SD-101 + Pembrolizumab for Pancreatic Cancer

Overseen By Ann-Marie Hulstine

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: TriSalus Life Sciences, Inc.

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Chronic pancreatitis, Autoimmune disease, Hepatitis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new approach for treating locally advanced pancreatic cancer that cannot be surgically removed. The study examines the effectiveness of SD-101, administered directly to the pancreas, both alone and in combination with pembrolizumab, an immunotherapy drug that aids the immune system in fighting cancer. It targets individuals whose pancreatic cancer has not fully responded to previous treatments like chemotherapy or radiation. Participants should have pancreatic cancer that impacts daily life but without severe symptoms from cancer spreading to other organs. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this new treatment.

Do I need to stop my current medications to join the trial?

The trial requires that you have not received chemotherapy or targeted therapy within 14 days before screening. If you are on chronic anticoagulation therapy, you must be able to be temporarily removed from it. Other medications are not specifically mentioned, so it's best to discuss with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that SD-101, when combined with a checkpoint inhibitor, is generally well-tolerated. One study reported no serious side effects at the optimal dose. Common side effects included mild stomach issues, tiredness, and skin reactions.

Pembrolizumab, already approved by the FDA for other uses, is considered safe. However, it may cause mild to moderate side effects such as tiredness, skin reactions, and stomach issues.

Overall, studies indicate that both SD-101 and pembrolizumab are well-tolerated, with most side effects being mild or moderate. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike standard treatments for pancreatic cancer, which often involve surgery, chemotherapy, and radiation, the combination of SD-101 and Pembrolizumab introduces a unique approach by enhancing the immune system's ability to fight the cancer. SD-101 is delivered directly to the pancreas through a method called pancreatic retrograde venous infusion (PRVI), allowing for targeted treatment, which is different from typical intravenous delivery methods. Researchers are particularly excited about this combination because SD-101 may boost the effectiveness of Pembrolizumab, an immunotherapy that helps the immune system recognize and attack cancer cells. This targeted delivery and potential for enhanced immune response could provide new hope for patients with pancreatic cancer.

What evidence suggests that SD-101 and Pembrolizumab could be effective for pancreatic cancer?

Research has shown that SD-101, when combined with drugs like pembrolizumab, may help treat pancreatic cancer. In studies, this combination caused some patients' tumors to shrink. Specifically, two cases showed tumors shrinking by at least 30%, while five other cases saw reductions of 10% to 29%. In this trial, participants will receive SD-101, which activates certain immune cells to help the body fight cancer more effectively. Pembrolizumab is a well-known drug that aids the immune system in attacking cancer cells. Using these treatments together could enhance their effectiveness against pancreatic cancer. ^{1 3 5 6 7}

Are You a Good Fit for This Trial?

Adults with advanced pancreatic cancer who haven't had recent chemotherapy, radiation, or other cancers. They must understand the study, consent to it, have a life expectancy over 3 months, stable organ function and blood counts within certain limits. Women of childbearing age must not be pregnant and agree to contraception.

Inclusion Criteria

Has a QTc interval ≤480 msec

Has a life expectancy of >3 months at screening as estimated by the Investigator

Able to understand the study and provide written informed consent prior to any study procedures

Exclusion Criteria

I have previously been treated with SD-101.

Patients who were enrolled in the Phase 1 portion of the study will not be eligible for enrollment in Phase 1b

My liver disease is moderately to severely advanced.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 Treatment

Escalating doses of SD-101 administered alone via PRVI into the regional vessels of the pancreas

12 months

Phase 1b Treatment

SD-101 administered with systemic anti-PD-1 checkpoint blockade over 2 cycles, each cycle being about 6 weeks apart

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• SD-101

Trial Overview The trial is testing SD-101 delivered directly into the pancreas using pressure alongside pebrolizumab given intravenously. It's an early-phase study to see if this combination can help treat locally advanced pancreatic cancer that hasn't spread elsewhere.

How Is the Trial Designed?

Group I: SD-101 Experimental Treatment 2 Interventions

Two doses of SD-101 given over two cycles via pancreatic retrograde venous infusion (PRVI) using the PEDD method of administration.

Pembrolizumab is already approved in United States, European Union, United Kingdom for the following indications:

Approved in United States as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in European Union as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in United Kingdom as KEYTRUDA for:

• Untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1

Who Is Running the Clinical Trial?

TriSalus Life Sciences, Inc.

Lead Sponsor

Trials

10

Recruited

420+

Published Research Related to This Trial

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

In a study of 41 pancreas cancer patients treated with pembrolizumab, the median overall survival was 7.2 months, which is considered favorable compared to the benchmark of over 4 months.

Patients with specific genetic markers (dMMR, MSI-H, TMB-H, or Lynch syndrome) had a significantly lower risk of death, indicating that these biomarkers may help identify patients who could benefit more from pembrolizumab treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab near the end of life in patients with metastatic pancreatic cancer: a multi-site consecutive series to examine survival and patient treatment burden. Storandt, MH., Tran, N., Martin, N., et al.[2023]

Pembrolizumab, a PD-1 inhibitor used in cancer treatment, can lead to rare but serious immune-related adverse events, including type 1 diabetes mellitus, occurring in about 0.2% of cases.

A review of 42 cases revealed that patients may develop diabetic ketoacidosis during treatment, highlighting the need for blood glucose monitoring and awareness of this potential side effect among clinicians.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. Clotman, K., Janssens, K., Specenier, P., et al.[2022]

Pembrolizumab (Keytruda) is an approved treatment for metastatic or locally advanced esophageal and gastroesophageal junction cancer, indicating its efficacy in targeting these specific cancer types.

It is used in combination with platinum- and fluoropyrimidine-based chemotherapy, suggesting a synergistic approach to enhance treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Approved for Esophageal or Gastroesophageal Cancer. Aschenbrenner, DS.[2023]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

Citations

1. investors.trisaluslifesci.com investors.trisaluslifesci.com/news-releases/news-release-details/trisalus-life-sciences-presents-data-sd-101-delivered-trisalus

TriSalus Life Sciences Presents Data for SD-101 Delivered ... New data from PERIO-03 clinical trial indicates PEDD™ method resulted in modulation of the tumor microenvironment by enabling performance of ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04050085

SD-101, Nivolumab, and Radiation Therapy in Treating ... Giving SD-101, nivolumab, and radiation therapy may work better in treating patients with pancreatic cancer compared to nivolumab or radiation therapy alone.

3. targetedonc.com targetedonc.com/view/sd-101-and-checkpoint-blockade-shows-early-favorable-outcomes-in-umlm

SD-101 and Checkpoint Blockade Shows Early Favorable ... Among all patients, there were 2 partial responses (≥30% decrease) and 5 minor responses (10%-29% decrease) documented as the best on-treatment ...

4. letswinpc.org letswinpc.org/research/combination-including-immunotherapy-for-metastatic-pancreatic-cancer/

Testing a Combination for Metastatic Pancreatic Cancer SD-101 is an investigational drug that induces the activation of specific memory T helper cells, which promote anti-tumor T cell function.

5. jhoonline.biomedcentral.com jhoonline.biomedcentral.com/articles/10.1186/s13045-024-01613-x

Consensus, debate, and prospective on pancreatic cancer ... The primary endpoint was to achieve an 18-month DFS rate of 55%, based on a 38% 18-month DFS seen with gemcitabine alone in the CONKO-001 trial; ...

6. jitc.bmj.com jitc.bmj.com/content/11/Suppl_1/A739

647 PERIO-03: Pressure enabled intrapancreatic delivery ... The primary endpoints are safety and optimal SD-101 dose determination. Results We enrolled 3 patients at the lowest (0.5 mg) SD-101 dose.

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2020.38.4_suppl.TPS782

A pilot study of intratumoral SD-101 (toll-like receptor 9 ... The combination of SD-101, localized radiation, and checkpoint inhibitor is a promising therapeutic strategy for metastatic pancreatic adenocarcinoma.