Moreno‐Aspitia, Alvaro

536 Background: Folate receptor alpha (FRα) is overexpressed in ~80% of triple-negative breast cancers (TNBC). We previously demonstrated that patients (pts) with breast cancer naturally mount immune responses to FRα. In prior Phase I and II studies, a GM-CSF-adjuvanted FRα peptide vaccine (FRPV) was safe and induced durable FRα-specific T-cell immunity in 83–90% of pts with breast and ovarian cancer. Methods: Eligible pts were women ≥18 years with TNBC (ER/PR ≤10%) with 1+ of the following: stage ≥T1c disease, node-positivity, or residual disease after neoadjuvant chemotherapy. Pts were randomized 2:1 to receive FRPV or placebo (GM-CSF alone) every 28 days for cycles 2-7 and then every six months for 7 booster doses, with cycle 1 consisting of cyclophosphamide 50mg orally twice daily for days 1-7 and 15-21 (in both arms). Randomization was stratified by chemotherapy setting (adjuvant only vs neoadjuvant) and stage (I/II vs III). FRα expression was evaluated by immunohistochemistry. The study was designed to detect (at 30 months after the last pt enrolled) a disease-free survival (DFS) difference of 14% assuming a 3.5-year DFS rate of 70% in the control group and with 78% power. Results: 280 pts were enrolled (median age 52). The majority had stage I or II tumors (n = 219, 78%). There were numerically more node-positive tumors in the vaccine arm, 78 (41%) vs 27 (32%), p = 0.15. Median follow-up was 3.5 years, and 33 (FRPV: 25, placebo: 8) DFS events were observed; 3.5-year DFS rate was 88% with FRPV and 90% with placebo (HR 1.42, 95% CI 0.64–3.15; p = 0.39). Overall survival (OS) also did not differ by arm (HR 2.48, 95% CI 0.55–11.20; p = 0.22). Among node-positive pts (n = 105), DFS did not differ between arms (HR 0.95, 95% CI 0.34–2.66; p = 0.92). However, a numerical DFS event rate improvement (14% for vaccine vs. 26% for placebo) was observed in 61 patients with stage III disease (HR 0.51, 95% CI 0.16–1.68; p = 0.26). DFS did not differ by chemotherapy setting or by receipt of anthracycline, capecitabine, and/or an immune checkpoint inhibitor. FRPV was well tolerated, with predominantly grade 1–2 adverse events (AEs) and no vaccine-related grade ≥4 AEs. FRα expression was available from tumor in 230 pts, with 72% expressing > 0. Overall, DFS was not significantly associated with FRα expression (0 vs > 0; HR 0.55, 95% CI 0.21–1.44; p = 0.21), and no significant differences in DFS by FRα expression were observed between treatment arms. Conclusions: FRPV following oral cyclophosphamide was safe, with no vaccine-related high-grade AEs. While no significant improvement in DFS or OS was observed overall, a numeric trend toward improved DFS was observed in pts with stage III TNBC. This finding is hypothesis-generating and supports further evaluation of FRα-targeted vaccination in higher-risk TNBC. Immune correlative analyses are ongoing to better define vaccine immunogenicity and its relationship to clinical outcomes. Clinical trial information: W81XWH-15-1-0293.

Abstract Purpose: Activation of the RAS/MAPK pathway is associated with reduced tumor-infiltrating lymphocytes and poor outcomes in triple-negative breast cancer. Previous studies demonstrated that inhibition of the MAPK pathway with a MEK inhibitor is synergistic with immune checkpoint inhibitors. Patients and Methods: We conducted a phase I/II trial of pembrolizumab and binimetinib in patients with metastatic triple-negative breast cancer with ≤3 prior lines of therapy. There were two dose levels (DL) with binimetinib at 45 mg at DL 0 and 30 mg at DL −1. Results: The recommended phase II dose was the standard dose of pembrolizumab with binimetinib 30 mg twice daily. The objective response rate (ORR) was 30.4%, with a numerically higher ORR in patients without liver metastasis at 45.5%. Among patients who achieved objective responses, 80% had a duration of response >12 months and ongoing even after stopping treatment (5.4–69.0 months). Patients with PD-L1–positive tumors (modified proportion score ≥10) were more likely to respond with an ORR of 66.7%. However, clinical benefit was observed in 25% of patients with PD-L1–negative tumors. Consistent with preclinical studies, four of six patients with clinical benefit had either increased PD-L1 or decreased p-ERK expressions in serial circulating cancer-associated macrophage-like cells after starting binimetinib. Conclusions: Pembrolizumab and binimetinib at 30 mg are safe with manageable toxicities. Promising activity was observed in patients without liver metastases. Future larger clinical trials are warranted to further evaluate the efficacy of this chemotherapy-free combination.

Background: The Clinical Treatment Score post-5 years (CTS5) is a risk stratification tool used to determine the risk of late recurrence in hormone receptor–positive (HR+), HER2-negative breast cancer (BC). Limited data exist on its use in HR+, HER2-positive (HER2+) BC. Patients and Methods: CTS5 was evaluated in HR+, HER2+ BC in the North Central Cancer Treatment Group (NCCTG) N9831 (Alliance) and NSABP B-31 (NRG) trials. Results: A total of 1,862 patients with HR+, HER2+ BC without recurrence 5 years after enrollment were included. Overall, the CTS5 score was significantly associated with recurrence-free survival (RFS), with a hazard ratio (HR) of 1.35 (95% CI, 1.12–1.63; P=.002), but did not reach statistical significance in patients who received trastuzumab (n=829; HR, 1.29; 95% CI, 0.98–1.71; P=.07). CTS5 risk category was not significantly associated with RFS. In patients who received trastuzumab, other variables used in CTS5, including patient age and tumor size, were not significantly associated with RFS. N3 was significantly associated with worse outcomes (HR, 1.86; 95% CI, 1.09–3.17; P=.02) compared with N0–N1. Paradoxically, higher tumor grade was associated with better outcomes after 5 years in the multivariate analysis (HR, 0.71; 95% CI, 0.50–1.00; P=.05). The incidence of recurrences or deaths between years 5 to 10 was 10.6% in the CTS5 low-risk category, 5.6% in the intermediate-risk category, and 9.8% in the high-risk category. Conclusions: The CTS5 model does not accurately predict the risk of late recurrence in HR+, HER2+ BC treated with adjuvant trastuzumab in the N9831 and B-31 trials. This study underlines the need to develop a new prognostic model to better delineate the risk of late recurrence in patients with HR+, HER2+ BC receiving adjuvant trastuzumab. ClinicalTrials.gov identifiers: NCT00005970 (NCCTG N9831) and NCT00004067 (NRG/NSABP B-31).

550 Background: Residual disease after neoadjuvant chemotherapy (NAC) in HER2-positive breast cancer (BC) confers poor outcomes. Despite additional trastuzumab emtansine (T-DM1) in the adjuvant setting, a significant number of patients with residual disease still develop recurrence. H2NVAC is a multi-epitope T helper cell-activating peptide vaccine that is composed of 4 degenerate HER2-derived HLA-DR epitopes admixed with GM-CSF. Our previous phase I trial showed that this vaccine was safe and generated robust, long-lasting T and B cell immune responses. Methods: Patients with stage II-III HER2+ BC with any amount of residual disease in the breast /axilla after NAC were enrolled in a safety run-in phase of H2NVAC in combination with T-DM1. Patients were treated with H2NVAC and T-DM1 for 6 cycles, followed by 2 boosters at 3 and 12 months. Dose-limiting toxicity (DLT) was defined as any grade (G) ≥ 3 adverse events (AE) occurring within 21 days after the first vaccination. Results: A total of20 patients were enrolled with a median age of 51 years (range 27-69), 80% were White and 15% were Black. Most patients had hormone receptor-positive disease (90%). 40% were premenopausal, 40% were postmenopausal, and 20% were unknown. 14 patients had ypT1, 3 patients ypT2, 3 patients ypT3, 1 patient ypT4, 8 patients ypN0, 9 patients yp N1, 1 patient ypN1mi, and 2 patients ypN2. H2NVAC, in combination with T-DM1, was well tolerated, with no DLT being observed. Only grades 1 and 2 AEs were observed during the DLT period, with fatigue being the most common (G1 60%, G2 5%), followed by peripheral sensory neuropathy (G1 55%, G2 5%) and injection site reaction (G1 50%). Across all treatment cycles, the top 10 most common AEs that were at least possibly related to treatment include injection site reaction (G1 85%, G2 15%), AST increase (G1 65%), ALT increase (G1 45%), fatigue (G1 35%, G2 10%), peripheral sensory neuropathy (G1 35%, G-tube 10%), alk-phos increase (40% G1), nausea (G1 35%, G2 5%), arthralgia (G1 35%), myalgia (G1 25%, G2 5%), and platelet count decrease (G1 30%). There were four patients with G3 AEs at least possibly related to the vaccine observed after the DLT period, including allergic reaction, myositis/skin infection, urticaria, and pruritus/maculopapular rash. Conclusions: H2NVAC, in combination with T-DM1, was safe without DLT observed. The side effect profile was favorable, with the most common AE being the G1 injection site reaction. A multicenter, randomized, placebo-controlled, phase II trial of H2NVAC vs. placebo in combination with trastuzumab emtansine is currently ongoing through the ACCRU consortium. Clinical trial information: NCT04197687 .

Abstract Background: Tertiary lymphoid structure (TLS) is an organized form of ectopic lymphoid aggregates (LA) with secondary lymphoid organ structure. Several studies showed that the presence of TLS associates with improved outcomes in multiple cancers when treated with immune checkpoint inhibitors. However, data is currently limited regarding TLS and outcomes in HER2+ breast cancer patients (pts) treated with adjuvant trastuzumab. Furthermore, distinguishing TLS and simple LA is challenging in standard hematoxylin and eosin (H&E) staining, particularly when the germinal center is absent. Emerging studies also showed the prognostic value of MHC expression in breast cancer but mainly in triple-negative breast cancer. In this study, we evaluated integrated pathological quantification and genomic data to assess functional TLS in association with MHC expression and outcomes in the N9831 trial. Methods: Pathological evaluation of LA in H&E slides from pts treated in Arm A (chemotherapy alone) and Arm C (chemotherapy with concurrent trastuzumab) in N9831 was performed. NanoString was used to quantify mRNA of MHC class I and II expression as well as TLS-related immune genes, including IFNG, ICOSLG, CXCL13, CXCR3, BCL6, IL21R, ICOS, PDCD1, CXCR5, CXCL9, TBX21, CD38, CXCL10, CLXCL11, IL21, CD200, CD19, MS4S1. Wilcoxon rank sum test, Chi-squared test, Kaplan-Meier method, and Cox regression model were used to evaluate the association between LA and baseline characteristics, MHC expression, and outcomes. Results: LA was evaluated in 526 pts in Arm A and 485 in Arm C. Greater number of LA was significantly associated with stromal tumor-infiltrating lymphocytes (sTILs), hormone receptor negative, and higher tumor grade, but not stage and age. Using multivariable Cox regression analysis, increasing numbers of LA were associated with improved recurrence-free survival in both arms combined (RFS, p 0.028). However, when evaluating each arm separately, LA was associated with improved RFS only in Arm A (HR 0.6, 95%CI 0.43-0.84, p 0.003) but not in Arm C (HR 0.72, 95%CI 0.47-1.1, p 0.134). We further evaluated TLS-related immune genes in 252 pts in Arm C with LA ≥ 1. As a continuous variable, higher expression of BCL6 (HR 0.61, 95%CI 0.41-0.92, p 0.019) and IL21R (HR 0.78, 95%CI 0.62-0.98, p 0.03) were associated with improved RFS in Arm C pts with LA ≥ 1. However, these genes were not significantly associated with outcomes in Arm C pts without LA with BCL6 (HR1.07, 95%CI 0.67-1.71, p 0.776) and IL21R (HR 0.96, 95%CI 0.71-1.29, p 0.775). Moreover, we evaluated differential gene expression between tumors with LA ≥ 1 with high BCL6 vs. LA 0. All MHC class I and II (HLA A, B, C, E, DQ, DM, DO, DP, and DQ) were significantly higher in tumors with LA ≥ 1 with high BCL6 (p < 0.001). Conclusion: A greater number of LA was associated with improved outcomes in pts with early-stage HER2+ breast cancer, particularly when treated with chemotherapy alone. Using histologic and genomic integration with the combination of pathological LA and TLS-related immune genes, we identified that pts with functional TLS with LA ≥ 1 and higher expression of BCL6 or IL21R had significantly improved outcomes when treated with trastuzumab. High MHC class I and II expressions are associated with the presence of functional TLS, underscoring the crucial role of antigen presentation in the generation of an effective adaptive immune response. Support: U10 CA180821, U10 CA180882, U24 CA196171, https://acknowledgments.alliancefound.org; Genentech; Clinicaltrials.gov Id: NCT00005970 Citation Format: Saranya Chumsri, Tracy Shachner, Zhuo Li, Nadine Norton, Alvaro Moreno-Aspitia, Gerardo Colon-Otero, Edith Perez, Aziza Nassar, E. Thompson, Keith Knutson. MHC Class I and II Expression, Functional Tertiary Lymphoid Structure (TLS), and Outcomes in Early-Stage HER2-Positive (HER2+) Breast Cancer in NCCTG N9831 (Alliance) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-25-04.

Abstract Background: Activation of the RAS/MAPK pathway is associated with reduced tumor-infiltrating lymphocytes and poor outcomes in triple-negative breast cancer (TNBC). This trial evaluated the efficacy of pembrolizumab in combination with binimetinib, a MEK inhibitor. Methods: Patients with unresectable locally advanced or metastatic TNBC with ≤ 3 prior lines of therapy were enrolled. Treatment includes a 2-week run-in with binimetinib followed by pembrolizumab. There were 2 dose levels (DL) with binimetinib at 45 mg at DL 0 and 30 mg at DL -1. A standard 3+3 design was used in Phase I, and Simon’s two-stage Optimal design was used in Phase II. PD-L1 22C3 was performed in archival samples with CPS ≥ 10 considered as positive (PD-L1+). Tumor-infiltrating lymphocytes (TILs) were quantified into 0, 1, 2, and 3+. Circulating tumor cells (CTC) and circulating cancer-associated macrophage-like cells (CAML) were isolated using CellSieve microfilters and immunofluorescently labeled with PD-L1 and p-ERK. Wilcoxon rank sum test, Chi-square test, Cox regression model, and Spearman correlation were used for analysis. Results: 22 patients were enrolled with a median age of 58 years old. Dose-limiting toxicity (DLT) was observed in 2 out of 4 patients in DL 0, with grade 3 ALT abnormality, flank pain, and nausea. In the next 6 patients in DL -1, there was 1 DLT with grade 3 AST/ALT abnormality. There were 17 patients treated with DL -1 and were evaluable for response. The objective response rate (ORR) was 29.41% (95% CI: 10.31-55.9) with 1 complete response (CR) and 4 partial responses (PR). The clinical benefit rate (CBR ≥ 24 weeks) was 35.29% (95% CI: 14.21-61.67). ORR in patients without liver metastases was 55.56% (95% CI: 21.20 - 86.30) and CBR was 66.67% (95% CI: 29.93-92.51). No response was observed in all 5 patients with liver metastases. There were 40.9% of patients with PD-L1 CPS ≥ 10. ORR in patients with PD-L1+ was 80%. However, 11.1% of patients with PD-L1 negative tumors also had an objective response and 44.4% of patients had clinical benefit ≥ 24 weeks. PD-L1 expression in archival tissue was associated with ORR (p 0.032) but not CBR (p 0.198), progression-free survival (PFS, p 0.373), and overall survival (p 0.348). TILs in archival tissue were also not associated with CBR (p 0.155) and PFS (p 0.157). One patient with TILs 0 had a stable disease ≥ 24 weeks and 2 patients TILs 1+ also had an objective response. We further evaluated blood-based biomarkers with CTC and CAML. Baseline PD-L1 in CAML (p 0.04) and decline in CAML size (p 0.02) after 1 cycle was significantly associated with CBR. However, baseline CTC count, CAML count (p 0.64), CAML size (p 0.46), p-ERK in CAML (p 0.23), and changes in CTC count, CAML count (p 0.83), p-ERK (p 0.07), and PD-L1 (p 0.08) in CAML were not significantly associated with responses. Using Cox regression analysis, a reduction in CAML count (p 0.02), CAML size (p 0.01), and PD-L1 in CAML (p 0.03) were associated with significant improvement in overall survival but not the reduction in p-ERK (p 0.6). However, PD-L1 expression in CAML is not associated with PD-L1 expression in archival tissue (Spearman correlation 0.13). Conclusions: Pembrolizumab and binimetinib at 30 mg are safe with manageable toxicities. Consistent with the preclinical data that MEKi can restore T cell function, promising activity was observed even in patients with low TILs and PD-L1 negative, particularly in patients without liver metastases. PD-L1 expression in peripheral blood CAML rather than archival tumor tissue may serve as a better biomarker to predict the clinical benefit of this combination. Early reductions in CAML count and size, were also significantly associated with responses. Future larger clinical trials are warranted to further evaluate the efficacy of this chemotherapy-free combination. Citation Format: Saranya Chumsri, Joseph Larson, Daniel Adams, Kathleen Tenner, Cha-Mei Tang, Morgan Weidner, Amanda Arnold, Dana Haley, Pooja Advani, Kostandinos Sideras, Alvaro Moreno-Aspitia, Edith Perez, Keith Knutson. Phase I/II study of pembrolizumab in combination with oral binimetinib in patients with unresectable locally advanced or metastatic triple-negative breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-06-14.

Abstract Background: Taxane based chemotherapy (chemo) forms a critical part of breast cancer (BC) treatment in early and metastatic settings. Taxanes can cause peripheral neuropathy (CIPN)-sensory and motor, primarily of the hands and feet, resulting in quality of life decline and negaive impact on BC survival. Acral cryotherapy has shown benefit in reducing in in minimizing the incidence and severity ofcidence and severity of CIPN. However, these studies have included limited number of patients (pts) with inconclusive evidence to change US practice guidelines, have been primarily conducted in Asia, and did not include racially diverse patients. Methods: We conducted a single arm non randomized study at Mayo Clinic that included early BC pts who underwent standard of care paclitaxel or docetaxel based chemo. Pts had ECOG performance status 0-2, no sensory peripheral neuropathy at study entry and were able to give signed informed consent. Pts with metastatic BC, Raynaud's and peripheral vascular disease, cryoglobulinemia, cold intolerance, prior exposure to neurotoxic or taxane chemotherapy were excluded. Participating pts wore frozen gloves and socks (−20 to −10°C) on both hands and feet, 15 min before, during and until 15 min post taxane infusion. During chemo, grade (G) of CIPN (sensory) per CTCAE v5 was collected prior to each cycle of chemo, end of and 3 months after chemo. Schedule of events is listed in Table 1. Continuous variables were summarized using mean and standard deviation, and categorical variables were summarized with number and percentage of patients. Numeric variables were compared with t tests (paired and unpaired), and categorical variables were compared with Chi-Squared test for independent data and Mcnemar’s test for dependent data. All statistical tests were two-sided and were performed using R Statistical Software (version 4.1.2; R Foundation for Statistical Computing). Results: A total of 95 patients were included in this study. Median age is 54 years, 66.3% pts were White (W), 23.2% African American (AA), 4.2% Asian (A) and 4.2% Hispanic (H). Median BMI was 27.7. Most pts had stage I/II (75.8%), ER positive (64.9%) and HER2 negative (55.3%) BC and got adjuvant chemo (52.6%). Only 10.6% pts had diabetes, 55.3% used alcohol. Vitamin D3 use seen in 65.6%, B12 in 6.2% and folate, B12 and D3 in 6.2% pts. A total of 41 pts (44.1%) developed neuropathy at some point during chemo, of which 27 pts were W (43%), 10 pts AA (45%), 2 pts H, 1 Asian and 1 other. CIPN was G1 in 37 pts (90%). G2 CIPN was seen in 4 pts, at or after cycle 10 of weekly paclitaxel. Cold intolerance was seen in 24 pts (25%), G1 in 20 and G2 in 4 pts, all seen in cycle 1 with 1 pt withdrawal. Recovery to G0 was seen in 15 W pts at chemo end and 2 additional pts at 3 month after chemo. None of the AA pts, one H and one A pt had CIPN recovery to G0. In 4 AA pts who had G1 CIPN during chemo, G2 CIPN was noted at 3 month follow up. No Statistically significant differences in baseline characteristics and neuropathy results for W vs nonwhites (NW) were seen except Charleson score (p-value 0.023). Conclusion: Acral cryotherapy was found to be effective in reducing the incidence and severity of CIPN from taxane in our study. This is the only study with diverse racial/ethinic pt inclusion and incidence of CIPN was similar in W and NW. However, majority of G2 CIPN pts were AA and recovery to G0 CIPN was not seen in AA pts. Majority (63%) of W pts recovered to G0 at end of follow up. Analysis of objective testing of all pts is underway. Continued research into risk factors for AA pts to develop CIPN and its mitigation are warranted. XX XX Citation Format: Pooja Advani, Jinky Harvey, Ivy Vilches, Alex Hochwald, David Hodge, Amanda Arnold, Morgan Weidner, Dana Haley, Tanmayi Pai, Saranya Chumsri, Rohit Rao, Kostandinos Sideras, Cindy Tofthagen, Alvaro Moreno-Aspitia. Cryotherapy to Prevent Taxane-Induced Sensory Neuropathy of the Hands and Feet [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-12-10.

Abstract Background The current definition, prognosis, and optimal treatment (tx) for oligometastatic breast cancer (OMBC) are not fully known. With advances in multimodality breast cancer (BC) tx and overall improvement in patient (pt) outcomes, it is important to identify baseline pt factors that confer better prognosis in OMBC and assess the impact of local/regional tx and metastasis (mets)-directed tx on survival outcomes. Methods We reviewed 105 Mayo Clinic pts with OMBC (up to 5 mets) from 2003 to 2021. Pts were excluded from analysis if they were misidentified as having OMBC (n=6), did not have a primary breast mass (n=1), developed de novo BC during tx (n=1), or were lost to follow up (n=2). Categorical variables were summarized as counts. Continuous variables were reported as medians. Kaplan-Meier method was used to estimate survival and the time from diagnosis to next tx at 1, 3, and 5 years. Log-rank test was used to compare survival rates between baseline factors. Univariate Cox proportional hazards models were performed on both baseline and time-dependent factors. All tests were two-sided with p-value < 0.05 considered statistically significant. Results Total pts included were 95. Median age was 49 (range, 26-86), most (93.6%) pts were White, and 46.8% were postmenopausal. Invasive ductal carcinoma (89.5%) was the most common BC type. Median survival was 10.8 years; 1-, 3-, and 5-year survival rates were 98.9%, 87.7%, and 81%, respectively. 58 pts (61.1%) required a change in tx due to disease progression. No significant survival difference was observed in pre- vs. postmenopausal pts (p=0.71) or in groups based on hormone receptor and/or human epidermal growth factor receptor 2 status. 47 pts (49.5%) received local/regional tx; no significant difference in survival (HR 0.57, 95% CI 0.23-1.40; p=0.217) or time to next tx (HR 0.67, 95% CI 0.39-1.15; p=0.144) was seen in this subgroup. Of these pts, 36 (76.6%) received neoadjuvant chemotherapy and/or immunotherapy, 5 of whom (10.6%) also started endocrine tx preoperatively. Overall, 11/47 pts (23.4%) received neoadjuvant endocrine tx. 20 pts received systemic tx without eventual surgery, and 5 pts got palliative radiation (RT). Biopsy-confirmed mets were noted in 76 pts (80%), with bone-only mets in 50%, 30 pts (31.6%) with viscera-only mets and 7 pts (7.4%) with both bone and visceral mets. 18 pts had suspected mets on imaging but did not undergo biopsy. The hazard of death was 6.34 times higher in pts with both bone and visceral mets than those with bone-only mets (p=0.008). Pts with viscera-only mets had higher survival at 2 and 3 years than pts with bone-only or both bone and visceral mets (p=0.093). Pts with 3 mets (7/76, 7.4%) had decreased survival at 1, 2, and 3 years compared to pts with 1-2 (65/76, 85.5%) mets (p=0.6). 67 pts (70.5%) received mets-directed tx; RT alone was the most common modality (52/67, 77.6%), followed by surgery (6/67, 9%), RT plus surgery (5/67, 7.5%), and ablation alone (3/67, 4.5%). There was no significant difference in survival (HR 1.27, 95% CI (0.53, 3.07), p=0.589) or time to next tx (HR 0.95, 95% CI (0.56, 1.63), p=0.856) in pts who received mets-directed tx. Multivariate analysis was not performed because most findings were not statistically significant in univariate analysis. Conclusions We did not find any significant differences in survival based on characteristics like menopausal status or site or number of mets in pts with OMBC. There was a trend toward improved survival in pts with viscera-only mets, but this finding requires validation. Local/regional and mets-directed tx did not improve survival; however, survival at 1, 3, and 5 years was excellent in this OMBC pt population. Our study was limited by low pt numbers and heterogeneity in the pt population. Findings need validation in larger studies. Citation Format: Tanmayi Pai, Raza Zarrar, Zhongwei Peng, Zhuo Li, Lauren Cornell, Kostandinos Sideras, Rohit Rao, Alvaro Moreno-Aspitia, Saranya Chumsri, Sarah McLaughlin, James Jakub, Emmanuel gabriel, Sanjay Bagaria, Laura Vallow, Santo Maimone, Pooja Advani. Clinical Features and Survival Outcomes of Oligometastatic Breast Cancer Patients: The Mayo Clinic Experience [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-06-04.

Abstract Background: Residual disease after neoadjuvant chemotherapy (NAC) in breast cancer (BC) confers poor outcomes. Trastuzumab emtansine (T-DM1) is approved for HER2+ patients with residual disease after NAC. However, many patients still develop recurrence. H2NVAC is a multi-epitope CD4 helper T cell activating vaccine that includes a pool of 4 degenerate HER2-derived HLA-DR epitopes admixed with GM-CSF. Our previous phase I trial showed that this vaccine was safe and generated robust, long-lasting T and B cell immune responses. Method: We conducted a safety run-in phase of H2NVAC in combination with T-DM1 in stage II-III HER2+ BC with residual disease after NAC. Patients were treated with H2NVAC and T-DM1 for 6 cycles, followed by 2 boosters at 3 and 12 months. Dose-limiting toxicity (DLT) was defined as any grade (G) ≥ 3 toxicity occurring within 21 days after the first vaccination. Results: 20 patients were enrolled (median age 51; 27-69 years), including 80% White and 15% Black. 90% had hormone receptor-positive disease. There was no DLT observed in the safety run-in cohort. All adverse events (AEs) during the DLT period were grades 1 and 2, with fatigue being the most common (60% G1, 5% G2), followed by peripheral sensory neuropathy (55% G1, 5% G2), and injection site reaction (50% G1). Across all treatment cycles, the 10 most common AEs that were at least possibly related to treatment in all cycles are summarized in the table below. The injection site reaction was the most common AE, with 85% G1 and 15% G2. Conclusion: H2NVAC, in combination with T-DM1, was safe, with a favorable side effect profile. There was no DLT observed. The most common AE was injection site reaction, with the majority being G1. A multicenter, randomized, placebo-controlled, phase II trial of H2NVAC vs. placebo in combination with trastuzumab emtansine is currently ongoing through the ACCRU consortium (NCT04197687). Adverse Events Grades 1 2 N % N % Injection site reaction 17 85.0 3 15.0 Aspartate aminotransferase increase 13 65.0 Alanine aminotransferase increase 9 45.0 Fatigue 7 35.0 2 10.0 Peripheral sensory neuropathy 7 35.0 2 10.0 Alkaline phosphatase increase 8 40.0 Nausea 7 35.0 1 5.0 Arthralgia 7 35.0 Myalgia 5 25.0 1 5.0 Platelet count decrease 6 30.0 Citation Format: Saranya Chumsri, Sharmila Giri, Andy J. Ness, David W. Hillman, Nadine Norton, Davitte Cogen, Brian M. Necela, Aziza Nassar, Donald W. Northfelt, Pooja Advani, Rohit Rao, Kostandinos Sideras, Alvaro Moreno-Aspitia, Brenda J. Ernst, Kathryn J. Ruddy, Matthew P. Goetz, Keith L. Knutson. Safety and tolerability of multi-epitope HER2 peptide vaccines in combination with trastuzumab emtansine in HER2-positive breast cancer patients with residual disease after neoadjuvant chemotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5005.