage for HLA-E-positive clones in tumorigenesis, leading to inhibiting NK cell surveillance followed by reducing T cell infiltration. Citation Format: Tanjina Kader, Jia-Ren Lin, Shannon Coy, Clemens Hug, Yu-An Chen, Roxanne J. Pelletier, Mariana Leon, John Lee, Yi-Lin Xu, Clarence Yapp, Natalie Shih, Gabriel Mingo, Euihye Jung, Srishti Rathore, Judith Agudo, Charles Drescher, Peter K. Sorger, Ronny Drapkin, Sandro Santagata. Multimodal spatial profiling reveals the emergence of an immune suppressive microenvironment at the initial stages of high-grade serous ovarian cancer development [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB311.

Multiple antigens, autoantibodies (AAb), and antigen-autoantibody (Ag-AAb) complexes were compared for their ability to complement CA125 for early detection of ovarian cancer. Twenty six biomarkers were measured in a single panel of sera from women with early stage (I-II) ovarian cancers (n = 64), late stage (III-IV) ovarian cancers (186), benign pelvic masses (200) and from healthy controls (502), and then split randomly (50:50) into a training set to identify the most promising classifier and a validation set to compare its performance to CA125 alone. Eight biomarkers detected ≥ 8% of early stage cases at 98% specificity. A four-biomarker panel including CA125, HE4, HE4 Ag-AAb and osteopontin detected 75% of early stage cancers in the validation set from among healthy controls compared to 62% with CA125 alone (p = 0.003) at 98% specificity. The same panel increased sensitivity for distinguishing early-stage ovarian cancers from benign pelvic masses by 25% (p = 0.0004) at 95% specificity. From 21 autoantibody candidates, 3 AAb (anti-p53, anti-CTAG1 and annt-Il-8) detected 22% of early stage ovarian cancers, potentially lengthening lead time prior to diagnosis. A four biomarker panel achieved greater sensitivity at the same specificity for early detection of ovarian cancer than CA125 alone.

AbstractSerial CA125 and second line transvaginal ultrasound (TVS) screening in the UKCTOCS indicated a shift towards detection of earlier stage ovarian cancer (OvCa), but did not yield a significant mortality reduction. There remains a need to establish additional biomarkers that can complement CA125 for even earlier and at a larger proportion of new cases. Using a cohort of plasma samples from 219 OvCa cases (59 stage I/II and 160 stage III/IV) and 409 female controls and a novel Sensitivity Maximization At A Given Specificity (SMAGS) method, we developed a blood-based metabolite-based test consisting of 7 metabolites together with CA125 for detection of OvCa. At a 98.5% specificity cutpoint, the metabolite test achieved sensitivity of 86.2% for detection of early-stage OvCa and was able to capture 64% of the cases with low CA125 levels (< 35 units/mL). In an independent test consisting of 65 early-stage OvCa cases and 141 female controls, the metabolite panel achieved sensitivity of 73.8% at a 91.4% specificity and captured 13 (44.8%) out of 29 early-stage cases with CA125 levels < 35 units/mL. The metabolite test has utility for ovarian cancer screening, capable of improving upon CA125 for detection of early-stage disease.

Introduction ARID1A mutation (ARID1Amut) has a high incidence in OCCC (up to 60%) and EC (up to 40%), with evidence as a negative prognostic marker for treatment resistance and outcomes. EZH2 inhibition in ARID1Amut solid tumors results in tumor growth inhibition (Bitler et al. Nat Med 2015;21:231–238). Preliminary Phase II (NCT04104776) efficacy, safety, and biomarker findings from OCCC and EC cohorts receiving tulmimetostat are reported. Methods The Phase II study is evaluating tulmimetostat 350 mg once daily in 6 disease-based cohorts, including ARID1Amut OCCC/EC. Per Simon 2-stage design, expansion of enrolment (plus n=19 patients per cohort in Stage 2) requires objective response rate (ORR) ≥1/10 in Stage 1. Primary endpoint is ORR; secondary endpoints include safety. Evaluation of two additional dose levels was implemented for both cohorts, per FDA recommendation of Project Optimus, to inform on optimal tulmimetostat dose. Results 24 patients were enrolled (OCCC, n=14; EC, n=10); 50% of each cohort have received ≥3 prior treatment lines. Both cohorts are eligible for Stage 2 expansion, with 1 and 2 confirmed partial responses in patients with OCCC and EC, respectively (table 1). The manageable safety profile across all 6 tumor cohorts (n=81) was consistent with known class effects; Grade ≥3 related adverse events (≥10% of patients) included thrombocytopenia, anemia, neutropenia, and diarrhea. Next generation sequencing did not reveal a specific hotspot for ARID1Amut locations impacting clinical outcome in patients with OCCC/EC. Conclusion/Implications These preliminary findings in heavily pre-treated patients with ARID1Amut OCCC/EC support continued investigation of tulmimetostat monotherapy.

PURPOSE:The TAPUR Study is a pragmatic basket trial evaluating antitumor activity of commercially available targeted agents in patients with advanced cancers harboring potentially actionable genomic alterations. Data from a cohort of patients with endometrial cancer (EC) with ERBB2 or ERBB3 (ERBB2/3) amplification, overexpression, or mutation treated with pertuzumab plus trastuzumab (P + T) are reported.METHODS:Eligible patients had advanced EC, no standard treatment options, measurable disease (RECIST v1.1), Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, and tumors with ERBB2/3 amplification, overexpression, or mutation. Simon's two-stage design was used with a primary end point of disease control (DC), defined as objective response (OR) or stable disease (SD) of at least 16 weeks (SD16+) duration. Secondary end points include safety, duration of response, duration of SD, progression-free survival (PFS), and overall survival (OS).RESULTS:Twenty-eight patients were enrolled from March 2017 to November 2019; all patients were evaluable for efficacy and toxicity. Seventeen patients had tumors with ERBB2/3 amplification and/or overexpression, eight with both ERBB2 amplification and ERBB2/3 mutations, and three with only ERBB2 mutations. Ten patients had DC (two partial response and eight SD16+); all 10 had ERBB2 amplification, and 6 of the 10 patients with DC had >1 ERBB2/3 alteration. DC and OR rates were 37% (95% CI, 21 to 50) and 7% (95% CI, 1 to 24), respectively; the median PFS and median OS were 16 weeks (95% CI, 10-28) and 61 weeks (95% CI, 24-105), respectively. One patient experienced a grade 3 serious adverse event (muscle weakness) at least possibly related to P + T.CONCLUSION:P + T has antitumor activity in heavily pretreated patients with EC with ERBB2 amplification and warrants additional study.

384 Background: Ovarian cancer is the fifth leading cause of cancer death among women in the United States (US). Optimizing care for patients with ovarian cancer using a systematic, guideline-concordant approach improves outcomes. However, notable gaps persist for most patients with ovarian cancer in the US. Beginning in 2018, the Association of Community Cancer Centers (ACCC) implemented a quality improvement (QI) initiative in community and academic cancer centers to address care gaps. From this work, our expert steering committee published a quality document to inform evidence based ovarian cancer care delivery. Methods: In Phase II of this project we used the quality document to inform a qualitative baseline self-assessment and development of four six-month QI initiatives at cancer centers in the US. Based on this work, we developed a quality assessment tool to aid cancer centers in performing QI needs-assessments using the ovarian cancer quality document. The assessment tool applies evidence-based care recommendations in key areas identified by our multidisciplinary steering committee comprised of experts in ovarian cancer care. Results: The assessment tool includes a series of program-level questions and addresses seven key domains: 1. Care coordination and patient education, 2. Prevention and screening, 3. Diagnosis and initial management, 4. Treatment planning, 5. Disease surveillance, 6. Equity in care, and 7. Quality of life. Each domain has between two and seven key recommendations identified. Sites rate themselves on a four-point scale (1-unsatisfactory, 2-needs improvement, 3-acceptable, 4-good) for each key recommendation. Each key recommendation is given equal weight, and a combined score from 0-100 is calculated for each of the seven domains. The tool includes a macro-enabled spreadsheet that makes necessary calculations and provides an overall score, domain-specific sub-scores, and a list of key recommendations that received low ratings. The tool is to be used by clinical sites to self-assess the quality of ovarian cancer care currently provided at their cancer program and serves as a needs assessment. It is recommended that the site team performs the self-assessment in the context of a facilitated half-day multidisciplinary team meeting. After the self-assessment, sites are encouraged to develop QI initiatives to address the gaps identified using the format and structure we have previously described. Conclusions: The QI Assessment tool provides an important resource for cancer centers to conduct needs assessments in key areas of ovarian cancer care. The needs assessment can be used to inform the implementation of program-specific QI initiatives to elevate quality care delivery.