PRGN-2009 Plus Bintrafusp Alfa Shows Early Activity in HPV-Associated Malignancies


James L. Gulley, MD, PhD, reviews the safety and efficacy of PRGN-2009 alone and in combination with bintrafusp alfa in HPV-associated cancers and explains how this kind of approach may address an unmet clinical need.

James L. Gulley, MD, PhD

James L. Gulley, MD, PhD

Treatment with the replication-incompetent gorilla adenovirus targeting HPV 16/18, PRGN-2009, in combination with bintrafusp alfa (M7824) elicited responses and had acceptable tolerability in patients with recurrent or metastatic human papillomavirus–associated cancers, according to data from a phase 1 trial (NCT04432597) presented at the 2023 ASCO Annual Meeting.

In evaluable patients who received PRGN-2009 at the recommended phase 2 dose plus bintrafusp alfa (arm 1b; n = 10), the objective response rate (ORR) was 30% (95% CI, 6.7%-65.3%), which comprised 1 complete response (CR) and 2 partial responses (PRs). One patient had stable disease (SD) and 6 patients experienced progressive disease (PD).

Moreover, treatment with PRGN-2009 monotherapy and in combination with bintrafusp alfa was determined to be safe and well tolerated in this population. with only grade 1 or 2 adverse effects (AEs) related to treatment.

“The real unmet clinical need is in patients who have [HPV-associated] cancer and have been treated with immunotherapy, but that immunotherapy is now no longer working for them,” James L. Gulley, MD, PhD, explained in an interview with OncLive®. “Coming in with combination approaches to get the immune system reengaged in fighting the cancer is going to be critical as we seek cures in these patients.”

In the interview, Gulley reviewed the safety and efficacy of PRGN-2009 alone and in combination with bintrafusp alfa in HPV-associated cancers and explained how this kind of approach may address an unmet clinical need. Gulley is a senior investigator at the Center for Immuno-Oncology and the acting clinical director for the Center for Cancer Research at the National Cancer Institute, in Bethesda, Maryland.

OncLive: What was the rationale for evaluating PRGN-2009 with or without bintrafusp alfa in patients with HPV-associated cancers?

Gulley: There are different targets within the cancer that may be immunologically relevant for HPV-associated cancers. These include viral antigens that are present within the tumor that are not present in normal tissues in the body, making it a good target for the immune system. These viral targets include E6 and E7; viruses that cause HPV-associated malignancies include HPV 16 and HPV 18.

There’s a vaccine that targets both HPV 16 and 18 that has E6 and E7 targets within it, that provides broad coverage for a wide range of patients with HPV-associated malignancies. PRGN-2009. We combined PRGN-2009 with an immune checkpoint inhibitor, bintrafusp alfa, which sequesters transforming growth factor-beta [TGFβ] and has had some activity in HPV-associated malignancies.

What patient population was enrolled in this study?

This study included patients with HPV-associated malignancies; this includes head and neck cancer, cervical cancer, and anal cancer. Multiple cancers are associated with HPV infection. What we were able to do was enroll patients who had [progressed on] standard-of-care therapies and test them with this vaccine, either alone in a dose-escalation component, or in combination with this immune checkpoint inhibitor.

What was observed with this approach?

[At the meeting, we] presented findings [related to] the safety of this approach, as well as the efficacy. In the dose-escalation [cohort], we showed that [PRGN-2009] was safe, and we got to a recommended phase 2 dose. We then did an expansion cohort, where we looked at the combination, and again showed that [the regimen] was safe.

What we saw in the dose-escalation [portion of the research,] with the vaccine alone, was SD as the best response. However, when we [examined] the combination, we saw that of the 11 patients treated, 2 of them had an objective response. We [saw] 1 CR, 1 PR, and there was 1 other unconfirmed PR. This patient had long-term disease decrease, finally making the PR threshold, but also had a new lesion at that time.

The patients who had an objective response by RECIST [criteria] both had prior immune checkpoint inhibitor therapy, and the patient who had prolonged disease control also had prior immunotherapy with therapy targeting HPV.

Moreover, 16 patients were evaluated for their ability to [develop] immune responses to HPV, and 14 out of these 16 patients had strong immune responses.

Should anything else be noted about the safety of the vaccine?

The safety profile for PRGN-2009 is similar to the profile that we’ve seen for many different vaccines. [We see] local injection site reaction, as well as systemic AEs, including flu-like symptoms that are transient and go away with antibiotics.

[Combining PRGN-2009] with the immune checkpoint inhibitor adds some AEs that are often seen with immune checkpoint inhibitor therapy. In this case, this immune checkpoint inhibitor also sequestered TGFβ. There were 2 cases of patients who had duodenal bleeding; we do see mucosal bleeding sometimes with a TGFβ-based approach.

What are the anticipated next steps for this research?

The next steps for this research are to be able to do a combination approach in patients with HPV-associated malignancies. What we hope to do is to [conduct] a study in patients with cervical cancer, which is the most common HPV-associated malignancy, in those who had immune checkpoint inhibitor therapy [fail them]. This can include pembrolizumab [Keytruda], for instance, and if [that] failed, we would take patients and randomize them between an immune checkpoint inhibitor alone vs an immune checkpoint inhibitor plus vaccine, [and evaluate] outcomes in those patients.


Floudas CS, Strauss J, Redman JM, et al. Phase I evaluation of PRGN-2009 alone and in combination with bintrafusp alfa in patients (pts) with recurrent/metastatic (R/M) HPV-associated cancers (HPV-C). J Clin Oncol. 2023;41(suppl 16):2628. doi:10.1200/JCO.2023.41.16_suppl.2628.

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