Study Of CRS-207, Pembrolizumab, Ipilimumab, And Tadalafil In Metastatic Pancreatic Cancer

Study Overview

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

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.

N/A

Pancreatic Cancer

DRUG: Tadalafil
DRUG: Pembrolizumab
DRUG: Ipilimumab
DRUG: CRS-207

J2180
IRB00291762 (OTHER Identifier) (OTHER: Johns Hopkins Medical Institution)
5P01CA247886 (U.S. NIH Grant/Contract)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2021-08-13	Results First Submitted 2025-01-08	Last Update Submitted that met QC Criteria 2025-04-07
First Submitted that Met QC Criteria 2021-08-13	Results First Submitted that Met QC Criteria 2025-01-08	Last Update Posted (ACTUAL) 2025-04-16
First Posted (ACTUAL) 2021-08-20	Results First Posted 2025-01-30	Last Verified 2025-04

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Arm A - Tadalafil, Pembrolizumab, Ipilimumab, CRS-207	DRUG: 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. 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. 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. 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.

Participant Group/Arm

Intervention/Treatment

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

DRUG: 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.

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.

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.

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.

Primary Outcome Measures	Measure Description	Time Frame
Objective Response Rate (ORR) Using Response Evaluation Criteria for Solid Tumors (RECIST 1.1)	Objective Response Rate (ORR) is defined as the number of patients achieving a complete response (CR) or partial response (PR) based on RECIST 1.1 criteria. CR = disappearance of all target lesions, PR is =>30% decrease in sum of diameters of target lesions. Participants who discontinue due to toxicity or clinical progression prior to post-baseline tumor assessments will be considered as non-responders. Participants who discontinue for other reasons prior to their first dose of study drug will not included in the analysis.	9 months

Secondary Outcome Measures	Measure Description	Time Frame
Number of Participants Experiencing Drug-Related Adverse Events (AEs) Requiring Treatment Discontinuation		9 months

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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.

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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Lustgarten Foundation
National Cancer Institute (NCI)

Investigators

PRINCIPAL_INVESTIGATOR: Katherine Bever, MD, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Medical Institution

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

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