289TiPALEXANDRA/IMpassion030: A phase III study of standard adjuvant chemotherapy with or without atezolizumab in early stage triple negative breast cancer
AbstractBackgroundEarly stage triple negative breast cancer (TNBC) is associated with a high risk of distant relapse. Because TNBC does not currently have specific targeted agents approved for use in the early setting it is treated primarily with chemotherapy. TNBC may be more immunogenic than other subtypes of breast cancer. On March 8th 2019, the Food and Drug Administration approved anti –PD-L1 antibody, atezolizumab, in combination with chemotherapy for the treatment of PD-L1-positive unresectable locally advanced or metastatic TNBC based on the results of the randomized phase 3 IMpassion130 trial. ALEXANDRA/IMpassio...
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research
509TiPA phase I dose-escalation and expansion trial of intratumorally administered CV8102, alone and in combination with anti-PD-1 in patients with advanced solid tumours
AbstractBackgroundIntratumoral injection of immunomodulating agents is a promising approach to prime antitumor immune responses and to control tumor growth while avoiding major systemic toxicities. Intratumoral CV8102, a TLR7/8/RIG-1 agonist based on noncoding single stranded RNA showed dose dependent single agent activity and synergism with PD-1 blockade in preclinical models.Trial designCV-8102-008 (NCT03291002) is a phase I, open-label, dose escalation and expansion study of intratumoral CV8102 in patients with advanced, inoperable cutaneous melanoma (cMEL), squamous cell carcinoma of the skin (cSCC) or head and neck (h...
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research
288TiPA randomized phase II study of peri-operative ipilimumab, nivolumab and cryoablation versus standard care in women with residual, early stage/resectable, triple negative breast cancer after standard-of-care neoadjuvant chemotherapy
AbstractBackgroundLocal tumor destruction with cryoablation (cryo) induces inflammation and releases antigens that can activate tumor-specific immune responses. Pre-clinically, cryo with checkpoint inhibition augmented tumor-specific immune responses and prevented recurrence. Clinically, we established that peri-operative (peri-op) cryo with ipilimumab (ipi) +/- nivolumab (nivo) was not only safe in patients (pts) with operable, early stage breast cancer (ESBC) but also generated robust intra-tumoral and systemic immune responses. In this randomized phase 2 study, we evaluate the disease specific impact of peri-op ipi/nivo...
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research
287TiPNeoadjuvant HER2-targeted therapy with or without immunotherapy with pembrolizumab (neoHIP): An open label randomized phase II trial
AbstractBackgroundImmune checkpoint inhibition (ICI) is synergistic with HER2-directed therapy in pre-clinical models. Clinically, pembrolizumab (K)-mediated ICI plus HER2-directed therapy with trastuzumab (H) is safe and demonstrated modest activity in H-resistant HER2-positive (HER2+) metastatic breast cancer. Because ICI may confer more robust activity when administered earlier in the course of disease, HER2-directed therapy with ICI administered in the curative-intent, treatment-naive setting may allow for de-escalation of cytotoxic backbones; confer life-long, tumor-specific immunity; and ultimately, improve cure rate...
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research
1178PDA phase I trial of GEN-009, a neoantigen vaccine using ATLAS ™, an autologous immune assay, to identify immunogenic and inhibitory tumour mutations
ConclusionsGEN-009 is a neoantigen vaccine that identifies tumor specific immune targets from the individual patient ’s repertoire. Immunogenicity data show that ATLAS can, with very high frequency, identify relevant neoantigens and exclude suppressive peptides. Clinical vaccination with PD-1 blockade is in process.Clinical trial identificationNCT03633110, issued 6-Aug-2018.Legal entity responsible for the studyGenocea Biosciences.FundingGenocea Biosciences.DisclosureP. Twardowski: Advisory / Consultancy, Speaker Bureau / Expert testimony: Bayer; Speaker Bureau / Expert testimony: Janssen; Speaker Bureau / Expert testimo...
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research
286TiPPhase II randomized trial of neoadjuvant trastuzumab and pertuzumab (TP) with either palbociclib + letrozole (Pal+L) or paclitaxel (Pac) for elderly patients with estrogen receptor & amp; HER2 positive (ER+/HER2+) breast cancer (BC) (International Breast Cancer Study Group IBCSG 55-17, TOUCH)
AbstractBackgroundHER2 blockade in combination with chemotherapy (CT) remains the treatment of choice for patients with early HER2+ BC, irrespective of ER status. Patients with HER2+ early BC co-expressing ER may benefit from HER2 blockade in combination with endocrine therapy (ET) and new targeted agents. Elderly patients benefit from HER2 blockade as much as younger ones but they have higher risks of adverse events, mostly induced by the CT partner, making de-escalation of CT appealing. Recent data have elucidated cyclin-dependent kinases 4 and 6 (CDK4/6) as key therapeutic targets functioning downstream of both ER and H...
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research
1173TiPA randomized phase II study on the OPTimization of Immunotherapy in squamous carcinoma of the head and neck (SCCHN) - OPTIM (AIO-KHT-0117)
AbstractBackgroundIn most SCCHN patients receiving palliative treatment with platinum-based chemotherapy, the tumor eventually progresses and requires further treatment options. PD-1 inhibitor nivolumab was authorized in this setting in 2017 after proving superior to single agent chemotherapy in objective response and overall survival. But there are still patients who progress rapidly with nivolumab monotherapy. In this population, prompt escalation of immunotherapy by adding the CTLA-4 antagonist ipilimumab to nivolumab may be beneficial, as this combined checkpoint blockade has proven superior to nivolumab alone in sever...
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research
263PPatients with a 21-gene assay in South East London differ from the TAILORx trial population
ConclusionsOur patients have a higher clinical risk than the TAILORx population. They are younger and have larger, higher grade cancers. This population is under-represented in the TAILORx study which was unable to exclude benefit in the ≤ 50 subset and may thus underestimate benefit from chemotherapy in our population. The current RS reporting is biased towards an older, low-risk population.Legal entity responsible for the studyThe authors.FundingHas not received any funding.DisclosureC. Gousis: Travel / Accommodation / Expenses: Roche. H. Kristeleit: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / A...
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research
260PPAM50 and CGH-array genomic characterization of HER2-equivocal breast cancers defined by the 2018 ASCO/CAP recommendations
ConclusionsUsing PAM50, the majority of HER2-equivocal cases were classified as Luminal tumors (Luminal B 52% and A 22%) and harbored mostly at the genomic level chr 17 segmental or large copy number gains. As there is no evidence of benefit of anti-HER2 therapy in these cases, it emphasizes the need of genomic status determination of HER2-equivocal cases.Legal entity responsible for the studyAnne Vincent-Salomon.FundingHas not received any funding.DisclosureP. Morel: Full / Part-time employment: Nanostring. H.A. Brauer: Full / Part-time employment: Nanosting. A. Vincent-Salomon: Advisory / Consultancy, Consulting fees: Ro...
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research
1478OResults of the ASCEND-7 phase II study evaluating ALK inhibitor (ALKi) ceritinib in patients (pts) with ALK+ non-small cell lung cancer (NSCLC) metastatic to the brain
ConclusionsEfficacy of ceritinib, either in pts with or without a prior exposure to crizotinib, as reported in other studies, is confirmed in this study where only pts with active brain metastases were eligible. Safety profile of ceritinib in these pts remain consistent to what was reported earlier.Clinical trial identificationNCT02336451.Editorial acknowledgementShiva Krishna Rachamadugu, Novartis Healthcare Pvt Ltd, Hyderabad, India.Legal entity responsible for the studyNovartis Pharmaceuticals Corporation.FundingNovartis Pharmaceuticals Corporation.DisclosureL.Q. Chow: Advisory / Consultancy, Consultation Honoraria/Revi...
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research
1595TiPNivolumab plus ipilimumab (NI) versus chemotherapy plus nivolumab (CN) in squamous cell lung cancer (SqCLC): The SQUINT trial
AbstractBackgroundTreatment landscape for patients with advanced NSCLC is rapidly evolving, with recent randomized phase III trials demonstrating superiority of chemo-immuno combinations versus chemotherapy alone. Role of chemo-free combinations, including NI, is under investigation with limited available data. Aim of the present trial is to investigate outcome of SqCLC patients when treated with NI or CN.Trial designSQUINT (NCT03823625) is an open-label, randomized, parallel, non-comparative phase II study designed to assess the efficacy of NI (Arm A) or CN (Arm B) in patients with advanced, metastatic SqCLC. Eligibility ...
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research
1148PACCURACY a phase (P) II trial of AL101, a pan-Notch inhibitor, in recurrent/metastatic (R/M) adenoid cystic carcinoma (ACC) patients (pts) with Notch activating mutations (Notch act mut): Preliminary safety and efficacy data
ConclusionsIn the stage 1 of the ACCURACY trial, 12 pts with Notch1-4act mut are being treated with the pan-Notch inhibitor AL101. The trial will advance to stage 2 if ≥ 2 pts respond. Efficacy/safety data on these first 12 pts will be presented at the meeting. Accrual to stage 2 is ongoing.Clinical trial identificationNCT03691207.Editorial acknowledgementFrancesca Balordi, PhD, of The Lockwood Group (Stamford, CT, USA), in accordance with Good Publication Practice (GPP3) guidelines, funded by Ayala Pharmaceuticals, Inc.Legal entity responsible for the studyAyala Pharmaceuticals, Inc.FundingAyala Pharmaceuticals, In...
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research
474PPharmacokinetic (PK) and updated survival data from the Canadian cancer trials group IND.226 study of durvalumab ± tremelimumab in combination with platinum-doublet chemotherapy
ConclusionsStandard platinum-doublet chemotherapy regimens did not alter the PK of D+T or D compared with historical monotherapy therapy data. Toxicities were manageable and were not associated with PK.Clinical trial identificationNCT02537418.Legal entity responsible for the studyCanadian Cancer Trials Group (CCTG).FundingAstraZeneca provided drug and partial funding to support of this Canadian Cancer Trials Group (CCTG) study.DisclosureD. Hao: Honoraria (self), Advisory Board: Roche; Honoraria (self), Advisory Board; funding for clinical trial: BMS; Honoraria (self), Research grant / Funding (institution), Advisory Board;...
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research
1594TiPRadiosurgery followed by tumour treating fields (TTFields) for brain metastases (1-10) from NSCLC in the phase III METIS trial
AbstractBackgroundTumor Treating Fields (TTFields) are non-invasive, loco-regional, anti-mitotic treatment modality comprising alternating electric fields. TTFields have demonstrated efficacy in preclinical non-small cell lung cancer (NSCLC) models. TTFields treatment to the brain was safe and extended overall survival in newly-diagnosed glioblastoma. The METIS study [NCT02831959] investigates the efficacy and safety of TTFields in NSCLC patients with brain metastases.Trial designNSCLC patients (N = 270) with 1-10 brain metastases are randomized 1:1 to stereotactic radio surgery (SRS) followed by continuous TTFields (...
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research
1593TiPPhase Ib dose-escalation/expansion study of BI 836880, a VEGF/Ang2-blocking nanobody ®, in combination with BI 754091, an anti-PD-1 antibody, in patients with advanced solid tumours
AbstractBackgroundPreclinical evidence shows that vascular endothelial growth factor (VEGF) and angiopoietin 2 (Ang2) promote an immunosuppressive state in the tumour microenvironment, and that the combination of anti-VEGF/Ang2 with anti-PD-1 therapy promotes an immunopermissive state supportive of T-cell mediated tumour cell killing. BI 836880, a humanised bispecific nanobody that targets VEGF and Ang2, and BI 754091, an anti-PD-1 antibody, have shown safety and preliminary antitumour activity as monotherapies in phase I studies (RP2D, 720 mg iv q3w for BI 836880 and 240 mg iv q3w for BI 754091). The safety and effic...
Source: Annals of Oncology - October 1, 2019 Category: Cancer & Oncology Source Type: research
