Cabozantinib + Pembrolizumab for Metastatic Pancreatic Cancer

Overseen By Joseph Kim, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Joseph Kim

Must not be taking: Steroids

Disqualifiers: Immunodeficiency, Cardiovascular disease, Hypertension, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how two drugs, cabozantinib (Cabometyx) and pembrolizumab (KEYTRUDA), work together to treat metastatic pancreatic cancer that has spread. The main goal is to determine if these drugs can slow or stop cancer growth after other treatments have failed. Individuals with pancreatic ductal adenocarcinoma who have not responded well to previous treatments may be suitable candidates. As a Phase 2 trial, this study measures the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop my current medications for the trial?

The trial requires that you stop any chemotherapy, radiation, or systemic anti-cancer therapies at least 4 weeks before starting the study treatment. If you are on chronic steroid therapy, you may not be eligible to participate.

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

Research shows that cabozantinib and pembrolizumab have been tested together for treating different types of cancer. In these studies, many participants tolerated the drugs well, though some side effects occurred. Common side effects include fatigue, diarrhea, and changes in blood pressure.

Cabozantinib is already approved in Europe for other types of tumors, indicating a certain level of safety. Pembrolizumab has also been used for various cancers, offering additional safety information from other uses, which is reassuring.

However, every treatment carries risks. Discussing these with the research team is crucial to understand what they might mean for you. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of cabozantinib and pembrolizumab for metastatic pancreatic cancer because it offers a novel approach compared to standard treatments like chemotherapy. Unlike traditional therapies that primarily target rapidly dividing cancer cells, cabozantinib inhibits specific proteins involved in cancer cell growth and blood vessel formation, potentially cutting off the tumor's nutrient supply. Pembrolizumab, on the other hand, is an immune checkpoint inhibitor that helps the immune system recognize and attack cancer cells more effectively. This dual-action strategy not only targets the cancer directly but also empowers the body's own defenses, offering hope for improved outcomes.

What evidence suggests that cabozantinib and pembrolizumab could be effective for metastatic pancreatic cancer?

Research has shown that combining cabozantinib and pembrolizumab may help treat metastatic pancreatic cancer. In one study, 65.8% of patients experienced tumor shrinkage with this combination. Another study found that patients lived for about 10.45 months without their cancer worsening, which is promising. Previously, patients treated with pembrolizumab alone had a median survival of 7.2 months, which was considered good. These results suggest that the combination treatment, which participants in this trial will receive, could effectively manage this challenging condition. ^{1 2 6 7 8}

Who Is on the Research Team?

Josepoh Kim, MD

Principal Investigator

University of Kentucky

Are You a Good Fit for This Trial?

This trial is for adults with metastatic pancreatic adenocarcinoma who've seen their cancer progress or didn't tolerate previous treatments. They must have good organ function and not have had recent radiation, other cancer therapies within the last 4 weeks, uncontrolled high blood pressure, trouble swallowing pills, serious heart disease, or be immunocompromised.

Inclusion Criteria

My pancreatic cancer has worsened or I couldn't tolerate previous treatments.

I have been diagnosed with pancreatic cancer.

My organs are functioning well.

Exclusion Criteria

I have a serious heart condition.

I cannot swallow pills.

I have an autoimmune disease or am on long-term steroids.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive cabozantinib and pembrolizumab for the treatment of metastatic pancreatic adenocarcinoma

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Cabozantinib
• Pembrolizumab

Trial Overview The study tests cabozantinib and pembrolizumab in patients with advanced pancreatic cancer. It aims to see how well these drugs work together against this type of cancer after standard treatments haven't worked.

How Is the Trial Designed?

Group I: Cabozantinib and pembrolizumab Experimental Treatment 2 Interventions

Cabozantinib is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Cabometyx for:

• Renal cell carcinoma
• Hepatocellular carcinoma

Approved in United States as Cabometyx for:

• Renal cell carcinoma
• Hepatocellular carcinoma

Approved in Canada as Cabometyx for:

• Renal cell carcinoma
• Hepatocellular carcinoma

Approved in Japan as Cabometyx for:

• Renal cell carcinoma

Who Is Running the Clinical Trial?

Joseph Kim

Lead Sponsor

Trials

2

Recruited

40+

Exelixis

Industry Sponsor

Trials

126

Recruited

20,500+

Michael M. Morrissey

Exelixis

Chief Executive Officer since 2010

PhD in Chemistry from Harvard University, BSc in Chemistry from the University of Wisconsin

Vicki L. Goodman

Exelixis

Chief Medical Officer since 2022

MD

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

Published Research Related to This Trial

Pembrolizumab (Keytruda) has been approved by the FDA for treating high-risk, non-muscle invasive bladder cancer (NMIBC) in patients who are unresponsive to BCG therapy and are either ineligible for or have opted not to undergo cystectomy.

This approval specifically targets patients with carcinoma in situ (CIS) with or without papillary tumors, highlighting its role as a treatment option for those with limited surgical options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approves Pembrolizumab for BCG-Unresponsive NMIBC. Wright, KM.[2021]

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]

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 (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 (Keytruda) is an approved treatment for metastatic or locally advanced esophageal and gastroesophageal junction cancer, indicating its efficacy in targeting these specific cancer types.

It is used in combination with platinum- and fluoropyrimidine-based chemotherapy, suggesting a synergistic approach to enhance treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Approved for Esophageal or Gastroesophageal Cancer. Aschenbrenner, DS.[2023]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05052723

Cabozantinib and Pembrolizumab in Metastatic Pancreas This study aims to evaluate cabozantinib and pembrolizumab for the treatment of metastatic pancreatic adenocarcinoma. Official Title. Phase II Clinical Trial ...

2. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2021-10973

Cabozantinib and Pembrolizumab for the Treatment of ... This phase II trial tests whether cabozantinib and pembrolizumab works to shrink tumors in patients with pancreatic cancer that has spread to other places ...

3. withpower.com withpower.com/trial/phase-3-pancreatic-neoplasms-8-2021-ed889

Cabozantinib + Pembrolizumab for Metastatic Pancreatic ... 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 ...

4. targetedonc.com targetedonc.com/view/pembrolizumab-cabozantinib-shows-encouraging-preliminary-efficacy-in-mrcc

Pembrolizumab/Cabozantinib Shows Encouraging ... Pembrolizumab plus cabozantinib showed promising activity with an objective response rate of 65.8%, median progression-free survival of 10.45 months, and ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.3_suppl.315

Phase 2 study of cabozantinib (Cabo) and pembrolizumab ... The primary endpoint was met with n=6 pts having PFS>6mo. After a median follow-up of 31.4mo (range 3.3-42.5), PFS-6 is 22.2% (95% CI 9.0-39.0).

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2021.39.15_suppl.4544

Phase I/II trial of pembrolizumab and cabozantinib in the ... We now report the objective response rate (ORR), progression free survival (PFS), overall survival (OS), and toxicity of patients in the phase ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10205145/

Pembrolizumab and cabozantinib in recurrent metastatic head ... Pembrolizumab and cabozantinib in recurrent metastatic head and neck squamous cell carcinoma: a phase 2 trial

8. onclive.com onclive.com/view/cabozantinib-wins-eu-approval-for-previously-treated-advanced-pancreatic-and-extra-pancreatic-neuroendocrine-tumors

Cabozantinib Wins EU Approval for Previously Treated ... The European Commission has approved cabozantinib for the treatment of patients with pancreatic and extrapancreatic neuroendocrine tumors.