About Lymphoma | Advocacy | Art | CAM | Clinical trials 
Doctors - Experts - Centers | Guidelines at Diagnosis | News
Risk Factors | Side Effects | Statistics | Support | Symptoms |
Tests | Treatments | Types of Lymphoma | How to Help

Guidelines at Diagnosis | About Clinical Trials

Search Site

evidence-based support and information

 

Treatment Overview > Agents that Target Disease Pathways

Last update: 01/05/2018

Alphabetical list of targeted agents for lymphoma OR CLL: 
based on trials, promising reports, and recent approvals

Index | Immunotherapies |
 Terms related to targeted drugs in lay language 

 

Also see:

About Targeted Drugs

7 Reasons to Consider Trials based on our unique clinical circumstances

Since choosing a trial is complicated, we believe it's important also to consult specialists.  To assist we provide:

Trial Talk - specialists to consult about trials

 Study drug name 1 / alternate name 
(short name for target or mechanism) 2
Find Trials 3 

1 – background articles
2 – mechanism or target
3 – lists clinical trials for agent

bullet
ABT-199  / venetoclax (activates apoptosis - programmed cell death - through bcl2 pathway) 
 Find trials  | Full prescribing info for CLL
bullet
Abexinostat  (oral, pan HDAC inhibitor / epigenetic -  activating or quieting genes to induce tumor cell death)
 Find trials 
bullet
Acalabrutinib (ACP-196) (inhibits btk / B-cell receptor pathway - an overactive pathway in b-cell lymphomas) 
Find trials  ASH15 Report

NCI Drug Dictionary http://bit.ly/2x5nKvE  
bullet
ADCT-301 (anti-CD25-PBD antibody-drug conjugate)  NCI Drug Dictionary  Find trials
bullet
Adcetris ® / SGN-35 / brentuximab vedotin  (antibody-drug conjugate: anti-cd30 + antitubulin - more selective delivery of a toxin to cancer cells)  Find trials
bullet
AEB071 /Sotrastaurin  (early: Protein Kinase C Inhibitor of t-cell activation / CD79A/B-mutated ABC subtype of DLBCL) Find trials
bullet
AGS67E (anti-cd37 antibody-drug conjugate)  Find Trials
bullet
Alisertib (MLN8237) Aurora Kinase A inhibitor Find trials
bullet
ALT-803 (interleukin-15-based superagonist, induces memory CD8) Find trials  >
bullet
APTO-253 HCl  (early, thought to activate tumor suppressor gene) Trial early-phase
bullet
Arzerra ® (Ofatumumab) cd20 antibody approved for CLL Find trials
bullet
ASN002 (Syk/Jak inhibitor) Find trials
About ASN002:  Blood Journal http://bit.ly/2vZTPQx
bullet
Atezolizumab  / MPDL3280A (immune checkpoint antibody - pd-1 pathway) Find Trials
bullet
BI 836826 (IgG1 chimerized and Fc-engineered anti-CD37)  Find Trials
bullet
Belinostat PXD101 (epigenetic - recently approved for t-cell lymphoma) Find trials
bullet
BET protein inhibitor -  BET family regulate the transcription of growth-promoting genes)
Find trials
bullet
Betalutin  (Lu-tetraxetan-tetulomab) radioimmunotherapy antibody targeting cd37
Find trials
bullet
Bendamustine / Treanda (cytotoxic)
Find trials
bullet
BKM120 (PI3K inhibitor - BCR pathway)
Find trials 
bullet
Blinatumomab (BiTe) cd3 cd19 bi-specific antibody 
Find trials
bullet
Brentuximab Vedotin (anti-cd30 antibody-drug conjugate)
Find Trials
bullet
Buparlisib / BKM120 (oral inhibitor of the pan-class class I PIK3 pathway)
Find Trials
bullet
Carfilzomib (Velcade-like proteasome inhibitor) With Ibrutinib (BTK Inhibitor)  Relapse/Refractory Mantle Cell Lymphoma
Trial of interest
 
bullet
CC-122 (immune-modulating, pleiotropic pathway modifier)
Find Trials 
bullet
Cd19 CAR T-cell therapy (adoptive immunotherapy)  Find trials 
bullet
Chimeric antigen receptor (CARs) of any type (cd19, cd20, cd22 (adoptive t-cell therapy)
Find Trials 
bullet
Cirmtuzumab (Anti-ROR1 Mab) 
Find Trials
bullet
Copanlisib / BAY 80-6946
(PI3Kα/β inhibitor given by vein)
Find Trials
bullet
CPI-613 (targets mitochondrial metabolism)
Find Trials 
bullet
CPI-0610 (BET protein inhibitor - 
BET family regulate the transcription of growth-promoting genes)
Find trials
bullet
CUDC-907 (dual inhibitor of PI3K and HDAC)
Find Trials
bullet
Daratumumab  (anti-cd38)
Find Trials
bullet
Denintuzumab Mafodotin /SGN-CD19A, (cd19 antibody-drug conjugate ) Trial of interest | 
Find Trials
bullet
DT2219ARL (anti-CD19 & 22 antibody-drug conjugate)
Find trials
bullet
Duvelisib / IPI-145  
(PI3K)-delta / PI3K-gamma)
Find trials

Duvelisib with Rituximab vs Rituximab in Previously Treated Follicular Lymphoma Trial of interest
bullet
Entospletinib (SYK inhibitor in BCR pathway)
 Find trials
bullet
Epratuzumab (cd22 antibody a b-cell receptor)
Find trials
bullet
Epratuzumab tetraxetan anti-CD22 with fractionated Yttrium 90 
Find trials
bullet
EZH2 inhibitors (inhibits an epigenetic pathway that contributes to abnormal growth)  
Find Trials
bullet
EPZ-6438 ((EZH2 Histone Methyl Transferase [HMT] Inhibitor)
bullet
G100 toll-like receptor 4 (TLR4) agonist
bullet
Ibrutinib (inhibits b-cell receptor / btk pathway) 
Find trials
Ibrutinib + Rituximab vs FCR  in CLL
Trial of interest
bullet
Idasanutlin (p53 tumor suppressor gene activator)
Find trials
bullet
Idelalisib / GS-1101 / CAL101 (PI3K kinase inhibitor / b-cell receptor pathway)
Find trials
bullet
IMO-8400 (Toll-like receptor  inhibitor)
Find Trials
 
bullet
IMMU-114 (anti–HLA-DR Mab)   Find Trials
bullet
INCB050465 oral (PI3Ks inhibitor - same class as Idelalisib) 
Find Trials
bullet
IPH2201 (immune modulating - Natural Killer cell checkpoint inhibitor)
Find Trials
bullet
Inotuzumab Ozogamicin  /CMC-544 (cd20 antibody-drug conjugate)
Find trials
bullet
Ipilimumab anti-CTL-A (MXD-010)  (Immune checkpoint blockade) CTL-A t-reg
Find trials 
bullet
JNJ-64052781 (Humanized CD19 x CD3 Dual-Affinity Re-Targeting Protein) 
Find Trials  
| NCI Drug Dictionary
bullet
Lirilumab (NK-cell agonist) Find Trials | Report
bullet
Lenalidomide / Revlimid (immune modulation and direct activity)  Find trials 
Our topic
bullet
MEDI-551 (humanized cd19 antibody) Find trials
bullet
MEDI-570 (anti-ICOS antibody for t-cell lymphoma) Find Trials
bullet
Mogamulizumab / POTELIGEO® anti-CCR4 antibody, approved in Japan for CCR4-positive adult T-cell leukemia-lymphoma. Find trials
bullet
Monalizumab (CD94/NKG2A checkpoint mab) for| CLL OR lymphoma Find Trials 
bullet
MOR00208 /XmAb5574)  (cd19 antibody) Find Trials 
bullet
MEDI-570 (Anti-ICOS Monoclonal Antibody) for Peripheral T-cell Lymphoma Follicular Variant or Angioimmunoblastic T-cell Lymphoma
 Study of Interest 
bullet
MLN9708 (Ixazomib, GATA-3 inhibitor) for Relapsed/Refractory Cutaneous and Peripheral T-cell Lymphomas Trial of interest
bullet
MT-3724 (CD20-specific Engineered Toxin Body ) Find Trials

- NCI Drug Dictionary http://bit.ly/2iXLewi
bullet
Obinutuzumab / GA-101 (next gen cd20 antibody)  Find trials 
bullet
Palbociclib (oral, reversible, selective, small-molecule inhibitor of cyclin-dependent kinases (CDK) -- of interest for MCL)  Find Trials
bullet
PD1/L antibodies (removes block on immune system - immune checkpoint blockade)  Find trials | Open trials only

-
Atezolizumab  / MPDL3280A (pd-1 pathway) Find Trials
  NCI Drug Dictionary http://bit.ly/2vZJdRz

- Nivolumab (immune checkpoint blockade) in  Lymphoma Trial of Interest

- Pembrolizumab /
CT-011) / BMS-936558  | Lambrolizumab (Merck)
  NCI Drug Dictionary http://bit.ly/2eWHQOa
 
bullet
PF-05082566 (immunotherapy - anti-4-1BB agonistic antibody targeting the immune checkpoint molecule 4-1BB (CD137) Find Trials  | Report
bullet
Polatuzumab Vedotin (cd22 drug-antibody conjugate) Find trials 

Polatuzumab Vedotin With cd20 antibody With Bendamustine in Relapsed or Refractory Follicular DLBC Lymphoma Trial of interest
bullet
Pomalidomide  (Lenalidomide derived - Immune modulating) Find trials
bullet
PNT2258 (first-in-class DNAi -- BCL-2-targeted liposomal formulation of a 24-base DNA oligonucleotide )  Find trials
bullet
Romidepsin  (FDA approved, HDAC inhibitor) Find trials  

Romidepsin + Pralatrexate (novel chemo)  in Relapsed/Refractory Lymphoid Malignancies - PTCL only for expansion phase Trial of interest
bullet
RP6530 (dual PI3K inhibitor) Find trials
bullet
SAR 245409 oral pan-inhibitor of PI3K Find trials
bullet
Selinexor  /KPT-330
(activates tumor suppress gene  Find trials
|  Safety report | Report

NCI Drug Dictionary http://bit.ly/2x5nKvE  
bullet
TAK659  (Syk inhibitor) Find Trials
bullet
TazemetostatEZH2 inhibitors (inhibits an epigenetic pathway that contributes to abnormal growth)   Find Trials
bullet
TGR-1202 (PI3k Delta Inhibitor) Find Trials

TGR-1202 + Ibrutinib in Patients With Select B-Cell lymphoma http://1.usa.gov/1zvYgmu

TGR-1202
(PI3K Delta Inhibitor) With Brentuximab Vedotin for Hodgkin's Lymphoma Patients”
Trial of interest
bullet
TRU-016 (cd37 antibody) Find trials
bullet
Ublituximab (next gen cd20 antibody) Find Trials
bullet
varlilumab   (cd27 immune modulating  )  Find Trials
bullet
Veltuzumab / Immu-106 / Ha20  (next gen cd20 antibody)  Find trials
bullet
Venetoclax | ABT-199  / (activates apoptosis - programmed cell death - through bcl2 pathway)  Findtrials
Full prescribing info for CLL
bullet
Vidaza ® / 5-Azacytidine (epigenetic - activating or shutting off genes) Find trials 
bullet
YM155 (Survivin inhibitor)  Find Trials >
bullet
Zevalin ® /(Ibritumomab tiuxetan)  (anti-CD20 + Yttrium 90 ) cd20 Find trials

Back to top


Terms related to targeted therapies

The purpose is to introduce terms used for targeted therapies for lymphoma

bullet
Cancer is caused by genetic abnormalities or defects in genes called mutations.

Genes are recipes that our cells follow to make cellular proteins

These proteins lead to signals within the cell that determine (or
drive) the cell behavior. 

... The signals involve many parts of the cell called
molecular pathways.  (Analogy: the electrical system in an automobile is similar to a pathway; distinct from the fuel system.

Mutations in key genes (oncogenes) can cause the affected cell to divide too rapidly and/or to persist too long

This so-called malignant behavior, can lead to the accumulation of the cancer cells called
tumors.
 
bullet
An effective targeted drug is one that binds to a molecule of tumor cells leading to stopping the growth or tumor cell death. 

For this reason targeted therapy is sometimes called molecular or precision medicine. 

The molecule or target that the drug binds to can be external or internal.
 

An external target is typically a receptor that is on the surface of the cell that's unique to the type of cell or tumor cell, such as cd20 in b-lymphocytes. 

An internal target is typically a molecule inside the cell that is involved in a signaling pathway that is overactive because of a mutation in the gene.

The best targeted drugs have good
specificity and affinity.  Specificity means the target is unique to the tumor cell.  Affinity means how well the drug binds and remains bound to the target.  A drug with high specificity will have less off-target effects (side effects).  A drug with high affinity is more likely to be active against the disease.
Limitations and considerations
That a study drug is  targeted does not mean it will prove to be effective or safe for a given type of lymphoma or cancer when tested in clinical trials. 

Important questions for patients, and consideration for referring physicians:

1) Is the targeted agent first-in-class (never before tested in humans), or
has a similar agent proven effective in clinical tests in patients with your type of lymphoma?  

2) Is there is a companion diagnostic test to help determine if the target exists based on your tumor sample.
bullet
The molecular target might vary leading to good or poor binding.
bullet
The internal pathway might not be driving the malignancy, or the tumor cells might adapt leading to a limited activity against the behavior of the cells.

Or, the external
receptor might not be related to cell growth or survival.
bullet
The targeted agent might have off-target effects (binding to similar molecules on normal cells) leading to toxicity.
bullet
The targeted agent might not be safe or tolerable at a dose needed to have anti-cancer effects.

Note:  When testing targeted drugs that have been approved in other types of cancer, the clinically active and safe dose will be based on prior clinical experience.  Therefore the recommended dose and risks will be better understood and can be monitored for with more assurance.

Back to top


Immunotherapies

An alphabetical list of investigational or approved agents that may enlist the immune system to fight abnormal lymphocytes (a type of blood cell) called lymphoma.  The agent name links to reports in Google Scholar.  The Find Trial link shows studies for the agent in the ClinicalTrials.gov registry.

ALT-803 (interleukin-15-based superagonist, induces memory CD8 t-cells) Find trials  >

Adcetris ® / SGN-35 / brentuximab vedotin  (antibody-drug conjugate: anti-cd30 + antitubulin - more selective delivery of a toxin to cancer cells) Approved for Hodgkins  Find trials

Allogeneic Stem Cell Transplant (graft cells versus lymphoma effect)

antibodies (monoclonal) any type | Find Trials

Arzerra ® (Ofatumumab) cd20 antibody approved for CLL Find trials

BI-1206 and an Anti-CD20 Antibody in Patients With CD32b Positive B-cell Lymphoma or Leukaemia http://bit.ly/2lLrPQo

BI 836826 (IgG1 chimerized and Fc-engineered anti-CD37)  Find Trials

Betalutin  (Lu-tetraxetan-tetulomab) radioimmunotherapy antibody targeting cd37)
Find trials

Blinatumomab (BiTe) cd3 cd19 bi-specific antibody) Find trials 

Chimeric antigen receptor (CAR T-cell cellular therapy)
of any type (cd19, cd20, cd22 (adoptive t-cell therapy) Find Trials 
Cd19 CAR T-cell therapy (adoptive immunotherapy)  Find trials 

CD30 t-cell CAR for CD30-Expressing Lymphomas http://bit.ly/2n7LPNq

Daratumumab  (anti-cd38 antibody) Find Trials >

Epratuzumab (cd22 antibody a b-cell receptor) Find trials

Epratuzumab tetraxetan anti-CD22 with fractionated Yttrium 90  Find trials

Ipilimumab (MXD-010) (anti-CTL-A, immune checkpoint blockade)  Find trials 

JNJ-64052781 (Humanized CD19 x CD3 Dual-Affinity Re-Targeting Protein)  Find Trials
Lirilumab (NK-cell agonist) Report | Find Trials

Lenalidomide / Revlimid (immune modulation and direct activity)  Find trials  Our topic

Obinutuzumab / GA-101 (next gen cd20 antibody) Approved for follicular lymphoma Find trials 
PD1/L antibodies (immune checkpoint antibodies)  Find trials 

-  
Atezolizumab  / MPDL3280A (pd-1 pathway) Find Trials

-  Nivolumab (immune checkpoint blockade) in  Lymphoma Trial of Interest

-  Pembrolizumab / CT-011) / BMS-936558  | Lambrolizumab (Merck)
PF-05082566 (anti-4-1BB agonistic antibody targeting the immune checkpoint molecule 4-1BB (CD137) Find Trials  | Report

Pomalidomide  (Lenalidomide derived - Immune modulating) Find trials

Rituxan (cd20 antibody) Approved for b-cell lymphoma | Our topic
TRU-016 (cd37 antibody) Find trials
Ublituximab (next gen cd20 antibody) Find Trials
Vaccines for lymphoma (stimulating recognition of tumor antigens) | Our topic | Find open trials
Veltuzumab / Immu-106 / Ha20  (next gen cd20 antibody) | Find trials

Zevalin ® /(Ibritumomab tiuxetan)  (anti-CD20 + Yttrium 90 )
Approved for Follicular lymphoma Our topic | Find trials

OTHER:

Intranodal Immunotherapy (SIIT)


BI-1206 is a fully-human anti-CD32b antagonistic antibody that, in addition to directly killing tumour cells, is thought to work by maintaining CD20 antibodies on the cell membrane of cancer cells, preventing them from becoming resistant to the current state-of-the-art treatment, rituximab.

Back to top

To Do

bullet EPZ-6438 ((EZH2 Histone Methyl Transferase [HMT] Inhibitor)
bullet G100 toll-like receptor 4 (TLR4) agonist
bullet PF-05082566, a 4-1BB agonist monoclonal antibody (mAb)
bullet Cytochrome P450 (CYP) 3A inhibitor (erythromycin) and a strong CYP3A inhibitor (voriconazole)

New Trials of interest http://bit.ly/1mqxQ0b 
Back to top
 
Other terms (coming soon)

Genes have different names, such as BRAF.  Oncogenes are genes that can lead to cancer when mutated.  The changes/  rearrangements / mutations to genes can take place in different portions of the gene (codon, exon), leading to activation of different pathways. 

Most targeted drugs inhibit the pathway ... do not correct the gene mutation.

The changes to genes leading to cancer are almost always acquired (somatic), not inherited (germline).

bullet
codon
bullet
exon
bullet
phosphorylation
bullet
cellular signal transduction
bullet
Recurrent mutations in exon NUMBER of GENE NAME (eg. BRAF)
bullet
wild type MUTATION NAME (BRAF).
bullet
GENE NAME rearrangements (mutations) fuse the kinase domain NAME with a partner gene which leads to constitutive activation of the NAMED pathway

Back to top

bullet

Further reading?

What is a gene mutation and how do mutations occur? - Genetics Home Reference http://1.usa.gov/1E8ACZP

 
Disclaimer:  The information on Lymphomation.org is not intended to be a substitute for 
professional medical advice or to replace your relationship with a physician.
For all medical concerns,  you should always consult your doctor. 
Copyright © 2004,  All Rights Reserved.