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

NCT03727880 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: CTMS 25-0012STUDY00001506
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Resectable Pancreatic Ductal Adenocarcinoma (PDAC); Pancreatic Ductal Adenocarcinoma

Keywords

Pembrolizumab; Defactinib; Immunotherapy; Anti-PD-1; Antibody; PD-L1; Pancreatic cancer; Neoadjuvant chemotherapy; Adjuvant chemotherapy; PDAC - Pancreatic Ductal Adenocarcinoma; FAK (focal adhesion kinase) inhibitor; Resectable Pancreatic Adenocarcinoma; High Risk Resectable Pancreatic Cancer; Tumor microenvironment; CA 19-9; Surgery; Pancreatectomy

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Overall Survival (OS)

  4 years

• Disease Free Survival (DFS)

  4 years

• Number of Participants Experiencing Study Drug-related Toxicities

  4 years

Study Arms (2)

Arm A - Pembrolizumab and Defactinib

EXPERIMENTAL

Drug: Pembrolizumab; Drug: Defactinib

Arm B - Pembrolizumab

EXPERIMENTAL

Drug: Pembrolizumab

Interventions

Pembrolizumab DRUG

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.

Also known as: MK-3475, Keytruda

Arm A - Pembrolizumab and Defactinib; Arm B - Pembrolizumab

Defactinib DRUG

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.

Arm A - Pembrolizumab and Defactinib

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Lei Zheng: lead
• Merck Sharp & Dohme LLC: collaborator
• Verastem, Inc.: collaborator

Study Sites (3)

Samuel Oschin Cancer Center at Cedars-Sinai

Los Angeles, California, 90048, United States

Location

Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21231, United States

Location

The University of Texas Health Science Center San Antonio

San Antonio, Texas, 78229, United States

Location

Related Publications (1)

• 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.

  PMID: 37598000 DERIVED

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

pembrolizumab; defactinib

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Results Point of Contact

• Title: Arsen Osipov, MD
• Organization: Cedars Sinai

arsen.osipov@cshs.org

310-423-6313

Study Officials

• Lei Zheng, MD

  The University of Texas Health Science Center San Antonio

  PRINCIPAL INVESTIGATOR

• Arsen Osipov, MD

  Cedar Sinai

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Executive Director of University of Texas Health Science Center at San Antonio Cancer Center

Study Record Dates

• First Submitted: October 31, 2018
• First Posted: November 1, 2018
• Study Start: June 4, 2019
• Primary Completion: January 15, 2025
• Study Completion: January 15, 2025
• Last Updated: February 4, 2026
• Results First Posted: February 4, 2026

Record last verified: 2026-01

Locations

US (3)