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.
Sponsor: Precigen, Inc (industry)
Phase: 2
Start date: March 21, 2025
Planned enrollment: 46
Show Summary from Sponsor
Show for: PRGN-2009
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)
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)
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)
Notes: PRGN‑2009 remains investigational; no regulatory approvals have been granted. Current human efficacy data are limited to the Phase 1 study (including combination with bintrafusp alfa) and do not yet include outcomes for pembrolizumab combinations now being tested in Phase 2. (ascopubs.org)
Last updated: Oct 2025
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
Caution: ClinicalTrials.gov appears to have newer eligibility criteria than the version saved here. Review the current criteria in ClinicalTrials.gov.
Show Criteria
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.
Little Rock, Arkansas, 72205, United States
[email protected] / 501-320-7749
Status: Recruiting
Bethesda, Maryland, 20892, United States
[email protected] / No phone
Status: Recruiting
Seattle, Washington, 98109, United States
[email protected] / 866-932-8588
Status: Recruiting
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