Resectable Pancreatic Ductal Adenocarcinoma (PDAC)Phase 2NCT03727880
Study of Pembrolizumab With or Without Defactinib Following Chemotherapy as a Neoadjuvant and Adjuvant Treatment for Resectable Pancreatic Ductal Adenocarcinoma
A Phase 2 study testing Pembrolizumab and Defactinib in people with Resectable Pancreatic Ductal Adenocarcinoma (PDAC) and Pancreatic Ductal Adenocarcinoma, run by Lei Zheng at 3 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Resectable Pancreatic Ductal Adenocarcinoma (PDAC), Pancreatic Ductal Adenocarcinoma
- What is being tested?
- Pembrolizumab and Defactinib
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 3 sitesUnited States
- Study dates
- 4 Jun 2019to 15 Jan 2025
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, 21231
Samuel Oschin Cancer Center at Cedars-Sinai
Los Angeles, California, 90048
The University of Texas Health Science Center San Antonio
San Antonio, Texas, 78229
About this study
Official title: 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.
- Being tested
- Pembrolizumab, Defactinib
- 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
- Medical subject headings
- Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabDrug
Also called MK-3475, Keytruda
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.
DefactinibDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Arm A - Pembrolizumab and Defactinib | Experimental | Not described Receives: Drug: Pembrolizumab; Drug: Defactinib |
| Arm B - Pembrolizumab | Experimental | Not described Receives: Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 4 years
Secondary outcomes (3)
Overall Survival (OS)
Number of months until death
Measured: 4 years
Disease Free Survival (DFS)
Number of months until disease recurrence
Measured: 4 years
Number of Participants Experiencing Study Drug-related Toxicities
Number of participants experiencing drug-related adverse events as defined by CTCAE v5.0
Measured: 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Nov 2018
- Study start4 Jun 2019
- Primary completion15 Jan 2025
- Study completion15 Jan 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Resectable Pancreatic Ductal Adenocarcinoma (PDAC)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- Lei Zheng
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC, Verastem, Inc.
- Responsible party
- Sponsor-investigator, Lei Zheng, The University of Texas Health Science Center at San Antonio
- Investigators
- Lei Zheng, MD, Principal investigator, The University of Texas Health Science Center San AntonioArsen Osipov, MD, Study chair, Cedar Sinai
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03727880
- Sponsor's protocol ID
- CTMS 25-0012
- Other IDs
- STUDY00001506
- Status last verified
- Jan 2026
- First submitted
- 31 Oct 2018
- Last updated
- 4 Feb 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
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.
PubMed 37598000
Study at a glance
From the registry record, last updated by the sponsor on 4 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT03727880
- Acronym / sponsor ID
- CTMS 25-0012
- Keywords
- Pembrolizumab, Defactinib, Immunotherapy, Anti-PD-1, Antibody, PD-L1, Pancreatic cancer, Neoadjuvant chemotherapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- Lei ZhengUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC, Verastem, Inc.
- Study start
- 4 Jun 2019 (actual)
- Primary completion
- 15 Jan 2025 (actual)
- Study completion
- 15 Jan 2025 (actual)
- First posted
- 1 Nov 2018 (actual)
- Results
- Posted 4 Feb 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A - Pembrolizumab and Defactinib | Experimental | Drug: Pembrolizumab, Drug: Defactinib |
| Arm B - Pembrolizumab | Experimental | Drug: Pembrolizumab |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (16 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PembrolizumabAlso: MK-3475, KeytrudaFollowing 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. | Drug | Arm A - Pembrolizumab and Defactinib, Arm B - Pembrolizumab |
| DefactinibFollowing 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. | Drug | Arm A - Pembrolizumab and Defactinib |
Primary outcome
Pathologic Complete Response (pCR) Rate
Time frame: 4 years
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).
3 secondary outcomes
Overall Survival (OS)
Time frame: 4 years
Disease Free Survival (DFS)
Time frame: 4 years
Number of Participants Experiencing Study Drug-related Toxicities
Time frame: 4 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Feb 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37598000Fard 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lei Zheng, MD principal investigator
The University of Texas Health Science Center San Antonio
Arsen Osipov, MD study chair
Cedar Sinai
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pembrolizumab and Defactinib in people with Resectable Pancreatic Ductal Adenocarcinoma (PDAC) and Pancreatic Ductal Adenocarcinoma, run by Lei Zheng at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Feb 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pathologic Complete Response (pCR) Rate (time frame: 4 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03727880, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Feb 2026.