SurVaxM vaccine for glioblastoma advances in trials, offers hope for longer survival

Glioblastoma, the most common primary brain cancer, is known to be highly aggressive and deadly.

Although it is generally treated with surgery, chemotherapy and radiation, glioblastoma often recurs within a year of treatment. For this reason, it has been an area of priority in cancer research.

“There are about 15,000 cases a year in the U.S. and very few treatment options,” Michael Ciesielski, PhD, professor of neurosurgery at Roswell Park Comprehensive Cancer Center, said in an interview with Healio. “Treatment hasn’t changed since 2005, when the most recent form of chemotherapy was introduced. There have been marginal increases here and there, but nothing you could say was an astounding success.”

To address the relative lack of advances in glioblastoma treatment, Ciesielski and Robert Fenstermaker, MD, chair of the department of neurosurgery at Roswell Park, developed SurVaxM (MimiVax), an immunotherapy that targets survivin, a protein present in many cancer types that enables cancer cells to survive.

At this year’s ASCO Annual Meeting, Ciesielski presented findings from the completed phase 2a study of SurVaxM. Ciesielski said he has been encouraged by the results as the drug has progressed through the clinical trial process.

“We’ve had great data along the way. Some of the patients we treated very early on had a prognosis of maybe 3 to 6 months, and standard available therapies had failed these patients,” Ciesielski said. “Some of these patients ended up surviving for over a year. Some were with us 6 years later, after having recurrent glioblastoma. That’s unheard of.”

Ciesielski spoke with Healio about the mechanism of SurVaxM, its success in trials so far and next steps in its ongoing development.

Healio: What prompted you to develop this treatment for glioblastoma?

Ciesielski: I’m a molecular immunology PhD, and I’ve been in neuro-oncology for 25 years. We’ve been looking for something we could use to treat our patients through the clinics at Roswell Park. Immunotherapy looked like it had a great deal of promise. We decided to further develop a vaccine in the lab that would ultimately be a vaccine against brain tumors, particularly glioblastoma, which is the worst of the worst. We’ve been moving it ourselves through phase 1 and phase 2 clinical trials. Now, we’re up to a phase 2b clinical trial, which is a much larger, bigger brother to some of the early-stage trials we’ve done.

Our phase 2a trial included 64 patients at five centers, mostly here in the northeastern U.S., Boston and Cleveland. These patients had newly diagnosed glioblastoma, which doesn’t have a great prognosis on average — about 15 months. In that trial, we saw survival increase to a little over 25 months. So, we nearly doubled survival on average for those patients. The study is becoming more mature now, and we’re also seeing patients who are alive 4 to 5 years after the start of the study.

Healio: What is the status of the phase 2b trial?

Ciesielski: This is a precursor to a pivotal study and will include about 300 patients. Right now, it’s open in about 12 major cancer centers across the United States. We’re actively enrolling patients and, based on how this goes and the data that come out of it, we hope to have the opportunity to convert this into a pivotal study and move the drug that much closer to being approved and available to patients with brain tumors.

Healio: What is the mechanism of SurVaxM?

Ciesielski: SurVaxM is a peptide-based vaccine that stimulates the patient’s own immune system. We’re basically revving up the patient’s own natural immunity to kill the tumor. That’s what’s really exciting, because it doesn’t carry any of the nasty side effects that we normally see with cancer therapies. It improves quality of life. Patients get a shot in the arm and go home.

Some patients, as they’ve progressed further in the study and are still doing well, have come off chemotherapy. So, the only thing they are taking is the vaccine. It’s a great thing to be able to benefit these patients’ lives in such a meaningful way.

Healio: Do you expect SurVaxM to be used alone, or will it be used with other cancer treatments?

Ciesielski: The vaccine is given in addition to standard of care. Patients will get some benefit from it, and we’re not adding any toxicity or burden to the patient. The standard of care usually consists of surgery and radiation. Then patients start chemotherapy, but that only goes so far. Patients are typically on that for 6 months or so. Patients can also continue to take the vaccine as long as it continues to work for them. We’ve had some patients who have had 20 to 30 doses of vaccine at this point. They’ve been free of significant toxicity.

Healio: What are your plans for a pediatric trial of SurVaxM?

Ciesielski: The pediatric trial is still at a phase 1 level. This is a new study looking at children with various types of high-grade brain tumors — high-grade glioma, recurrent medulloblastoma, recurrent ependymomas.

This study is sponsored through a partnership we formed with the Pediatric Brain Tumor Consortium. It’s being conducted at their 17 consortium centers, and we’re starting with older children aged 17 years. We treat three patients and then move back a number of years, to three children aged 12 years. It’s what they call a three-by-three toxicity study. You need to make sure it is safe in the older kids, and then we can keep scaling it back to younger children, all the way down to children aged 1 year. It’s also going to include an arm for diffuse intrinsic pontine glioma, or DIPG. This is one of the worst childhood brain tumors, and we truly hope we can show some benefit in that population, as well.

Healio: Do you think SurVaxM has the potential to change the prognosis on glioblastoma in the future?

Ciesielski: We hope to be able to give patients a much better chance at longer survival. We’ve seen that longer survival in our studies already. So, we really hope to be able to recapitulate that in a pivotal study that leads to approval, so that many more patients can get the drug.

Glioblastoma is a devastating diagnosis, even for those of us treating patients here. I often refer to the fact that National Comprehensive Cancer Network guidelines suggest consulting with clinical trials as the first treatment listed for glioblastoma. It doesn’t spark much hope. Our goal is to be able to give these patients some options if they are failed by standard therapy. For some of these hard-to-treat cancers, any hope is encouraging.

Healio: Is there anything else you’d like to add?

Ciesielski: This has been very much a grassroots effort — we’re a small group. Dr. Fenstermaker and I developed SurVaxM and have been moving it along together; we’re learning as we go. And this drug and study have been supported through the center finding ways to fund the studies for us. A lot of that has come from donations to Roswell Park. That is something we’re proud to be part of — seeing the community come together to help us give these patients hope.

For more information:

Michael Ciesielski, PhD, can be reached at Roswell Park Comprehensive Cancer Center, Elm and Carlton streets, Buffalo, NY 14263.