Displaying One Session

Amphithéâtre Bordeaux 25.02.2019 14:05 - 15:20
Date
25.02.2019
Time
14:05 - 15:20
Location
Amphithéâtre Bordeaux
Chairs
  • J. De Bono
  • C. Massard
Proffered Paper session : Immunotherapy Proffered Paper session

Session DOI (ID 219)

Lecture Time
14:05 - 14:05
Location
Amphithéâtre Bordeaux, Palais des Congrès, Paris, France
Date
25.02.2019
Time
14:05 - 15:20
Proffered Paper session : Immunotherapy Proffered Paper session

3O - Applicability of the lung immune prognostic index (LIPI) in patients with metastatic solid tumors when treated with immune checkpoint inhibitors (ICI) in early clinical trials (ID 184)

Presentation Number
3O
Lecture Time
14:05 - 14:20
Speakers
  • A. Varga
Location
Amphithéâtre Bordeaux, Palais des Congrès, Paris, France
Date
25.02.2019
Time
14:05 - 15:20
Authors
  • A. Varga
  • A. Bernard-Tessier
  • E. Auclin
  • L. Mezquita Pérez
  • C. Baldini
  • D. Planchard
  • A. Marabelle
  • A. Hollebecque
  • B. Besse
  • C. Massard

Abstract

Background

Lung Immune Prognostic Index (LIPI) is a score that combines pretreatment dNLR (neutrophils/ (leucocytes-neutrophils) and lactate dehydrogenase (LDH) and is correlated with outcomes of patients treated with Immune Checkpoint Inhibitors (ICI) by tumor type. It has been shown for melanoma patients, NSCLC, SCLC, HNSCC, or TNBC but not in an all tumor type population.

Methods

dNLR and LDH were retrospectively collected from 360 patients with metastatic disease treated since September 2015 to November 2017 at Gustave Roussy, in the Drug Development Department. LIPI portrays 3 groups: good group (GG) if dNLR< 3 and normal LDH, intermediate group (IG) if dNLR> 3 or LDH> upper limit of normal (ULN), and poor group (PG) if dNLR>3 and LDH>ULN. ICI benefit was analyzed according to overall survival (OS) and progression free survival (PFS).

Results

From the 360 patients treated with ICI in early clinical trials, 353 (98%) were ICI naïve, 214 (59%) were male, 209 (58%) had a performance status of 1 with a median age at ICI treatment of 60 (range, 25-88), 322 (89%) received either a PD-1 or PD-L1 inhibitor and 268 (74%) as combination therapy. The most frequent tumor types were: NSCLC (14%), colorectal (14%), bladder (13%), renal (8%), breast (7%), HNSCC (7%) and cervix (6%). The median follow-up duration was of 14.1 months (m) [95%CI 12.9-16.1]. LIPI stratified the population into good group with 160 patients (44%), intermediate group with 161 patients (44%) and poor group with 39 patients (11%). The median OS was 17.8m [95%CI 13.1-not reached (NR)] vs. 11.68m [95%CI 8.8-15.3] vs. 3.9m [95%CI 2.1-6.4] for good, intermediate and poor group while the median PFS was of 4.6m [95%CI 4.0-6.2] for GG vs. 2.8m [95%CI 2.5-3.6] for IG vs. 1.4m [95%CI 1.2-2.0] for PG (both p < 0.0001).

Conclusions

Poor LIPI score, combining dNLR>3 and LDH>ULN is associated with a poorer outcome in patients treated with ICI. Calculating LIPI prior starting ICI therapy can be useful in identifying patients that will not benefit from such a treatment choice.

Legal entity responsible for the study

Drug Development Department, Gustave Roussy.

Funding

Has not received any funding.

Disclosure

A. Varga: Courses, trainings: Astra Zeneca, MSD, Roche; Travel funds: Boehringer Ingelheim, Clovis Oncology. L. Mezquita Pérez: Consulting, advisory role:  Roche Diagnostics; Lectures and educational activities: Bristol-Myers Squibb, Tecnofarma, Roche, AstraZeneca; Travel, Accommodations, Expenses: Chugai. C. Baldini: Research Grants: Roche, Amgen, Pfizer, Abbvie, BMS; Travel and accommodation expenses: Roche, Amgen, Pfizer; Paid expert testimony: Abbvie, BMS. D. Planchard: Consulting, advisory role or lectures: AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly, Merck, Novartis, Pfizer, prIME Oncology, Peer CME, Roche; Honoraria: AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Merck, Novartis, Pfizer, prIME Oncology, Peer CME, Roche; Clinical trials research: AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, Merck, Novartis, Pfizer, Roche, Medimmun, Sanofi-Aventis, Taiho Pharma, Novocure, Daiichi Sankyo; Travel, Accommodations, Expenses: AstraZeneca, Roche, Novartis, prIME Oncology, Pfizer. A. Marabelle: Research Grants: Merus, BMS, Boehringer Ingelheim, Transgene; Member of Committee/Board: GSK, AstraZeneca, Oncovir, Merck Serono, eTheRNA, Lytix pharma, Kyowa Kirin Pharma, Bayer, Novartis, BMS, Symphogen, Genmab, Amgen, Biothera, Nektar, Pfizer, Seattle Genetics, Flexus Bio, Roche/Genentech, OSE immunotherapeutics, Transgene, Gritstone, Merck (MSD), Cerenis, Innate pharma, Protagen, Partner Therapeutics, Servier; Teaching/Speaker activities: Roche/Genentech, BMS, Merck (MSD), Merck Serono, Astra Zeneca/Medimmune, Amgen, Sanofi; Consulting: Roche, Pierre Fabre, Onxeo, EISAI, Bayer, Genticel, Rigontec, Daichii Sankyo, Imaxio, Sanofi, BioNTech, Corvus, GLG, Deerfield, Guidepoint Global, Edimark, SYSTEM ANALYTICS, imCheck, Sotio, Bioncotech. A. Hollebecque: Consultant/Advisory role: Amgen, Spectrum Pharmaceuticals, Lilly Travel and accommodation expenses: Servier, Amgen, Lilly; Courses, trainings: Bayer. C. Massard: Consultant/Advisory fees: Amgen, Astellas, Astra Zeneca, Bayer, BeiGene, BMS, Celgene, Debiopharm, Genentech, Ipsen, Janssen, Lilly, MedImmune, Novartis, Pfizer, Roche, Sanofi, Orion; Principal/sub-Investigator of Clinical Trials: Aduro Biotech, Agios Pharmaceuticals, Amgen, Argen-X Bvba, Arno Therapeutics, Astex Pharmaceuticals, Astra Zeneca, Aveo, Bayer Healthcare Ag, Bbb Technologies Bv, Beigene, Bioalliance Pharma, Biontech Ag, Blueprint Medicines, Boehringer Ingelheim, Bristol Myers Squibb, Ca, Celgene Corporation, Chugai Pharmaceutical Co., Clovis Oncology, Daiichi Sankyo, Debiopharm S.A., Eisai, Exelixis, Forma, Gamamabs, Genentech, Inc., Gilead Sciences, Inc, Glaxosmithkline, Glenmark Pharmaceuticals, H3 Biomedicine, Inc, Hoffmann La Roche Ag, Incyte Corporation, Innate Pharma, Iris Servier, Janssen, Kura Oncology, Kyowa Kirin Pharm, Lilly, Loxo Oncology, Lytix Biopharma As, Medimmune, Menarini Ricerche, Merck Sharp & Dohme Chibret, Merrimack Pharmaceuticals, Merus, Millennium Pharmaceuticals, Nanobiotix, Nektar Therapeutics, Novartis Pharma, Octimet Oncology Nv, Oncoethix, Oncomed, Oncopeptides, Onyx Therapeutics, Orion Pharma, Oryzon Genomics, Pfizer, Pharma Mar, Pierre Fabre, Rigontec Gmbh, Roche, Sanofi Aventis, Sierra Oncology, Taiho Pharma, Tesaro, Inc, Tioma Therapeutics, Inc., Xencor; Research Grants: Astrazeneca, BMS, Boehringer Ingelheim, Janssen Cilag, Merck, Novartis, Pfizer, Roche, Sanofi; Non-financial support (drug supplied): AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Johnson & Johnson, Lilly, Medimmune, Merck, NH TherAGuiX, Pfizer, Roche. B. Besse: Sponsored Research at Gustave Roussy Cancer Center: Abbvie, Amgen, AstraZeneca, Biogen, Blueprint Medicines, BMS, Celgene, Eli Lilly, GSK, Ignyta, IPSEN, Merck KGaA, MSD, Nektar, Onxeo, Pfizer, Pharma Mar, Sanofi, Spectrum Pharmaceuticals, Takeda, Tiziana Pharma. All other authors have declared no conflicts of interest.

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Proffered Paper session : Immunotherapy Proffered Paper session

Q&A (ID 205)

Lecture Time
14:20 - 14:30
Speakers
  • J. De Bono
  • C. Massard
Location
Amphithéâtre Bordeaux, Palais des Congrès, Paris, France
Date
25.02.2019
Time
14:05 - 15:20
Authors
  • J. De Bono
  • C. Massard
Proffered Paper session : Immunotherapy Proffered Paper session

2O - A phase Ib/II study of APG-115 in combination with pembrolizumab in patients with unresectable or metastatic melanomas or advanced solid tumors (ID 173)

Presentation Number
2O
Lecture Time
14:30 - 14:45
Speakers
  • A. Tolcher
Location
Amphithéâtre Bordeaux, Palais des Congrès, Paris, France
Date
25.02.2019
Time
14:05 - 15:20
Authors
  • A. Tolcher
  • D. Fang
  • Y. Li
  • Y. Tang
  • J. Ji
  • H. Wang
  • R. Karim
  • C. Rosas
  • Y. Huang
  • Y. Zhai

Abstract

Background

Emerging evidence suggests that p53 participates in the regulation of tumor immunity. TP53 activation in the myeloid linage suppresses alternative (M2) macrophage polarization and attenuates tumor development and invasion. Retrospective clinical analyses suggested that MDM2 amplification is associated with hyper-progression. Targeting MDM2-p53 pathway may represent a novel strategy for reversing immunosuppression and enhancing antitumor immunity of PD-1/PD-L1 blockade. APG-115 is a potent and orally active small-molecule MDM2 protein inhibitor. Binding to MDM2 protein, APG-115 restores p53 expression, activates p53 - mediated apoptosis in tumor cells retaining wild-type p53. Preclinical studies demonstrated that APG-115 promoted the production of proinflammatory cytokines in T cells, enhanced CD4+ T cell activation, and increased PD-L1 expression on tumor cells. Enhanced antitumor activity was demonstrated in syngeneic tumor models after APG-115 combined with PD-1 blockade.

Methods

APG-115 has been evaluated as a single agent in a Phase I study in US (NCT02935907). In this study, total six dose levels (10 mg, 20 mg, 50 mg, 100 mg, 200 mg and 300 mg) have been tested. The preliminary results suggested a favorable safety and tolerability profile. APG-115 exhibited an approximately dose proportional increase in exposure in PK analyses. A Phase Ib/II study of APG-115 in combination with pembrolizumab for treatment of patients with metastatic solid tumor is ongoing. Pembrolizumab is administrated as a fixed dose of 200mg IV on d1 of a 21-d cycle. Safety, tolerability, and determination of the MTD and RP2D are primary objectives of phase Ib.

Results

The second cohort (APG 115 at 100 mg) has enrolled, no DLT was observed, and evidence of antitumor activity has been observed. Biomarker studies are ongoing to identify potential selection criteria. Updated clinical data will be presented.

Conclusions

This represents one of the first clinical trials to evaluate MDM2-mediated resistance to immunotherapy.

Clinical trial identification

NCT03611868.

Legal entity responsible for the study

Ascentage Pharma Group Corp Limited.

Funding

Ascentage Pharma Group Corp Limited.

Disclosure

A.W. Tolcher: Research funding: AbbVie, ADC Therapeutics, Adagene, Aminex, Acentage, Asana, Birdie, C Stone, Arrys, GlaxoSmithKline, Inhibrx, Innate, Kiromic, NatureWise, NextCure, Nitto BioPharma, Pfizer, Pieris, Deciphera, Syndax, Symphogen, Tizona, Mersana, Zymeworks; Consultancy (includes travel funding): AbbVie, Adagene, ADC Therapeutics, Agenus, Ascentage, AxImmune, Bayer, Bioinvent, Birdie, Boston Biomedical (Syneos), EMD Serono, Forbius (Formerly Formation Biologics), Gilde Healthcare Partners, HBM Partners, Ignyta, Immunome, ImmunoMet, Innate, Jazz Pharmaceuticals, Mekanistic, Nanobiotix, NBE Therapeutics, Nuvalent, Pelican, Pierre Fabre, Ridgeway, Scitemex, Sesen (formerly EBIO), Seattle Genetics, Symphogen, Syneos. D.D. Fang, Y. Li, Y. Tang, J. Ji, H. Wang, Y. Huang, Y. Zhai: Employee of Affiliates of Ascentage Pharma Group Corp Limited (“Ascentage Pharma”); Stock ownership: Ascentage Pharma. All other authors have declared no conflicts of interest.

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Proffered Paper session : Immunotherapy Proffered Paper session

Q&A (ID 206)

Lecture Time
14:45 - 14:55
Speakers
  • J. De Bono
  • C. Massard
Location
Amphithéâtre Bordeaux, Palais des Congrès, Paris, France
Date
25.02.2019
Time
14:05 - 15:20
Authors
  • J. De Bono
  • C. Massard
Proffered Paper session : Immunotherapy Proffered Paper session

29O - The 18-year-old clinical trial inclusion limit is a major barrier in the access to immunotherapies and targeted therapies for adolescents and young adults (AYAs) with cancer (ID 196)

Presentation Number
29O
Lecture Time
14:55 - 15:10
Speakers
  • T. De Rojas
Location
Amphithéâtre Bordeaux, Palais des Congrès, Paris, France
Date
25.02.2019
Time
14:05 - 15:20
Authors
  • T. De Rojas
  • A. Neven
  • M. Garcia-Abos
  • L. Moreno
  • N. Gaspar
  • J. Peron

Abstract

Background

The 18-years-old age limit for inclusion in clinical trials constitutes a major hurdle for adolescents and young adults (AYAs) with cancer that the main stakeholders are advocating to overthrow. The purpose of this study was 1) to analyze the access for adolescents with cancer to targeted therapies and immunotherapies and to innovation (measured in number of mechanisms of action –MoA-), when compared to young adults; and 2) to describe the time lapse between the first adult trial for a specific drug and the first trial recruiting adolescents for that same drug.

Methods

ClinicalTrials.gov was searched to identify all the clinical trials including patients with malignancies relevant for AYAs (Hodgkin lymphoma, anaplastic large cell lymphoma, extracranial germ cell tumors, medulloblastoma, rhabdomyosarcoma, synovial sarcoma, Ewing sarcoma, osteosarcoma, melanoma, thyroid cancer), starting between Jan/2007-Jul/2018. Only trials investigating immunotherapies and/or targeted therapies were included. The trials, drugs, and MoA were categorized as “available for adolescents” (including patients 12-18 years old) and “available for young adults” (18-25 years).

Results

Out of 2765 identified trials, 1369 were included: 1352 (99%) available for young adults vs 233 (17%) available for adolescents. A total of 384 novel drugs (target therapies or immunotherapies) were investigated, all 384 available for young adults vs 108 (28%) for adolescents. All 184 investigated MoA were accessible for young adults vs 61 (33%) for adolescents. Out of the 108 drugs investigated in adolescents for the included malignancies, 59 were investigated first in adults, with a median delay of 35 months (IQR 23-60). No time trend in this delay was observed over the years of the study.

Conclusions

There is a major gap in the access to novel drugs and innovation between adolescents and young adults, with the 18-years-old limit posing a large barrier. There is also a prominent delay in the opening of trials for adolescents, with no improvement observed over the last decade. Greater efforts are needed to improve clinical research for AYAs with cancer.

Legal entity responsible for the study

EORTC.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Proffered Paper session : Immunotherapy Proffered Paper session

Q&A (ID 207)

Lecture Time
15:10 - 15:20
Speakers
  • J. De Bono
  • C. Massard
Location
Amphithéâtre Bordeaux, Palais des Congrès, Paris, France
Date
25.02.2019
Time
14:05 - 15:20
Authors
  • J. De Bono
  • C. Massard