Study of Pembrolizumab With or Without Defactinib Following Chemotherapy as a Neoadjuvant and Adjuvant Treatment for Resectable Pancreatic Ductal Adenocarcinoma

A Randomized Phase II Study of Pembrolizumab With or Without Defactinib, a Focal Adhesion Kinase Inhibitor Following Chemotherapy as a Neoadjuvant and Adjuvant Treatment for Resectable Pancreatic Ductal Adenocarcinoma (PDAC)

This study will test the effectiveness (anti-tumor activity), safety, and ability to increase the body's immune system to fight pancreatic cancer by combining standard chemotherapy before and after surgery, with study drug PD-1 antibody, pembrolizumab, with and without study drug, focal adhesion kinase inhibitor (FAK), defactinib, in people with "high risk" resectable (surgically removable) pancreatic cancer. The purpose of this study is to evaluate if reprograming the tumor microenvironment by targeting FAK following chemotherapy can potentiate anti-programmed death-1 (PD-1) antibody.

Study Overview

• Status: Completed
• Conditions: Pancreatic Ductal Adenocarcinoma; Resectable Pancreatic Ductal Adenocarcinoma (PDAC)
• Intervention / Treatment: Drug: Pembrolizumab; Drug: Defactinib

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90048
      • Samuel Oschin Cancer Center at Cedars-Sinai
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Sidney Kimmel Comprehensive Cancer Center
  • Texas
    • San Antonio, Texas, United States, 78229
      • The University of Texas Health Science Center San Antonio

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥18 years.
• Has pancreatic ductal adenocarcinoma
• Has resectable disease at the time of diagnosis
• Has not received any systemic therapy for pancreatic ductal adenocarcinoma
• Has stage ≤ IIb disease at time of diagnosis and enrollment
• Elevated tumor marker, CA (carbohydrate antigen) 19-9 >200
• ECOG performance status 0 or 1
• Patient must have adequate organ function defined by the study-specified laboratory tests.
• Must use acceptable form of birth control while on study.
• Ability to understand and willingness to sign a written informed consent document.

Exclusion Criteria:

Patients who have received any prior chemotherapy, radiotherapy or investigational agents for pancreatic cancer.

• Patients who have received prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4, or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137).
• Has received prior therapy with FAK inhibitor.
• Woman who are pregnant or breastfeeding.
• Have received a live vaccine or live-attenuated vaccine within 30 days prior to study drug.
• Is currently or has participated in another investigational study within 4 weeks prior to receiving study drug.
• History or current use of immunosuppressive medications within 7 days prior to study medications.
• Has a known additional malignancy that is progressing or has required active treatment within the past 2 years or that is expected to require active treatment within two years.
• Has active autoimmune disease that has required systemic treatment in the past 2 years.
• Has a history of (non-infectious) pneumonitis/interstitial lung disease or current pneumonitis.
• Has an active infection requiring systemic therapy.
• Infection with HIV or hepatitis B or C.
• Patient with uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Known allergy or hypersensitivity to the study drugs.
• Received any growth factors including, but not limited to, granulocyte-colony stimulating factor (G-CSF), GM-CSF, erythropoietin, within 14 days of study drug administration.
• Has history of any organ transplant, including corneal transplants.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A - Pembrolizumab and Defactinib	Drug: Pembrolizumab; Following standard of care neoadjuvant chemotherapy, subjects will receive two doses of pembrolizumab (200mg) IV 3 weeks apart prior to surgery. After surgery, subjects will receive adjuvant standard of care chemotherapy. Following adjuvant chemotherapy, subjects will receive 8 doses of pembrolizumab (200mg) IV 3 weeks apart.; Other Names: Keytruda; MK-3475; Drug: Defactinib; Following 2 cycles of standard of care neoadjuvant chemotherapy, subjects will receive 400 mg defactinib twice a day up until 2 days preceding their surgery (approximately 6 weeks) during the immunotherapy cycles with pembrolizumab. After surgery, subjects will receive adjuvant standard of care chemotherapy. Following adjuvant chemotherapy, subjects will receive 400mg defactinib twice a day for 24 weeks.
Experimental: Arm B - Pembrolizumab	Drug: Pembrolizumab; Following standard of care neoadjuvant chemotherapy, subjects will receive two doses of pembrolizumab (200mg) IV 3 weeks apart prior to surgery. After surgery, subjects will receive adjuvant standard of care chemotherapy. Following adjuvant chemotherapy, subjects will receive 8 doses of pembrolizumab (200mg) IV 3 weeks apart.; Other Names: Keytruda; MK-3475

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathologic Complete Response (pCR) Rate	Percent of subjects with a pathologic complete response (pCR) per the tumor regression grade scores established by the College of American Pathologist: Grade 0= complete response (no viable cancer cells), Grade 1= near complete response (single cells or rare small groups of cancer cells), Grade 2= partial response (residual tumor with evidence of regression), or Grade 3= no response (extensive residual tumor with no evidence of regression).	4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	Number of months until death	4 years
Disease Free Survival (DFS)	Number of months until disease recurrence	4 years
Number of Participants Experiencing Study Drug-related Toxicities	Number of participants experiencing drug-related adverse events as defined by CTCAE v5.0	4 years

Collaborators and Investigators

• Sponsor: Lei Zheng
• Collaborators: Merck Sharp & Dohme LLC; Verastem, Inc.
• Investigators: Principal Investigator: Lei Zheng, MD, The University of Texas Health Science Center San Antonio; Study Chair: Arsen Osipov, MD, Cedar Sinai

Publications and helpful links

General Publications

• Fard D, Giraudo E, Tamagnone L. Mind the (guidance) signals! Translational relevance of semaphorins, plexins, and neuropilins in pancreatic cancer. Trends Mol Med. 2023 Oct;29(10):817-829. doi: 10.1016/j.molmed.2023.07.009. Epub 2023 Aug 17.

Study record dates

Study Major Dates

• Study Start (Actual): June 4, 2019
• Primary Completion (Actual): January 15, 2025
• Study Completion (Actual): January 15, 2025

Study Registration Dates

• First Submitted: October 31, 2018
• First Submitted That Met QC Criteria: October 31, 2018
• First Posted (Actual): November 1, 2018

Study Record Updates

• Last Update Posted (Actual): February 4, 2026
• Last Update Submitted That Met QC Criteria: January 16, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Surgery; Adjuvant chemotherapy; Immunotherapy; Anti-PD-1; Pancreatectomy; Pembrolizumab; Antibody; PD-L1; Pancreatic cancer; Neoadjuvant chemotherapy; Tumor microenvironment; CA 19-9; Defactinib; PDAC - Pancreatic Ductal Adenocarcinoma; FAK (focal adhesion kinase) inhibitor; Resectable Pancreatic Adenocarcinoma; High Risk Resectable Pancreatic Cancer
• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; pembrolizumab; defactinib
• Other Study ID Numbers: CTMS 25-0012; STUDY00001506 (Other Identifier: UTHSCSA IRB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No