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Research & Development

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We recognize the urgency of our mission to help patients in need of anticancer alternatives in the IO space. As of September 2018, we have 8 compounds in the ongoing IO clinical trials. We are committed to bringing novel IO agents into the clinic.

Explore the assets in our IO product pipeline


BEYOND SINGLE AGENTS: THE POTENTIAL TO HELP MORE PATIENTS THROUGH IO COMBINATIONS

Currently approved immunotherapies, which can include checkpoint inhibitors, have shown tumor activity in some cancers. These agents work for many but not all patients and work differently in different tumor types.1-3 However, in patients who do respond, response is generally durable and long lasting.1

In patients who do not respond to IOs with single agents, we are investigating combination therapy as an option.

Although higher tumor response rates have been reported in some studies, they have been seen mostly in select groups of patients.1
PD-1 = programmed death 1; PD-L1 = programmed death ligand 1
1NIH-National Cancer Institute. Checking in on checkpoint inhibitors. Cancer currents blog. https://www.cancer.gov/news-events/cancer-currents-blog/2015/gulley-checkpoint. Published December 18, 2015. Accessed November 3, 2016.
2Richter V. Clinical trials show success for new cancer treatment. Cosmos. https://cosmosmagazine.com/biology/clinical-trial-show-success-for-new-cancer-treatment. Published June 13, 2016. Accessed November 3, 2016.
3Gorman C. Cancer immunotherapy: the cutting edge gets sharper. Scientific American. https://www.scientificamerican.com/article/cancer-immunotherapy-the-cutting-edge-gets-sharper/. Published October 1, 2015. Accessed November 4, 2016.

DIVERSE IO PATHWAYS, EMERGING TECHNOLOGIES AND APPROACHES

At Pfizer Oncology, we understand the need for better, more targeted cancer treatments. That’s why we are exploring the underlying mechanisms of the immune system, the microenvironment in which cancer cells grow, and the multiple pathways that contribute to the growth and spread of tumors. We’re investigating a number of technologies to target these pathways.

Question Pairs: 
Question: 

PD-1

Answer: 

PD-1 (programmed death-1) is a checkpoint protein found on T-cells that helps keep the immune response in check. When PD-1 binds to another protein called PD-L1 (programmed death ligand-1), it helps keep T-cells from killing other cells, including cancer cells. Blockade of PD-1 with a checkpoint inhibitor may increase the ability of T-cells to kill cancer cells.1

1NIH-National Cancer Institute. NCI Dictionary of Cancer Terms. https://www.cancer.gov/publications/dictionaries/cancer-terms?cdrid=45290. Accessed November 13, 2016.
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PD-L1

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PD-L1 (programmed death ligand-1) is a checkpoint protein that binds to a protein called PD-1 (programmed death-1) to help keep the immune response in check. The PD-L1/PD-1 pathway involves both innate and adaptive immune systems.1,2 Tumors may engage both of these systems to evade detection.3 Blockade of the PD-1/PD-L1 interaction may restore the ability of the adaptive immune system to recognize and eliminate tumor cells via T-cell-mediated respones.4-6

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1Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012;12:252-264.
2Momtaz P, Postow MA. Immunologic checkpoints in cancer therapy: focus on the programmed death-1 (PD-1) receptor pathway. Pharmgenomics Pers Med. 2014;7:357-365.
3Colombo MP, Piconese S. Regulatory T-cell inhibition versus depletion: the right choice in cancer immunotherapy. Nat Rev Cancer. 2007;7:880-887.
4Dolan DE, Gupta S. PD-1 pathway inhibitors: changing the landscape of cancer immunotherapy. Cancer Control. 2014;2:231-237.
5Furness AJS, Vargas FA, Peggs KS, Quezada SA. Impact of tumor microenvironment and Fc receptors on the activity of immunomodulatory antibodies. Trends Immunol. 2014;35:290-298.
6Philips GK, Atkins M. Therapeutic uses of anti-PD-1 and anti-PD-L1 antibodies. Int Immunol. 2015;27:39-46.
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CTLA-4

Answer: 

The CTLA-4 (cytotoxic T-lymphocyte–associated antigen-4) checkpoint pathway is involved in suppressing T-cell immune function. Inhibition of this pathway may result in increased activation of the immune system. CTLA-4 is believed to stop potentially reactive T-cells at their initial stage of activation, typically in the lymph nodes.1

1Buchbinder EI, Desai A. CTLA-4 and PD-1 pathways. Similarities, differences, and implications of their inhibition. Am J Clin Oncol. 2016;39(1):98-106.
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4-1BB

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The 4-1BB receptors are found on certain T-cells (primarily on CD8+, but also on CD4+ memory T- cells) and natural killer (NK) cells.1,2 Molecules that bind to 4-1BB receptors have been shown to stimulate and increase the number of immune cells. This may help augment anti-tumor immune function.1

1Fisher TS, Kamperschroer C, Oliphant T, et al. Targeting of 4-1BB by monoclonal antibody PF-05082566 enhances T-cell function and promotes anti-tumor activity. Cancer Immunol Immunother. 2012;61(10):1721-1733.
2Westwood JA, Potdevin Hunnam TC, Pegram HJ, Hicks RJ, Darcy PK, Kershaw MH. Routes of delivery for CpG and anti-CD 137 for the treatment of orthotopic kidney tumors in mice. PLoS ONE. 2014;9(5):110e95847.doi:10.1371/journal.pone.0095847.
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OX40

Answer: 

The OX40 protein is found mostly on T-cells (primarily CD4+ and CD8+ memory T-cells) that have recently been exposed to antigens. When an OX40 agonist, or activator, binds to the OX40 protein receptor, it triggers a co-stimulatory signal that is associated with an increased production of T-cells and inflammatory cytokines. This mechanism may activate dormant immune settings, which may then help fight cancer cells.1

1Croft M, Takanori S, Duan W, Soroosh P. The significance of OX40 and OX40L to T cell biology and immune disease. Immunol Rev. 2009;229(1):173-191.
Question: 

MCSF

Answer: 

The MCSF (macrophage colony-stimulating factor) pathway appears to be involved in regulating processes such as tumor angiogenesis, or new blood vessel formation, and metastases. The MCSF pathway may also induce expression of VEGF (vascular endothelial growth factor), a protein that signals the induction of angiogenesis.1 Inhibition of the MCSF pathway may have the potential to counter tumor growth and progression.

1Curry JM, Eubank TD, Roberts RD, et al. M-CSF signals through the MAP/ERK pathway via SP1 to induce VEGF production and induces angiogenesis in vivo. PLoS ONE 2008;3(10):e3405. doi:10/1371/journal.pone.0003405.
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BCMA

Answer: 

BCMA (B cell maturation antigen) is a member of the tumor necrosis factor receptor super family,1 which can cause cell death in some tumor types.2 BCMA binds to B-cell-activating factor and a ligand (molecule on the cell surface) that stimulate cell growth. By bioengineering T-cells to express chimeric antigen receptors that recognize the tumor-associated antigens BCMA, it may be possible to disrupt growth and multiplication of cancer cells.1

1Carpenter RO, Evbuomwan MO, Pittaluga S. B-cell maturation antigen is a promising target for adoptive T-cell therapy of multiple myeloma. Clin Cancer Res. 2013;19(8):2048-2060.
2NIH-National Cancer Institute. Dictionary of Cancer Terms. https://www.cancer.gov/publications/dictionaries/cancer-terms?cdrid=45290. Accessed November 16, 2016.
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Monoclonal antibodies

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Monoclonal antibodies, or mAbs, are proteins made in the laboratory that can bind to substances in the body such as cancer cells. There are many different types of monoclonal antibodies, and each is made to bind to only one substance, or antigen. Monoclonal antibodies may help treat cancer or carry drugs, toxins, or radioactive substances directly to cancer cells.1

1NIH-National Cancer Institute. Dictionary of Cancer Terms. https://www.cancer.gov/publications/dictionaries/cancer-terms?cdrid=45290. Accessed November 13, 2016.
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P-cadherin (bispecific)

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Targeting P-cadherin with a bispecific antibody is a novel anti-tumor approach. Bispecific antibodies contain specialized fragments of two antibodies, to address two different cancer targets with the same molecule. A bispecific can target a tumor cell with one of its fragments (directed against P-cadherin in this case) and cause co-localization of another cell/particle/protein via its other antibody fragment (directed against CD3 in this case, thus bringing a cytotoxic T-cell into proximity).1 Targeting P-cadherin–bearing cells may inhibit tumor cell invasion and proliferation.2,3

1Kontermann RE, Brinkmann U. Bispecific antibodies. Drug Discovery Today. 2015;20(7):838-847. http://www.sciencedirect.com/science/article/pii/S135964461500077X. Accessed November 4, 2016.
2Vieira AF, Paredes J. P-cadherin and the journey to cancer metastasis. Mol Cancer. 2015;14:178-180.
3Miami Cancer Institute. Drug Dictionary. http://miamicancer.com/drug-dictionary/category/P/. Accessed November 16, 2016.
Question: 

CAR-T

Answer: 

CAR-T (chimeric antigen receptor T-cell therapy) cells are bioengineered T-cells collected from a patient’s own blood (autologous) or a donor’s blood (allogeneic). Collected T-cells are modified so that engineered chimeric antigen receptors are expressed, which can then interact with specific tumor antigens to activate an immune response. CAR-T cells are then multiplied and infused into the bloodstream1,2 CAR-T cells are designed to kill cancer cells with the targeted antigen, while continuing to multiply in the body.2

1Chimeric antigen receptor (CAR) T-cell therapy. Leukemia and Lymphoma Society. https://www.lls.org/treatment/types-of-treatment/immunotherapy/chimeric-antigen-receptor-car-t-cell-therapy. Accessed November 4, 2016.
2NIH-National Cancer Institute. CAR T-cell therapy: Engineering patients’ immune cells to treat their cancers. https://www.cancer.gov/about-cancer/treatment/research/car-t-cells. Accessed November 4, 2016.
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Oncolytic virus

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An oncolytic virus is bioengineered to selectively infect and kill cancer cells but not healthy cells. Although an oncolytic virus can enter normal cells and cancer cells alike, normal cells have mechanisms to kill the virus, while cancer cells do not. As the virus replicates, it causes cancer cells to burst and die. The dying cells release new viruses, GM-CSF, and tumor-specific antigens to stimulate an immune response.1 Oncolytic viruses may help make it easier to kill tumor cells with radiation or chemotherapy.2

GM-CSF=granulocyte macrophage colony-stimulating factor.

1NIH-National Cancer Institute. Oncolytic virus therapy shows benefit in patients with melanoma. Cancer Currents Blog. July 21, 2015. https://www.cancer.gov/news-events/cancer-currents-blog/2015/oncolyticvirus-melanoma. Accessed November 16, 2016.
2NIH-National Cancer Institute. NCI Dictionary of Cancer Terms. https://www.cancer.gov/publications/dictionaries/cancer-terms?cdrid=45290. Accessed November 16, 2016.
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VBIR

Answer: 

In VBIRs (vaccine-based immunotherapy regimens), a cancer vaccine may work synergistically with an immunotherapy to induce an immune response.1 Cancer vaccines activate cell-killing T-cells and direct them to recognize and act against specific types of cancer. To accomplish this, vaccines introduce one or more cancer-specific antigens into the body, where they induce an immune response that results in T-cell activation or antibody production.2 Immunotherapy with a checkpoint inhibitor may boost the immune response induced by a cancer vaccine.1

1Kleponis J, Skelton R, Zheng L. Fueling the engine and releasing the brake: combinational therapy of cancer vaccines and checkpoint inhibitors. Cancer Biol Med. 2015;12:201-208. doi:10.7497/j.issn.2095-3941.2015.00462.
2NIH-National Cancer Institute. Cancer vaccines. Available at: https://www.cancer.gov/about-cancer/causes-prevention/vaccines-fact-sheet#q4. Accessed November 16, 2016.
Question: 

CXCR4

Answer: 

The CXCR4 (C-X-C chemokine receptor 4) pathway is thought to play an important role in signaling the movement of cells during inflammation. When a molecule, or ligand, known as CXCL12 binds to CXCR4 receptors in tumor cells, the result can be cell growth, migration, and invasion, resulting in metastases. Therefore, blocking the interaction between CXCL12 and CXCR4 may hinder cancer progression.1

1Chatterjee S, Azad BB, Nimmagadda S. The intricate role of CXCR4 in cancer. Adv Cancer Res. 2014;124:31-82. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4322894/. Accessed November 4, 2016.
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*Efficacy and safety of agents targeting these pathways are currently under investigation. Regulatory approval of any of these agents is dependent upon completion of the study programs and regulatory review by authorities. The clinical trial information is available at www.clinicaltrials.gov. This information is current as of October 2018.


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Our Pipeline

Our strategy is built on the depth and breadth of our portfolio:

  • Our pipeline is not bound by one modality, platform, or disease, and this is particularly exemplified in our approach to immunotherapy
  • We have strong capabilities in developing traditional compounds, including small molecules and monoclonal antibodies
  • We focus on the novel use of innovative technologies in the development of IO vaccines, oncolytic viruses, and bispecific antibodies
  • We have an array of compounds at various stages of clinical development

Explore the IO assets in our product pipeline


Find out about Pfizer IO clinical trials

Find Pfizer IO clinical trials that are enrolling patients


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Our R&D Program

We continue to make contributions to the science of IO with research and development efforts that span diverse modalities and mechanisms of action.

We see our R&D program as being in a strong position to help advance IO science because our pipeline includes 4-1BB, OX40 agent, BCMA bispecific, and VBIR. As of September 2018, we have 8 compounds in ongoing IO clinical trials. We are committed to going wherever the science leads.

In addition to our IO assets, we are also exploring a broad range of antibody-drug conjugates (ADCs) and small molecules in various combinations.

Learn more about our IO clinical trials in the National Institutes of Health registry


OVERVIEW OF OUR IO CLINICAL TRIALS PROGRAM*

Click below to see all of the IO combinations we’re investigating.

PD-L1 Monoclonal Antibodies BackBone

Question Pairs: 
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Combinations with Pfizer-targeted agents

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PARP inhibitor
Androgen receptor
inhibitor
ALK inhibitors
Multiple tyrosine
kinase inhibitor
       

 

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Combinations with Pfizer IO agents

Answer: 
4-1BB agonist VBIR OX40 agonist
MCSF inhibitor        
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Combinations developed through external collaborations

Answer: 
hulL agonist Cancer vaccine CD20 inhibitor
FAK inhibitor HDAC inhibitor Traditional
chemotherapy
DNA demethylating
agent
IAP inhibitor    
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⚪ Ongoing studies
∇  Planned studies

*Efficacy and safety of agents targeting these pathways are currently under investigation. Regulatory approval of any of these agents is dependent upon completion of the study programs and regulatory review by authorities. The clinical trial information is available at www.clinicaltrials.gov. This information is current as of October 2018.


RESEARCH PERSPECTIVES

Meet the hardworking scientists behind Pfizer’s investigational IO molecules and find out what they’re working on.

JEAN-FRANCOIS MARTINI ON HARNESSING THE IMMUNE SYSTEM TO FIGHT TUMORS

Senior Director, Early Development, Translational and Immuno-Oncology

Quote / Citation: 
Citations: 

We’re attempting to speed our ability to bring breakthroughs to patients with cancer by bringing forward various potential opportunities and IO combinations very rapidly.

Author: 
Steffan Ho, MD, PhD Executive Director, Head of Translational Oncology, Pfizer Global Product Development