Pembrolizumab +/− Defactinib for Pancreatic Cancer

Recruiting at 2 trial locations

Overseen By Colleen Apostol, RN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: The University of Texas Health Science Center at San Antonio

Must not be taking: Immunosuppressants, Anti-PD-1, FAK inhibitors

Disqualifiers: Pregnancy, Active infection, Autoimmune, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

36 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you've used immunosuppressive medications within 7 days before the study or if you have an active infection requiring treatment. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Pembrolizumab for pancreatic cancer?

Pembrolizumab has shown some promise in treating pancreatic cancer, particularly in patients with specific genetic markers like dMMR (deficient mismatch repair) or high PD-1 expression, where it has been used successfully as maintenance therapy to prevent cancer progression. However, its overall benefit for most pancreatic cancer patients is minimal, and more research is needed to explore its potential in combination with other treatments. ^{1 2 3 4 5}

What safety information is available for Pembrolizumab and Defactinib in humans?

Pembrolizumab, also known as Keytruda, has been associated with some immune-related side effects, including a rare risk of developing type 1 diabetes in 0.2% of cases. Common side effects include fatigue, cough, nausea, rash, and diarrhea, while more serious immune-related reactions can affect the lungs, liver, and thyroid. ^{1 2 6 7 8}

How is the drug pembrolizumab +/− defactinib unique for pancreatic cancer?

Pembrolizumab is a drug that helps the immune system attack cancer cells by blocking a specific pathway (PD-1/PD-L1) that tumors use to hide from immune cells. This trial is exploring its use with or without defactinib, which may enhance its effects, making it a novel approach for pancreatic cancer, a condition with limited effective treatments. ^{2 4 6 8 9}

What is the purpose of this trial?

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.

Research Team

Lei Zheng, MD

Principal Investigator

The University of Texas Health Science Center San Antonio

Eligibility Criteria

Adults over 18 with resectable pancreatic cancer, not previously treated for it, and in good physical condition can join. They must have a specific tumor marker level (CA 19-9 >200) and be able to conceive children only using approved birth control methods. Exclusions include pregnancy, recent other treatments or studies, immune system suppressants within the last week, known allergies to study drugs, active infections or autoimmune diseases.

Inclusion Criteria

My condition can be treated with surgery.

I have pancreatic cancer.

Ability to understand and willingness to sign a written informed consent document

Exclusion Criteria

I have been treated with a FAK inhibitor before.

I have an autoimmune disease treated within the last 2 years.

I have another cancer that is getting worse or needed treatment in the last 2 years.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Chemotherapy

Participants receive standard chemotherapy before surgery

8-12 weeks

Surgery

Participants undergo surgery to remove the pancreatic tumor

1 week

Adjuvant Treatment

Participants receive pembrolizumab with or without defactinib following surgery

12-24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 years

Treatment Details

Interventions

• Defactinib
• Pembrolizumab

Trial Overview The trial is testing pembrolizumab (a PD-1 antibody) with or without defactinib (a FAK inhibitor), alongside standard chemotherapy before and after surgery for high-risk pancreatic cancer patients. It aims to see if targeting FAK can enhance the body's immune response against cancer when combined with PD-1 inhibition.

Participant Groups

Group I: Arm B - Pembrolizumab Experimental Treatment 1 Intervention

Group II: Arm A - Pembrolizumab and Defactinib Experimental Treatment 2 Interventions

Who Is Running the Clinical Trial?

The University of Texas Health Science Center at San Antonio

Lead Sponsor

Trials

486

Recruited

92,500+

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Lead Sponsor

Trials

578

Recruited

33,600+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Verastem, Inc.

Industry Sponsor

Trials

42

Recruited

2,800+

Findings from Research

In a study of 41 pancreas cancer patients treated with pembrolizumab, the median overall survival was 7.2 months, which is considered favorable compared to the benchmark of over 4 months.

Patients with specific genetic markers (dMMR, MSI-H, TMB-H, or Lynch syndrome) had a significantly lower risk of death, indicating that these biomarkers may help identify patients who could benefit more from pembrolizumab treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab near the end of life in patients with metastatic pancreatic cancer: a multi-site consecutive series to examine survival and patient treatment burden. Storandt, MH., Tran, N., Martin, N., et al.[2023]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

Pembrolizumab, an FDA-approved treatment for advanced pancreatic cancer, showed promising results as a maintenance therapy in three patients with different stages of pancreatic ductal adenocarcinoma (PDAC), with one patient remaining progression-free for 4 years after treatment.

The cases suggest that pembrolizumab may be effective for patients with dMMR mutations or PD-1 expression, indicating a potential role in reducing recurrence and prolonging survival when used alone or in combination with other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survival Benefit of Pembrolizumab for Patients With Pancreatic Adenocarcinoma: A Case Series. Zhao, L., Singh, V., Ricca, A., et al.[2022]

Pembrolizumab is a monoclonal antibody that effectively blocks the PD-1 receptor on T cells, enhancing their ability to attack cancer cells, particularly in melanoma patients.

In a Phase I study involving 411 patients, pembrolizumab demonstrated high durable response rates with minimal toxicity, indicating its potential as a safe and effective treatment option for melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. Hersey, P., Gowrishankar, K.[2017]

A study of 112 patients with non-small cell lung cancer (NSCLC) found that EBUS TBNA is effective for obtaining samples suitable for PD-L1 testing, with 82% of samples adequate for all ancillary tests.

The results showed a high satisfaction rate for PD-L1 expression testing, with 86% of cases yielding satisfactory results and 32% of patients exhibiting high PD-L1 expression levels (>50%), which is important for treatment decisions with pembrolizumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical performance of endobronchial ultrasound-guided transbronchial needle aspiration for assessing programmed death ligand-1 expression in nonsmall cell lung cancer. Biswas, A., Leon, ME., Drew, P., et al.[2018]

Pembrolizumab, a PD-1 inhibitor used in cancer treatment, can lead to rare but serious immune-related adverse events, including type 1 diabetes mellitus, occurring in about 0.2% of cases.

A review of 42 cases revealed that patients may develop diabetic ketoacidosis during treatment, highlighting the need for blood glucose monitoring and awareness of this potential side effect among clinicians.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. Clotman, K., Janssens, K., Specenier, P., et al.[2022]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

A systematic review of four trials involving 3425 patients found that lower doses of pembrolizumab (2 mg/kg every 3 weeks) are equally effective as higher doses (10 mg/kg) in treating advanced melanoma and non-small-cell lung cancer (NSCLC).

The safety profile of pembrolizumab was similar across different doses, suggesting that the lower dose may be sufficient for routine treatment without compromising efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of efficacy and safety of different pembrolizumab dose/schedules in treatment of non-small-cell lung cancer and melanoma: a systematic review. Abdel-Rahman, O.[2018]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Pembrolizumab near the end of life in patients with metastatic pancreatic cancer: a multi-site consecutive series to examine survival and patient treatment burden. [2023]

2. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

3. Canada pubmed.ncbi.nlm.nih.gov

Survival Benefit of Pembrolizumab for Patients With Pancreatic Adenocarcinoma: A Case Series. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. [2017]

5. United States pubmed.ncbi.nlm.nih.gov

Clinical performance of endobronchial ultrasound-guided transbronchial needle aspiration for assessing programmed death ligand-1 expression in nonsmall cell lung cancer. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]

9. England pubmed.ncbi.nlm.nih.gov

Evaluation of efficacy and safety of different pembrolizumab dose/schedules in treatment of non-small-cell lung cancer and melanoma: a systematic review. [2018]