Editor’s Note: This story was updated June 22, 2020 with new data from the study.
Mesothelioma presents quite a few obstacles for the people with this cancer and the doctors trying to help them. One of the most significant hurdles? How advanced — and untreatable — mesothelioma often is at the time of diagnosis.
A therapy currently in testing might be the solution to this problem.
Targovax, the maker of the treatment ONCOS-102, announced promising clinical study results at the 12-month check-up. These successes are follow-ups to the reported outcomes from three months ago and six months ago, when the company offered hope for late-stage pleural mesothelioma patients.
With the success, Targovax is looking ahead to the next step: combining ONCOS-102 and chemotherapy with an immunotherapy checkpoint inhibitor drug.
If you’re a mesothelioma patient and interested in this clinical trial — or another study — we can help connect you. Email our patient advocate and registered nurse, Jenna Campagna, at email@example.com to learn more about the available trials.
How ONCOS-102 Stops Late-Stage Mesothelioma
The ONCOS-102 clinical trial is designed to test the treatment against late-stage (stage 3 or stage 4) mesothelioma. Each year, there are approximately 3,000 new mesothelioma cases. Most of them involve a late-stage diagnosis.
At this point, the cancer is usually too widespread to stop with surgery. Chemotherapy and radiation can slow down the disease — but often won’t stop it permanently. Patients with stage 3 mesothelioma or stage 4 mesothelioma often receive a prognosis of a few months.
In the clinical study, the group that received ONCOS-102 — combined with chemotherapy — was comprised mostly of stage 3 and stage 4 patients. The comparison group, which received only chemotherapy, involved early-stage patients.
According to Targovax, 20 patients have received ONCOS-102 plus chemotherapy and reached the 12-month follow-up. The Norway-based company said that progression-free survival for the ONCOS-102 participants is around nine months. The disease control rate was around 90%.
Progression-free survival means the disease has not grown or spread since the treatment began. By comparison, the chemotherapy-only participants had progression-free survival of approximately seven months and disease control rate of 83%.
Other noteworthy stats from the 12-month follow-up include:
- One-year survival rate of 64% for the ONCOS-102 group
- One-year survival rate of 50% for the chemotherapy-only group
In summary, the late-stage mesothelioma patients showed more survival benefits and disease response than the early-stage patients did. The reason appears to be ONCOS-102 — and how it helps the immune system.
What Is ONCOS-102?
ONCOS-102 is essentially a combination of virotherapy and immunotherapy. It’s an adenovirus armed with immune system-stimulating proteins. The proteins, called cytokines, signal to the immune system to activate and find diseased cells.
This treatment kills mesothelioma tumors in two ways:
- The adenovirus replicates and breaks up the cells.
- Once released, the proteins signal to the immune system that cancer is present.
The adenovirus is injected into the tumor site, where ONCOS-102 replicates until it breaks apart the diseased cells. The virus only targets mesothelioma cells — and leaves healthy ones alone.
Once a cell breaks up, the adenovirus releases the cytokines. They alert the immune system’s T-cells, which are the body’s primary defenders against cancer.
However, T-cells have difficulty identifying the mesothelioma cells as intruders. They look for “antigens”, which are molecules that trigger an immune system response.
Typically, these antigens are held within the mesothelioma cells. They’re hidden from the T-cells, which cannot identify mesothelioma as dangerous. ONCOS-102 releases these antigens and gives the T-cells evidence of mesothelioma — and an example of what to look for.
The T-cells now have the knowledge to identify diseased cells. Targovax published a video explaining how the T-cells use this information.
“The activated T-cells start to circulate in the body in search of cancer cells,” the video’s narrator says. “When a T-cell encounters a cancer cell expressing the particular tumor antigens it has been activated to recognize, it darts to the cancer cell and secretes powerful enzymes which kill the cancer cell.”
What’s Next? ONCOS-102 Paired With Immunotherapy
Targovax officials said the next phase of the study will involve pairing the therapy with an immunotherapy drug. Researchers hope this combination enhances the immune system even further.
The Targovax press release mentions the recent durvalumab trial, which resulted in a 70.4% one-year survival rate. Durvalumab is an immunotherapy checkpoint inhibitor that blocks the PD-L1 protein sometimes expressed on mesothelioma cells.
“It is expected that addition of checkpoint inhibition to ONCOS-102 and (chemotherapy) will provide even further clinical benefit due to engagement of distinct and complementary biological mechanisms,” the press release states. “As such, Targovax’s future clinical development of ONCOS-102 will focus on first-line mesothelioma with the triple combination of a checkpoint inhibitor, ONCOS-102 and (chemotherapy). A randomized phase II trial is currently being planned in collaboration with a pharma partner.”
T-cells have PD-1 receptors, while mesothelioma cells have PD-L1 receptors. When they connect, the T-cells are tricked into thinking mesothelioma cells are safe. The PD-1/PD-L1 link disguises the cancer.
Targovax officials plan to use a checkpoint inhibitor, such as pembrolizumab (Keytruda) or nivolumab (Opdivo). These drugs block the interaction between two proteins, PD-1 and PD-L1.
Show Sources & Author
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https://www.targetedonc.com/view/mesothelioma-tumors-respond-to-oncos-102-plus-pemetrexed-and-cisplatin. Accessed: 05/04/2020.
- Targovax ASA Webcast. Royalcast. Retrieved from:
https://channel.royalcast.com/hegnarmedia/#!/hegnarmedia/20200121_1. Accessed: 01/28/2020.
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- Targovax’s ONCOS-102 mesothelioma 12-month data powerfully demonstrate broad immune activation linked to clinical benefit. Targovax. Retrieved from: https://www.targovax.com/en/targovaxs-oncos-102-mesothelioma-12-month-data-powerfully-demonstrate-broad-immune-activation-linked-to-clinical-benefit/ Accessed: 06/22/2020.