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Treatment Overview > Agents that Target Disease Pathways

Last update: 03/16/2017

Alphabetical list of targeted agents: 
Index | By Class | Immunotherapies
 

 7 Reasons to Consider Trials based on our unique clinical circumstances | Trial Talk - specialists to consult about trials
 T
erms related to targeted drugs in lay language  | Printable PDF brochure on targeted drugs

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Introduction to targeted drugs for Lymphoma

Desirable binding sites for a drug are those that inhibit a pathway that promotes the abnormal growth and survival of the malignant cells and have few
off-target effects

You can click the image to open an illustration of pathways within the b-cells -
and to appreciate the complexity of human biology

Our goal is to foster a general understanding of how targeted agents for lymphoma are thought to work  as an aid to informed decision-making when considering clinical trials.  

A cancer develops from genomic damage (mutations) to cells that lead to the abnormal growth and persistence of the cells (malignant behavior). 

The mutations can lead to epigenomic changes that turn on or off specialized genes that would protect the cell from
becoming a cancer (such as tumor suppressor genes) or being detected by the immune system (such as immune checkpoint blockade). 

It's important to note that lymphoma is highly sensitive to standard cytotoxic chemotherapy and radiotherapy, which work by damaging the DNA of rapidly dividing cells causing the cells to initiate programmed cell death.  Targeted approaches may work with or sometimes replace standard treatments.  They can be used before, with, or just after standard cytotoxic therapies to improve outcomes.

Mechanisms of action for targeted drugs:

1) by inhibiting pathways inside the tumor cell that are activated by the mutations -- driving the malignant behavior of the tumor cells.  Many of these are small molecule drugs taken orally (such as ibrutinib)

There are many kinds of pathways and binding points within a pathway.  Many pathways are involved in the transcription of genes -- making proteins that promote cell growth.  Some pathways silence genes that protect against uncontrolled cell growth; other pathways may help to hide  the tumor cell from the immune system or inhibit immune function.

2) by
activating genes that have been silenced, or turning off over-active genes.  Sometimes called epigenetic agents (
such as HDAC inhibitors or Abexinostat) 

4) by
binding to surface antigens that are expressed on the surface of the type of cell,  such as cd19, cd20, cd22, cd30 ...  on lymphocytes
- by binding - activating signals within b-cell  (Rituxan)
- by inducing immunity against the bound cell 
- by delivering a toxin (antibody-drug conjugate)
- by delivering radiation (radioimmunotherapy)

5) by inhibiting how the cancer cells "hijack" the host system, such as the immune system (immune checkpoints) or the blood supply (angiogenesis).  May also be described as immune modulating drugs.

6) with adoptive immunotherapy - by infusions of immune cells adopted from a donor or the patient ... that are primed or engineered to target malignant cells (e.g., CART 19, allogeneic stem cell transplant)

7) by damaging rapidly dividing cells (cytotoxic) - inducing cell death (apoptosis) - a standard approach.

So targeted drugs can work in many different ways - commonly by interfering with a pathway inside the cell or outside the cell that supports the growth or persistence of the abnormal cells.

The electrical and fuel systems of an automobile might be called pathways that control how fast or slow an engine runs.  Just as a faulty fuel system can cause an engine to race ahead, a faulty pathway in the cells can cause the cells to grow too fast or to resist cell death.

A cell pathway can be modified by a drug when it binds to the part of the cell that supports the cell activity - similar to how a mechanic must turn a specific screw to change the fuel-air mixture to modify how fast an engine runs.  

The binding sites of targeted drugs may be on the cell surface or inside of the cells. Targeted drugs may also bind to normal bystander cells that promote malignant behavior -- sometimes referred to as the tumor microenvironment. 

The binding of the drug to the cell is similar to how a key will fit only one kind of lock. Desirable binding sites for a drug are those that can interrupt or turn off a pathway that promotes abnormal cell growth and survival in the malignant cells.

Effective targeted drugs may also activate (turn on) pathways that help the cell to self-destruct. This would be similar to an intervention by a mechanic that turns on the breaking system allowing the automobile to stop normally.  Other targeted drugs may prevent signals from the tumor cells that shut down an attack by the immune system.

An active drug inhibits or activates a pathway that causes tumor cells to die. An effective drug achieves this with acceptable side effects - leading to the patient living longer and or better (clinical benefit).   The goal of early phases of clinical research is find a safe dose that shows activity against the disease.  The later phases are done to see if the active dose is also effective - provides meaningful clinical benefit.

The binding sites for the drug on the cell may be highly specific to the tumor cells (not found on any other cell) or they may be expressed (turned on) in a limited type of normal cells, such as only on mature b-cells.

In general, the higher the specificity of the drug to the tumor, the fewer kinds of side effects (off-target effects) there will be. However, the significance of the off-target effects depends on the type of cells that are affected: heart cell versus skin cell, for example.  

For lymphoma there are many promising targets for cancer dugs that bind to and kill only mature b-cells. A well-known example is CD20, the binding site of Rituxan, which is found only on the surface of mature b-cells. After therapy that eradicates mature b-cells, these cells can emerge from the immature b-cells that the drug did not stick to. 

Notably, some targeted therapies, such as antibodies, may kill lymphoma cells indirectly by eliciting an immune response.  The binding of the drug to the cell acts like a flag attracting immune cells that then kill the cells.

One reason for optimism that progress against lymphoma will continue is the number of targets that are specific to mature b-cells that can be targeted in this way; another is the high sensitivity of lymphoma cells to regular (chemotherapy and radiotherapy) therapies.

Some targeted drugs have already been proven to be effective in the treatment of lymphoma, such as Rituxan. However, testing is needed for each new agent. That a new drug is "targeted" does not mean it will also prove to be more effective or safer than regular treatments for lymphoma.

It's important to note that regular therapies can be very effective against lymphoma. Indeed, in more than one type of lymphoma cytotoxic chemotherapy is curative and adding immunotherapy has improved outcomes further (Rituxan with chemotherapy). While single and multi-drug combinations of targeted drugs may eliminate the need for chemotherapy one day, the most effective use of targeted agents may be when used concurrently with regular therapy.

Targeted agents may also be used before regular treatment (as "priming" therapy) with or after regular treatment (as consolidation or maintenance therapy) to improve the quality and duration of the response to treatment.

Targeted Agents by Class:

Antibodies | Antibody-drug conjugates | Antibody-radiation conjugates | Apoptosis - targeting |  Btk-inhibitors (ibrutinib) | Engineered T-cells (CARS) | Epigenetic therapy - HDAC inhibitors |  Immune Checkpoint Blockade | Lenalidomide |
PI 3K kinases (Idelalisib)  AND ...  In the News 

Targeted Agents

For reports and to find trials for targeted agents:

* Find Clinical Trials by Type of Treatment Agent

* Also see:  Anticancer Agents - My Cancer Genome http://bit.ly/1powkfa

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Antibodies  - about by PAL

Targets proteins on the surface of normal mature b-cells, such as cd20 (Rituxan)
Pathways:  triggers the death of the cells it binds to directly; elicits or calls an immune response
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Antibody-drug conjugates 

Find trials for this type of agent

Targets proteins on the surface of normal mature b-cells
Delivers toxins or chemotherapy to the targeted cells
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Antibody-radio-isotope conjugates - radioimmunotherapy

Find trials for this type of agent

Targets proteins on the surface of normal mature b-cells
Delivers radiation to the targeted cells

See also
About radioimmunotherapy by PAL
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BCL-2 inhibitors  (coming soon)

Find Trials for this type of agent

Targets pathways inside the cell that prevent programmed cell death (apoptosis)

Cancer cells and resistance of cancer cells to treatment are thought to be caused by
"defects in the apoptotic pathway"
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Btk-inhibitors  About by PAL 

Find Trials for this type of agent

Target a pathway inside the cell that prevents programmed cell death.
This particular kinase is related to the function of the b-cell receptor on mature b-cells

 
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Engineered T-cells:  Chimeric Antigen receptors that target CD19 (CAR19 t-cells/CTL019)

See
Programming T-cells to work like antibodies PAL
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HDAC inhibitors:  About by PAL | Find Trials
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Immune Checkpoint Blockade
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Immune modulating agent: Lenalidomide

Targets cells in the tumor microenvironment
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PI 3K kinases
bullet Activating tumor suppressor genes  (coming soon)
* Andrew Wolf:  On role of tumor suppressor genes in cancer 
 
bullet 2006: Tumor suppressor gene methylation in follicular lymphoma: a comprehensive review” http://1.usa.gov/1uCiK6I

Snips:  "Tumor suppressor genes function by one of the following mechanisms: protect the genome from mutagenic events, impede dysregulated progression through the cell cycle, induce apoptosis in cells that escape normal cell cycle controls, and inhibit cellular migration and metastasis." 

In the future, four unique settings exist to investigate hypomethylating agents in FL: i. refractory disease; ii. transformed lymphoma; iii. alternative to traditional cytotoxic chemotherapy; iv. adjuvant to induction cytotoxic chemotherapy.

Patients with refractory cancers are often considered for early development trials as they have already failed standard therapies. Given lymphoma patients short duration of response in phase I trials of DNMT inhibitors, we expect DNMT inhibitors will be most active when incorporated into a multi-drug regimen. Additionally, FL transformation is associated with aberrant methylation of cyclin dependent kinase inhibitors and therapeutic reversal should be explored in this setting. Another appealing strategy is to treat FL patients without cytotoxic therapies. If the hypomethylating agents can induce the expression of androgen receptor, DAPK, and IL-12 receptor β-2, then concurrent treatment with their respective ligands may be investigated clinically. Finally, if a clinical benefit is demonstrated in these settings, DNMT inhibitors could be evaluated as an adjuvant to FL induction chemotherapy regimens.

SHP1, also known as PTP1C, PTPN6, HCP, and SHPTP1, is a phosphotyrosine phosphatase that plays many important roles in regulating immune system cell differentiation and activation

DNA promoter hypermethylation of the androgen receptor gene is a common finding in FL and other lymphomas.

Methylation of DAPK may be a common epigenetic event in FL. In two published studies, twenty-five of twenty-nine (86%) FL samples were positive for aberrant DAPK methylation

The loss of p16 activity, either through gene mutation or promoter hypermethylation, is a common step in tumor development and progression.

In a recent study, eight of eighteen FL samples (44%) had methylation of the p57 promoter region []. A similar proportion of p57 methylation is found in diffuse large B-cell lymphoma samples

IL-12 may serve as a tumor suppressor across a wide variety of B cell malignancies and methylation of IL-12 receptor β-2 gene may be a common step in the development of B cell malignancies.


epigenetic agents,  epigenetic agents
 


In the News and Related Resources

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Exploring Precision Cancer Medicine for Sarcoma and Rare Cancers (2013-2017) | CBSSM http://bit.ly/1Edel0E
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ASCO Post: “Novel Agents Show Activity in relapsed Non-Hodgkin Lymphoma”  including CRs http://bit.ly/1dSn1gv
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Medscape: The Current Status and Future Impact of Targeted Therapies in Non-Hodgkin Lymphoma http://bit.ly/13wa3eE

Chaitra Ujjani, MD; Bruce D. Cheson, MD
 
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The Hematologist: Inhibition of B-Cell Receptor Signaling as a Therapeutic Strategy for Treatment of CLL  http://bit.ly/12zzCfN
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Biomarkers
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The Hematologist: All in the Family: Fine Tuning Targeted Attack on BCL-2
bullet "BET family has a pivotal role in regulating the transcription of growth-promoting genes” http://1.usa.gov/1Q7vWyI
 
bullet The Eph-Receptor A7 Is a Soluble Tumor Suppressor for Follicular Lymphoma: Cell http://bit.ly/1jAyorL


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  PAL 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 | PAL topic
TRU-016 (cd37 antibody) Find trials
Ublituximab (next gen cd20 antibody) Find Trials
Vaccines for lymphoma (stimulating recognition of tumor antigens) | PAL 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 PAL 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.

 

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 
 
Alphabetical Index of Targeted Agents for lymphoma

Based on trials, promising reports, and recent approvals

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

1 – shows background
2 – mechanism or target
3 – lists clinical trials for agent
Recently added agents are highlighted

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ABT-199  / venetoclax  (activates apoptosis - programmed cell death - through bcl2 pathway)  Find trials
  Full prescribing info for CLL
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Abexinostat  (oral, pan HDAC inhibitor / epigenetic -  activating or quieting genes to induce tumor cell death ) Find trials 
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Acalabrutinib (ACP-196) (inhibits btk / B-cell receptor pathway - an overactive pathway in b-cell lymphomas)  Find trials  ASH15 Report
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Adcetris ® / SGN-35 / brentuximab vedotin  (antibody-drug conjugate: anti-cd30 + antitubulin - more selective delivery of a toxin to cancer cells)  Find trials
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AEB071 /Sotrastaurin  (early: Protein Kinase C Inhibitor of t-cell activation / CD79A/B-mutated ABC subtype of DLBCL) Find trials
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AGS67E (anti-cd37 antibody-drug conjugate)  Find Trials
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Alisertib (MLN8237) Aurora Kinase A inhibitor Find trials
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ALT-803 (interleukin-15-based superagonist, induces memory CD8) Find trials  >
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APTO-253 HCl  (early, thought to activate tumor suppressor gene) Trial early-phase
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Arzerra ® (Ofatumumab) cd20 antibody approved for CLL Find trials
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ASN002 (Syk/Jak inhibitor) Find trials
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Atezolizumab  / MPDL3280A (immune checkpoint antibody - pd-1 pathway) Find Trials
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BI 836826 (IgG1 chimerized and Fc-engineered anti-CD37)  Find Trials
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Belinostat PXD101 (epigenetic - recently approved for t-cell lymphoma) Find trials
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BET protein inhibitor -  BET family regulate the transcription of growth-promoting genes) Find trials
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Betalutin  (Lu-tetraxetan-tetulomab) radioimmunotherapy antibody targeting cd37
Find trials
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Bendamustine / Treanda (cytotoxic) Find trials
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BKM120 (PI3K inhibitor - BCR pathway) Find trials  >
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Blinatumomab (BiTe) cd3 cd19 bi-specific antibody Find trials
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Brentuximab Vedotin (anti-cd30 antibody-drug conjugate) Find Trials
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Buparlisib / BKM120 (oral inhibitor of the pan-class class I PIK3 pathway) Find Trials
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Carfilzomib (Velcade-like proteasome inhibitor) With Ibrutinib (BTK Inhibitor)  Relapse/Refractory Mantle Cell Lymphoma Trial of interest 
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CC-122 (immune-modulating, pleiotropic pathway modifier) Find Trials 
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Cd19 CAR T-cell therapy (adoptive immunotherapy)  Find trials 
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Chimeric antigen receptor (CARs) of any type (cd19, cd20, cd22 (adoptive t-cell therapy) Find Trials 
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Copanlisib / BAY 80-6946
(PI3Kα/β inhibitor given by vein) Find Trials
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CPI-613 (targets mitochondrial metabolism) Find Trials  >
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CPI-0610 (BET protein inhibitor - 
BET family regulate the transcription of growth-promoting genes) Find trials
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CUDC-907 (dual inhibitor of PI3K and HDAC) Find Trials
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Daratumumab  (anti-cd38) Find Trials >
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Denintuzumab Mafodotin /SGN-CD19A, (cd19 antibody-drug conjugate )  Trial of interest | Find Trials
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DT2219ARL (anti-CD19 & 22 antibody-drug conjugate) | Find trials
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Duvelisib / IPI-145  
(PI3K)-delta / PI3K-gamma)
Find trials

Duvelisib with Rituximab vs Rituximab in Previously Treated Follicular Lymphoma Trial of interest
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Entospletinib (SYK inhibitor in BCR pathway)  Find trials >
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Epratuzumab (cd22 antibody a b-cell receptor) Find trials
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Epratuzumab tetraxetan anti-CD22 with fractionated Yttrium 90  Find trials
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EZH2 inhibitors (inhibits epigenetic pathway that contributes to abnormal growth)   Find Trials
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EPZ-6438 ((EZH2 Histone Methyl Transferase [HMT] Inhibitor)
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G100 toll-like receptor 4 (TLR4) agonist
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Ibrutinib (inhibits b-cell receptor / btk pathway) Find trials
Ibrutinib + Rituximab vs FCR  in CLL
Trial of interest
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Idelalisib / GS-1101 / CAL101 (PI3K kinase inhibitor / b-cell receptor pathway)  Find trials
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IMO-8400 (Toll-like receptor  inhibitor) Find Trials 
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IMMU-114 (anti–HLA-DR Mab)   Find Trials
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IPH2201 (immune modulating - Natural Killer cell checkpoint inhibitor) Find Trials
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Inotuzumab Ozogamicin  /CMC-544 (cd20 antibody-drug conjugate) Find trials
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Ipilimumab anti-CTL-A (MXD-010)  (Immune checkpoint blockade) CTL-A t-reg Find trials 
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JNJ-64052781 (Humanized CD19 x CD3 Dual-Affinity Re-Targeting Protein)  Find Trials
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Lirilumab (NK-cell agonist) Find Trials | Report
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Lenalidomide / Revlimid (immune modulation and direct activity)  Find trials  PAL topic
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MEDI-551 (humanized cd19 antibody) Find trials
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MEDI-570 (anti-ICOS antibody for t-cell lymphoma) Find Trials
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Mogamulizumab / POTELIGEO® anti-CCR4 antibody, approved in Japan for CCR4-positive adult T-cell leukemia-lymphoma. Find trials
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MOR00208 /XmAb5574)   (cd19 antibody) Find Trials 
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MLN9708 (Ixazomib, GATA-3 inhibitor) for Relapsed/Refractory Cutaneous and Peripheral T-cell Lymphomas Trial of interest
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Obinutuzumab / GA-101 (next gen cd20 antibody)  Find trials 
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Palbociclib (oral, reversible, selective, small-molecule inhibitor of cyclin-dependent kinases (CDK) -- of interest for MCL)  Find Trials
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PD1/L antibodies (removes block on immune system - immune checkpoint blockade)  Find trials | Open trials only

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

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

- Pembrolizumab /
CT-011) / BMS-936558  | Lambrolizumab (Merck)
 
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PF-05082566 (immunotherapy - anti-4-1BB agonistic antibody targeting the immune checkpoint molecule 4-1BB (CD137) Find Trials  | Report
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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
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Pomalidomide  (Lenalidomide derived - Immune modulating) Find trials
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PNT2258 (first-in-class DNAi -- BCL-2-targeted liposomal formulation of a 24-base DNA oligonucleotide )  Find trials
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Romidepsin  (FDA approved, HDAC inhibitor) Find trials  

Romidepsin + Pralatrexate (novel chemo)  in Relapsed/Refractory Lymphoid Malignancies - PTCL only for expansion phase Trial of interest
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RP6530 (dual PI3K inhibitor) Find trials
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SAR 245409 oral pan-inhibitor of PI3K Find trials
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Selinexor  /KPT-330 (activates tumor suppress gene  Find trials |  Safety report | Report
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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
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TRU-016 (cd37 antibody) Find trials
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Ublituximab (next gen cd20 antibody) Find Trials
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Veltuzumab / Immu-106 / Ha20  (next gen cd20 antibody)  Find trials
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Venetoclax | ABT-199  / (activates apoptosis - programmed cell death - through bcl2 pathway)  Findtrials
Full prescribing info for CLL
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Vidaza ® / 5-Azacytidine (epigenetic - activating or shutting off genes) Find trials 
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YM155 (Survivin inhibitor)  Find Trials >
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Zevalin ® /(Ibritumomab tiuxetan)  (anti-CD20 + Yttrium 90 ) cd20 Find trials

Terms related to targeted therapies

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

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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.
 
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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.
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The molecular target might vary leading to good or poor binding.
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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.
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The targeted agent might have off-target effects (binding to similar molecules on normal cells) leading to toxicity.
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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.
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).

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

 

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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. 
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