Pembrolizumab +/− Defactinib for Pancreatic Cancer

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new ways to treat pancreatic cancer by testing the combined effectiveness of two drugs, pembrolizumab (an immunotherapy drug) and defactinib. The aim is to enhance the immune system's ability to fight cancer alongside standard chemotherapy before and after surgery. Participants will receive either both drugs or just pembrolizumab to determine which combination is more effective. Individuals with surgically removable pancreatic cancer who have not yet received treatment may be suitable for this trial. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of defactinib and pembrolizumab is generally safe and well-tolerated. Studies have found that using these drugs with gemcitabine, another chemotherapy drug, did not cause major safety issues. Participants in these studies managed the treatment well, and no unexpected side effects occurred.

Pembrolizumab has been used to treat other cancers like melanoma. Some studies suggest it might be helpful for pancreatic cancer and is generally safe for patients. However, it has not been proven safe or effective specifically for pancreatic cancer yet, according to some reports.

Overall, the evidence suggests that these treatments are fairly well-tolerated and do not cause severe side effects. It is always important to discuss any concerns with the healthcare team conducting the study. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Pembrolizumab and Defactinib for pancreatic cancer because these drugs target the disease differently than standard chemotherapy options like gemcitabine and FOLFIRINOX. Pembrolizumab is an immunotherapy that boosts the body's immune system to detect and attack cancer cells by targeting the PD-1 pathway. Defactinib, on the other hand, is a FAK inhibitor that disrupts cancer cell survival and spread by targeting cell adhesion and migration. The combination of these mechanisms offers a novel approach that could potentially enhance treatment effectiveness and provide new hope for patients with pancreatic cancer.

What evidence suggests that this trial's treatments could be effective for pancreatic cancer?

This trial will compare two treatment approaches for pancreatic cancer: one group will receive a combination of pembrolizumab and defactinib, while another group will receive pembrolizumab alone. Studies have shown that combining pembrolizumab with defactinib holds promise for treating pancreatic cancer. Research suggests that defactinib can alter the tumor environment, enhancing its response to pembrolizumab. This combination, along with chemotherapy, has been found safe and may help the immune system fight tumors more effectively. Pembrolizumab alone has shown some success, with patients living over 4 months on average. However, adding defactinib aims to improve these results by better preparing the tumor for an immune response. ^{2 6 7 8 9}

Who Is on the Research Team?

Lei Zheng, MD

Principal Investigator

The University of Texas Health Science Center San Antonio

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Lei Zheng

Lead Sponsor

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+

Published Research Related to This Trial

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]

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 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]

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]

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]

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, 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]

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, 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]

Citations

1. tgh.amegroups.org tgh.amegroups.org/article/view/5943/html

Pancreatic cancer and immune checkpoint inhibitors—still a ... The median overall survival was 4.0 months in the pancreatic cancer subgroup, although it should be noted that the median duration of response was 13.4 months.

2. oncodaily.com oncodaily.com/oncolibrary/immunotherapy-success-rate-for-pancreatic-cancer

Immunotherapy Success Rate for Pancreatic Cancer Across most clinical trials, single-agent checkpoint inhibitors have achieved response rates below 5% (Royal et al., 2010).

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0959804923002010

Efficacy of immune checkpoint inhibitors in microsatellite ... This retrospective analysis suggests that ICIs are effective and well tolerated in patients with MSI/dMMR advanced PDAC.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10272060/

Pembrolizumab near the end of life in patients with ... This multisite study examined consecutive pancreas cancer patients, who received pembrolizumab from 2004 through 2022. Median overall survival of > 4 months ...

5. oncotarget.com oncotarget.com/news/pr/rare-pancreatic-cancer-patients-show-strong-response-to-immunotherapy/

Rare Pancreatic Cancer Patients Show Strong Response ... The median progression-free survival was 12 months, and most patients were still alive at follow-up, with survival rates of 80% at one year and ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02305186

Study Details | NCT02305186 | Safety and Immunological ... Pembrolizumab has been approved for treatment of patients with melanoma but has not been proven to be safe or helpful in patients with pancreatic cancer and is ...

7. onclive.com onclive.com/view/bxcl701-plus-pembrolizumab-is-safe-and-generates-early-antitumor-activity-in-advanced-pdac

BXCL701 Plus Pembrolizumab is Safe and Generates ... Benjamin A. Weinberg, MD, FACP, discusses the potential role of BXCL701 plus pembrolizumab in advanced pancreatic ductal adenocarcinoma.

8. merck.com merck.com/news/five-year-data-for-mercks-keytruda-pembrolizumab-plus-chemotherapy-showed-sustained-survival-benefit-versus-chemotherapy-alone-in-two-studies-for-metastatic-non-small-cell-lung-cancer-nsclc/

Five-Year Data for Merck's KEYTRUDA® (pembrolizumab ... Five-year overall survival rate of 19.4% and 18.4% for KEYTRUDA plus chemotherapy in KEYNOTE-189 and KEYNOTE-407, respectively.

9. aacrjournals.org aacrjournals.org/clincancerres/article/21/19/4286/125563/Phase-I-Study-of-Pembrolizumab-MK-3475-Anti-PD-1

Phase I Study of Pembrolizumab (MK-3475; Anti–PD-1 ... Purpose: This phase I study evaluated the safety, maximum tolerated dose, antitumor activity, and pharmacokinetics and pharmacodynamics of pembrolizumab in ...