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Background: AZD9833 is an oral selective estrogen receptor (ER) antagonist and degrader (SERD) in Phase 2 clinical development for the treatment of ER+ HER2− breast cancer. Here we report data from Parts C and D of the ongoing Phase 1 study (SERENA-1) examining AZD9833 in combination with palbociclib, together with updated data from Parts A and B examining AZD9833 monotherapy. Methods: SERENA-1 (NCT03616587) is an ongoing open-label Phase 1 study of AZD9833 in pre- and post-menopausal women with ER+, HER2− advanced breast cancer who have previously received ≥1 endocrine therapy and ≤2 prior chemotherapies. Prior treatment with fulvestrant and/or CDK4/6 inhibitors was permitted. The primary objective is to determine the safety and tolerability of once daily (QD) AZD9833, with dose-limiting toxicities (DLTs) in the first 28 days defining the maximum tolerated dose. Secondary objectives include anti-tumor response (including circulating tumor [ct] DNA response) and pharmacokinetics. Parts A (escalation) and B (expansion) assess AZD9833 as a monotherapy, and Parts C (escalation) and D (expansion) assess AZD9833 in combination with palbociclib. Results: At a data cut-off of March 24 2020, 17 patients had received either 150 mg or 300 mg AZD9833 in combination with palbociclib, given according to its product labeling. Eighty patients had received AZD9833 monotherapy at doses of 25, 75, 150, 300, and 450 mg QD. In patients treated with AZD9833 and palbociclib, treatment-related adverse events (AEs; experienced by ≥10% of patients) included visual disturbances*, bradycardia*, asthenia, anemia, QTcF prolongation, nausea, neutropenia, decreased white blood cell count, and vomiting (*combined terms). All instances of AZD9833-related bradycardia were Grade 1. One DLT was observed in the 150 mg cohort: CTCAE Grade 2 visual disturbances, which began on Cycle 1 Day 8 and resolved by Cycle 1 Day 9 following dose interruption. The patient restarted treatment on Cycle 1 Day 15 at 75 mg and continued this dose until data cut-off. No causally related AEs led to discontinuation of AZD9833. The tolerability of AZD9833 with palbociclib was consistent with the observed tolerability profile of AZD9833 monotherapy, and the known tolerability profile of palbociclib. Pharmacokinetic analysis showed similar AZD9833 exposure for monotherapy and palbociclib combination therapy. Similarly, palbociclib exposure was comparable with simulations using a published population pharmacokinetic model. In Part A, ESR1 hotspot mutations were detected in ctDNA at baseline in 26/56 (46%) patients; 13/26 (50%) of these patients achieved a partial response or stable disease at 24 weeks, including 5/10 (50%) with a Y537S ESR1 mutation. Further, in patients with ESR1 mutations and samples available for longitudinal ctDNA analysis, 17/20 (85%) exhibited a reduction or loss of mutant ESR1 on treatment with AZD9833. Efficacy data to be presented include objective response rate and clinical benefit rate at 24 weeks. Of note, unconfirmed partial responses have been observed in Part C after the data cut-off for this abstract. Conclusions: AZD9833 continues to show an encouraging efficacy and dose-dependent safety profile as a monotherapy or in combination with palbociclib. A Phase 2 study comparing the efficacy and safety of three doses of AZD9833 versus fulvestrant (NCT04214288), and a Phase 2 pre-surgical ‘window of opportunity’ study (EUDRA-CT; 2019-003706-2) are ongoing. Citation Format: Richard Baird, Mafalda Oliveira, Eva Maria Ciruelos Gil, Manish R Patel, Begoña Bermejo de las Heras, Manuel Ruiz-Borrego, Javier García-Corbacho, Anne Armstrong, Udai Banerji, Chris Twelves, Valentina Boni, Jason Incorvati, Peter Kabos, Adam L Cohen, Bruno de Paula, Marta Capelán Rodríguez, Judy S Wang, Christina Hernando, Alejandro Falcón Gonzalez, Ivan Victoria Ruiz, Julia Lai-Kwon, Anosheh Afghani, Christos Vaklavas, Tim Brier, Steven Fox, Bistra Kirova, Teresa Klinowska, Chris Leach, Justin PO Lindemann, Richard Mather, Rhiannon Maudsley, Christopher J Morrow, Nitharsan Sathiyayogan, Andy Sykes, Li Zhang, Erika Hamilton. Updated data from SERENA-1: A Phase 1 dose escalation and expansion study of the next generation oral SERD AZD9833 as a monotherapy and in combination with palbociclib, in women with ER-positive, HER2-negative advanced breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS11-05.

Recommendations from national regulatory agencies for ongoing cancer trials during the COVID-19 pandemicthe Birmingham Environment for Academic Research local Cloud. 10 UKCCMP delivers meaningful real-time data to all UK cancer centres and clinicians to allow more personalised approaches to individual patient care and inform clinical decision making. This initiative will improve cancer care in the UK and beyond at this time of unprecedented global turmoil and reliance on health-care resources.We declare no other competing interests. We thank the oncologists, acute physicians, and health-care staff working tirelessly on the frontlines of the COVID-19 pandemic. The UK Coronavirus Monitoring Project team donated time and resources to support the project. The project was initially funded through the donation of time and resources from the supporters and advocates of the project. The University of Birmingham initiated this process, with the Pro-Vice-Chancellor dedicating the computational and human resources of the University's Centre for Computational Biology, the Institute of Translational Medicine, and scientists from the Institute of Cancer and Genomic Sciences. Other academic institutions dedicating time and staff to the project include the

The estrogen receptor (ER) has been targeted for breast cancer treatment for over a century, but many challenges persist. ER-positivity identifies the largest breast cancer subgroup, and ER-directed therapies prolong survival and improve symptoms in the advanced setting with a very favorable side effect profile. Treatment strategies have included decreasing estrogen synthesis and modulating or degrading the ER. However, ER+ breast cancer once diagnosed in the advanced setting still represents an incurable condition. Many efforts are ongoing to circumvent resistance mechanisms with a few strategies already incorporated into clinical practice such as the combination of endocrine agents with drugs that interfere with other signaling pathways and cell-cycle progression. Important questions remain as how best to select each available strategy, how to sequence them and ultimately how to extend benefits to the largest number of patients in need.

Background: Triple negative breast cancer (TNBC) is characterized rapid tumor growth, and increased metastatic potential compared to other breast cancer subtypes. However, pathological complete response (pCR) to neoadjuvant chemotherapy (NACT) can predict patients with a better prognosis. Clinical predictors of pCR such as tumor size (TS) are controversial. This study aims to evaluate the influence of TS on achieving pCR, and the associated survival outcomes. Methods: Medical records from 310 TNBC patients treated with NACT between 2010 and 2013 in National Cancer Institute Brazil were screened. The aim study was to examine the impact of TS on pCR. We used descriptive statistics to organize and summarize TS data and all the other variables of interest. Logistic regression has done to assess if any of these variables were associated with pCR. Survival data were extrapolated using Kaplan-Meier analysis and log-rank tests. Results: Thirty-nine (21%) of 187 enrolled patients achieved pCR. Median age was 48 years, 50.27% were postmenopausal, 93.03% T3/T4 and 75.39% axillar clinical node-positive; 92.51% received an anthracycline regimen followed by a taxane. Age >40 years (P=0.04, OR 0.45, 95% CI, 0.20-0.95) and tumor infiltrating lymphocytes (TILs) presence (P<0.01, OR 3.71, 95% CI, 1.60-8.60) were factors significantly associated with increased rates of pCR. Neither the TS (IQR: 4; P=0.22, OR 0.93, 95% CI, 0.83-1.03) nor the other subgroups analysed demonstrated any association with achieving pCR. Median follow-up was 36 months. The 5-year OS and RFS of the study population was 71.20% and 61.10% respectively. Conclusions: Preoperative TS did not significantly impact pCR rate in our cohort of patients receiving NACT for TNBC. Characteristics associated with higher pCR rate included TILs and age >40 years. In addition, pCR, was indicative of better survival outcomes.

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Background: Preclinical evidence suggests that zoledronic acid (ZOL) works synergistically with chemotherapy by enhancing anti-tumor activity. ZOL blocks the mevalonate pathway and may indirectly interact with human epidermal growth factor receptor 2 (HER2) pathway activation. The clinical efficacy and biological rationale of chemotherapy plus anti-HER2 therapy and ZOL as a part of neoadjuvant therapy has not been previously tested. Patients and methods: We conducted a phase II clinical trial to evaluate the efficacy and safety of ZOL as part of a neoadjuvant treatment in patients with HER2-positive breast cancer (BC). The protocol consisted of four cycles of doxorubicin/cyclophosphamide with ZOL, followed by four cycles of docetaxel with trastuzumab and ZOL prior to surgery. The primary endpoint was the pathologic complete response (pCR) rate. Secondary endpoints were safety and the identification of clinicopathological characteristics associated with pCR. Results: A total of 71 patients with stage IIA to IIIB BC were included, with 60 eligible for the safety assessment and 58 for the efficacy analysis. Overall, the pCR rate was 42%, with higher rates in hormone receptor (HR)-positive tumors (40%), which contrasts with the results of pivotal trials. The most commonly observed grade 3 and 4 events were febrile neutropenia (grade 3, 20%; grade 4, 3%) and diarrhea (grade 3, 12%). Conclusions: The addition of ZOL as a repositioning drug in neoadjuvant treatment was an effective and well-tolerated therapy. This drug combination might overcome endocrine and anti-HER2 resistance. The higher pCR rates in the HR-positive subgroup deserve further translational investigation.

PS of 0 (n¼39, 15.18%) or 1 (n¼203, 78.99%). The treatment of apatinib was mainly first-line treatment (n¼103, 40.08%), second-line treatment (n¼64, 24.90%), and adjuvant treatment (n¼42, 16.34%). The starting dose of apatinib was 250mg in 132 patients and 500mg in 125 patients. The treatment regimens were: apatinib combined with chemotherapy drugs (178/257), apatinib monotherapy (64/257), apatinib combined with chemotherapy drugs plus PD-1 antibody drug (8/275), and apatinib combined with PD-1 antibody drug (7/275). Thirty-three patients achieved partial response, 69 patients achieved stable disease, and 26 patients had progressive disease, and no CR was achieved, illustrating an ORR of 25.78% and a DCR of 79.69%. During the treatment, the overall incidence of adverse events was 70.82%. The most common adverse events were hypertension (32.68%), leukopenia (26.46%), hand-foot syndrome (25.29%), neutropenia (20.23%), etc.Conclusions: This real-world research showed current treatment status and provided preliminary evidence for the efficacy and safety of apatinib in the treatment of gastric cancer in China. More data would be analyzed and reported in future.[ChiCTR2000035597]Legal entity responsible for the study: The authors.