James L. Gulley, MD, PhD, senior investigator, Center for Immuno-Oncology, acting clinical director, Center for Cancer Research, National Cancer Institute, discusses a phase 1 trial of PRGN-2009 alone and in combination with bintrafusp alfa (M7824) in patients with recurrent and/or metastatic HPV-associated cancers.

At the 2023 ASCO Annual Meeting, investigators shared efficacy and safety findings for both PRGN-2009 alone and in combination with bintrafusp alfa, Gulley begins. Patients were assigned to arm 1A or arm 1B, where they were treated with PRGN-2009 monotherapy in dose escalation or PRGN-2009 administered at the recommended phase 2 dose in combination with 1200 mg of bintrafusp alfa once every 2 weeks, respectively. In the dose escalation arm, investigators determined that treatment of PRGN-2009 could be given safely at the recommended phase 2 dose.

In arm 1A, investigators noted stable disease as the best response, Gulley says. Results from arm 1B showed that PRGN-2009 was safe. Additionally, when evaluating responses in the combination arm, investigators noted that of 10 evaluable patients treated, 3 had objective response, 1 had a complete response (CR), and 2 had a partial response (PR), Gulley explains. Notably, one of the PRs was unconfirmed, Gulley adds. Moreover, the CR and confirmed PR were documented in patients with immune checkpoint blockade–resistant disease, Gulley concludes.

Videos

James L. Gulley, MD, PhD, discusses a phase 1 trial of PRGN-2009 alone and in combination with bintrafusp alfa in patients with recurrent and/or metastatic HPV-associated cancers.


Dr Gulley on the Investigation of PRGN-2009 Plus Bintrafusp Alfa in HPV-Associated Cancers

James L. Gulley, MD, PhD, Chief, Genitourinary Malignancies Branch, Senior Investigator, Head, Immunotherapy Section, Director, Medical Oncology Service, CCR Office of the Clinical Director, National Cancer Institute, discusses checkpoint inhibitors in bladder cancer.

Checkpoint inhibitors are currently being investigated in a wide range of clinical trials in bladder cancer. Data has suggested significant activity of atezolizumab, pembrolizumab, avelumab in patients with metastatic bladder cancer.

Now that activity is being seen, further investigation is needed to determine if these agents should be used as single agents or in earlier settings, says Gulley.

Dr. Gulley on Checkpoint Inhibitors in Bladder Cancer

James L. Gulley, MD, PhD, Head, Clinical Trials Group, Deputy Laboratory Chief, National Cancer Institute, discusses measuring response to vaccines.

The best definition of vaccine response, Gulley says, is the length of a patient's survival, as there are very few PSA responses and objective responses.

In the completed phase II trial analyzing PROSTVAC, robust responses were seen, as the placebo arm had a median overall survival of 16.1 months compared with about 25 months in the vaccine arm. In this trial, there was a PSA response of less than 5%. 

Dr. Gulley Discusses Vaccine Responses

James L. Gulley, MD, PhD, Head, Clinical Trials Group, Deputy Laboratory Chief, National Cancer Institute (NCI), gives an overview of the adverse event profile for PROSTVAC.

PROSTVAC is an immunotherapeutic vaccine for men with castration-resistant prostate cancer. The adverse event profile for PROSTVAC was just updated for all trials by the NCI, Gulley says. The analysis found that the majority of patients experienced few side effects.

The most common side effect was an injection site reaction: redness or a bump where the injection was given. This type of side effect is clinically insignificant, Gulley says. Some patients, about 5-10%, experienced mild to moderate flu-like symptoms, which is indicative of a strong immune response.

James L. Gulley, MD, PhD

Articles

Dr Gulley on the Investigation of PRGN-2009 Plus Bintrafusp Alfa in HPV-Associated Cancers

Dr. Gulley on Checkpoint Inhibitors in Bladder Cancer

Dr. Gulley Discusses Vaccine Responses

Dr. Gulley on the Adverse Event Profile for PROSTVAC