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

Sponsor

Precigen, Inc (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT06157151

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Arms

49.9

Anticipated Duration (Months)

0.9

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Cervical Cancer HPV-Related Carcinoma HPV-Related Malignancy	Biological: PRGN-2009 plus Pembrolizumab Drug: Pembrolizumab alone	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

46 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

This is an open-label, randomized study.This is an open-label, randomized study.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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.

Anticipated Study Start Date :

Dec 3, 2023

Anticipated Primary Completion Date :

Jan 30, 2028

Anticipated Study Completion Date :

Jan 30, 2028

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

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

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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.