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

Phase 2

Active, not recruiting

Conditions: Pancreatic Cancer

Interventions: Drug: Tadalafil
Drug: Pembrolizumab
Drug: Ipilimumab
Drug: CRS-207

Registration Number: NCT05014776

Lead Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: ACTIVE_NOT_RECRUITING

Sex: All

Target Recruitment: 17

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Arm A - Tadalafil, Pembrolizumab, Ipilimumab, CRS-207	Tadalafil	-
Arm A - Tadalafil, Pembrolizumab, Ipilimumab, CRS-207	Pembrolizumab	-
Arm A - Tadalafil, Pembrolizumab, Ipilimumab, CRS-207	Ipilimumab	-
Arm A - Tadalafil, Pembrolizumab, Ipilimumab, CRS-207	CRS-207	-

Primary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR) Using Response Evaluation Criteria for Solid Tumors (RECIST 1.1)	9 months	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.

Secondary Outcome Measures