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

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.

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.

Study Overview

• Status: Recruiting
• Conditions: Cervical Cancer; HPV-Related Malignancy; HPV-Related Carcinoma
• Intervention / Treatment: Biological: PRGN-2009 plus Pembrolizumab; Drug: Pembrolizumab alone

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 Type: Interventional
• Enrollment (Estimated): 46
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Amy Lankford; Phone Number: 3015569900; Email: clinicaltrials@precigen.com

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Recruiting
      • University of Arkansas for Medical Sciences
      • Contact: Matthew Kovak; Phone Number: 501-686-8274; Email: MRKovak@uams.edu
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • Recruiting
      • National Institute Of Health
      • Contact: Erica Redmond; Email: erica.redmond@nih.gov

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Biological: PRGN-2009 plus Pembrolizumab; 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.
Active Comparator: Pembrolizumab alone; Pembrolizumab, 400mg q6w	Drug: Pembrolizumab alone; Subjects randomized will receive IV infusion of pembrolizumab (400 mg) administered every 6 weeks.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Precigen, Inc
• Collaborators: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2024
• Primary Completion (Estimated): January 30, 2028
• Study Completion (Estimated): January 30, 2028

Study Registration Dates

• First Submitted: November 27, 2023
• First Submitted That Met QC Criteria: November 27, 2023
• First Posted (Actual): December 5, 2023

Study Record Updates

• Last Update Posted (Actual): April 17, 2024
• Last Update Submitted That Met QC Criteria: April 16, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Cervix Cancer; Pembrolizumab; Cervical Cancer; Human Papilloma Virus; Therapeutic Vaccine; Resistance to Checkpoint Inhibitors
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Uterine Cervical Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Pembrolizumab
• Other Study ID Numbers: PRGN-2009-201

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No