Browsing Over 268 Presentations
49O - IMpower133: Patient-reported outcomes (PROs) in a ph1/3 study of first-line (1L) atezolizumab (atezo) + carboplatin + etoposide (CP/ET) in extensive-stage SCLC (ES-SCLC) (ID 316)
- A. Mansfield (Rochester, MN, United States of America)
- R. Califano (Manchester, United Kingdom)
- A. Każarnowicz (Olsztyn, Poland)
- N. Karaseva (St Petersburg, Russian Federation)
- A. Sánchez (Seville, Spain)
- S. V. Liu (Washington DC, MD, United States of America)
- L. Horn (Nashville, TN, United States of America)
- C. Quach (South San Francisco, CA, United States of America)
- W. Yu (South San Francisco, CA, United States of America)
- F. Kabbinavar (South San Francisco, CA, United States of America)
- S. Lam (South San Francisco, CA, United States of America)
- A. Mansfield (Rochester, MN, United States of America)
Abstract
Background
In IMpower133 (NCT02763579), 1L treatment (tx) with atezo + CP/ET for ES-SCLC provided a significant improvement in survival v placebo (PBO) + CP/ET and no unexpected safety signals. PROs were assessed to inform the overall tx benefit of adding atezo to CP/ET.
Methods
Patients (pts) were randomised to atezo + CP/ET (1200 mg + AUC 5/100 mg/m2) (N = 201) or PBO + CP/ET (N = 202) IV q3w x 12 wks, then maintenance atezo or PBO q3w until progression/intolerable toxicity/clinical benefit loss. Descriptive analyses of EORTC QLQ-C30 and QLQ-LC13 scales (score range 0–100) included change from baseline (BL), cumulative distribution function curves of change at wk 12 and time to deterioration (TTD). A ≥ 10-point change from BL was prespecified as clinically meaningful.
Results
Completion rates were ≥85% at BL and ≥70% to wk 75 in both arms; BL PRO scores were comparable. At wks 27 and 54, 108 and 34 pts remained on study and eligible to complete assessments, respectively. Pts in both arms reported early, notable lung cancer (LC) symptom palliation (Table) with numeric trends of greater improvement with atezo + CP/ET. Higher proportions of atezo + CP/ET pts reported LC symptom relief at wk 12 v PBO + CP/ET. No apparent differences in TTD of cough or chest pain were seen; a numeric delay in TTD of dyspnoea favoured atezo + CP/ET (HR 0.75; 95% CI 0.55–1.02). Atezo + CP/ET pts reported improved physical function above BL until wk 51 and clinically meaningful health-related quality of life (HRQoL) improvements that persisted at most visits through wk 54. Changes in tx-related symptoms (diarrhoea, nausea/vomiting) were similar across arms.Mean score change from BL at wk 12 (negative value reflects improvement) Atezo + CP/ET (n = 124) PBO + CP/ET (n = 131) Arm/shoulder pain −7.0 −2.5 Chest pain –7.8 –4.1 Cough –14.8 –15.5 Dyspnoea –6.5 –2.3
Conclusions
Atezo + CP/ET tx provided a significant improvement in survival as well as immediate and tangible improvements in pt-reported LC symptoms. PROs indicating sustained function and improved HRQoL with minimal impact from tx toxicities further support the positive benefit:risk of atezo + CP/ET in 1L ES-SCLC.
Editorial acknowledgement
Support for third-party writing assistance for this abstract, furnished by Daniel Clyde, PhD, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland.
Clinical trial identification
NCT02763579, May 5, 2016.
Legal entity responsible for the study
F. Hoffmann-La Roche Ltd/Genentech, Inc.
Funding
F. Hoffmann-La Roche Ltd/Genentech, Inc.
Disclosure
R. Califano: Honoraria for consultancy, speaker bureau and advisory board: Roche. S.V. Liu: Research grant (institution): AZ, Bayer, Blueprint, Clovis, Corvus, Esanex, Genentech, Lilly, Lycera, Merck, Molecular Partners, OncoMed, Pfizer, Threshold; Consultant: AZ, BMS, Celgene, Genentech, Heron, Lilly, Pfizer, Regeneron, Taiho (DSMB), Takeda. L. Horn: Consultancy: AbbVie, AstraZeneca, Merck, Incyte, Xcovery, Genentech, EMD Serono. C. Quach, F. Kabbinavar, S. Lam: Employment and stock: Roche/Genentech. W. Yu: Employment: Genentech. A. Mansfield: Honoraria for participation in advisory boards (institution): Genentech, AbbVie, BMS; Grants: Novartis, Verily. All other authors have declared no conflicts of interest.
28TiP - CHECK'UP: A prospective cohort study to identify predictive factors of response and mechanisms of resistance to PD-1 and PD-L1 antagonists (ID 219)
- F. Penault-Llorca (Clermont-Ferrand, France)
- F. Penault-Llorca (Clermont-Ferrand, France)
- C. Caux (Lyon, France)
- S. Depil (Lyon, France)
- C. Le Tourneau (Paris, France)
- M. Pérol (Lyon, France)
- C. Robert (Villejuif, France)
- V. Soumelis (Paris, France)
- D. Couch (Paris, France)
- N. Isambert (Dijon, Cedex, France)
- Y. Fernandez (Vandoeuvre-lès-Nancy, France)
- T. Filleron (Toulouse, France)
- G. Vassal (Villejuif, France)
Abstract
Background
Immune checkpoint blockade represents a major breakthrough in cancer therapy with recent approvals of PD-1 or PD-L1 antagonists in a range of indications. Phase 3 studies have demonstrated response rates varying from 13% (head and neck squamous cell carcinoma [HNSCC]) to 40% (melanoma) in sensitive diseases, and impressively durable responses in individual patients. The overall rate of response remains relatively low however. Even in immune-sensitive diseases such as melanoma the majority of tumours do not respond to immunotherapy alone and most tumours will eventually develop resistance to the treatment. Furthermore, although PD-1/PD-L1 antagonists are generally well tolerated, a small but significant number of patients experience severe immune-related toxicity, the risk factors of which are poorly understood. Identifying which patients will most benefit from PD-1/PD-L1 antagonist therapy and the mechanisms of resistance are of critical importance for clinicians. The CHECK’UP trial aims to address this question by studying approved PD-1/PD-L1 antagonist treatment across three cancer indications: melanoma, non-small cell lung cancer (NSCLC) and HNSCC.
Trial design
This prospective, multicentre cohort trial will study 670 patients in 3 parallel groups set to receive one of the single agent PD-1 or PD-L1 antagonists authorised for use in France as standard care for melanoma, NSCLC or HNSCC. Clinical and biological sample data (tumour, blood, microbiome) collected at study entry and throughout the treatment period will be analysed to identify potential response biomarkers. Patients will be followed for 5 years. A penalized logistic regression model will be used to identify associations between different parameters and response to treatment in a training cohort, made up of the first patients included, and to develop a predictive response signature for each indication. The performance of this signature will then be tested in an independent validation cohort comprised of the remaining patients. Mechanisms of primary and acquired resistance, occurrence of long-term treatment related toxicity and a cost/benefit assessment of treatment in a real-life setting will also be explored.
Legal entity responsible for the study
UNICANCER.
Funding
Fondation ARC pour la recherche sur le cancer.
Disclosure
All authors have declared no conflicts of interest.
67P - The predictive value of 18F-FDG PET/CT after ipilimumab for treatment response evaluation in metastatic melanoma patients (ID 375)
- S. Vari (London, United Kingdom)
- S. Vari (London, United Kingdom)
- A. Annovazzi (Rome, Italy)
- R. Pasqualoni (Rome, Italy)
- R. Sciuto (Rome, Italy)
- D. Giannarelli (Rome, Italy)
- F. Cognetti (Rome, Italy)
- V. Ferraresi (Roma, Italy)
Abstract
Background
In previous reports it has been demonstrated that the 18F-FDG PET/CT performs better than contrast-enhanced CT in assessing the response to immunotherapy treatment in patients affected by metastatic melanomas. Aim of the present study was to evaluate if the first 18F-FDG PET/CT scan performed after the completion of 4 cycles of Ipilimumab treatment was predictive of patient clinical outcome.
Methods
26 patients who performed a PET/CT scan before treatment (PET0), after 4 cycles of Ipilimumab (PET1) and at least an additional later evaluation without starting new therapeutic regimen (PET2), were retrospectively evaluated. Response to treatment was evaluated according to PERCIST criteria for PET1 and PET2 and compared with patient clinical outcome. A total of 69 metastatic lesions were also singularly analyzed.
Results
PET1 were performed after a mean of 6 weeks from the end of IPI and PET2 after a mean of 12 weeks from PET1. Patients were classified at PET1 as having progressive metabolic disease (PMD) in 15 cases, stable metabolic disease (SMD) in 6, partial metabolic response (PMR) in 2 and complete metabolic response (CMR) in 3. Discordant results between PET2 and PET1 were observed in 6 patients (from SMD to PMD in 4 cases, from SMD to CMR in 1 and from PMD to CMR in 1).
Conclusions
The results showed that the first PET/CT evaluation after IPI was not always representative for the definitive response to treatment. The immediate start of a new therapeutic line can be proposed for PMD, in all other cases and in particular for SMD an early PET/CT restaging should be performed to confirm the patient clinical outcome.
Legal entity responsible for the study
Ethical Committee.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Understanding the mechanisms to develop combinations of immunoregulatory agents with radiotherapy (ID 30)
- E. Cheadle (Manchester, United Kingdom)
- E. Cheadle (Manchester, United Kingdom)
102P - Targeting human CD141+ DC using CLEC9A antibodies for cancer immunotherapy (ID 351)
- K. Masterman (Brisbane, Australia)
- K. Masterman (Brisbane, Australia)
- F. E. Pearson (WOOLLOONGABBA, Australia)
- K. Tullett (Clayton, ACT, Australia)
- O. Haigh (WOOLLOONGABBA, QLD, Australia)
- C. Walpole (WOOLLOONGABBA, QLD, Australia)
- G. Daraj (WOOLLOONGABBA, QLD, Australia)
- M. H. Lahoud (Clayton, ACT, Australia)
- I. Leal Rojas (WOOLLOONGABBA, QLD, Australia)
- K. Radford (WOOLLOONGABBA, Australia)
Abstract
Background
Dendritic cells (DC) are a heterogeneous cell population, with specialist subtypes driving specific immune responses. In mice, the cDC1 subset (also referred to as Batf3-dependent DC, XCR1+ DC, CD8+ DC in lymphoid tissues and CD103+ DC in peripheral tissues) is essential for the induction of tumour immune responses and for the efficacy of checkpoint inhibitor blockade and adoptive T cell immunotherapies. Vaccines that can deliver antigens (Ag) directly to DCs in vivo are more effective than cell-based therapies in mouse models and are promising approaches to translate to humans. CD141+ DC are the human cDC1 equivalent and specifically express the C-type lectin-like receptor CLEC9A, that facilitates cross-presentation of dead cell Ag. Targeting tumour-associated Ag (TAA) to human CD141+ DC using CLEC9A antibody (Ab) is therefore an attractive strategy to induce or boost tumour immune responses.
Methods
NYESO1 and WT1 are well characterised, highly immunogenic TAA expressed by a broad array of tumour types. We developed recombinant human chimaeric IgG4 Ab specific for human CLEC9A genetically fused to NYESO1 or WT1. For comparison we developed TAA fusions with chimaeric IgG4 Ab specific for human DEC-205, which is expressed by many human leukocytes, and β-galactosidase as an irrelevant isotype control. CLEC9A-NYESO1 and CLEC9A-WT1 Abs retained their binding specificity for CD141+ DC. Following uptake of CLEC9A-WT1, CD141+ DC cross-presented a WT-1 HLA-A24-restricted epitope for recognition by specific CD8+ cytotoxic T cells. Likewise, a HLA-A2-restricted NYESO1 epitope was cross-presented Ag specific CD8+ T cells by CD141+ DC following uptake of CLEC9A-NYESO1.
Results
For both TAA, the CLEC9A Abs were more efficient at delivery of Ag for cross-presentation than DEC-205 or isotype control Abs. Moreover, using a humanised mouse model in which functional human CD141+ DC and Ag-specific T cells develop, CLEC9A-TAA Ab induced priming of Ag-specific T cells.
Conclusions
Our data advocate further development of human CLEC9A targeting Abs as cancer vaccines.
Legal entity responsible for the study
Mater Research Institute.
Funding
Department of Defense, USA.
Disclosure
All authors have declared no conflicts of interest.
Phenotype markers to identify tumor reactive (neoantigen specific) T cells (ID 62)
- A. Gros (Barcelona, Spain)
- A. Gros (Barcelona, Spain)
Session DOI (ID 510)
Immunosuppression in primary brain tumors (ID 95)
- M. Platten (Heidelberg, Germany)
- M. Platten (Heidelberg, Germany)
1O - Advanced CT imaging features reflect distinct tissue immune profiles and exhibit high prognostic impact on NSCLC (ID 309)
- G. Mazzaschi (Parma, Italy)
- G. Mazzaschi (Parma, Italy)
- P. Pagano (Parma, Italy)
- G. Milanese (Parma, Italy)
- D. Madeddu (Parma, Italy)
- A. Falco (Parma, Italy)
- G. Armani (Parma, Italy)
- G. Bocchialini (Parma, Parma/PR, Italy)
- D. Marturano (Parma, Italy)
- L. Ampollini (Parma, Italy)
- B. Lorusso (Parma, Italy)
- C. Lagrasta (Parma, Italy)
- N. Sverzellati (Parma, Italy)
- M. Silva (Parma, Italy)
- M. Tiseo (Parma, Italy)
- F. Quaini (Parma, Italy)
- G. Roti (Parma, Italy)
Abstract
Background
Intersecting genetic, biologic and clinico-pathological features with high-throughput imaging may pave the way to precision oncology. We advanced the hypothesis that the tumor immune microenvironment (TIME) may imprint on CT scan parameters in a qualitative and quantitative (radiomics) fashion, providing a non-invasive approach to identify new prognostic factors in NSCLC patients.
Methods
In this study, we enrolled sixty (31 Adenocarcinoma, 29 Squamous Cell Carcinoma) surgically resected patients. We defined TIME by the quantitative assessment of PD-L1 expression and a detailed morphometric evaluation of Tumor Infiltrating Lymphocytes (TILs). Next, from each tumor associated images we extrapolated 841 CT radiomic features through an open-source (3d Slicer) software.
Results
We observed high levels of tissue PD-L1 in radiologic lesions displaying a solid texture and any effect on the surrounding parenchyma (p < 0.05), while well defined CT margins were seen in TILs-rich cases (p < 0.05). The combined analysis of predetermined risk factors from TIME and CT texture had a striking impact on clinical outcome. Patients with low PD-1 expression on CD8+ TILs and CT evidence of tumor effect on parenchyma had significantly increased (p < 0.001) OS with respect to their counterpart (median 50 vs 30 months, HR = 16.82). We also documented prolonged survival (p < 0.05) in cases with well defined CT margins and high CD8-to-CD3 TILs (46 vs 35 months, HR = 2.66). Intriguingly, when an unsupervised hierarchical clustering model was applied to radiomics data, we identified two clusters (A and B) with oppositely regulated features: the first of 57 cases (A), further branching into two continuous different clusters, the second (B) comprised only three patients sharing a mutual genetic (EGFR and KRAS mutations), immunologic (PD-L1, CD3+ and CD8+ TILs, PD-1/CD8 ratio), radiologic (shape, effect, texture and structure) and clinical (relapse and death) profile.
Conclusions
A highly significant prognostic score can be obtained in NSCLC by integrating TIME with CT features. Distinct tissue immune backgrounds may entail imaging textures potentially able to portray a radiologic signature of lung cancer.
Legal entity responsible for the study
University of Parma.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
23P - The effect of tumor derived HMBG1 on intra-tumoral B cells in esophageal squamous cell carcinoma (ID 258)
- D. L. Kwong (Hong Kong, Hong Kong PRC)
- D. L. Kwong (Hong Kong, Hong Kong PRC)
- Y. N. Kam (Hong Kong, Hong Kong PRC)
- X. Y. Guan (Hong Kong, Hong Kong PRC)
Abstract
Background
Tumor microenvironment (TME) is often hypoxic and characterized by diverse cell populations (tumor cells and lymphocytes). An intranuclear architectural protein termed high mobility group box chromosomal protein 1 (HMGB-1) is enriched in hypoxic environment, where it acts as a chemokine to promote recruitment of inflammatory cells. We studied the effect of tumor derived HMBG1 on B cell migration and phenotype differentiation in esophageal squamous cell carcinoma (ESCC).
Methods
Immunohistochemistry (IHC) staining for HMGB-1 was performed on tissue microarray (TMA) of ESCC and correlated with survival outcome. An immunostaining scoring system corresponding to total staining intensity as follows; (strong staining score =3; moderate staining score=2; weak staining scores= 1; no staining scores= 0). Co-staining with CD20+B was also performed to study B cells distribution in the tumor. ESCC cell lines were transfected with HMGB-1 and transwell migration of B cells were studied.
Results
TMA containing 78 paired primary tumors and normal tissue from ESCC patients was analyzed by IHC using an anti-HMGB1 antibody. We found that HMGB1 was expressed at a higher level as compared to paired normal tissue. Survival curves were estimated by the Kaplan-Meier method and compared with log-rank test to evaluate the relationship between biomarker HMGB1 and survival outcomes. Patients were divided into two groups based on the optimal cutoffs of low (score 0-1), high (score 2-3) staining of HMGB1, we found out that HMGB1 staining were not correlated to patient survivals (p = 0.363). We then performed double-staining and demonstrated that B cells were located in the stroma along HMGB1-stained tumor. Stable HMGB1 ESCC cell lines were established where boyden chamber and wound-healing assays demonstrated that B cells migrated and proliferated at higher rates towards HMGB1-overexpressing cell lines.
Conclusions
Our findings indicate that HMGB1 was over-expressed in tumor compared with normal tissue. HMGB1 expression per se was not correlated to survival in our log-rank analysis. HMGB1 expression has probable role in B cells recruitment, migration/proliferation.
Legal entity responsible for the study
Dora LW Kwong.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
62P - First-line systemic real-world treatment of patients with advanced/metastatic NSCLC in the UK (ID 308)
- M. Wang (Uxbridge, United Kingdom)
- M. Wang (Uxbridge, United Kingdom)
- P. Dhokia (Uxbridge, United Kingdom)
- S. Menon (London, United Kingdom)
- B. Martindale (Collegeville, United States of America)
Abstract
Background
Immuno-oncology (IO) has changed treatment (Tx) landscape of non-small cell lung cancer (NSCLC). IO is efficacious and a less toxic alternative to standard chemotherapy in treating NSCLC. This study analysed 1st line (1L) Tx patterns of patients with stage IIIb/IV NSCLC in real-world setting.
Methods
IQVIA Oncology Dynamics (OD) database was used to identify stage IIIb/IV NSCLC patients who initiated and received 1L Tx between June 2017 and March 2018 in the UK. IQVIA OD is a syndicated database collecting longitudinal, anonymized, patient-level oncology data through a quarterly physician panel survey. The UK panel characteristics were: 94% public, 65% university, 12% Scotland/Northern Ireland - 6% Wales - 82% England. The response rate ranged 13-72% among circa 225 physicians per quarterly pulse. Data on patient/disease characteristics, Tx, and biomarkers were extracted and analysed.
Results
In total, data from 738 stage IIIb/IV NSCLC patients receiving 1L cancer Tx were analysed. At questionnaire completion, 57% of patients were male and 68% were aged >60 years. Most patients had cancers with non-squamous histology (79%); fewer had squamous (20%) and other (1%). ECOG performance status was assessed as 0 in 14% and 1 in 76% of patients, and metastases were mostly found in the lung (49%), bone and liver (34% each), lymph nodes local (36%) and distant (25%). COPD was the most common comorbidity (28%); 40% of patients reported none. 49% were former smokers and 22% current smokers. Chemotherapy and targeted therapies were the most frequent 1L Tx received by 301 (41%) and 219 (30%) patients, respectively. 30% of patients (n = 218) received IO Tx in 1L; pembrolizumab was the most common IO therapy (n = 216, 29%). PD-L1 testing was performed among 76% of the latest quarter patients (n = 195/255); 106 (54%) were positive (PD-L1+; ≥50%), 82 (42%) negative (PD-L1-; <50%) and 7 awaiting results. Most PD-L1+ patients received pembrolizumab in 1L (86%), whereas PD-L1- patients were mostly treated with chemotherapy (73%) and one third received targeted therapies.
Conclusions
In the current UK treatment landscape for stage IIIb/IV NSCLC, only 30% of patients were treated with IO Tx in 1L. A high proportion of 1L patients is still treated with traditional chemotherapy.
Editorial acknowledgement
Editorial assitance was provided by Eleonora Morais from IQVIA.
Legal entity responsible for the study
Outcome Sciences LLC (an IQVIA company).
Funding
Bristol-Myers Squibb Pharmaceuticals LTD.
Disclosure
M. Wang: Employee of Bristol-Myers Squibb Pharmaceuticals Ltd. S. Menon, B. Martindale: Employee of IQVIA (IQVIA Oncology Dynamics, a syndicated database collecting oncology data).
Handling of GI toxicity from immune checkpoint inhibitors (ID 25)
- F. Carbonnel (Le Kremlin Bicetre, France)
- F. Carbonnel (Le Kremlin Bicetre, France)