Study of CRS-207, Pembrolizumab, Ipilimumab, and Tadalafil in Metastatic Pancreatic Cancer

NCT ID: NCT05014776

Last Updated: 2025-04-16

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 17 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-08-22
• Study Completion Date: 2026-04-03

Brief Summary

The purpose of this study is to evaluate the safety and clinical activity of tadalafil, pembrolizumab, ipilimumab, and CRS-207 in subjects with metastatic pancreatic adenocarcinoma who have progressed after at least 1 prior chemotherapy regimen.

Conditions

Pancreatic Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A - Tadalafil, Pembrolizumab, Ipilimumab, CRS-207

Group Type: EXPERIMENTAL

Tadalafil

Intervention Type: DRUG

Patients will receive treatment every 3 weeks for 6 cycles of treatment within a course (total of 18 weeks). Tadalafil (20 mg) will be administered orally every day on days 3-21 for cycles 1-6.

Pembrolizumab

Intervention Type: DRUG

Patients will receive treatment every 3 weeks for 6 cycles of treatment within a course (total of 18 weeks). Pembrolizumab (200 mg) will be administered IV on Day 1 of cycles 1-6.

Ipilimumab

Intervention Type: DRUG

Patients will receive treatment every 3 weeks for 6 cycles of treatment within a course (total of 18 weeks). Ipilimumab (50mg) will be administered IV on Day 1 of Cycles 1, 3, and 5.

CRS-207

Intervention Type: DRUG

Patients will receive treatment every 3 weeks for 6 cycles of treatment within a course (total of 18 weeks). CRS-207 \[1 × 10\^9 colony forming units (CFU) in 100ml NS\] will be administered IV on Day 2 of Cycles 1-6.

Interventions

Tadalafil

Patients will receive treatment every 3 weeks for 6 cycles of treatment within a course (total of 18 weeks). Tadalafil (20 mg) will be administered orally every day on days 3-21 for cycles 1-6.

Intervention Type: DRUG

Pembrolizumab

Patients will receive treatment every 3 weeks for 6 cycles of treatment within a course (total of 18 weeks). Pembrolizumab (200 mg) will be administered IV on Day 1 of cycles 1-6.

Intervention Type: DRUG

Ipilimumab

Patients will receive treatment every 3 weeks for 6 cycles of treatment within a course (total of 18 weeks). Ipilimumab (50mg) will be administered IV on Day 1 of Cycles 1, 3, and 5.

Intervention Type: DRUG

CRS-207

Patients will receive treatment every 3 weeks for 6 cycles of treatment within a course (total of 18 weeks). CRS-207 \[1 × 10\^9 colony forming units (CFU) in 100ml NS\] will be administered IV on Day 2 of Cycles 1-6.

Intervention Type: DRUG

Other Intervention Names

CIALIS®; KEYTRUDA®; YERVOY®

Eligibility Criteria

Inclusion Criteria

• Age ≥18 years.
• Have histologically or cytologically proven adenocarcinoma of the pancreas.
• Have previously treated metastatic disease.
• Have radiographic disease progression.
• Patients with the presence of at least one measurable tumor lesion.
• Patient's acceptance to have a tumor biopsy at baseline and on
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Patients must have adequate organ and marrow function defined by study-specified laboratory tests.
• For both Women and Men, must use acceptable form of birth control while on study.
• Ability to understand and willingness to sign a written informed consent document.

Exclusion Criteria

• Known history or evidence of brain metastases.
• Had chemotherapy, radiation, or biological cancer therapy within the last 14 days.
• Have received an investigational agent or device within the last 28 days.
• Had surgery within the last 28 days.
• Expected to require any other form of systemic or localized cancer therapy while on study.
• Have received a vaccine within the last 14 days (7 days for the COVID vaccine) or received a live vaccine within the last 30 days.
• Have received steroids within the last 14 days.
• Use more than 4 g/day of acetaminophen.
• Use of organic nitrates.
• Use of guanylate cyclase (GC) stimulators such as riociguat.
• Consumption of substantial amounts of alcohol (≥5 units/day)
• Use of strong or moderate cytochrome P450 3A4 (CYP3A4) inhibitor or inducer.
• Patients on immunosuppressive agents within the last 7 days
• Known allergy to both penicillin and sulfa.
• Severe hypersensitivity reaction to any monoclonal antibody.
• History of severe hypersensitivity to tadalafil.
• Have implant(s) or device(s) that has not and cannot be easily removed.
• Have artificial joints or implanted medical devices that cannot be easily removed.
• Have any evidence of clinical or radiographic ascites.
• Have significant and/or malignant pleural effusion
• Uncontrolled intercurrent illness.
• Subjects with active, known or suspected autoimmune disease.
• Have a tissue or organ allograft, including corneal allograft.
• Have been diagnosed HIV, Hepatitis B or C positive.
• Is on supplemental home oxygen.
• Has an unhealed surgical wound or ulcer, or a bone fracture considered non-healing.
• Has clinically significant heart disease
• Prior history of non-arterial ischemic optic retinopathy.
• History of significant hypotensive episode requiring hospitalization within 6 months.
• Has insufficient peripheral vein access.
• Is unwilling or unable to follow the study schedule for any reason.
• Is pregnant or breastfeeding.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Lustgarten Foundation

OTHER

Sponsor Role: collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Katherine Bever, MD

Role: PRINCIPAL_INVESTIGATOR

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Medical Institution

Locations

Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

IRB00291762

Identifier Type: OTHER

Identifier Source: secondary_id

5P01CA247886

Identifier Type: NIH

Identifier Source: secondary_id

View Link

J2180

Identifier Type: -

Identifier Source: org_study_id