Pembrolizumab for Cervical Dysplasia

Overseen By Rosleen Mala

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Jonsson Comprehensive Cancer Center

Must not be taking: Immunosuppressants, Steroids, Live vaccines, others

Disqualifiers: Pregnancy, Autoimmune disease, HIV, 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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 24 weeks

25 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of pembrolizumab, an immunotherapy drug, against cervical intraepithelial neoplasia (CIN), a pre-cancerous condition affecting the cervix. Pembrolizumab may help the immune system combat cancer cells and prevent their growth and spread. Women diagnosed with CIN grade 2 or 3 or carcinoma in situ (early-stage cervical cancer that hasn't spread) and who haven't undergone surgery might be suitable for this trial. Participants will receive the drug through an IV every six weeks for 24 weeks. As a Phase 2 trial, this research focuses on evaluating 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. However, if you are on certain treatments like systemic steroids or immunosuppressive therapy, you may need to stop them before starting the trial. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that pembrolizumab is likely to be safe for humans?

Research has shown that pembrolizumab, a treatment that aids the immune system in fighting cancer, presents some safety concerns. A recent study on its use for cervical cancer found that 21% of patients experienced serious side effects, known as grade 3 adverse events. These more severe side effects might require medical care. Considering these findings is crucial when deciding to join a trial with pembrolizumab, as the treatment can be effective but may also have significant side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for cervical dysplasia?

Pembrolizumab is unique because it harnesses the power of the immune system to fight cervical dysplasia, unlike traditional treatments such as surgery or cryotherapy. It works as a checkpoint inhibitor, blocking the PD-1 pathway, which can help the immune system recognize and attack abnormal cells more effectively. Researchers are excited about pembrolizumab because it offers a targeted, non-invasive approach that could potentially reduce the need for more aggressive treatments and improve patient outcomes.

What evidence suggests that pembrolizumab might be an effective treatment for cervical dysplasia?

Research has shown that pembrolizumab holds promise for treating cervical cancer. Studies have found it extends survival in patients with persistent, recurrent, or metastatic cervical cancer. Patients with high levels of the protein PD-L1 in their cancer cells appear to benefit more from this treatment. Pembrolizumab also proves effective when combined with other treatments like chemotherapy. These findings suggest that pembrolizumab, which participants in this trial will receive, could help combat cervical intraepithelial neoplasia by enhancing the immune system's ability to attack cancer cells. ^{1 6 7 8 9}

Who Is on the Research Team?

John A. Glaspy, MD

Principal Investigator

UCLA / Jonsson Comprehensive Cancer Center

Are You a Good Fit for This Trial?

Women over 21 with a confirmed diagnosis of CIN grade 2 or 3, or carcinoma in situ without invasive components. Participants must not be pregnant, breastfeeding, and should agree to contraceptive guidance post-treatment. They need normal organ function, an ECOG status of 0-1, and willingness to undergo biopsies and surgical procedures if not contraindicated.

Inclusion Criteria

I have provided a recent or past biopsy sample of my tumor that was not treated with radiation.

I am a woman over 21 with a confirmed diagnosis of CIN 2/3 or carcinoma in situ.

The participant (or legally acceptable representative if applicable) provides written informed consent for the trial

Exclusion Criteria

Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment

Has a known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known active hepatitis C virus (defined as HCV ribonucleic acid [RNA] [qualitative] is detected) infection. Note: no testing for hepatitis B and hepatitis C is required unless mandated by local health authority

A WOCBP who has a positive urine pregnancy test within 72 hours prior to allocation. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab intravenously over 30 minutes on day 1, with treatment repeating every 6 weeks for 4 cycles

24 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-6 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab

Trial Overview

The trial is testing the effectiveness of pembrolizumab on cervical intraepithelial neoplasia (CIN). Pembrolizumab is a monoclonal antibody that may boost the immune system's ability to fight cancer by preventing tumor growth and spread.

How Is the Trial Designed?

Group I: Treatment (pembrolizumab) Experimental Treatment 1 Intervention

Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 6 weeks for 4 cycles (24 weeks).

Pembrolizumab is already approved in United States, European Union, United Kingdom for the following indications:

Approved in United States as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in European Union as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in United Kingdom as KEYTRUDA for:

• Untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1

Who Is Running the Clinical Trial?

Jonsson Comprehensive Cancer Center

Lead Sponsor

Trials

373

Recruited

35,200+

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 is an FDA-approved immune checkpoint inhibitor specifically targeting the PD-1 receptor, showing promise in treating recurrent or metastatic cervical cancer in patients whose tumors express PD-L1.

Clinical studies suggest that pembrolizumab could become a preferred treatment option for advanced cervical cancer, but further research is needed to identify which patients will benefit the most from this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for advanced cervical cancer: safety and efficacy. De Felice, F., Giudice, E., Bolomini, G., et al.[2021]

The KEYNOTE-826 trial demonstrated that adding pembrolizumab to chemotherapy significantly improved overall survival (OS) in women with persistent, recurrent, or metastatic cervical cancer, with hazard ratios favoring pembrolizumab across various patient subgroups.

Pembrolizumab also enhanced progression-free survival (PFS) in all subgroups analyzed, indicating its efficacy in combination with chemotherapy, regardless of prior treatment history or tumor type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab or Placebo Plus Chemotherapy With or Without Bevacizumab for Persistent, Recurrent, or Metastatic Cervical Cancer: Subgroup Analyses from the KEYNOTE-826 Randomized Clinical Trial. Tewari, KS., Colombo, N., Monk, BJ., et al.[2023]

Pembrolizumab, an antibody targeting the PD-1 receptor, has shown limited effectiveness as a standalone treatment for recurrent and/or metastatic cervical cancer in the general patient population, but it has received accelerated approval from the FDA for patients with PD-L1-expressing tumors due to its potential for durable responses.

Future research is focusing on combining pembrolizumab with other therapies like chemotherapy and radiotherapy, and identifying additional biomarkers beyond PD-L1 expression will be crucial to better select patients who are likely to benefit from this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of cervical cancer. Marret, G., Borcoman, E., Le Tourneau, C.[2020]

In a phase 3 trial involving 548 patients with PD-L1-positive metastatic cervical cancer, adding pembrolizumab to chemotherapy significantly improved progression-free survival, with a median of 10.4 months compared to 8.2 months for the placebo group.

Overall survival at 24 months was also better in the pembrolizumab group (53.0%) compared to the placebo group (41.7%), indicating that pembrolizumab enhances the effectiveness of chemotherapy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for Persistent, Recurrent, or Metastatic Cervical Cancer. Colombo, N., Dubot, C., Lorusso, D., et al.[2023]

Pembrolizumab, a PD-1 inhibitor, has been approved by the FDA as a second-line treatment for recurrent or metastatic cervical cancer in patients with a PD-L1 combined positive score of at least 1.

In a phase II trial, pembrolizumab demonstrated an objective response rate of 14.3%, indicating its potential efficacy in this specific patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab OK'd for Cervical Cancer. [2019]

In a study of 11 heavily pretreated patients with recurrent cervical cancer, pembrolizumab demonstrated a clinical benefit rate of 36%, with 18% of patients showing a partial response and another 18% achieving disease stabilization.

The treatment was generally well tolerated, with a median overall survival of 26 weeks and a 6-month survival rate of 65%, indicating promising efficacy and manageable safety in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activity of Pembrolizumab in Recurrent Cervical Cancer: Case Series and Review of Published Data. Kranawetter, M., Röhrich, S., Müllauer, L., et al.[2019]

Cervical cancer remains a significant global health issue, particularly for patients with advanced disease, where current treatment options have not improved prognosis significantly.

Pembrolizumab, a PD-1 blocking therapy, is the only approved immunotherapy for cervical cancer and shows promise for personalized treatment strategies, with ongoing trials exploring its expanded clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting the PD-1 Axis with Pembrolizumab for Recurrent or Metastatic Cancer of the Uterine Cervix: A Brief Update. Verhoeven, Y., Quatannens, D., Trinh, XB., et al.[2021]

In a study of 117 patients with recurrent cervical cancer treated with pembrolizumab, the overall response rate was 9.4%, with a higher response rate of 18.9% in patients with better performance status (ECOG ≤1).

While pembrolizumab demonstrated modest antitumor activity, safety concerns were noted, with 47% of patients experiencing adverse events, including two treatment-related deaths, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Experience of Pembrolizumab Monotherapy in Patients with Recurrent or Persistent Cervical Cancer: A Korean Multi-Center Retrospective Study (KGOG1041). Choi, MC., Kim, YM., Lee, JW., et al.[2020]

In a study of 4 patients with advanced cervical cancer treated with pembrolizumab, all patients tolerated the treatment well, with one patient achieving a remarkable 21-month progression-free survival, indicating potential efficacy of this PD-1 inhibitor.

Biomarker analysis revealed that patients with a combined positive score (CPS) for PD-L1 of ≥1 and specific somatic mutations, such as in PIK3CA, may benefit from pembrolizumab, suggesting that further research into predictive biomarkers could enhance patient selection for this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor molecular profiling of responders and non-responders following pembrolizumab monotherapy in chemotherapy resistant advanced cervical cancer. Ngoi, NYL., Heong, V., Lee, XW., et al.[2020]

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

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