PRGN-2009 in Combination With Pembrolizumab Versus Pembrolizumab in Patients With Recurrent or Metastatic Cervical Cancer

Study Overview
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Brief Summary
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This randomized trial will evaluate the efficacy and safety of PRGN-2009 in combination with pembrolizumab compared to pembrolizumab alone in patients with pembrolizumab-resistant recurrent or metastatic cervical cancer.

Detailed Description
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This is a randomized, two-arm study of PRGN-2009 in patients with recurrent or metastatic cervical cancer who are pembrolizumab resistant. Patients meeting all eligibility criteria who consent to participate in the study will be randomized 1:1 to receive a combination of PRGN-2009, plus pembrolizumab, or to receive pembrolizumab alone.

Official Title
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A Randomized, Open-label, Two-arm, Phase 2 Study to Evaluate Efficacy and Safety of PRGN-2009 in Combination With Pembrolizumab Versus Pembrolizumab in Patients With Recurrent or Metastatic Cervical Cancer.

Conditions
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Cervical Cancer, HPV-Related Carcinoma, HPV-Related Malignancy

Intervention / Treatment
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* Biological: PRGN-2009 plus Pembrolizumab
* Drug: Pembrolizumab alone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 years and older. Recurrent or metastatic cervical cancer (histologically or cytologically confirmed) that meets the criteria of pembrolizumab-resistant. Must have been treated with pembrolizumab, either as monotherapy or in combination Patients must have received no more than two prior systemic regimens in the recurrent or metastatic setting Tumors are confirmed positive for PD-L1 and HPV16/18 Measurable disease that can be accurately measured by RECIST v1.1 criteria Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Life expectancy ≥ 12 weeks from the time of enrollment. Must have adequate organ function Negative serum pregnancy test. Women of child-bearing potential (WOCBP) must agree to use adequate contraception prior to study entry and for at least 6 months following completion of study treatment. All patients must have the ability to understand and willingness to sign a written informed consent. Exclusion Criteria: Patients with presence of other active malignancy within 1 year prior to study entry Known Central Nervous System (CNS) disease Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients. Known history of active tuberculosis (TB, Bacillus tuberculosis). Pregnant and lactating women are excluded from this study. Patients with a history of solid organ transplant. Patients currently participating in a study of an investigational agent or have used an investigational device within 4 weeks prior to the first dose of study treatment. Patients, who in the opinion of the investigator, may not be able to comply with the monitoring requirements of the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is an open-label, randomized study.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PRGN-2009 plus Pembrolizumab<br>PRGN-2009 at a dose of 5 x 10^11 PU q3W for 3 administrations, then q6w, plus Pembrolizumab, 400mg q6w | Biological: PRGN-2009 plus Pembrolizumab<br>* Subjects randomized will receive PRGN-2009 (5 x 10^11 PU, subcutaneous (SC) injection) every 3 weeks for three administrations, thereafter subjects will continue to receive PRGN-2009 administrations every 6 weeks. Pembrolizumab will be administered concurrently as intravenous (IV) infusion (400 mg) every 6 weeks.<br>|
| Active Comparator: Pembrolizumab alone<br>Pembrolizumab, 400mg q6w | Drug: Pembrolizumab alone<br>* Subjects randomized will receive IV infusion of pembrolizumab (400 mg) administered every 6 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the Objective Response Rate (ORR) following treatment with PRGN-2009 in combination with pembrolizumab or pembrolizumab alone in patients with pembrolizumab-resistant recurrent or metastatic cervical cancer. | The ORR will be calculated as the combination of subjects achieving a complete response or a partial response per RECIST v1.1. ORR will be calculated and presented with 2-sided 95% confidence interval. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of PRGN-2009 in combination with pembrolizumab or pembrolizumab alone | Systemic toxicity will be assessed through the capture of Treatment Emergent Adverse Events ( TEAEs). The severity of the TEAEs will be assessed using the Common Terminology Criteria for Adverse Events (CTCAE) v 5.0 scale. | 1 year | 
| Progression-Free Survival (PFS) and Overall Survival (OS) following treatment with PRGN-2009 in combination with pembrolizumab or pembrolizumab alone | Duration of PFS and OS will be summarized using the Kaplan-Meier Product Limit estimator along with the corresponding two sided-95% Confidence intervals. | 1 year | 
| Best Overall Responses (BOR) and Disease Control Rate (DCR) per RECIST v1.1 following treatment with PRGN-2009 in combination with pembrolizumab or pembrolizumab alone | The proportion of subjects with BOR and DCR will be summarized using descriptive statistics. | 1 year | 
| Time to Response and Duration of Responses following treatment with PRGN-2009 in combination with pembrolizumab or pembrolizumab alone | TTR and DOR will be summarized using descriptive statistics. | 1 year | 
| Vector shedding following subcutaneous administration of PRGN-2009 | Samples collected before and at specific intervals after treatment will be evaluated for presence of adenoviral vector. | Up to 4 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Human Papilloma Virus, Cervical Cancer, Pembrolizumab, Therapeutic Vaccine, Cervix Cancer, Resistance to Checkpoint Inhibitors