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Karen Ritter, RN BSN
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Important Facts About ONCOS-102 for Mesothelioma
- 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 oncolytic virus therapy, which involves delivering a virus into the body that targets diseased cells and ignores healthy cells. Another medical term for this is “virotherapy.” 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.
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.
To summarize how ONCOS-102 works for mesothelioma:
A virus enters mesothelioma cells, replicates, and dismantles the cells
The broken-up mesothelioma cells release unique antigens and a cytokine called GM-CSF
The cytokines and antigens cause dendritic cells to swarm to the tumor location
Dendritic cells carry the antigens to the T-cells, which then look for cells with the same antigens
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
A phase 1/2 clinical trial paired ONCOS-102 with chemotherapy. Researchers compared this combination with chemotherapy on its own.
“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.”
Additionally, ONCOS-102 also received high praise for:
- A disease-control rate of 90%
- A one-year survival rate of 64%
“This excellent survival outcome suggests a great promise for ONCOS-102 to benefit mesothelioma patients,” said Dr. Jaderberg. “Importantly, we have confirmed that ONCOS-102 is active and effective in highly different types of solid tumors in both early and late lines of therapy. Based on the encouraging patient outcomes and deep mechanistic analysis from the phase 1/2 program, we are currently designing and preparing for the next phase in ONCOS-102 clinical development.”
In a more recent clinical trial, ONCOS-102 was paired with mesothelioma chemotherapy drugs: pemetrexed and cisplatin. The combination of the oncolytic virus with chemotherapy was compared with just chemotherapy. The oncolytic virus helped patients live longer:
- The median overall survival was 20.3 months for patients receiving ONCOS-102 and chemotherapy, while it was 13.5 months for patients receiving just chemotherapy.
- The 30-month (2.5 years) survival rate was 34% for patients receiving ONCOS-102 and chemotherapy, while it was 0% for patients receiving only chemotherapy.
- There were no significant adverse events for patients receiving ONCOS-102 and no patients stopped treatment due to adverse events.
“By day 36, ONCOS-102 was associated with increased T-cell infiltration and immune-related gene expression that was not observed in the control cohort,” the study authors wrote. “Substantial immune activation in the tumor microenvironment was associated with survival at month 18 in the ONCOS-102 cohort.”
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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.
Frequently Asked Questions About ONCOS-102 for Mesothelioma
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.
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.
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 25 months in one study and 20 months in another study. The therapy’s two-year mesothelioma survival rate is approximately 50% and the 2.5-year survival rate is approximately 34%.
Sources & Author
- Targovax ASA Webcast. Royalcast. Retrieved from: https://channel.royalcast.com/hegnarmedia/#!/hegnarmedia/20200121_1. Accessed: 01/28/2020.
- ONCOS-102. Immuno-Oncology News. Retrieved from: https://immuno-oncologynews.com/oncos-102/. Accessed: 01/28/2020.
- ONCOS -102 Mechanism of Action. YouTube. Retrieved from: https://www.youtube.com/watch?time_continue=32&v=K_PfmBpa38A&feature=emb_title. Accessed: 01/28/2020.
- ONCOS – Oncolyctic Virus. Targovax. Retrieved from: https://www.targovax.com/en/oncos-oncolyctic-virus/. Accessed: 01/28/2020.
- Continued survival benefit in Targovax’s ONCOS-102 trial in mesothelioma at the 21-month follow-up. PRNewswire. Retrieved from: https://www.prnewswire.com/news-releases/continued-survival-benefit-in-targovaxs-oncos-102-trial-in-mesothelioma-at-the-21-month-follow-up-301233073.html. Accessed: 02/23/2021.
- Targovax ASA: ONCOS-102 achieves 25.0 months median overall survival in first line mesothelioma. Biospace. Retrieved from: https://www.biospace.com/article/releases/targovax-asa-oncos-102-achieves-25-0-months-median-overall-survival-in-first-line-mesothelioma/. Accessed: 12/20/2021.
- Fast Track. U.S. Food and Drug Administration. Retrieved from: https://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/fast-track. Accessed: 03/23/2021.
- ONCOS-102 plus pemetrexed and platinum chemotherapy in malignant pleural mesothelioma: a randomized phase 2 study investigating clinical outcomes and the tumor microenvironment. Journal for Immunotherapy of Cancer. Retrieved from: https://pubmed.ncbi.nlm.nih.gov/37661097/. Retrieved from: 09/04/2023.