A Pilot Study to Assess Changes in Tumor Biology Following Second-line Treatment With Pembrolizumab Plus Lenvatinib in Patients With Advanced Pancreatic Ductal Adenocarcinoma

This is a clinical research study to learn if pembrolizumab in combination with lenvatinib can help to control pancreatic ductal adenocarcinoma.

Inclusion Criteria: In order to be eligible for participation in this trial, the patient must: 1. Have histologically or cytologically confirmed diagnosis of metastatic pancreatic adenocarcinoma based on pathology report 2. Have received at least one prior regimen of therapy for metastatic disease. May have received an unlimited number of treatments in the neoadjuvant or adjuvant setting prior to the appearance of metastatic disease. 3. Be willing and able to provide written informed consent for the trial. 4. Be 18 years of age on day of signing informed consent. 5. Have measurable disease based on RECIST 1.1. Target lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions. 6. Have documented objective radiographic progression on or after stopping treatment with first-line therapy. Note: the same image acquisition and processing parameters should be used throughout the study for a given patient. 7. Be willing to provide tissue from a newly obtained core- or excisional biopsy of a tumor lesion from a metastatic site. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on Day 1. Patients for whom newly-obtained samples cannot be provided (e.g. inaccessible or patient-safety concern) may submit an archived specimen only upon agreement from Merck. The specimen must be from a biopsy site that would be accessible for at least one subsequent biopsy after initiation on the trial. 8. Has the ability to swallow and retain oral medication. 9. Has adequately controlled BP with or without antihypertensive medications, defined as BP ≤150/90 mm Hg with no change in antihypertensive medications within 1 week prior to randomization 10. Have a performance status of 0 or 1 on the ECOG performance status scale within 5 days of starting study treatment. 11. Have a predicted life expectancy of greater than 3 months. 12. Demonstrate adequate organ function as defined in Table 2. All screening labs should be performed within 10 days of treatment initiation. 13. Male subjects are eligible to participate if they agree to the following during the intervention period and for at least 30 days after the last dose of lenvatinib * Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent OR * Must agree to use contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause \[Appendix 5\]) as detailed below: * Agree to use a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a WOCBP who is not currently pregnant. Note: Men with a pregnant or breastfeeding partner must agree to remain abstinent from penile-vaginal intercourse or use a male condom during each episode of penile-vaginal penetration. Please note that 30 days after lenvatinib is stopped, if the subject is on pembrolizumab only, no male contraception measures are needed. 14. A female subject is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: * Is not a WOCBP OR * Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of \480 ms. 29. Has clinically significant cardiovascular disease within 12 months from first dose of study intervention, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability. Note: Medically controlled arrhythmia would be permitted. 30. Has a history of arterial thromboembolism within 12 months of start of study drug.