Browsing Over 268 Presentations
Invited Discussant LBA4 and 49O (ID 492)
- S. Peters (Lausanne, Switzerland)
- S. Peters (Lausanne, Switzerland)
T cell therapy for lymphoid malignancies (ID 72)
- C. Arber Barth (Lausanne, TX, Switzerland)
- C. Arber Barth (Lausanne, TX, Switzerland)
DOI session (ID 520)
Visual a new path forward: Simultaneously detect up to 37 protein markers all from a single scan with Imaging Mass Cytometry (ID 109)
- R. Spada (Les Ulis, France)
- R. Spada (Les Ulis, France)
6P - Predictive score using clinical and blood biomarkers in advanced non-small cell lung cancer (aNSCLC) patients treated with immunotherapy (ID 459)
- A. Prelaj (Milan, Italy)
- A. Prelaj (Milan, Italy)
- S. Rebuzzi (Genova, Italy)
- P. Pizzutilo (Bari, Italy)
- M. Montrone (Bari, Italy)
- F. Pesola (Bari, Italy)
- V. Longo (Bari, Italy)
- V. Lapadula (Bari, Italy)
- F. Cassano (Bari, Italy)
- P. Petrillo (Bari, Italy)
- D. Bafunno (Bari, Italy)
- N. Varesano (Bari, Italy)
- V. Lamorgese (Bari, Italy)
- A. Mastrandrea (Bari, Italy)
- D. Ricci (Bari, Italy)
- A. Catino (Bari, Italy)
- G. Domenico (Bari, Italy)
Abstract
Background
Despite the overall survival (OS) benefit, only 18-20% of aNSCLC patients respond to immune-checkpoint inhibitors (ICI) as second-line therapy with a median progression-free survival (mPFS) of 2-4 months. The identification of predictive and prognostic biomarkers to select patients most likely to respond to ICI is greatly needed in guiding clinical practice.
Methods
We conducted a retrospective monocentric analysis of 154 aNSCLC patients receiving single-agent Nivolumab or Pembrolizumab as second-line (68%) and >3rd line (32%). We collected complete blood cell count at baseline and evaluated LDH, absolute neutrophil count (ANC), lymphocyte count (ALC), monocyte count (AMC) and eosinophil count (AEC) and their ratio such as neutrophil-lymphocyte ratio (NLR), derived-NLR (dNLR) and lymphocyte-monocyte ratio (LMR). Univariate and multivariate analyses were performed to identified indipendent predictors factors for immunotherapy (using Kaplan–Meier and Cox Progression analyses).
Results
The multivariate analysis on clinical factors showed the negative predictive role of ECOG PS 2 and liver metastasisand the positive predicitive role of smoking status. The multivariate analysis for PFS showed the negative predictive role of higher ANC (>6000/mL) and LDH (>400 mg/dl) and positive predictive role of higher ALC (>2200/mL). Also, according to stepwise regression analyses, NLR>4 playsa negative predictive and prognostic role at baseline. Finally, five predictive clinical and blood biomarkers at baseline (smoking status, ECOG PS, liver metastases, LDH and NLR), were used to create a predictive score for immunotherapy. Three predictive groups were defined as high, intermediate and low with a mPFS of 10.2 vs 4.9 vs 1.7 months respectively (HR 4.18 95% IC 2.64–6.62, p < 0.001).Predictive Factor Assessment Point ECOG PS 0-1 2 0 1 Smoking (pack-years) > 43 < 43 0 1 Liver metastases No Yes 0 1 LDH (mg/dl) < 400 > 400 0 1 NLR < 4 > 4 0 1 Predictive groups (Points): 1 = 0 2 = 1-2 3 = 3-5 PFS (months): 10.2 4.9 1.7 HR 4.18 95% IC (2.64 – 6.62) p < 0.001
Conclusions
In advanced NSCLC patients treated with second-line immunotherapy, the identification of five and predictive clinical and blood biomarkers at baseline, combined in a predictive score, may help identify patients most likely to benefit from immunotherapy.
Legal entity responsible for the study
Clinical Cancer Center Giovanni Paolo II, Bari, Italy.
Funding
Has not received any funding.
Disclosure
G. Domenico: Advisory board: Bristol-Myers Squibb. All other authors have declared no conflicts of interest.
75P - Cemiplimab, a human PD-1 monoclonal antibody, in patients (pts) with recurrent or metastatic cervical cancer: Interim data from phase I cohorts (ID 434)
- D. Rischin (Melbourne, Australia)
- D. Rischin (Melbourne, Australia)
- M. Gil-Martin (Barcelona, Spain)
- A. González-Martin (Madrid, Spain)
- I. Brana (Barcelona, Spain)
- J. Y. Hou (New York, NY, United States of America)
- D. Cho (New York, NY, United States of America)
- G. Falchook (Denver, CO, United States of America)
- S. Formenti (New York, NY, United States of America)
- S. Jabbour (New Brunswick, NJ, United States of America)
- K. Moore (Oklahoma City, OK, United States of America)
- A. Naing (Houston, TX, United States of America)
- K. P. Papadopoulos (San Antonio, TX, United States of America)
- J. Baranda (Fairway, KS, United States of America)
- A. Weise (Detroit, MI, United States of America)
- M. G. Fury (Tarrytown, NY, United States of America)
- M. Feng (Basking Ridge, NJ, United States of America)
- J. Li (Basking Ridge, NJ, United States of America)
- I. Lowy (Tarrytown, United States of America)
- M. Mathias (Tarrytown, NY, United States of America)
Abstract
Background
For pts who progress after first-line platinum based therapy for recurrent/metastatic cervical cancer, there are no therapies available that have been demonstrated to improve survival or quality of life. Cemiplimab (REGN2810), a human monoclonal antibody to PD-1, exhibited encouraging efficacy and acceptable tolerability in a phase 1 dose escalation study. The present report focuses on interim data from the phase 1 cervical cancer expansion cohorts (ECs) of cemiplimab as a monotherapy (EC 23) or in combination with hypofractionated radiotherapy (hfRT) (EC 24) (NCT02383212).
Methods
Pts with recurrent or metastatic cervical cancer resistant to or intolerant of platinum and taxane doublet therapy received cemiplimab 3 mg/kg Q2W IV for up to 48 weeks, in ECs 23 and 24, and hfRT (9 Gy x 3 times/week given 1 week after first dose of cemiplimab) in EC 24. The co-primary objectives were to evaluate the safety, tolerability, and efficacy of cemiplimab monotherapy or in combination with hfRT. Tumour response assessments (in non-irradiated target lesions) were performed by RECIST 1.1 Q8W.
Results
As of 1 Sept, 2017, these ECs were fully enrolled with 20 pts (EC 23, n = 10, EC 24, n = 10). Median (range) age was 55.0 (31–76) years (EC 23) and 51.5 (29–65) years (EC 24). ECOG performance status 1 vs. 0 was 60% vs. 40% and 80% vs. 20%, respectively, for EC 23 and EC 24. Investigator-assessed overall response rate (ORR; complete response [CR] + partial response [PR]) was 10.0% (0 CR and 1 PR) in each of EC 23 and EC 24. At the time of data cut-off, both responses were ongoing with durations of 3.7+ months. The most common treatment-emergent adverse events (TEAEs) of any grade were diarrhoea (40.0%), fatigue, hypokalaemia and pain in extremity (each 30.0%) in EC 23, and diarrhoea and urinary tract infection (each 30.0%) in EC 24. There was no grade ≥3 TEAE reported in > 1 patient in either cohort.
Conclusions
Cemiplimab as monotherapy and in combination with hfRT demonstrated antitumour activity with an acceptable safety profile in pts with metastatic or recurrent cervical cancer. Cemiplimab monotherapy vs. chemotherapy in ≥ 2nd line cervical cancer is currently being evaluated in a global randomised phase 3 study (NCT03257267).
Editorial acknowledgement
Medical writing support under the direction of the authors was provided by Emmanuel Ogunnowo, PhD, of Prime (Knutsford, UK) and funded by Regeneron Pharmaceuticals, Inc. and Sanofi according to Good Publication Practice guidelines.
Clinical trial identification
NCT02383212.
Legal entity responsible for the study
Regeneron Pharmaceutical Inc. and Sanofi.
Funding
Regeneron Pharmaceutical Inc. and Sanofi.
Disclosure
D. Rischin: Research funding: Genentech/Roche, Merck, Amgen, Regeneron, Bristol-Myers Squibb. A. González-Martin: Consulting, advisory, speakers’ bureau, travel accommodation expenses: AstraZeneca, Tesaro, Roche, Pharmamar. J.Y. Hou: Consultant and fees: Foundation Medicine, Massive Bio, Inc. D. Cho: Consulting fees: Pfizer, BMS, Exelixis, Genentech, Prometheus. G. Falchook: Funding for trial for submitted work. S. Jabbour: Research funding grants: Merck, Nestle outside of the submitted work. K. Moore: KInstitutional consultancy (honorarium and ad board) fees: Tesaro, Genentech Roche, Clovis, AstraZeneca (for agents not involved in the SOLO-1 study), Immunogen, VBL Therapeutics, Janssen. M.G. Fury: Employee and shareholder: Regeneron Pharmaceuticals, Inc.; Patents, royalties, other intellectual property: Regeneron Pharmaceuticals, Inc. M. Feng: Employee and shareholder: Regeneron Pharmaceuticals, Inc., Bayer. J. Li: Employee and shareholder: Regeneron Pharmaceuticals, Inc., Novartis. I. Lowy: Employee, shareholder, fees for travel and accommodation expenses, leadership: Regeneron Pharmaceuticals, Inc. M. Mathias: Employee and shareholder: Regeneron Pharmaceuticals, Inc. All other authors have declared no conflicts of interest.
Chemotherapy combos in NSCLC (ID 35)
- E. F. Smit (Amsterdam, Netherlands)
- E. F. Smit (Amsterdam, Netherlands)
107TiP - Phase I safety and pharmacokinetics of ADU-1604, an anti-CTLA-4 antibody, in adults with metastatic melanoma (ID 265)
- M. Hendriks (Oss, Netherlands)
- M. Hendriks (Oss, Netherlands)
- E. De Cock (Oss, Netherlands)
- K. Maplestone (Oss, Netherlands)
- H. Namini (Oss, Netherlands)
- A. Van Elsas (Oss, Netherlands)
Abstract
Background
ADU-1604 is a humanized IgG1 monoclonal antibody in development for use as monotherapy or in combination with other anti-cancer therapies. It targets a novel epitope on the validated inhibitory receptor, CTLA-4. ADU-1604 was characterized in vitro and shown to bind to human CTLA-4, block binding of CD80 and CD86 to CTLA-4, and stimulate IL-2 production by activated lymphocytes. ADU-1604 enhanced T cell dependent hepatitis B surface antigen vaccine-induced antibody responses in cynomolgus monkeys and demonstrated anti-tumor activity in a non-small cell lung cancer patient-derived xenograft humanized mouse model. The primary objective of the first-in-human study is to determine the recommended phase 2 dose (RP2D) by evaluating the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of ADU-1604 administered as an intravenous (IV) infusion.
Trial design
This first-in-human, open-label, multicenter, dose-escalation study is conducted in adults with metastatic melanoma without further established treatment options. The study includes two parts: 1) Dose Escalation starts with 0.3 mg/kg of ADU-1604 IV infusion in 3-6 subjects and dosing is escalated until the RP2D is defined (represented by the dose tolerated while not exceeding the maximum tolerated dose or maximum dose (10 mg/kg)). 2) In Dose Confirmation, 7-10 additional subjects receive ADU-1604 at the RP2D until the maximum number of planned doses are administered (4 treatment cycles), disease progression is confirmed, or consent is withdrawn, whichever occurs first. The end of the study is defined as the date when all subjects have completed the final protocol-specified safety assessment and/or discontinued study participation. Primary endpoints include incidence of dose limiting toxicity, treatment-emergent adverse events (TEAEs), and changes from baseline in safety parameters. Secondary endpoints include severity of TEAEs, serious adverse events, changes from baseline in safety assessments, serum concentration-time profiles and PK parameters (including Cmax, AUC), and incidence of anti-ADU-1604 antibodies. This study is designed to provide the RP2D of ADU-1604 based on the totality of PK-PD, as well as clinical responses and safety.
Clinical trial identification
NCT03674502.
Legal entity responsible for the study
Aduro Biotech Europe.
Funding
Aduro Biotech Europe.
Disclosure
M. Hendriks, E. de Cock, K. Maplestone, H. Namini, A. van Elsas: Employee of and holds stock in Aduro Biotech Europe at the time of this work.
Self and viral antigens-HPV vaccine for therapy (ID 67)
- M. J. Welters (Leiden, Netherlands)
- M. J. Welters (Leiden, Netherlands)
Session DOI (ID 515)
When 1+1 = 3: Unlocking the potential of the IL-2 pathway with NKTR-214 in combination treatment (ID 103)
- J. Zalevsky (San Francisco, United States of America)
- J. Zalevsky (San Francisco, United States of America)
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.