Immunotherapy for Pancreatic Cancer
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Will Immunotherapy Help Us Cure Pancreatic Cancer?

Reviewed By: Elizabeth Jaffee, M.D.
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Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD
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The pancreas is an organ located behind the stomach, bordering the spleen and small intestine. The endocrine part of the pancreas releases insulin and glucagon into the bloodstream, while the exocrine part of the pancreas produces digestive enzymes that are released into the small intestine.

Traditional treatments for pancreatic cancer include:

  • Surgical resection
  • Radiation
  • Ablative treatments
  • Chemotherapy

Immunotherapy (or immuno-oncology) represents another exciting area of treatment for pancreatic cancer. While a pancreatic cancer cure does not currently exist, new immunotherapies are currently being tested in pancreatic cancer clinical trials and several have shown impressive results.

To learn more about these pancreatic cancer clinical trials, please consult our Clinical Trial Finder.

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Pancreatic Cancer Treatment and Clinical Trials

Immunotherapy research on pancreatic cancer is ongoing and holds the promise of new pancreatic cancer therapy options. The table below provides information on select pancreatic cancer immunotherapy treatments that are being studied in clinical trials, organized by type of therapy.

Therapies
  • Checkpoint Inhibitors/Immune Modulators
  • Therapeutic Vaccines
  • Adoptive Cell Therapy
  • Monoclonal Antibodies
  • Oncolytic Virus Therapies

A promising avenue of clinical research in pancreatic cancer is the use of immune checkpoint inhibitors. These treatments work by targeting molecules that serve as checks and balances in the regulation of immune responses. By blocking inhibitory molecules or, alternatively, activating stimulatory molecules, these treatments are designed to unleash or enhance pre-existing anti-cancer immune responses. Several checkpoint inhibitors, targeting multiple different checkpoints, are currently in development:

Nivolumab (Opdivo®): A PD-1 Antibody +/- Ipilimumab (Yervoy®): A CTLA-4 Antibody

  • A phase I/II trial of nivolumab or nivolumab combined with ipilimumab in patients with advanced or metastatic solid tumors, including pancreatic cancer (NCT01928394).
  • A phase I/II trial of nivolumab for patients with advanced cancer, including pancreatic cancer (NCT02423954).
  • A phase I trial of nivolumab for patients with advanced cancer, including pancreatic cancer, in combination with FPA008, an antibody that inhibits colony stimulating factor-1 receptor (CSF1R), which targets immune cells (NCT02526017).
  • A phase I trial of ipilimumab (Yervoy®) and gemcitabine in treating patients with stage III-IV or recurrent pancreatic cancer that cannot be removed by surgery (NCT01473940).
  • A phase I study to test ipilimumab (Yervoy®) combined with MGA271, an antibody that targets B7-H3, in patients with refractory cancer, including pancreatic cancer (NCT02381314).

Pembrolizumab (Keytruda®, MK-3475): A PD-1 Antibody

  • A phase I/II trial for patients with advanced cancer, including pancreatic cancer, combined with PLX3397, a tyrosine kinase inhibitor of KIT, CSF1R, and FLT3 (NCT02452424).
  • A phase I/II trial for patients with resectable or borderline resectable pancreatic cancer (NCT02305186).
  • A phase I/II trial for patients with advanced cancer, including pancreatic cancer, in combination with chemotherapy (NCT02331251).
  • A phase I study for patients with refractory cancer, including pancreatic cancer, combined with MGA271, an antibody that targets B7-H3 (NCT02475213).
  • A phase I trial for patients with advanced pancreatic cancer, with Reolysin®, an oncolytic virus that is able to replicate specifically in cancer cells bearing an activated RAS pathway, and chemotherapy (NCT02620423).
  • A phase I trial for patients with advanced cancer, including pancreatic cancer, combined with defactinib, a focal adhesion kinase (FAK) inhibitor, and gemcitabine (NCT02546531).

Durvalumab (MEDI4736): A PD-L1 Antibody +/- Tremelimumab: A CTLA-4 Antibody

  • A phase I trial of durvalumab, tremelimumab, or the combination for patients with unresectable pancreatic cancer (NCT02311361).
  • A phase I study of durvalumab plus tremelimumab for patients with metastatic pancreatic cancer (NCT02639026).
  • A phase I trial of durvalumab for patients with pancreatic cancer, in combination with selumetinib, an inhibitor of MEK 1 and 2 (NCT02586987).
  • A phase I study of durvalumab plus mogamulizumab, an antibody directed against CC chemokine receptor 4 (CCR4), or tremelimumab plus mogamulizumab in patients with advanced cancer (NCT02301130).

Other Drugs

  • A phase I study to test MGD009, a B7-H3 x CD3 DART protein, in patients with unresectable or metastatic B7-H3-expressing cancer, including pancreatic cancer (NCT02628535).
  • A phase I trial of RO70097890, a CD40 antibody, for patients with newly diagnosed resectable pancreatic cancer (NCT02588443).

 

Cancer vaccines are designed to elicit an immune response against tumor-specific or tumor-associated antigens, encouraging the immune system to attack cancer cells bearing these antigens. Several trials of vaccines, given alone or with other therapies, are currently enrolling patients with pancreatic cancer:

  • A phase II trial of a vaccine that targets the NY-ESO-1 protein in patients with advanced cancer whose cancers express NY-ESO-1 (NCT01697527).
  • A phase I/II study of GVAX vaccine +/- nivolumab (Opdivo®) in patients with surgically resectable pancreatic cancer (NCT02451982).
  • A phase I trial of a dendritic cell vaccine plus standard-of-care chemotherapy for patients with resectable, borderline resectable, or locally advanced pancreatic cancer or patients with metastatic pancreatic cancer, newly diagnosed/untreated metastatic pancreatic cancer, or metastatic pancreatic cancer who have undergone prior neo-adjuvant therapy (NCT02548169).
  • A phase I study of two vaccines—one to target the TERT, which has been detected in more than 85% of all human cancers, and one to target the interleukin 12 (IL-12), which enhances immune cell activity—for patients with select tumors, including pancreatic cancer (NCT02327468).

 

Another major avenue of immunotherapy for pancreatic cancer is adoptive T cell transfer. In this approach, T cells are removed from a patient, genetically modified or treated with chemicals to enhance their activity, and then re-introduced into the patient with the goal of improving the immune system’s anti-cancer response. Several trials of adoptive cell transfer techniques are currently under way for patients with pancreatic cancer, including:

  • A phase II trial taking enriched tumor-infiltrating immune cells and re-infusing them in patients with metastatic digestive tract cancers, including pancreatic cancer (NCT01174121).
  • A phase II study of T cells genetically reengineered to target the NY-ESO-1 antigen in patients with NY-ESO-1-positive cancers (NCT01967823).
  • A phase I/II trial is also testing CAR T cells modified to recognize mesothelin in patients with pancreatic cancer (NCT01583686).
  • A phase I/II trial of T cells genetically reengineered to target the anti-MAGE-A3 protein in advanced cancer (NCT02111850).
  • A phase I study of T cells engineered to recognize the NY-ESO-1, MAGE-A4, PRAME, survivin, and SSX markers in patients with solid tumors, including pancreatic cancer (NCT02239861).

 

Monoclonal antibodies are molecules, generated in the lab, that target specific antigens on tumors. Many monoclonal antibodies are currently used in cancer treatment, and some appear to generate an immune response.

  • A phase II study of MM-141, an antibody targeting HER3 and IGF-1R, plus chemotherapy in patients with front-line metastatic pancreatic cancer (NCT02399137).
  • A phase I/II trial testing IMMU-132, an antibody-drug conjugate targeting Τrop-2, in patients with pancreatic and other cancers (NCT01631552).
  • A phase I trial of MVT-5873, an antibody against the carbohydrate antigen 19-9, in patients with pancreatic cancer (NCT02672917). CA19-9 is overexpressed on a number of different tumor cell types, and plays a key role in tumor cell survival and metastasis.

 

Oncolytic virus therapy uses a modified virus that can cause tumor cells to self-destruct and generate a greater immune response against the cancer.

  • A phase I/II trial of ParvOryx, an oncolytic parvovirus that infects and destroys cancer cells, in patients with metastatic, inoperable pancreatic cancer (NCT02653313).
  • A phase I trial of Reolysin®, an oncolytic virus that is able to replicate specifically in cancer cells bearing an activated RAS pathway, pembrolizumab (Keytruda®, MK-3475), a PD-1 antibody, and chemotherapy for patients with advanced pancreatic cancer (NCT02620423).

Go to our Clinical Trial Finder to find clinical trials of immunotherapies for pancreatic cancer that are currently enrolling patients.

 

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*Immunotherapy results may vary from patient to patient.

Patient education information supported by a charitable donation from Bristol-Myers Squibb Company.
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