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

Phase 2

Recruiting

• Conditions: Cervical Cancer; HPV-Related Carcinoma; HPV-Related Malignancy; Recurrent Cervical Carcinoma; Metastatic Cervical Cancer
• Interventions: Drug: Pembrolizumab alone; Biological: PRGN-2009 plus Pembrolizumab

• Registration Number: NCT06157151
• Lead Sponsor: Precigen, Inc

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2023-11-27
• Study First Submitted QC: 2023-11-27
• Study First Posted: 2023-12-05
• Status Verified: 2024-11
• Study Start: 2024-11
• Last Update Submitted: 2024-11-06
• Last Update Posted: 2024-11-08
• Primary Completion: 2028-01-30
• Study Completion: 2028-01-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 46

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Pembrolizumab alone	Pembrolizumab alone	Pembrolizumab, 400mg q6w
PRGN-2009 plus Pembrolizumab	PRGN-2009 plus Pembrolizumab	PRGN-2009 at a dose of 5 x 10\^11 PU q3W for 3 administrations, then q6w, plus Pembrolizumab, 400mg q6w

Primary Outcome Measures

Name	Time	Method
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.	1 year	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.

Secondary Outcome Measures

Name	Time	Method
Safety of PRGN-2009 in combination with pembrolizumab or pembrolizumab alone	1 year	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.
Progression-Free Survival (PFS) and Overall Survival (OS) following treatment with PRGN-2009 in combination with pembrolizumab or pembrolizumab alone	1 year	Duration of PFS and OS will be summarized using the Kaplan-Meier Product Limit estimator along with the corresponding two sided-95% Confidence intervals.
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	1 year	The proportion of subjects with BOR and DCR will be summarized using descriptive statistics.
Time to Response and Duration of Responses following treatment with PRGN-2009 in combination with pembrolizumab or pembrolizumab alone	1 year	TTR and DOR will be summarized using descriptive statistics.
Vector shedding following subcutaneous administration of PRGN-2009	Up to 4 months	Samples collected before and at specific intervals after treatment will be evaluated for presence of adenoviral vector.

Trial Locations

Locations (3)

University of Washington; 🇺🇸 Seattle, Washington, United States

University of Arkansas for Medical Sciences; 🇺🇸 Little Rock, Arkansas, United States

National Institute of Health; 🇺🇸 Bethesda, Maryland, United States