Combination Immunotherapy for Pancreatic Cancer

Overseen By Colleen Apostal, RN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Must not be taking: Steroids, Organic nitrates, Immunosuppressants, others

Disqualifiers: Brain metastases, Autoimmune disease, HIV, 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

Compensation: Varies

Number of Visits: Unknown

Duration: 9 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new combination of treatments to determine their safety and effectiveness for individuals with pancreatic cancer that has spread and worsened despite previous chemotherapy. The treatment combines four drugs: tadalafil, pembrolizumab (also known as KEYTRUDA or MK-3475), ipilimumab (also known as Yervoy), and CRS-207. The trial seeks participants with worsening pancreatic cancer who have undergone chemotherapy at least once. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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

The trial does not specify if you need to stop all current medications, but you cannot use certain medications like steroids, strong CYP3A4 inhibitors, or immunosuppressive agents shortly before or during the study. It's best to discuss your current medications with the trial team.

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

Research has shown that a combination of four treatments—tadalafil, pembrolizumab, ipilimumab, and CRS-207—is being tested for safety in people with pancreatic cancer. These treatments can challenge the immune system. Pembrolizumab and ipilimumab are types of immunotherapy, which help the body's immune system fight cancer but can also cause side effects like tiredness, skin rash, and diarrhea.

CRS-207 is a cancer vaccine designed to boost the immune system to attack cancer cells. In earlier studies, most participants tolerated it well, though some experienced fever and chills. Tadalafil is already used for other health issues, such as erectile dysfunction and high blood pressure in the lungs, and its safety is well-established.

This combination is in the middle stages of testing, providing some information about its safety, though it remains under study. Participants might experience mild to moderate side effects, while serious side effects are less common. Discussing any concerns with the trial team is important to fully understand the risks and benefits. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this combination immunotherapy for pancreatic cancer because it uses a unique approach by combining CRS-207, Ipilimumab, and Pembrolizumab. Unlike standard treatments like chemotherapy, which broadly targets rapidly dividing cells, this combination specifically harnesses the body's immune system to target and destroy cancer cells. CRS-207 is a cancer vaccine that stimulates the immune response, while Ipilimumab and Pembrolizumab are immune checkpoint inhibitors that help immune cells recognize and attack tumors. This targeted strategy has the potential to improve the effectiveness and specificity of treatment, offering hope for better outcomes in this challenging condition.

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

Research has shown that a combination of drugs—tadalafil, pembrolizumab, ipilimumab, and CRS-207—may help the immune system combat pancreatic cancer cells. Participants in this trial will receive this combination therapy. Previous patients who received similar treatments demonstrated some promise in activating their immune systems, despite pancreatic cancer's usual resistance to therapies. This drug combination aims to strengthen the body's natural defenses against cancer. Although not all studies have shown improved survival with this approach, it could offer a new way to address this challenging cancer. ^{1 2 4 5 6}

Who Is on the Research Team?

Katherine Bever, MD

Principal Investigator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Medical Institution

Are You a Good Fit for This Trial?

Adults over 18 with metastatic pancreatic cancer that's worsened after chemotherapy can join this trial. They must understand and agree to the study, have at least one measurable tumor, be in good physical condition (ECOG 0 or 1), use birth control, and have proper organ function. Exclusions include allergies to penicillin/sulfa, brain metastases, recent treatments or surgeries, uncontrolled illnesses, certain drug uses, severe hypersensitivities, significant heart disease or infections like HIV.

Inclusion Criteria

My cancer has worsened as shown by imaging tests.

My blood and organ tests meet the study's requirements.

My cancer is a type of pancreatic cancer confirmed by lab tests.

Exclusion Criteria

I use more than 4 grams of acetaminophen daily.

You are currently using extra oxygen at home.

I had surgery within the last 4 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive tadalafil, pembrolizumab, ipilimumab, and CRS-207

9 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• CRS-207
• Ipilimumab
• Pembrolizumab
• Tadalafil

Trial Overview The trial is testing a combination of drugs: Tadalafil plus immunotherapies Pembrolizumab and Ipilimumab along with CRS-207 vaccine therapy on those with advanced pancreatic cancer who've had prior chemo. It aims to assess safety and how well these work together against the cancer.

How Is the Trial Designed?

Group I: Arm A - Tadalafil, Pembrolizumab, Ipilimumab, CRS-207 Experimental Treatment 4 Interventions

Who Is Running the Clinical Trial?

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Lead Sponsor

Trials

578

Recruited

33,600+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Lustgarten Foundation

Collaborator

Trials

27

Recruited

5,500+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05014776

Study of CRS-207, Pembrolizumab, Ipilimumab, and ... The purpose of this study is to evaluate the safety and clinical activity of tadalafil, pembrolizumab, ipilimumab, and CRS-207 in subjects with metastatic ...

2. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/76/NCT05014776/Prot_SAP_000.pdf

A Phase 2 Study of the Safety, Efficacy, and Immune Response ... ... pancreatic cancer treated with tadalafil, pembrolizumab, ipilimumab, and CRS-207. ... Effective immunotherapy in pancreatic cancer may require combinations ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12070857/

Inflammation, Immunosuppression, and Immunotherapy in ... The results from the ECLIPSE study showed that the combination of Cy/GVAX and CRS-207 did not improve survival compared to chemotherapy [94]. In ...

4. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05014776/study-of-crs-207-pembrolizumab-ipilimumab-and-tadalafil-in-metastatic-pancreatic-cancer

Study of CRS-207, Pembrolizumab, Ipilimumab, and ... The purpose of this study is to evaluate the safety and clinical activity of tadalafil, pembrolizumab, ipilimumab, and CRS-207 in subjects with ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2950247025000878

An overview of current immunotherapy approaches for ... Pancreatic cancer, characterized by its immunologically "cold" microenvironment, has shown limited response to immunotherapy. However, strategies that combine ...

6. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT05014776/

Clinical Trial: NCT05014776 The purpose of this study is to evaluate the safety and clinical activity of tadalafil, pembrolizumab, ipilimumab, and CRS-207 in subjects ...