Trial: PRGN-2009 in Combination With Pembroliz…

Trial Details

Sponsor: Precigen, Inc (industry)

Phase: 2

Start date: March 21, 2025

Planned enrollment: 46

Trial ID: NCT06157151

More trial details at ClinicalTrials.gov

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Investigational Drug AI Analysis

Show for: PRGN-2009

Overview

PRGN-2009 is an investigational, off‑the‑shelf therapeutic vaccine for HPV‑associated cancers. It uses a replication-deficient gorilla adenovirus vector (AdenoVerse platform) engineered to deliver multiple T‑cell epitopes from HPV16/18 E6/E7 oncoproteins, aiming to elicit robust cytotoxic T‑cell responses against HPV‑positive tumors. Preclinical studies demonstrated antitumor activity and induction of HPV‑specific T cells, supporting clinical evaluation. (insight.jci.org)

Active clinical development includes: - A completed first‑in‑human Phase 1 trial (NCT04432597) testing PRGN‑2009 alone and with bintrafusp alfa in recurrent/metastatic HPV‑associated cancers, with results presented at ASCO 2023. (ascopubs.org) - Ongoing Phase 2 studies in newly diagnosed HPV‑associated oropharyngeal cancer (neoadjuvant PRGN‑2009 + pembrolizumab; NCT05996523) and in pembrolizumab‑resistant recurrent/metastatic cervical cancer (randomized PRGN‑2009 + pembrolizumab vs pembrolizumab; NCT06157151). (ascopubs.org)

Mechanism of action

Vector/platform: replication‑deficient gorilla adenovirus (AdenoVerse) with low human seroprevalence, enabling repeat dosing without significant neutralizing antibody formation in early studies. (insight.jci.org)
Antigen design: encodes 35 non‑HLA‑restricted T‑cell epitopes from HPV16/18 E6/E7 to drive broad CD8+/CD4+ responses. (ascopubs.org)
Preclinical activity: reduced tumor volumes and increased tumor‑infiltrating T cells in HPV16+ models, including humanized mice bearing SiHa tumors. (insight.jci.org)

Efficacy

Phase 1 (NCT04432597; ASCO 2023 abstract): - Monotherapy (n=6): stable disease in 4/6 patients; no objective responses reported. (ascopubs.org) - Combination with bintrafusp alfa (n=11; 10 evaluable): ORR 30.0% (95% CI 6.7–65.3) with 1 complete response (duration 15.3 months) and 2 partial responses; clinical activity observed despite most patients being checkpoint‑blockade resistant. Median OS was 12.5 months (95% CI 9.6–not estimable) in the combination cohort at the data cut. (ascopubs.org)

Ongoing Phase 2 programs (no efficacy readouts yet as of October 7, 2025): - Neoadjuvant PRGN‑2009 + pembrolizumab for newly diagnosed HPV‑associated oropharyngeal cancer (primary endpoint: intratumoral immune response; NCT05996523). (ascopubs.org) - Randomized PRGN‑2009 + pembrolizumab vs pembrolizumab in pembrolizumab‑resistant recurrent/metastatic cervical cancer; primary endpoint ORR; trial recruiting (NCT06157151). (ascopubs.org)

Safety

Phase 1 (ASCO 2023 abstract): - Monotherapy: no dose‑limiting toxicities; treatment‑related adverse events were Grade 1–2 (flu‑like symptoms, injection‑site reactions, fatigue, rash). Recommended Phase 2 dose: 5×10^11 particle units SC. (ascopubs.org) - Combination with bintrafusp alfa: Grade 3–4 treatment‑related adverse events occurred and were attributed to bintrafusp alfa (e.g., duodenal hemorrhage, pharyngeal mucositis); no treatment‑related deaths reported. (ascopubs.org)

HealthScout AI Analysis

Goal: Evaluate whether adding the investigational HPV-targeted therapeutic vaccine PRGN-2009 to pembrolizumab improves antitumor activity versus pembrolizumab alone in patients with pembrolizumab-resistant recurrent or metastatic cervical cancer, and to characterize safety.

Patients: Adults (≥18 years) with histologically or cytologically confirmed recurrent or metastatic cervical cancer that is resistant to prior pembrolizumab, with no more than two prior systemic regimens in the recurrent/metastatic setting. Tumors must be PD-L1 positive and HPV16/18 positive, with measurable disease by RECIST v1.1, ECOG 0–1, adequate organ function, and life expectancy ≥12 weeks. Key exclusions include active CNS disease, other active malignancy within 1 year, prior severe hypersensitivity to pembrolizumab, active TB, pregnancy/lactation, prior solid organ transplant, and recent use of other investigational agents.

Design: Multicenter, randomized, open-label, two-arm phase 2 study with 1:1 allocation to combination therapy versus pembrolizumab monotherapy. Planned enrollment is 46 patients.

Treatments: Experimental arm: PRGN-2009 plus pembrolizumab. PRGN-2009 is a replication-defective gorilla adenoviral vector vaccine (AdenoVerse/GC46) encoding multiple T-cell epitopes from HPV16/18 E6/E7 to induce robust HPV-specific CD8+ and CD4+ T-cell responses; the platform’s E1/E4 deletions are designed to permit repeat dosing with limited anti-vector immunity. Early-phase data in HPV-associated cancers showed immunogenicity with increased HPV-specific T cells and manageable safety; in combination with bintrafusp alfa, objective responses including a complete response were observed in small cohorts, though definitive benefit remains unproven and requires randomized validation. Dosing: PRGN-2009 5 × 10^11 particle units every 3 weeks for three doses, then every 6 weeks, with pembrolizumab 400 mg every 6 weeks. Control arm: Pembrolizumab 400 mg every 6 weeks, a PD-1 inhibitor standardly used in PD-L1–positive cervical cancer.

Outcomes: Primary: Objective response rate per RECIST v1.1 at approximately 1 year. Secondary: safety and treatment-emergent adverse events graded by CTCAE v5.0; progression-free survival and overall survival (Kaplan-Meier with 95% CIs); best overall response and disease control rate per RECIST v1.1; time to response and duration of response. Additional: vector shedding following subcutaneous PRGN-2009 administration up to 4 months.

Burden on patient: Moderate. Treatment visits occur every 3 weeks initially for PRGN-2009 administration, then every 6 weeks aligned with pembrolizumab, requiring regular clinic travel and routine safety labs. Imaging for RECIST assessments will be periodic and similar to standard oncology practice. The vector-shedding substudy adds scheduled sample collections within the first 4 months but no invasive procedures are specified. No intensive pharmacokinetic sampling or mandatory biopsies are described, limiting extra procedural burden compared with many early-phase immunotherapy studies.

Last updated: Oct 2025

Eligibility

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Sites (3)

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University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

[email protected] / 501-320-7749

Status: Recruiting

National Institute of Health

Bethesda, Maryland, 20892, United States

[email protected] / No phone

Status: Recruiting

University of Washington

Seattle, Washington, 98109, United States

No email / No phone

Status: Active, not recruiting

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