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.

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.

More details:

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.

Overview

PRGN-2009 is an investigational therapeutic vaccine for HPV-associated cancers. Human results are available from a small, nonrandomized phase 1 study in previously treated patients with recurrent or metastatic disease. Phase 2 studies are evaluating it in other settings, but the phase 1 findings do not establish whether PRGN-2009 improves outcomes. (pmc.ncbi.nlm.nih.gov)

Mechanism of action

PRGN-2009 uses a gorilla adenoviral vector to prompt immune responses against the HPV16 and HPV18 E6 and E7 proteins and the HPV16 E5 protein. It is intended to generate HPV-specific T cells that recognize cancer cells expressing those proteins. (pmc.ncbi.nlm.nih.gov)

Efficacy

In the phase 1 study, none of six patients receiving PRGN-2009 alone had an objective tumor response, although four had stable disease. Among 10 response-evaluable patients receiving PRGN-2009 plus bintrafusp alfa, two (20%) had a confirmed response: one complete and one partial response. Because the groups were small and there was no randomized comparison, the contribution of PRGN-2009 to the combination’s responses is unknown. (pmc.ncbi.nlm.nih.gov)

Safety

With PRGN-2009 alone, five of six patients had treatment-related adverse events, all grade 1 or 2; these included injection-site reactions and flu-like symptoms. With the combination, three of 11 (27%) had grade 3 or 4 treatment-related events, including two duodenal hemorrhages and one case of pharyngeal mucositis. One patient with duodenal hemorrhage died. These combination findings cannot be attributed to PRGN-2009 alone. (pmc.ncbi.nlm.nih.gov)

Further reading

• Peer-reviewed phase 1 study (link.springer.com)
• Phase 2 oropharyngeal cancer study abstract (ascopubs.org)
• Phase 2 cervical cancer study abstract (ascopubs.org)

Last updated: Sep 2026

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.