4538 - Can we improve patient selection for phase 1 clinical trials (Ph1) based on Immuno-Oncology score prognostic index (VIO)?

Background

Life expectancy longer than 12 weeks(w) is a common inclusion criteria for most Ph1. Despite the presence of several prognostic indeces in drug development, their value for patient selection in clinical trials is not well established. VIO is a immune-oncology score validated in patients treated in Ph1 with immunotherapy (Hierro C. ESMO 2018), which includes 5 variables: albumin<35g/L, lactate dehydrogenase > upper limit normal, dNLR (derived neutrophil/(leukocytes minus neutrophils) ratio) >3, >2 sites of metastases, and presence of liver metastases.

Methods

VIO variables were retrospectively collected from 384 patients with advanced disease treated in Ph1 with immune checkpoint inhibitors (ICIs) or targeted agents (TAs) since 2011 to 2017 at Vall d´Hebron Hospital. The following VIO clusters were defined based on Kaplan Meier OS estimates: good prognosis (0‐1), intermediate (2‐3) and poor prognosis (4‐5). We aimed to improve patient selection for Ph1 (independent of treatment type) by developing a composite VIO score that is associated with overall survival (OS), progression free survival (PFS) and objectively estimated life expectancy at 12 w.

Results

From the 384 patients treated with ICIs (53.6%) or TAs (45.4%) in Ph1, 206 (53.6%) were female, 210 were treated with monotherapy (54.7%). Most frequent tumor types were: colorectal (17.4%), breast (14.1%) and lung (9.4%). The median follow-up was of 8.4 months (m) [IC95% 7.3-9.5]. Estimated median OS in good prognosis (33.3% of all pts), intermediate (54.2%) and poor prognosis (12.5%) was 16.2 m (13.3‐19.1), 7.8 m (6.9‐8.6) and 2.9 m (2.1-3.8), respectively (log rank test, p < 0.001), while the median PFS was 3.3 m (2.6‐3.9), 1.9 m (1.7‐2.1) and 1.2 m (0.8-1.6), respectively (log rank test, p < 0.001). Proportions of patients with life expectancy < 12 w were 52.2%, 13.1% and 4.3% in poor, intermediate and good prognosis VIO score groups, respectively (chi square<0.001).

Conclusions

VIO score is a strong prognostic index independent of the treatment type and it could be useful as a tool to estimate objectively life expectancy <12 w. More than 50% of patients with VIO score 4-5 (poor prognosis) died within 12 w, an estimate that can guide recruitment in phase 1 trials.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

This research has been funded by the Comprehensive Program of Cancer Immunotherapy & Immunology (CAIMI) supported by the Banco Bilbao Vizcaya Argentaria Foundation (FBBVA) (grant 89/2017).

Disclosure

J. Martin-Liberal: Advisory / Consultancy: Bristol-Myers Squibb, Novartis, Pierre Fabre, Roche; Speaker Bureau / Expert testimony: Astellas, Bristol-Myers Squibb, MSD, Novartis, Pierre Fabre, Pfizer, Roche; Honoraria (self): Bristol-Myers Squibb, MSD, Novartis, Pierre Fabre, Pfizer, Roche, Ipsen. A. Azaro: Honoraria (self), Advisory / Consultancy: Novartis, Roche, Orion. I. Brana: Advisory / Consultancy: Orion pharma; Speaker Bureau / Expert testimony: BMS; Speaker Bureau / Expert testimony: AstraZeneca; Speaker Bureau / Expert testimony: Merck Serono; Research grant / Funding (self): AstraZeneca, BMS, Celgene, Gliknik, GSK, Janssen, KURA, MSD, Novartis, Northern Biologics, Orion Pharma, Pfizer, Roche.. M. Vieito Villar: Honoraria (self), Travel grant: Roche. E. Muñoz-Couselo: Advisory / Consultancy: Amgen, Bristol-Myers Squibb, Merck, Sharp & Dohme, Novartis, Pierre Fabre, and Roche; Honoraria (self): Amgen, Bristol-Myers Squibb, Merck, Sharp & Dohme, Novartis, Pierre Fabre, Sanofi and Roche. E. Elez Fernández: Honoraria (institution): Array, MSD, Abbvie, Amgen, GSK, AstraZeneca,Bristol-Myers Squibb, Novartis, Boehringer Ingelheim, Hoffman La-Roche; Advisory / Consultancy: Hoffman La-Roche, Bristol-Myers Squibb, Servier, Amgen, Merck Serono, Array, Sanofi. E. Felip: Advisory / Consultancy, Speaker Bureau / Expert testimony: AbbVie, AstraZeneca, Blueprint medicines, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Guardant Health, Janssen, Medscape, Merck KGaA, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Takeda, Touchtime; Research grant / Funding (self): Fundación Merck Salud, Grant for Oncology Innovation EMD Serono.. J. Carles: Research grant / Funding (self): AB Science, Aragon Pharmaceuticals, Arog Pharmaceuticals, INC, Astellas Pharma., AstraZeneca AB, Aveo Pharmaceuticals INC, Bayer AG, Blueprint Medicines Corporation, BN Immunotherapeutics INC, Boehringer Ingelheim España, S.A., Bristol-Myers Squibb Inter; Advisory / Consultancy: Bayer / Johnson & Johnson / Bristol-Myers Squibb / Astellas Pharma / Pfizer / Sanofi / MSD Oncology / Roche/ AstraZéneca; Speaker Bureau / Expert testimony: Bayer / Johnson & Johnson / Asofarma / Astellas Pharma. J. Tabernero: Advisory / Consultancy: Array Biopharma, AstraZeneca, Bayer, BeiGene, Boehringer Ingelheim, Chugai, Genentech, Inc., Genmab A/S, Halozyme, Imugene Limited, Inflection Biosciences Limited, Ipsen, Kura Oncology, Lilly, MSD, Menarini, Merck Serono, Merrimack, Merus, Molecular Part. R. Dienstmann: Advisory / Consultancy: Roche; Speaker Bureau / Expert testimony: Roche, Symphogen, Ipsen, Amgen, Sanofi, MSD, Servier; Research grant / Funding (self): Merck. E. Garralda: Advisory / Consultancy: F.Hoffmann-La Roche,Ellipses Pharma ,Neomed Therapeutics1 Inc,Boehringer Ingelheim ,Janssen Global Services; Speaker Bureau / Expert testimony: Bristol-Mayers Squibb; Honoraria (self): Menarini, Glycotope, Menirarini. All other authors have declared no conflicts of interest.