PURPOSE:Evaluating fitness to drive among patients with brain tumours remains a challenge for clinicians. Due to difficulties in conducting prospective driving studies in this patient cohort, a Delphi study was performed to formulate new driving guidelines for patients with brain tumours. METHODS:The survey questions, which were designed by utilising Australian driving guidelines and previous Delphi studies, established panelists' expertise, and then used a 9-point Likert scale to formulate new driving guidelines. An expert group of panelists comprising medical oncologists, radiation oncologists, neurosurgeons, and neurologists were chosen based on membership to professional societies with validation in part one of the survey. Two rounds of anonymised surveys were performed using REDCap for data entry, and a novel automated methodology on R for data analysis. RESULTS:46 statements regarding fitness to drive were developed. Among the 37 surveys distributed, there were 26 responses (70.3% response rate) from round one, and 17 responses (65.4% response rate) for round two. Among the 46 statements, 19 (41.3%) achieved consensus. In addition to establishing a framework for assessing patients, there was notable consensus agreement for stable imaging required as part of evaluation and the need for continual reassessment. CONCLUSION:Despite clinicians being aware of driving guidelines, determining fitness to drive among patients with brain tumours remains a challenge. This Delphi study identified consensus agreement for the need for stable imaging, and continually reassessing fitness to drive. These novel findings could be translated into future driving guidelines and consensus statements can be integrated into clinical practice.

Introduction and objectives: Neoadjuvant pembrolizumab combined with chemotherapy has become the standard of care since 2022, for patients with triple negative breast cancer (TNBC) in Australia, following the KEYNOTE-522 trial, which identified significantly higher pathological complete response (pCR) compared to placebo, acknowledging the serious immune-related adverse events (irAEs) (1). A secondary analysis of this trial included patients enrolled in Asia and found similar rates of grade 3-4 irAEs in the pembrolizumab and placebo groups (3). Reports of adverse outcomes are often overshadowed by the significant benefit of pembrolizumab in TNBC, a subtype of breast cancer with significant risk of recurrence and mortality (2). Our objective was to collect real-world data relating to the use of neoadjuvant pembrolizumab in patients with TNBC, to identify the pattern of adverse events and outcomes. Methods: Retrospective data was collected across three tertiary hospitals in Melbourne, Australia, for patients diagnosed with TNBC, who received neoadjuvant pembrolizumab; baseline demographics, medical background, primary tumour details, pembrolizumab and chemotherapy regimen, serious adverse events and their management, breast surgery and pathological response. Results: There were 54 female patients who received neoadjuvant pembrolizumab; median age 52 years and median follow up of 11 months. 4 patients had a history of autoimmune disease and 2 had immunosuppressant therapy during or within 2 years prior to treatment with pembrolizumab. At primary diagnosis, 69% had nodal involvement. At least one irAE occurred in 54% of patients; thyroiditis (22%), adrenal insufficiency (20%), colitis (7%), hepatitis (6%) rash of at least grade 3 severity (4%) and pneumonitis (4%). Other less frequent irAEs include autoimmune haemolytic anaemia, transverse myelitis, arthralgia and type 1 diabetes mellitus. Of those with irAEs, 45% were hospitalised, 1 patient required intensive care and 69% have ongoing sequelae. The median time from commencement of pembrolizumab to irAE onset was 84 days. An interruption in pembrolizumab dose occurred in 23 patients, with 70% of these discontinuing therapy early. 41 patients underwent surgical intervention, and 40 had lymph node dissection. pCR was achieved in 37%, while 60% of those who achieved pCR experienced at least one irAE. Conclusion: There are significant immune related adverse events associated with the use of neoadjuvant pembrolizumab, a notable proportion of whom required hospitalisation, which poses an important and concerning burden for patients and the healthcare system. These real-world outcomes will continue to be monitored. Further work should also look at survival outcomes and quality of life, to better inform shared-decision making. References: Schmid, P. et al. (2020) ‘Pembrolizumab for early triple-negative breast cancer’, New England Journal of Medicine, 382(9), pp. 810–821. doi:10.1056/nejmoa1910549. Hudis, C.A. and Gianni, L. (2011) ‘Triple-negative breast cancer: An unmet medical need’, The Oncologist, 16(S1), pp. 1–11. doi:10.1634/theoncologist.2011-s1-01. Takahashi, M. et al. (2023) ‘Pembrolizumab plus chemotherapy followed by pembrolizumab in patients with early triple-negative breast cancer’, JAMA Network Open, 6(11). doi:10.1001/jamanetworkopen.2023.42107. Citation Format: Evon Jude, Jasmine Grisold, Sarah Jaboury, Qing Ze Fang, Josephine Stewart, Frances Barnett, Bianca Devitt, Belinda Yeo. Retrospective analysis of adverse events and outcomes of patients receiving neoadjuvant pembrolizumab for triple negative breast cancer in Australia [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P3-10-12.

Background: Breast cancer is the second most common cancer occurring during pregnancy with limited evidence for appropriate staging (1,2). A Delphi study was performed to develop consensus guidelines. Methods: Guideline recommendations were constructed based on available evidence and included statements targeting highlighted areas of uncertainty from a clinician-based survey. Statements were divided into two domains: one focused on indications for staging and the second addressed imaging selection. A two round Delphi study was performed. Medical, radiation and surgical oncologists from Australia and New Zealand were invited to participate. Participants who had worked in their field for >5 years were considered experts. Participants voted using a 9-point Likert scale selecting from 1 (strongly disagree) to 9 (strongly agree). Consensus was achieved when >75% participants selected < 3, or >7 for a statement. Statements that did not reach consensus in the first round were refined and re-presented for subsequent voting. Results: 15 Australian and New Zealand experts agreed to participate: 8 medical oncologists, 3 radiation oncologists and 4 breast surgeons. 87% (13/15) of participants completed round one. Of the 18 recommendations, six did not meet consensus. These were revised, with seven recommendations re-presented in round two. 11/13 (85%) participants completed round two, with one further recommendation achieving consensus. Consensus was achieved on indications for staging including women with locally advanced or inflammatory breast cancer and clinical suspicion of metastatic disease. Staging should be delayed until after pregnancy if it will not immediately change management decisions. Staging should not routinely be used in stage I and II breast cancers. Where staging is indicated, it was agreed that visceral disease should be screened for; however, consensus was not achieved for whether screening for bone metastases should be performed. There was consensus for liver ultrasound as the imaging modality of choice for liver metastases screening. Participants did not agree on whether chest x-ray or CT chest was best practice for pulmonary metastases nor optimal imaging for bone metastases. There was also discord as to whether there is a role for PET scan. Conclusion: Consensus guidelines have been developed to standardise breast cancer staging during pregnancy. Consensus was achieved for indications for staging and use of liver ultrasound to screen for liver metastases. Optimal staging practices for bone and pulmonary metastases warrants further investigation. Acknowledgements: We thank the experts who participated in this Delphi study. References: 1. Lee YY, Roberts CL, Dobbins T, Stavrou E, Black K, Morris J, et al. Incidence and outcomes of pregnancy-associated cancer in Australia, 1994–2008: a population-based linkage study. BJOG Int J Obstet Gynaecol. 2012;119(13):1572–82. 2. Cottreau CM, Dashevsky I, Andrade SE, Li DK, Nekhlyudov L, Raebel MA, et al. Pregnancy-Associated Cancer: A U.S. Population-Based Study. J Womens Health. 2019 Feb 1;28(2):250–7. Citation Format: Harriet R. Herbison, Abigail Miller, Darryl Shnier, Sally Greenberg, Bianca Devitt. Consensus guidelines for breast cancer staging during pregnancy. A Delphi Study. [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-04-10.

Introduction Bruton's tyrosine kinase inhibitors (BTKi) have improved 1 st line therapy efficacy in elderly (Wang NEJM 2022) and young, fit, MCL-the latter with intermittent dosing during RCHOP in an alternating RCHOP/cytarabine-based regimen (Dreyling Blood 2022). However direct combination of BTKi & intensive chemo is toxic in DLBCL studies. (Kuruvilla Haematol Oncol 2017). The highly selective BTKi, acalabrutinib (A), has proven efficacy and tolerability in relapsed MCL (Wang Lancet 2018). RDHAOx chemotherapy (rituximab, dexamethasone, cytarabine, oxaliplatin) prior to ASCT provides a complete response (CR) rate of 77% and favourable toxicity compared to many induction regimens (Le Gouill Blood 2017). Furthermore, Obinutuzumab-DHAP yields undetectable minimum residual disease (MRD) in 85% of young MCL patients. (Le Gouill Haematol Oncol 2019). Here we report the primary endpoint from the Australasian Leukaemia & Lymphoma Group phase 2 ‘WAMM’ trial exploring a ‘sandwich’ model of an acalabrutinib-rituximab (AR) ‘window’ before RDHAOx +/- ASCT, followed by fixed-duration AR-maintenance to improve therapy response and minimise additional toxicity. Methods NHL33'WAMM' (ACTRN12619000990123) is a multicentre single-arm phase 2 trial. Key eligibility included: age 18-70 years, untreated histologically-proven stage II-IV MCL, ECOG<2; no contraindications to ASCT or BTKi. Pts received 2 cycles of AR (AR window); ‘A’ dose; 100mg BD PO, ‘R’ dose; 375mg/m 2 IV (day 1) every 4 weeks, followed by RDHAOx x4 cycles. Those with an objective response (CR or partial response-PR) underwent BEAM ASCT (carmustine, etoposide, cytarabine, melphalan) then AR maintenance (A; 1yr continuous & R; 3-monthly x 8 cycles). Those who did not undergo BEAM ASCT were able to remain on study and proceed to maintenance AR in the event of ongoing response. Co-primary endpoints (EP) were safety; defined by lack of prohibitive toxicity causing treatment cessation AND PET-determined complete response (CR) rate after AR+RDHAOx. Secondary EP include overall response rates (ORR), toxicity, overall survival (OS) & progression-free survival (PFS), MRD negativity rates and quality of life. Only Grade 3+ toxicity related to acalabrutinib was collected during the ASCT period. Baseline whole exome sequencing was performed to identify mutations, MRD analysis was done by LymphoTrack® Dx and MRD Assay platform (Invivoscribe, Inc) using Illumina® MiSeq. This study was the first Australian blood cancer trial to use telehealth and a ‘hub-and-spoke’ transplant model. Results 44 pts were enrolled from Sept 2020 to Apr 2022 (43 evaluable for the primary endpoint). Baseline characteristics were typical of a young MCL cohort: median age 59 years (Interquartile range 54-64), 77% were male, ECOG was 0-1 in 98%, 84% had stage IV, lactate dehydrogenase was elevated in 35%, Ki-67 >30% in 66% and blastoid/pleomorphic histology 9%. TP53 by NGS will be reported at presentation. CR rate post AR+RDHAOx induction was 88%; (95%CI 72-95) with ORR 95% and no prohibitive toxicity. AR window ORR was 93% (CR 57%). MRD negativity was achieved in 18% (7/38) post AR window, and 94% (34/36) post RDHAOx. 43 patients remained evaluable for response after R-DHAOX and pre-maintenance with 35 (80%) who underwent ASCT and 38 (86%) who commenced AR maintenance; 7 remain on maintenance. Response in specific subgroups will be reported at the meeting. At data lock, 35 pts (81%) experienced ≥1 G3+ adverse events during induction or maintenance phases, most common were neutropenia (58% of pts), febrile neutropenia (27%), thrombocytopenia (25%), diarrhea (14%). No G5 treatment-related events have occurred to date. There have been 22 SAEs, most common were COVID (3), febrile neutropenia (2) and fever (2). 5 deaths have been reported: 4 in pts with progressive disease and 1 COVID pneumonitis during AR maintenance. After a median follow up of 22 months (range 17-28m), the 2-year OS was 89%. Analysis of survival, quality of life and biomarkers will be reported with more mature follow up. Conclusion AR delivered in a sandwich approach is active and safe. An AR window yields a high ORR and compared to historical studies, improves post-chemo induction CR rates and MRD negativity. A telehealth model allowed rapid recruitment in a rare cancer.

BACKGROUND Adding pertuzumab to trastuzumab in patients (pts) with HER2+ breast cancer improves pathological complete response (pCR) rates. Pertuzumab + trastuzumab + chemotherapy is approved in Australia as neoadjuvant therapy in early stage (>2 cm or node positive), locally advanced and inflammatory HER2+ breast cancer. This study captured real-world data on the safety and effectiveness of pertuzumab in the neoadjuvant setting. METHODS PeRSIA (ML39622) is a secondary data use non-interventional study of pts initiating neoadjuvant pertuzumab treatment for non-metastatic HER2+ breast cancer. The primary objective is to assess the effectiveness and safety of neoadjuvant pertuzumab when added to trastuzumab in the real-world setting. Deidentified data obtained from the pts’ medical notes were captured using REDCaP, hosted at the Walter and Eliza Hall Institute of Medical Research. This analysis reports the co-primary endpoints of breast pCR (bpCR) with or without in situ disease (ypT0/is or ypT0), total pCR (tpCR) with or without in situ disease (ypT0/is ypN0 or ypT0 ypN0), and the incidence of adverse events (AEs) related to pertuzumab. Secondary objectives include describing rates of breast and nodal surgery, relapse free survival (RFS) and overall survival (OS). RESULTS Ninety five pts receiving neoadjuvant pertuzumab were enrolled between March 2018 and July 2019, with data available for all pts. HER2-targeted neoadjuvant treatment was completed in 91 pts (95.8%) with a median number of 4 cycles [range 1-6] of pertuzumab and 5 cycles [range 1-6] of trastuzumab. Four pts did not complete the planned neoadjuvant therapy due to early CR (n=1), and pertuzumab-related AEs (n=3). The most common neoadjuvant chemotherapy regimens were sequential anthracyclines + taxanes (n=59, 62.1%) and single agent taxane (n=29, 30.5%). Surgery was performed in 92 pts (96.8%). Three pts did not proceed to surgery due to patient decision (n=1), physician decision (n=1), and development of a new non-breast cancer which resulted in death (n=1). Of those pts that underwent surgery, 65/92 (70.7%) had a bpCR and 59/92 (64.1%) had a tpCR. All pts who did not achieve a pCR obtained a partial response (33/92, 35.9%). Total pCR was seen in 27/34 (79.4%) pts with hormone receptor-negative and 32/58 (55.2%) pts with hormone receptor-positive cancers. 27/95 (28.4%) pts experienced an AE related to pertuzumab; diarrhea (21.1%) and rash (4.2%) were the most common AEs. Three pts (3.2%) discontinued pertuzumab due to an AE: cardiac toxicity, diarrhea and rash (n=1), cardiac toxicity (n=1), and diarrhea and sepsis (n=1). Following surgery, 93/95 (97.9%) patients received adjuvant HER2-directed therapy, and 4/95 (4.2%) received adjuvant chemotherapy. After a median follow-up from diagnosis of 21.2 [14.0-83.9] months, the RFS and OS were 92.6% and 99.0% respectively. Disease recurrence occurred in 6 pts (distant n=4, contralateral n=2). CONCLUSIONS This is the first multicenter, observational study of neoadjuvant therapy based on dual blockade with pertuzumab and trastuzumab for HER2+ non-metastatic breast cancer in Australia. The pCR rates achieved were numerically higher than previously reported in clinical trials. There were no significant safety findings outside of the expected safety profile for pertuzumab. Acknowledgments: Study sponsored by Roche Products, Pty. Limited. Theresa Wade (WriteSource Medical) provided medical writing. Table: Baseline Characteristics (n=95)CharacteristicNumber (%)Age, median (range)50.3 (24.4 -82.1)Charlson Comorbidity Index- 077 (81.1)- 19 (9.5)- 2 +9 (9.5)Tumour Size12 (12.6)- T156 (59.0)- T225 (26.3)- T3- Unreported2 (2.1)Tumour Grade- 10 (0)- 231 (32.6)- 362 (65.3)- Unreported2 (2.1)Nodal status- Positive63 (66.3)- Negative32 (33.7)Hormone Receptor Status- HR+60 (63.2)- HR-35 (36.8)Median baseline left ventricular ejection fraction (range)65.0% (35-79)Cardiac risk factors- 053 (55.8)- 122 (23.2)- 2+20 (21.1) Citation Format: Sheau Wen Lok, Richard De Boer, Sallt Baron-Hay, Peter Button, Bianca Devitt, Benjamin Forster, Peter Fox, Michael Harold, Sahisha Ketheeswaran, Ganessan Kichenadasse, Belinda E Kiely, Gavin Marx, Louise Nott, Laura Pellegrini, Ali Tafreshi, Peter GIbbs. Pertuzumab study for HER2-positive non-metastatic breast cancer in the neoadjuvant setting in Australia [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-13-38.

BACKGROUND: Interleukin-12 (IL-12) is a potent immunoregulatory cytokine that plays a key role in the crosstalk between innate (dendritic, macrophage, and natural killer) and adaptive (T and B) cells promoting anti-tumor immune responses. DNA plasmid-based IL-12 delivered to accessible tumors by intratumoral injection and electroporation (TAVO-EP) has been shown to induce activation of innate and adaptive tumor-infiltrating and peripheral immune cells, regression of treated and distant untreated lesions (abscopal effect), and expression of PD-L1 in patients with melanoma or triple-negative breast cancer (TNBC), without the systemic toxicity that has limited therapeutic use of IL-12 historically. The combination of TAVO-EP and pembrolizumab has demonstrated durable responses in melanoma patients with immunologically “cold” tumors or with prior progression on anti-PD1 therapy. Early clinical data indicate similar potential for eliciting strengthened immunogenic responses in TNBC. KEYNOTE-890 (OMS-I141) is a Phase 2 study in patients with metastatic TNBC to evaluate the safety and efficacy of TAVO-EP + pembrolizumab in the second-line or later (2L+) treatment setting (Cohort 1) or TAVO-EP + pembrolizumab + chemotherapy in the first-line (1L) setting (Cohort 2). Cohort 1 data are presented in a separate abstract. Enrollment in Cohort 2 is ongoing. METHODS: Cohort 2 of this Phase 2, open-label, multicenter study will be assessing the safety and efficacy of TAVO-EP in combination with pembrolizumab and chemotherapy as a first-line treatment for metastatic TNBC. Eligible patients are adults with metastatic TNBC (ER and PR staining <10%, HER2 0 to 1+ or [F]ISH-negative), no prior systemic therapy for advanced disease (neo/adjuvant therapy allowed if at least 6-month disease-free interval from last treatment), measurable disease by RECIST v1.1, at least one lesion accessible for TAVO-EP treatment, and biopsy tissue available for post-hoc central determination of PD-L1 expression. Patients will receive pembrolizumab (200 mg IV) every 3 weeks, TAVO-EP (0.5 mg/mL at dose volume of ~1/4 lesion volume) on Days 1, 5, and 8 every 6 weeks, and nab-paclitaxel (100 mg/m2 IV) on Days 1, 8, and 15 every 4 weeks. Additional chemotherapy options may be introduced in future protocol amendments. Tumor assessments will be performed every 12 weeks. On-study biopsies will be collected approximately 3 weeks after start of treatment and at disease progression. The primary endpoint will be ORR assessed by blinded independent review per RECIST v1.1. Additional endpoints will include safety and tolerability, duration of response, immune ORR, progression-free survival (PFS), immune PFS, disease control rate, and overall survival. Planned enrollment in Cohort 2 is 40 patients. Based on positive efficacy data in Cohort 1, additional cohorts are being planned and will be presented. ClinicalTrials.gov: NCT03567720 Citation Format: Melinda Telli, Bianca Devitt, Katharine Cuff, Shaveta Vinayak, Rita Nanda, Alberto J. Montero, Rina Hui, David A. Canton, Christopher Twitty, Sunny Xie, Donna Bannavong, Bridget O'Keeffe, Sandra Aung, Rohit Joshi. Trial in progress: Phase 2 study of intratumoral plasmid interleukin-12 (tavokinogene telseplasmid; TAVO™) plus electroporation in combination with pembrolizumab with or without chemotherapy in patients with inoperable locally advanced or metastatic triple-negative breast cancer (KEYNOTE-890/OMS-I141) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT2-01-03.

BACKGROUND: Electroporated plasmid interleukin-12 (tavokinogene telseplasmid; TAVO-EP) delivered to accessible tumors by intratumoral injection induces sustained local expression of IL-12. IL-12 is a potent immunoregulatory cytokine that plays a key role in the crosstalk between innate (dendritic, macrophage, and natural killer) and adaptive (T and B) cells, promoting anti-tumor immune responses. TAVO-EP has been shown to induce activation of innate and adaptive tumor-infiltrating and peripheral immune cells, regression of treated and distant untreated lesions (abscopal effect), and expression of PD-L1 in patients with melanoma or triple-negative breast cancer (TNBC), without the systemic toxicity that limited therapeutic use of IL-12 historically. The combination of TAVO-EP and pembrolizumab has demonstrated durable responses in melanoma patients with immunologically “cold” tumors or with prior progression on anti-PD1 therapy. Anti-PD1 monotherapy has just over 5% overall response rate (ORR) in the second-line or later (2L+) treatment setting for advanced TNBC. New antibody-directed conjugate (ADC) chemotherapy has increased rates of responses compared with prior standard chemotherapy in 2L+ advanced TNBC; however, short duration of response (DOR), and toxicity are issues of concern. Therapies that can induce durable responses with limited toxicity are needed. METHODS: Cohort 1 of this Phase 2, open-label, multicenter study assessed the safety and efficacy of TAVO-EP in combination with pembrolizumab as 2L+ treatment for advanced TNBC. Eligible patients had at least 1 line of prior systemic therapy for advanced or metastatic disease, measurable disease by RECIST v1.1, and ≥1 lesion accessible for TAVO-EP treatment. Patients received pembrolizumab (200 mg IV) every 3 weeks and TAVO-EP (0.5 mg/mL at dose volume of ~1/4 lesion volume) on Days 1, 5, and 8 every 6 weeks. Tumor assessments were performed every 12 weeks. The primary endpoint was RECIST v.1.1 ORR by investigator review. Secondary endpoints included safety and tolerability, DOR, progression-free survival (PFS), immune-related RECIST (iRECIST) ORR and PFS, disease control rate, and overall survival (OS). ClinicalTrials.gov: NCT03567720. RESULTS: Between 01Nov2018 and 30Jan2020, 26 patients were enrolled and received at least one dose of study treatment (median follow up of 11.1 months). Patients had a median of 2 prior lines of systemic therapy for advanced disease (range 1-5). Among 23 patients evaluable for response, the ORR was 17.4% (4 with partial response [PR]). One responder with centrally confirmed PD-L1-negative disease and chest wall and bulky liver metastases had a sustained PR and an iRECIST complete response (CR). One responder had near complete regression of a large fungating chest wall skin lesion. The median DOR was 16.6 months. Median OS was 11.0 months (range 0.6-27.5+). The most common treatment-related adverse events (TRAEs) (all grades) were administration site pain and fatigue. Grade 3 TRAEs were reported in 6 patients (23%) including fatigue (11.5%); acute kidney injury, enterocolitis, and myocarditis (3.8% each). There were no Grade 4 or 5 TRAEs. CONCLUSIONS: The combination of TAVO-EP and pembrolizumab in pretreated patients with advanced TNBC resulted in durable RECIST v1.1 responses, including in PD-L1-negative disease, and was well tolerated. This novel immunotherapeutic regimen warrants further evaluation in 2L+ advanced TNBC. Cohort 2 exploring TAVO-EP + pembrolizumab + chemotherapy in frontline TNBC is currently enrolling. Citation Format: Melinda L. Telli, Irene Wapnir, Bianca Devitt, Katharine Cuff, Hatem Soliman, Shaveta Vinayak, David A. Canton, Christopher G. Twitty, Sunny Xie, Ying Lu, Donna Bannavong, Bridget O'Keeffe, Sandra Aung, Rohit Joshi. Durable responses with intratumoral electroporation of plasmid interleukin-12 plus pembrolizumab in patients with advanced triple-negative breast cancer: Cohort 1 update from KEYNOTE-890 [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-14-06.

The pertuzumab study in the neoadjuvant setting for HER2+ nonmetastatic breast cancer in Australia (PeRSIA-ML39622) is an analysis of safety and effectiveness data from the pertuzumab patient registry. Although the prognosis of patients with early stage HER2+ breast cancer has been greatly improved by advances in chemotherapy approximately 25% to 30% of patients develop recurrent disease. Our study aimed to examine the effectiveness of neoadjuvant pertuzumab on surgical outcomes, describe the medium-term effectiveness outcomes of patients treated with pertuzumab, and describe the planned and actual anticancer treatment regimens that patients received. Deidentified data were collected from the patients' medical records and entered into REDCap, between March 2018 and July 2019 (n = 95). The adverse events (AEs) reported most frequently were diarrhea (20; 21.1%), rash (4; 4.2%), and LVSD (4; 4.2%; two patients during neoadjuvant treatment and two patients during adjuvant treatment). AEs, >= Grade 3 were diarrhea (2; 2.1%) and LVSD (1; 1.1%). Following surgery, a breast pathological complete response (bpCR) was achieved in 65 patients (70.7%; 95% CI: 60.2%-79.7%) and total pathological complete response (tpCR) in 59 patients (64.1%; 95% CI: 53.4%-73.9%). All patients who did not achieve a tpCR obtained a partial response (33/92, 35.9%). Our study is the first to capture real-world data on the use of pertuzumab in the neoadjuvant setting in Australia. The effectiveness and safety data are consistent with those reported in clinical trials of pertuzumab in patients with HER2+ breast cancer, with no new safety concerns.

Abstract BACKGROUND: Interleukin-12 (IL-12) is a potent immunoregulatory cytokine that plays a key role in the crosstalk between innate (dendritic, macrophage, and natural killer) and adaptive (T and B) cells promoting anti-tumor immune responses. DNA plasmid-based IL-12 delivered to accessible tumors by intratumoral injection and electroporation (TAVO-EP) has been shown to induce activation of innate and adaptive tumor-infiltrating and peripheral immune cells, regression of treated and distant untreated lesions (abscopal effect), and expression of PD-L1 in patients with melanoma or triple-negative breast cancer (TNBC), without the systemic toxicity that has limited therapeutic use of IL-12 historically. The combination of TAVO-EP and pembrolizumab has demonstrated durable responses in melanoma patients with immunologically “cold” tumors or with prior progression on anti-PD1 therapy. Early clinical data indicate similar potential for eliciting strengthened immunogenic responses in TNBC. KEYNOTE-890 (OMS-I141) is a Phase 2 study in patients with metastatic TNBC to evaluate the safety and efficacy of TAVO-EP + pembrolizumab in the second-line or later (2L+) treatment setting (Cohort 1) or TAVO-EP + pembrolizumab + chemotherapy in the first-line (1L) setting (Cohort 2). Cohort 1 data are presented in a separate abstract. Enrollment in Cohort 2 is ongoing. METHODS: Cohort 2 of this Phase 2, open-label, multicenter study will be assessing the safety and efficacy of TAVO-EP in combination with pembrolizumab and chemotherapy as a first-line treatment for metastatic TNBC. Eligible patients are adults with metastatic TNBC (ER and PR staining <10%, HER2 0 to 1+ or [F]ISH-negative), no prior systemic therapy for advanced disease (neo/adjuvant therapy allowed if at least 6-month disease-free interval from last treatment), measurable disease by RECIST v1.1, at least one lesion accessible for TAVO-EP treatment, and biopsy tissue available for post-hoc central determination of PD-L1 expression. Patients will receive pembrolizumab (200 mg IV) every 3 weeks, TAVO-EP (0.5 mg/mL at dose volume of ~1/4 lesion volume) on Days 1, 5, and 8 every 6 weeks, and nab-paclitaxel (100 mg/m2 IV) on Days 1, 8, and 15 every 4 weeks. Additional chemotherapy options may be introduced in future protocol amendments. Tumor assessments will be performed every 12 weeks. On-study biopsies will be collected approximately 3 weeks after start of treatment and at disease progression. The primary endpoint will be ORR assessed by blinded independent review per RECIST v1.1. Additional endpoints will include safety and tolerability, duration of response, immune ORR, progression-free survival (PFS), immune PFS, disease control rate, and overall survival. Planned enrollment in Cohort 2 is 40 patients. Based on positive efficacy data in Cohort 1, additional cohorts are being planned and will be presented. ClinicalTrials.gov: NCT03567720 Citation Format: Melinda Telli, Bianca Devitt, Katharine Cuff, Shaveta Vinayak, Rita Nanda, Alberto J. Montero, Rina Hui, David A. Canton, Christopher Twitty, Sunny Xie, Donna Bannavong, Bridget O'Keeffe, Sandra Aung, Rohit Joshi. Trial in progress: Phase 2 study of intratumoral plasmid interleukin-12 (tavokinogene telseplasmid; TAVO™) plus electroporation in combination with pembrolizumab with or without chemotherapy in patients with inoperable locally advanced or metastatic triple-negative breast cancer (KEYNOTE-890/OMS-I141) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT2-01-03.

Background: MCL is a rare and incurable disease representing 5-10% of all non-Hodgkin lymphoma cases. Although intensive chemotherapy induction and up-front ASCT can induce durable remissions in fit patients, toxicity can be significant. R-DHAOx chemoimmunotherapy provides adequate outcomes and a favourable toxicity profile compared to some other induction regimens (Le Gouill S Blood 2017). The highly selective Bruton tyrosine kinase inhibitor (BTKi) acalabrutinib has minimal off-target activity and proven efficacy in relapsed MCL (Wang M Lancet 2018), however, direct combination of BTKi & chemoimmunotherapy is toxic. Thus, it is postulated that up-front use with an acalabrutinib ‘window’ before chemoimmunotherapy, followed by maintenance after intensive chemotherapy will prolong time to next treatment and reduce overall treatment toxicity (Kuruvilla J Hematol Oncol 2017).