Study Of Pembrolizumab With Or Without Defactinib Following Chemotherapy As A Neoadjuvant And Adjuvant Treatment For Resectable Pancreatic Ductal Adenocarcinoma

Study Overview

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

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.

N/A

Resectable Pancreatic Ductal Adenocarcinoma (PDAC)
Pancreatic Ductal Adenocarcinoma

DRUG: Pembrolizumab
DRUG: Defactinib

CTMS 25-0012
STUDY00001506 (OTHER Identifier) (OTHER: UTHSCSA IRB)

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 2018-10-31	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2025-07-31
First Submitted that Met QC Criteria 2018-10-31	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2025-08-05
First Posted (ACTUAL) 2018-11-01	Results First Posted N/A	Last Verified 2025-05

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:
Randomized

Interventional Model:
Parallel

Masking:
None

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, 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, subject
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,

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,

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, subject

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,

Primary Outcome Measures	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	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

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.
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.

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.

Collaborators and Investigators

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

Merck Sharp & Dohme LLC
Verastem, Inc.

Investigators

PRINCIPAL_INVESTIGATOR: Lei Zheng, MD, The University of Texas Health Science Center San Antonio

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

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.

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