hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) still present significant treatment challenges.
If you, or someone you know has HCC or ICC and is 18 years of age or older, you may want to learn more about the PERIO-02 clinical trial. Talk to your doctor about participating.
The Pressure-Enabled Regional Immuno-Oncology (PERIO-02) clinical trial will study a new investigational drug, SD-101, delivered intravascularly by the TriNav® Infusion System using the Pressure-Enabled Drug Delivery™ (PEDD™) method of administration. The study will evaluate if this platform approach can improve the performance of systemic checkpoint inhibitors in treating patients with HCC or ICC.
- high intratumoral pressure (ITP)
Studying a Platform Designed
to Address both Treatment Challenges
CHALLENGE 1: Immunosuppression
How do the liver's natural processes interfere with immunotherapy?
Part of a healthy liver's function is controlling immune response.
It's the way the liver manages inflammation and maintains homeostasis.
What happens when tumor cells are present in the liver?
When tumor cells are present in the liver, they trick the immune system by turning anti-tumor mechanisms off.1
The large number of myeloid derived suppressor cells (MDSCs) in the liver create a highly immunosuppressive tumor microenvironment (TME), which is an obstacle to traditional treatment or immunotherapy.
What is the significance of MDSCs in the liver?
MDSCs are key drivers of immunosuppression in the liver and pancreas and accelerate growth of other types of suppressor cells2-4
High MDSC levels may predict poor outcomes in cancer patients5
How does investigational SD-101 address the immunosuppressive barrier?
Investigational SD-101 may stimulate an immune response that reduces and reprograms MDSCs.6,7
It has been shown in preclinical data to improve the ability of the immune system to attack the cancer and respond to certain therapies.8
Why is this approach being combined with a checkpoint inhibitor?
Our immune system protects us from disease, killing bacteria and viruses. It also helps fight cancer. A T cell is one type of immune cell that does this.
Proteins on T cells turn the immune system on when it needs to fight. Other proteins — checkpoint molecules — turn the system off when it is not needed.
Cancer can trick the immune system by turning T cells off where they're most needed. Checkpoint inhibitors (CPIs) have shown promise in turning T cells back on so they recognize and attack the disease. We are studying SD-101 to determine if it can boost the effectiveness of CPIs in liver tumors so that T cells can identify and attack the HCC and ICC cancer cells.
CHALLENGE 2: High Intratumoral Pressure (ITP)
How does tumor growth impact treatment?
As the tumor grows, the pressure inside of it increases.9 This intratumoral pressure (ITP) causes blood vessels in the area to collapse, reducing blood flow.9
The lack of blood flow, the high ITP, and the dense tumor tissue create a physical barrier to drug delivery.10
In some cases, <1% of therapy has been reported to reach the tumor with standard delivery approaches.11,12
What is PEDD™?
PEDD stands for Pressure-Enabled Drug Delivery.
PEDD is designed to overcome the physical barrier/high ITP challenge so that more of the drug is delivered directly to the tumor.13,14
In this study, PEDD will enable SD-101 to be delivered into the arteries that supply the liver.
Am I eligible to participate
in this clinical trial?
You may qualify to participate in the study if you:
Are ≥18 years of age
Are not pregnant or breastfeeding
Have a confirmed diagnosis of hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (ICC)
Do not have an active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
Have not received chemotherapy or an investigational agent within 14 days before screening
Do not have active coronavirus disease 2019 (COVID-19); other severe infection, including a liver infection, within 2 weeks before the first dose of study drug; or uncontrolled human immunodeficiency virus (HIV) infection at screening
Have no prior history of or concurrent malignancy unless the malignancy is clinically insignificant, and no ongoing treatment is required
Are clinically stable as judged by the clinical investigator
Do not have active, known, or suspected autoimmune disease or immune-mediated disease. Type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis or alopecia) not requiring systemic treatment or conditions not expected to recur in the absence of an external trigger are not exclusionary
Have not had bacterial pneumonia within 8 weeks of the first dose of the study drug
Get the PERIO-02 clinical trial brochure:
Find a physician affiliated with the
PERIO-02 Clinical Trial
The University of Texas MD Anderson
Houston, TX 77030
University of Colorado, Denver
Anschutz Cancer Pavilion
Aurora, CO 80045
McKenna Russen firstname.lastname@example.org
Columbia University Medical Center
Herbert Irving Pavilion, 8th floor
New York, NY 10032
Rhode Island Hospital
Rhode Island Hospital, APC 131
593 Eddy Street, Providence, RI 02903
Caitlyn Krar CKrar@Lifespan.org
Sopha Dionson sdionson@Lifespan.org
Massachusetts General Hospitals
Boston, MA 02114
Ashley O’Meara ALOMEARA@mgh.harvard.edu
University of Maryland Medical Center Radiation Oncology
Baltimore, Maryland 21201
Dr. Kevin Kim email@example.com
Kansas University Medical Center
Why should I participate
in a clinical trial?
Virtually every therapy and many medical advancements have been made possible by individuals who take part in clinical trials. Clinical trials are needed for the development of new treatment options for people living with HCC and ICC and other diseases.
Others are here to support you in the fight against HCC and ICC.
TriNav® is Rx Only. For the safe and proper use of the TriNav device, refer to the Instructions for Use.
1. Shimizu, Kanako, Tomonori Iyoda, Masahiro Okada, Satoru Yamasaki, and Shin-ichiro Fujii. “Immune Suppression and Reversal of the Suppressive Tumor Microenvironment.” International Immunology. 2018;30 (10): 445–55. https://doi.org/10.1093/intimm/dxy042. 2. Medina-Echeverz, J., Eggert, T., Han, M. & Greten, T. F. Hepatic myeloid-derived suppressor cells in cancer. Cancer Immunol. Immunother. 2015;(64)931-940.3. Thyagarajan A, Alshehri MSA, Miller KLR, Sherwin CM, Travers JB, Sahu RP. Myeloid-Derived Suppressor Cells and Pancreatic Cancer: Implications in Novel Therapeutic Approaches. Cancers (Basel). 2019;11(11):1627. doi:10.3390/cancers11111627 4. Thorn M, Guha P, Cunetta M, et al. Tumor-associated GM-CSF overexpression induces immunoinhibitory molecules via STAT3 in myeloid-suppressor cells infiltrating liver metastases. Cancer Gene Ther. 2016;(6):188-198. 5. Wang PF, Song SY, Wang TJ, et al. Prognostic role of pretreatment circulating MDSCs in patients with solid malignancies: A meta-analysis of 40 studies. Oncoimmunology 2018 Jul 30;7(10):e1494113. doi: 10.1080/2162402X.2018.1494113. 6. Yamamoto S., Kuramoto E, Shimada S, and Tokunaga T. “In vitro augmentation of natural killer cell activity and production of interferonalpha/beta and -gamma with deoxyribonucleic acid fraction from Mycobacterium bovis BCG.” Jpn J Cancer Res. 1988;79(7): 866-873. 7. Shirota, H. & Klinman, D. M. Effect of CpG ODN on monocytic myeloid derived suppressor cells. Oncoimmunology 2012;(1):780-782. 8. Ghosh C.C., et al. Regional administration of Class C CpG Oligodeoxynucleotides results in superior intrahepatic TLR9 activation and immunomodulation compared to systemic infusion. Poster presented at AACR. 2021. 9. Stylianopoulos, Triantafyllos, John D. Martin, Matija Snuderl, Fotios Mpekris, Saloni R. Jain, and Rakesh K. Jain. “Coevolution of Solid Stress and Interstitial Fluid Pressure in Tumors During Progression: Implications for Vascular Collapse.” Cancer Research. 2013;(13)73: 3833–41. https://doi.org/10.1158/0008-5472.CAN-12-4521. 10. Jain, Rakesh K. “Barriers to Drug Delivery in Solid Tumors.” Scientific American, 2013;8. 11. Wilhelm S, Tavares A, Dai Q, et al. Analysis of nanoparticle delivery to tumours. Nat Rev Mater. 2016:1. 12. Sheth, Rahul A., Robin Hesketh, David S. Kong, Stephan Wicky, and Rahmi Oklu. 2013. “Barriers to Drug Delivery in Interventional Oncology.” J Vascular and Interventional Radiology. 2013; 24 (8): 1201–1207. https://doi.org/10.1016/j.jvir.2013.03.034. 13. Titano JJ, et al. Cardiovasc Intervent Radiol. 2019;42:560-568. 14. Pasciak AS, et al. J Vasc Interv Radiol. 2015;26:660-669.