Verteporfin + Pembrolizumab for Pancreatic Cancer

Overseen By Clinical Trials Referral Office

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: HIV, Hepatitis B, Hepatitis C, others

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

Prior Safety Data This treatment has passed at least one previous human trial

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks per cycle, up to 1 year

25 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new combination treatment for pancreatic cancer that cannot be surgically removed and has spread locally or to other parts of the body. The treatment combines photoradiation, a light-based therapy using verteporfin that may help kill cancer cells, with pembrolizumab (KEYTRUDA), an immunotherapy that enhances the immune system's ability to fight cancer. Chemotherapy is also included to prevent cancer from growing and spreading. Individuals with pancreatic cancer that hasn't responded to more than one prior treatment and who have not used the chemotherapy regimen FOLFIRINOX might be suitable candidates for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on immunosuppressive therapy or systemic steroids, you may need to stop them at least 7 days before joining the trial. It's best to discuss your specific medications with the trial team.

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

Research shows that verteporfin, used in photodynamic therapy (PDT), is generally safe for people with pancreatic tumors. Studies have found it can shrink tumors more effectively than some surgeries. Additionally, verteporfin PDT is non-invasive, working without the need for surgery.

Pembrolizumab has approval for treating other cancers like melanoma. Although not specifically proven safe for pancreatic cancer, a study combining it with another drug found it safe for patients with advanced pancreatic cancer.

In summary, previous studies have shown both verteporfin and pembrolizumab to be safe. However, the safety of pembrolizumab for pancreatic cancer patients remains under investigation. Always consult a doctor about potential risks and benefits before joining a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Verteporfin and Pembrolizumab for pancreatic cancer because it offers a novel approach to treatment. Unlike standard therapies that primarily focus on chemotherapy, this combination introduces Verteporfin, a drug activated by light to target the tumor directly, in conjunction with Pembrolizumab, an immunotherapy that helps the body's immune system attack cancer cells. This dual mechanism not only aims to directly disrupt cancer cells but also enhances the immune response against them, potentially leading to more effective and sustained results compared to traditional chemotherapy alone.

What evidence suggests that this trial's treatments could be effective for pancreatic cancer?

Research shows that using verteporfin with light therapy effectively destroys tumor cells in pancreatic cancer. Studies have found that verteporfin leads to tumor cell death and is safe for patients with advanced pancreatic cancer. In this trial, participants will receive a combination of verteporfin and pembrolizumab. Pembrolizumab, a treatment that helps the immune system, has shown potential benefits for these patients, with some studies noting a median survival of over four months. This combination aims to boost the body's ability to find and destroy cancer cells. Together, these treatments have shown promise in improving outcomes for patients with complex pancreatic cancer. ^{2 6 7 8 9}

Who Is on the Research Team?

Vinay Chandrasekhara, MD

Principal Investigator

Mayo Clinic in Rochester

Are You a Good Fit for This Trial?

This trial is for patients with pancreatic cancer that can't be surgically removed, has spread locally or to other body parts. Participants must not have had prior treatments and should meet specific health conditions.

Inclusion Criteria

White blood cell (WBC) ≥ 2500/mm^3

Total bilirubin ≤ 1.5 x upper limit of normal (ULN)

Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)

Exclusion Criteria

Nursing persons

I have both hepatitis B and C.

Pregnant persons

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive verteporfin IV and undergo photoradiation, followed by pembrolizumab and standard chemotherapy. Treatment repeats every 6 weeks for up to 1 year.

6 weeks per cycle, up to 1 year

Multiple visits per cycle for IV treatments and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-ups at 30 and 90 days, then every 3 months to progression, and every 6 months for up to 3 years.

Up to 3 years

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• Verteporfin

Trial Overview The study tests photoradiation with verteporfin combined with pembrolizumab immunotherapy and standard chemotherapy (mFOLFIRINOX) against unresectable or metastatic pancreatic cancer.

How Is the Trial Designed?

Group I: Treatment (verteportin, photoradiation, pembrolizumab) Experimental Treatment 15 Interventions

Patients receive verteporfin IV and undergo a biopsy and intratumoral photoradiation over 60-90 minutes using EUS or CT guidance on day 0. Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 6 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients also receive standard of care oxaliplatin IV over 2-6 hours, leucovorin IV over 15 minutes - 2 hours, irinotecan IV over 90 minutes, and fluorouracil IV on days 3, 15 and 29 of cycle 1 only, then on days 1, 15, and 29 of remaining cycles. Cycles repeat every 42 days for up to 6 months in the absence of disease progression or unacceptable toxicity. Patients may optionally undergo lymph node biopsy on day 2 or 3 of cycle 1. Additionally, patients undergo blood sample collection, CT, PET/CT and optional PET/MRI on study.

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?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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]

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]

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, 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]

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]

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

Pembrolizumab is a monoclonal antibody that effectively blocks the PD-1 receptor on T cells, enhancing their ability to attack cancer cells, particularly in melanoma patients.

In a Phase I study involving 411 patients, pembrolizumab demonstrated high durable response rates with minimal toxicity, indicating its potential as a safe and effective treatment option for melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. Hersey, P., Gowrishankar, K.[2017]

In a study of 123 patients with advanced nonsquamous NSCLC, the combination of pembrolizumab and pemetrexed-carboplatin (PC) significantly improved the objective response rate (56.7% vs. 30.2% with PC alone) and progression-free survival (PFS) compared to PC alone, with a hazard ratio (HR) of 0.53.

The updated analysis showed a favorable overall survival (OS) hazard ratio of 0.56 for the pembrolizumab plus PC group, indicating a significant survival benefit, although 41% of patients experienced grade 3 to 5 treatment-related adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

24-Month Overall Survival from KEYNOTE-021 Cohort G: Pemetrexed and Carboplatin with or without Pembrolizumab as First-Line Therapy for Advanced Nonsquamous Non-Small Cell Lung Cancer. Borghaei, H., Langer, CJ., Gadgeel, S., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10272060/

Pembrolizumab near the end of life in patients with ... This multisite study examined consecutive pancreas cancer patients, who received pembrolizumab from 2004 through 2022. Median overall survival of > 4 months ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9119368/

Survival Benefit of Pembrolizumab for Patients With ... Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with 5-year survival rate of 10%. Evidence about pembrolizumab usage for ...

3. oncotarget.com oncotarget.com/news/pr/rare-pancreatic-cancer-patients-show-strong-response-to-immunotherapy/

Rare Pancreatic Cancer Patients Show Strong Response ... The median progression-free survival was 12 months, and most patients were still alive at follow-up, with survival rates of 80% at one year and ...

4. tgh.amegroups.org tgh.amegroups.org/article/view/5943/html

Pancreatic cancer and immune checkpoint inhibitors—still a ... The median overall survival was 4.0 months in the pancreatic cancer subgroup, although it should be noted that the median duration of response was 13.4 months.

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0959804923002010

Efficacy of immune checkpoint inhibitors in microsatellite ... This retrospective analysis suggests that ICIs are effective and well tolerated in patients with MSI/dMMR advanced PDAC.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02305186

Study Details | NCT02305186 | Safety and Immunological ... Pembrolizumab has been approved for treatment of patients with melanoma but has not been proven to be safe or helpful in patients with pancreatic cancer and is ...

7. onclive.com onclive.com/view/bxcl701-plus-pembrolizumab-is-safe-and-generates-early-antitumor-activity-in-advanced-pdac

BXCL701 Plus Pembrolizumab is Safe and Generates ... Benjamin A. Weinberg, MD, FACP, discusses the potential role of BXCL701 plus pembrolizumab in advanced pancreatic ductal adenocarcinoma.

8. oncologynewscentral.com oncologynewscentral.com/pancreatic-cancer/fda-actions-survival-data-and-more-pancreatic-cancer-news-rapid-roundup

FDA Actions, Survival Data, and More: Pancreatic Cancer ... The trial met its primary endpoint and improved median OS (10.1 months vs. 7.2 months). One-year survival doubled (44.1% vs. 22.3%), the risk ...

9. merck.com merck.com/news/merck-announces-phase-3-trial-of-subcutaneous-pembrolizumab-with-berahyaluronidase-alfa-met-primary-endpoints/

Merck Announces Phase 3 Trial of Subcutaneous ... Additionally, secondary endpoints of efficacy and safety were generally consistent for subcutaneous pembrolizumab administered with chemotherapy ...