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Imvax Begins Phase II Trial of Unique Autologous, Tumor-Derived Brain Cancer Therapy

Brain tumor

This article has been updated to clarify the regulatory characterization of Imvax's product and the overall survival results from its Phase Ib trial.  

NEW YORK – Last weekend, John Boockvar performed an unusual procedure on one of his newly diagnosed glioblastoma patients at Lenox Hill Hospital.

Boockvar, the vice chair of neurosurgery and director of the brain tumor center at the New York City hospital, implanted 20 dime-sized plastic vessels inside his patient's abdomen. Since this patient is a participant in a double-blinded trial testing the efficacy of a new investigational cell therapy, these plastic vessels, or "diffusibility" chambers, may have contained either a small sample of the patient's own brain tumor mixed with an antisense drug or an inactive placebo solution.

The surgical procedure is one of the steps in delivering the investigational cell therapy, IGV-001, which the Philadelphia-based company Imvax is evaluating in a Phase II randomized trial in newly diagnosed glioblastoma patients. Boockvar's patient is among the first of 93 patients with grade III or IV glioblastoma that investigators hope to enroll across 24 US sites.

The regimen, based on a platform Imvax calls Goldspire, involves three procedures, shipment to and from a central facility and a two-day manufacturing process, though the regimen is designed to be given to the patient over several days during the same hospital stay. It's a faster turnaround time than most US Food and Drug Administration-approved autologous cell therapies, which at best can take several weeks to a month to engineer and deliver to patients.

The step-by-step process involved in making and delivering Imvax's IGV-001, as Boockvar explained, starts with the patient getting a standard craniotomy. The surgeon removes the tumor and ships the tissue by courier to a central processing center. Imvax packages the tissue in diffusibility chambers, radiates them, and ships the chambers back to the doctor two days later. "At that point, I implant [the chambers] in the patient's abdominal musculature," Boockvar said. "Two days after, I remove it either at the bedside in the office or in the operating room and the patient goes home."

Imvax's Biodiffusion Chamber
The plastic implantable chambers are about the size of a dime. Credit: Imvax

IGV-001 is designed to train a patient's lymphocytes to recognize the tumor cells that they might not otherwise encounter were the patient to receive radiation directly to their brain tumor. This is due to the blood-brain barrier. "The brain remains privileged to immune cells," Boockvar said. "We are taking the tumor out of the brain and trying to stimulate the immune system out of the brain."

By radiating the tumor cells with low-dose radiation and by mixing the cells with an antisense oligodeoxynucleotide drug, dubbed IMV-001, which targets the insulin-like growth factor 1 receptor (IGF1R), Boockvar explained that Imvax's therapy is harnessing what's called the abscopal effect. When the tumor cells die inside the plastic chambers in the patient's abdomen — thanks to the cytotoxic radiation and the antisense — it releases the proteins necessary for the immune system to recognize the tumor. Those proteins diffuse through the pores in the small chamber and circulate in the abdomen, where they activate the systemic lymphocytes. "And by that peripheral activation, we will get a higher number of immune cells to recognize the brain tumor as foreign and hopefully actuate response," he said. The therapy is designed to initiate both an innate and adaptive response.

According to Boockvar, the abdominal muscles provide a relatively safe area for the implants. The key is that cell death is occurring outside of the blood-brain barrier and training the immune system to recognize the specific mutational signature of that patient's tumor so it can learn to attack it.

According to Imvax CSO Mark Exley, the pores in the small, round polycarbonate plastic biodiffusion chambers are smaller than a tumor cell, so that no intact glioblastoma tumor cells can escape the chamber, but the much smaller tumor antigens can. The material is known to be safe for humans, and the chambers are removed two days after they're implanted, Exley said. From a regulatory perspective, he said the biodiffusion chambers are considered class B implantable medical devices, and the IGV-001 product is considered a combination biologic regulated through the FDA's Center for Biologics Evaluation and Research (CBER).

Imvax Biodiffusion Chambers
The abdominal muscles provide a relatively safe area for the implants. Credit: Imvax

Imvax's autologous cell therapy is unique in that, instead of harvesting and reinfusing a patient's own immune cells, it involves resecting and reimplanting a patient's own tumor cells. It shares a similar mechanism to a vaccine, Exley explained.

"It's inducing a polyclonal immune response against many different antigens in the tumor," he said, adding that rather than selecting certain antigens for the vaccine, implanting small pieces of the whole tumor allow the immune system to recognize all mutations in the tumor, not just those that are necessary for tumor growth. "The more complete coverage you get by using the autologous tumor as the source of all potential antigens, the better," Exley said.

The company is encouraged by early clinical evidence on IGV-001. In a Phase Ib clinical trial, the results of which were published in Clinical Cancer Research in 2021, patients on the optimal dose — having 20 biodiffusion chambers implanted — lived a median of 17.1 months without their tumors progressing. The median overall survival was 38.2 months. Historically, the median life expectancy for advanced glioblastoma patients is around 16 months.

Imvax, which officially launched in 2015 as a spinout of Thomas Jefferson University, plans to apply the same process to treat other tumor types. The firm hopes to submit an investigational new drug application and start studying a treatment, dubbed IEC-001, in endometrial cancer patients within the coming year. There are early-stage programs in liver, urothelial, and ovarian cancer.

The firm hopes to reach full enrollment in the glioblastoma trial by March 2024 and unveil data by mid-2025. The trial's primary endpoint is progression-free survival, and secondary endpoints include safety, tolerability, and overall survival. Imvax is also exploring response biomarkers, such as MGMT status.

As of now, each IGV-001 therapy is manufactured in a central, good manufacturing practices (GMP) facility in Philadelphia, which Imvax built with a $2 million grant from the Redevelopment Assistance Capital Program in 2021. According to David Andrews, Imvax's cofounder and chief medical officer, this facility is a key milestone for the company, critical to starting clinical trials of its treatments.

In an initial meeting with the FDA's CBER, when Andrews and his team described the development process for its cell therapies, the agency said that every facility that manufactures the drugs must be up to GMP standards. Instead of GMP-certifying every trial site throughout the country where patients might receive this therapy, Imvax quickly built the Philadelphia facility, where patients' tumor samples could be sent.

"That was a heavy lift," Andrews said. "It was like the plane was on the tarmac and taking off, and we were still building the plane." But the FDA approved the trial protocol once the firm had its centralized facility. Eventually, he said, the firm will likely build additional facilities to expand the treatment's geographic reach.

Boockvar has been optimistic about IGV-001 since its inception. "It's a unique approach," he said. "This is a personalized, autologous, tumor-derived treatment. We don't have anything like this."

The main limitation from Boockvar's perspective is that newly diagnosed brain cancer patients may be hesitant to enroll in a randomized trial where they might receive a placebo. But he emphasized that in both arms, six weeks after patients have their brain tumors resected, they receive standard-of-care radiation and chemo. He likes to remind his patients and their families that the chances of getting an investigational therapy are better if they enroll in a trial than not.

"We have a desperate patient population, and the real way that we're going to defeat any disease is through our immune system," Boockvar said. "Particularly in glioblastoma, where our patients are immunosuppressed for reasons that we don't understand, this is a very promising therapy, and one that has a really good safety profile and strong scientific rationale."