ONCOS-102 for Mesothelioma

ONCOS-102 for mesothelioma is a combination of virotherapy and immunotherapy. The treatment is one of the most promising emerging therapies for malignant mesothelioma.

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Written by Jenna Campagna, RN

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Important Facts About ONCOS-102 for Mesothelioma

  • ONCOS-102 is an oncolytic adenovirus for malignant mesothelioma that breaks up cancer cells and sends signals to the immune system.
  • The therapy sends a virus into mesothelioma cells, causing a release of antigens, which allows the T-cells to recognize mesothelioma cells.
  • ONCOS-102 received FDA fast-track designation early in 2021. This grants speedier approval and review procedures for the therapy.
  • ONCOS-102 and chemotherapy together outperformed chemotherapy alone by a median survival of seven months. The one-year survival rate also was better due to ONCOS-102.
  • The manufacturer, Targovax, plans to use ONCOS-102 with an immunotherapy drug in future trials, hoping to further stimulate an immune response to target mesothelioma.

What Is ONCOS-102?

ONCOS-102 is an oncolytic adenovirus armed with an immune-stimulating transgene. The therapy delivers a virus into mesothelioma cells, and this virus carries cytokines that encourage a quick and powerful immune response.

How Does ONCOS-102 Work?

The first step for ONCOS-102 is injecting a virus into the tumor location. The virus enters mesothelioma cells explicitly while ignoring healthy cells. Once inside, the virus replicates within the cells and causes them to break apart.

This is a form of virotherapy: delivering a virus into the body that targets diseased cells and ignores healthy cells. It’s a response to cancer cells avoiding routine “cell death” while continuing to replicate and create a growing cluster of mutated cells.

The broken-up cells release antigens into the tumor environment. Antigens are molecules specific to cells, and they’re proof of cancer in the body. These antigens are basically fingerprints at a crime scene.

“What’s really interesting about viruses is they’re able to kill cancer cells so that the cancer cells become visible to the immune system,” said Dr. Magnus Jaderberg, the chief medical officer for Targovax, the manufacturer of ONCOS-102. “That’s the underlying principle of ONCOS-102.”

The virus dies, but it carries cytokines into the tumor location. Cytokines are cell-signaling proteins. The cytokine in ONCOS-102 is GM-CSF, which stands for a “granulocyte-macrophage-colony-stimulating factor.” This is how ONCOS-102 transitions to an immunotherapy for mesothelioma.

GM-CSF causes dendritic cells to swarm to the tumor site and process the released tumor antigens. Dendritic cells then deliver the antigens to the immune system’s T-cells, which are the front line of defense against diseases. The T-cells search for cancer cells with the specific antigen presented, eventually finding the mesothelioma tumors and attacking them.

“We are injecting the virus,” Dr. Jaderberg said. “The virus replicates and releases that barcode, the cancer antigen. Then there are antigen-presenting cells … that pick up the data signal of the cancer antigens, go into the lymph nodes where there is a production of mature, specialized T-cells.”

To summarize how ONCOS-102 works for mesothelioma:

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A virus enters mesothelioma cells, replicates, and dismantles the cells

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The broken-up mesothelioma cells release unique antigens and a cytokine called GM-CSF

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The cytokines and antigens cause dendritic cells to swarm to the tumor location

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Dendritic cells carry the antigens to the T-cells, which then look for cells with the same antigens

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The T-cells reach the site of mesothelioma and kill the cancer cells making up the tumors

ONCOS-102 and FDA Approval for Mesothelioma

The U.S. Food and Drug Administration (FDA) provided a “fast-track designation” to ONCOS-102 and its manufacturer, Targovax, for malignant pleural mesothelioma. The Norwegian cancer therapeutic company now has an advantage towards getting full approval.

The FDA grants fast-track designation to promising therapies for unmet needs in serious medical conditions. Malignant mesothelioma falls within the category of “serious medical condition” with “unmet needs” due to poor survival rates and scarce treatment options.

The FDA granted ONCOS-102 this designation due to success in recent clinical trials, especially compared to FDA-approved chemotherapy.

Fast-track designation provides numerous benefits:

  • Targovax can meet more frequently with the FDA to discuss the drug’s development and data collection needed for approval.
  • Targovax will receive more frequent written communication from the FDA regarding the design of proposed clinical trials.
  • ONCOS-102 is eligible for accelerated approval and priority review, which means the FDA will review parts of the new drug application to accelerate the approval process.

ONCOS-102 Survival Rates in Mesothelioma Clinical Trials

The most recent phase 2 ONCOS-102 trial paired the therapy with chemotherapy. Researchers compared this combination with chemotherapy on its own.

The median survival from the two-year follow-up is between 22 and 25 months, according to Targovax. The patients receiving just chemotherapy survived for a median of 14 months. Half the patients receiving ONCOS-102 plus chemotherapy were alive at the 21-month follow-up.

“The goal was to show that we’re able to activate the patients’ immune system,” Dr. Jaderberg said. “Mesothelioma is a type of cancer where it’s not that easy to get the immune system to activate.”

At the one-year follow-up:

  • The disease-control rate was 90%
  • The one-year survival rate was 64%

ONCOS-102 as a Multimodal Treatment for Mesothelioma

ONCOS-102 helps the immune system respond to the presence of mesothelioma. In past and ongoing trials, it’s a multimodal therapy paired with chemotherapy. It might also pair well with immunotherapy, as many experts believe.

Targovax is planning a future clinical trial with ONCOS-102 and an immune checkpoint inhibitor. Opdivo and Yervoy, two checkpoint inhibitor immunotherapy drugs, received FDA approval in 2020 for unresectable malignant pleural mesothelioma.

Dr. Jaderberg hinted at these plans in a podcast interview with Mesothelioma Guide. He expressed excitement at partnering with Memorial Sloan-Kettering Cancer Center and the Mayo Clinic to host part of the trial in the United States.

“(This trial) is the first time anyone has combined an oncolytic virus with a checkpoint inhibitor for this specific disease,” Dr. Jaderberg said.

ONCOS-102 may also work after surgery as a maintenance therapy to prevent postoperative recurrence.

Common Questions About ONCOS-102 for Mesothelioma

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What is ONCOS-102?

ONCOS-102 is an oncolytic adenovirus armed with an immune-stimulating feature. The virus breaks apart mesothelioma cells, which release antigens and a cytokine. These help the immune system track other mesothelioma cells with similar antigens and cytokines.

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How do Opdivo and Yervoy work?

ONCOS-102 has fast-track designation from the FDA for malignant pleural mesothelioma. This means the therapy has priority for expedited reviews. ONCOS-102’s manufacturer, Targovax, can coordinate with the FDA easily due to this designation.

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What are the survival rates for ONCOS-102?

ONCOS-102 survival rates exceed those of chemotherapy. The oncolytic virus thrived in clinical trials of mostly stage 3 and stage 4 mesothelioma patients. ONCOS-102 with chemotherapy had a median survival of 20.5 months. The therapy’s two-year mesothelioma survival rate is just below 50%.

Sources & Author

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About the Writer, Jenna Campagna, RN

Jenna Campagna is a registered nurse and patient advocate who is passionate about helping mesothelioma patients navigate their health care. She has over seven years of experience working with patients diagnosed with rare diseases including mesothelioma. Jenna is also a member of the Academy of Oncology Nurse & Patient Navigators and her goal is to connect patients to top mesothelioma specialists, treatment facilities, and clinical trials. Through her writing, she aims to simplify the complicated journey through mesothelioma by offering helpful tips and advice.