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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.

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