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8 januari 2018: lees ook dit artikel: 

https://kanker-actueel.nl/het-voordeel-van-immunotherapeutische-combinatie-behandelingen.html

8 januari 2018: klik op de titel voor het originele artikel:

Comprehensive analysis of the clinical immuno-oncology landscape

Wereldwijd zijn een aantal medicijnen reeds geregistreerd voor gebruik binnen immuuntherapie. Nog veel meer medicijnen worden in fase II en III studies onderzocht. Maar uit een onderzoek blijkt dat veel medicijnen zich richten op dezelfde mutaties en DNA afwijkingen waardoor veel dubbel onderzoek plaatsvindt. De onderzoekers van deze studie pleiten voor bundeling van onderzoek naar immuuntherapeutische medicijnen

De 940 klinische fase IO-medicijnen (IO = immuno oncology agents) worden uitgevoerd door 462 verschillende bedrijven of academische instellingen (supplementary Table S2, online beschikbaar op Annals of Oncology) en deze medicijnen richten zich op 271 verschillende doelen. Interessant is dat een nader onderzoek van de 940 medicijnen aan het licht bracht dat bijna de helft slechts 40 targets moduleert (Figure 2. We hebben bijvoorbeeld 164 medicijnen gevonden die zich richten op PD-1 of PD-L1 (PD-1 / L1), met 50 medicijnen in onderzoek in de klinische praktijk gericht tegen PD-1 / L1, waarvan 34 monoklonale antilichamen zijn (Figuur 3). Dit bevestigt onze veronderstelling van significante duplicatie, ondanks het feit dat vijf anti-PD-1 / L1 monoklonale antilichamen al zijn goedgekeurd [9]. Hoewel het nog steeds onduidelijk is of het richten op de PD-1-receptor of het ligand PD-L1 zal resulteren in verschillen in werkzaamheid en veiligheid, toont geen van de medicijnen of onderzoeken in onze database een beoordeling van het een-op-een klinische effect bij patiënten. In een ander voorbeeld vertegenwoordigen middelen die zich richten op niet-gespecificeerde tumor-geassocieerde antigenen (niet-gespecificeerd TAA) het grootste aantal klinische IO-medicijnen. Er zijn nu 114 medicijnen in onderzoek ijn klinische studies, waarvan 98 kankervaccins zijn. Van de 114 niet-specifieke TAA-gerichte IO-medicijnen is alleen sipuleucel-T (een autoloog dendritisch celvaccin) goedgekeurd voor prostaatkanker . Dit grote aantal medicijnen roept vragen op over de efficiëntie van middelen en, belangrijker, de patiënten die zich inschrijven voor klinische studies. De concentratie van immuuntherapeutische ontwikkeling en patiëntenbronnen op een paar doelen, sommige met al goedgekeurde geneesmiddelen, kan mogelijk toekomstige innovatie blokkeren. Integendeel, door investeren in deze kostbare hulpbronnen efficiënter te bundelen, kan de benodigde vooruitgang bij het vinden van genezing van deze dodelijke ziekte worden versneld.

immuuntherapie overzicht klinische studies

Hier nog enkele tabellen uit dit gratis te lezen studierapport: Comprehensive analysis of the clinical immuno-oncology landscape

A large number of IO drugs in clinical development with significant duplication

Overview of the Clinical Accelerator IO database

Our database included 2004 IO agents as of September 2017, 940 of which are in clinical development. On the basis of different mechanisms of actions, we classified these agents into six categories: (i) T-cell-targeted immunomodulators that act on inhibitory or activating molecules expressed by T cells (e.g. agents targeting CTLA-4, PD-1, CD40, and GITR); (ii) other immunomodulators that act on other immune cells or the tumor immune microenvironment to unleash antitumor immunity (e.g. agents modulating IFNAR, CSF1R, IDO1, A2AR, and KIR); (iii) cancer vaccines that induce antigen-specific antitumor immunity (e.g. sipuleucel-T); (iv) cell therapies that engineer immune cells such as T cells to directly attack cancer cells (e.g. anti-CD19 CAR-T); (v) oncolytic viruses that rely on both direct tumor killing and activation of antitumor immunity (e.g. T-VEC); and (vi) CD3-targeted bispecific antibodies that bring T cell to the targeted tumor cells for direct killing (e.g. blinatumomab) (Figure 1).

Figure 1.

The overview of 2004 immuno-oncology (IO) agents. Six classes of IO agents are identified on the basis of different mechanisms of actions.>>>>>>>>Reed more

Table 1.

The list of 26 approved immuno-oncology agents, company origins, and targets

Therapy type Therapy name Company Target 
T-cell-targeted immunomodulatory (six in total)  Ipilimumab  Bristol-Myers Squibb Co.  CTLA-4 
Nivolumab  Bristol-Myers Squibb Co.  PD-1 
Pembrolizumab  Merck & Co Inc.  PD-1 
Atezolizumab  Roche/Genentech Ltd  PD-L1 
Avelumab  Merck KGaA  PD-L1 
Durvalumab  AstraZeneca/MedImmune LLC  PD-L1 
Other immunomodulatory (eight in total)  Aldesleukin  Novartis AG  IL2R 
Imiquimod  Valeant Pharmaceuticals Intl Inc.  TLR7 
Interferon alfa  Sumitomo Dainippon Pharma Co Ltd  IFNAR1; IFNAR2 
Interferon alfa-1b  Shenzhen Kexing Biotech Co Ltd  IFNAR1 
Interferon alfa-2a  Cadila Healthcare Ltd  IFNAR1; IFNAR2 
Interferon alfa-2b  Merck & Co Inc.  IFNAR1; IFNAR2 
Interferon beta  Toray Industries Inc.  IFNAR1 
Interferon gamma-1a  Otsuka Pharmaceutical Co Ltd  IFNAR1 
Cancer vaccine (seven in total)  BCG Live  Shire Plc  TLR 
ImmuCyst  Sanofi  TLR 
Immuno BCG  Ataulpho Paiva Foundation  TLR 
Mycidac-C  Cadila Pharmaceuticals Ltd  TLR2 
Sipuleucel-T  Dendreon  Unspecified TAA 
TICE BCG  Merck & Co Inc.  TLR 
Uro-BCG  Medac Inc.  TLR 
Cell therapy (two in total)  Tisagenlecleucel  Novartis AG  CD19 
Axicabtagene ciloleucel  Gilead  CD19 
Oncolytic virus (two in total)  Oncorine  Shanghai Sunway Biotech Co Ltd  CD40L 
Talimogene laherparepvec  Amgen Inc.  GMCSFR 
CD3-targeted bispecific ab  Blinatumomab  Amgen Inc.  CD19 X CD3 

Abstract

Advances from immuno-oncology (IO) are changing the standard of care of many types of cancer, and the paradigm of cancer treatments and drug development is being rewritten on a regular basis. Moreover, an unprecedented number of new investigational agents and companies are entering the field of IO. As such, it has become challenging for oncology physicians conducting clinical trials, industry veterans developing IO drugs, and even regulators reviewing novel IO agents to keep track of the rapidly evolving landscape. To help the key stake holders in the field understand the latest IO landscape, we sought to present an unbiased, neutral, scientifically curated, and timely updated analysis of all the current IO agents in clinical development and the clinical trials testing these agents. We based our analyses on information collected from numerous trusted and publicly available sources. We have developed two databases. One database tracks 2004 IO agents (940 in clinical stage and 1064 in preclinical stage) against 303 targets, from 864 companies; the other tracks 3042 active clinical trials of these agents with a target enrollment of 577 076 patients. This report provides key analyses of these data. Furthermore, we will discuss a number of important and actionable trends in the current IO landscape: a large number of companies developing agents against the same IO targets; a rapid increase in the number of anti-PD-1/L1 combination studies, many of which are testing the same combinations and following inefficient patterns; and a significant increase in the number of small, investigator-initiated studies. For each of the findings, we speculate the causes and discuss a few initiatives that aim to address some of these challenges. Finally, by making these landscape analyses available, we aspire to inform the cancer community as they seek to strive for efficiencies and innovation while avoiding duplication.

References

1
Talpaz
M
,
Kantarjian
HM
,
McCredie
K
et al.  
Hematologic remission and cytogenetic improvement induced by recombinant human interferon alpha A in chronic myelogenous leukemia
.
N Engl J Med
 
1986
;
314
(
17
):
1065
1069
.
2
Hodi
FS
,
O'Day
SJ
,
McDermott
DF
et al.  
Improved survival with ipilimumab in patients with metastatic melanoma
.
N Engl J Med
 
2010
;
363
(
8
):
711
723
.
3
Ledford
H.
Melanoma drug wins US approval
.
Nature
 
2011
;
471
(
7340
):
561.
4
Topalian
SL
,
Hodi
FS
,
Brahmer
JR
et al.  
Safety, activity, and immune correlates of anti-PD-1 antibody in cancer
.
N Engl J Med
 
2012
;
366
(
26
):
2443
2454
.
5
Grupp
SA
,
Kalos
M
,
Barrett
D
et al.  
Chimeric antigen receptor-modified T cells for acute lymphoid leukemia
.
N Engl J Med
 
2013
;
368
(
16
):
1509
1518
.
6
Locke
FL
,
Neelapu
SS
,
Bartlett
NL
et al.  
Phase 1 results of ZUMA-1: a multicenter study of KTE-C19 anti-CD19 CAR T cell therapy in refractory aggressive lymphoma
.
Mol Ther
 
2017
;
25
(
1
):
285
295
.
7
Topp
MS
,
Kufer
P
,
Gokbuget
N
et al.  
Targeted therapy with the T-cell-engaging antibody blinatumomab of chemotherapy-refractory minimal residual disease in B-lineage acute lymphoblastic leukemia patients results in high response rate and prolonged leukemia-free survival
.
J Clin Oncol
 
2011
;
29
:
2493
2498
.
8
Emens
LA
,
Ascierto
PA
,
Darcy
PK
et al.  
Cancer immunotherapy: opportunities and challenges in the rapidly evolving clinical landscape
.
Eur J Cancer
 .
2017
;
81
:
116
129
.
9
Nishino
M
,
Ramaiya
NH
,
Hatabu
H
,
Hodi
FS.
Monitoring immune-checkpoint blockade: response evaluation and biomarker development
.
Nat Rev Clin Oncol
 
2017
;
14
(
11
):
655
668
.
10
DeFrancesco
L.
Landmark approval for Dendreon's cancer vaccine
.
Nat Biotechnol
 
2010
;
28
(
6
):
531
532
.
11
First-ever CAR T-cell therapy approved in U.S
.
Cancer Discov
 
2017
;
7
:
OF1
.
12
Golubovskaya
V.
CAR-T cell therapy: from the bench to the bedside
.
Cancers (Basel)
 
2017
;
9
(
11
):
150.
13
Curran
MA
,
Montalvo
W
,
Yagita
H
,
Allison
JP.
PD-1 and CTLA-4 combination blockade expands infiltrating T cells and reduces regulatory T and myeloid cells within B16 melanoma tumors
.
Proc Natl Acad Sci U S A
 
2010
;
107
(
9
):
4275
4280
.
14
Larkin
J
,
Chiarion-Sileni
V
,
Gonzalez
R
et al.  
Combined nivolumab and ipilimumab or monotherapy in untreated melanoma
.
N Engl J Med
 
2015
;
373
(
1
):
23
34
.
15
Langer
CJ
,
Gadgeel
SM
,
Borghaei
H
et al.  
Carboplatin and pemetrexed with or without pembrolizumab for advanced, non-squamous non-small-cell lung cancer: a randomised, phase 2 cohort of the open-label KEYNOTE-021 study
.
Lancet Oncol
 
2016
;
17
(
11
):
1497
1508
.
16
Antonia
SJ
,
Villegas
A
,
Daniel
D
et al.  
Durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer
.
N Engl J Med
 
2017
;
377
(
20
):
1919
1929
.
17
Kang
SP
,
Gergich
K
,
Lubiniecki
GM
et al.  
Pembrolizumab KEYNOTE-001: an adaptive study leading to accelerated approval for two indications and a companion diagnostic
.
Ann Oncol
 
2017
;
28
(
6
):
1388
1398
.
18
Robert
C
,
Ribas
A
,
Wolchok
JD
et al.  
Anti-programmed-death-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: a randomised dose-comparison cohort of a phase 1 trial
.
Lancet
 
2014
;
384
(
9948
):
1109
1117
.
19
Garon
EB
,
Rizvi
NA
,
Hui
R
et al.  
Pembrolizumab for the treatment of non-small-cell lung cancer
.
N Engl J Med
 
2015
;
372
(
21
):
2018
2028
.
20
Le
DT
,
Uram
JN
,
Wang
H
et al.  
PD-1 blockade in tumors with mismatch-repair deficiency
.
N Engl J Med
 
2015
;
372
(
26
):
2509
2520
.
21
Le
DT
,
Durham
JN
,
Smith
KN
et al.  
Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade
.
Science
 
2017
;
357
(
6349
):
409
413
.
22
Mullard
A.
Genetic biomarker trumps tissue type in landmark oncology approval
.
Nat Rev Drug Discov
 
2017
;
16
(
7
):
447.
23
Johnson
JR
,
Ning
YM
,
Farrell
A
et al.  
Accelerated approval of oncology products: the food and drug administration experience
.
J Natl Cancer Inst
 
2011
;
103
(
8
):
636
644
.
24
Dagher
R
,
Johnson
J
,
Williams
G
et al.  
Accelerated approval of oncology products: a decade of experience
.
J Natl Cancer Inst
 
2004
;
96
(
20
):
1500
1509
.
25
Woodcock
J
,
LaVange
LM.
Master protocols to study multiple therapies, multiple diseases, or both
.
N Engl J Med
 
2017
;
377
(
1
):
62
70
.
26
Barker
AD
,
Sigman
CC
,
Kelloff
GJ
et al.  
I-SPY 2: an adaptive breast cancer trial design in the setting of neoadjuvant chemotherapy
.
Clin Pharmacol Ther
 
2009
;
86
(
1
):
97
100
.
27
Herbst
RS
,
Gandara
DR
,
Hirsch
FR
et al.  
Lung master protocol (Lung-MAP)—a biomarker-driven protocol for accelerating development of therapies for squamous cell lung cancer: SWOG S1400
.
Clin Cancer Res
 
2015
;
21
(
7
):
1514
1524
.
28
Chen
DS
,
Mellman
I.
Elements of cancer immunity and the cancer-immune set point
.
Nature
 
2017
;
541
(
7637
):
321
330
.

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