Novel Oncolytic Therapy Holds Promise for Pretreated Solid Tumors

Tumor microenvironment background with cancer cells, T cells, nanoparticles, molecules, and blood vessels: © ratatosk - stock.adobe.com

June is Cancer Immunotherapy Month, and Targeted Oncology is highlighting stories on this developing field of research.

A phase 1/2 study (NCT04673942) presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting investigated a new approach to treating certain solid tumors that have not responded to checkpoint inhibitors.

AdAPT-001 is an oncolytic virus combined with a TGF-β trap that stimulates the immune system to fight the tumor. This study included 36 patients with various solid tumors, including sarcoma, head and neck cancer, and triple-negative breast cancer. Patients received either AdAPT-001 alone or AdAPT-001 combined with a checkpoint inhibitor.

The combination treatment was well-tolerated with mostly mild adverse events. The overall response rate of the combination was 29.1% compared with 22.2% for the monotherapy. The benefit was also observed in patients who had failed prior checkpoint inhibitor treatment.

Moreover, the progression-free survival was 3.5 months, which warrants further evaluation in larger studies. Additionally, some patients with stable tumors on scans showed visible improvement, suggesting this treatment may work in ways not fully captured by standard measurements.

In an interview with Targeted Oncology^TM, Anthony Conley, MD, medical oncologist in the Department of Sarcoma Medical Oncology, Division of Cancer Medicine, at MD Anderson Cancer Center, discussed findings and potential next steps from this research.

Anthony Conley, MD

Targeted Oncology: What was the population this study focused on?

Conley: This study was focused on patients that basically had advanced solid tumors that had at least 1 site of disease that could be accessible by a direct injection or by ultrasound guidance.

What was the study evaluating? What was the methodology of the study?

This was a phase 1/2 study of an oncolytic virus known as AdAPT-001 in combination with checkpoint inhibitors. The idea was to determine if this combination would be more effective at treating patients with an oncolytic virus than what you typically get with an immunotherapy, such as an immune checkpoint inhibitor, by itself. Importantly, about 70% of the patients had prior exposure to immune checkpoint inhibitors.

Could you summarize your findings?

What was interesting, as I mentioned before, was that 70% of the patients had prior immune checkpoint inhibitor experience. What we found was that in this heavily pretreated population, approximately 20% of patients had a response by RECIST criteria. There were several patients that had disease progression by RECIST, and in those cases, we continued treatment. They then went on to respond, increasing the overall response rate from 20% to the30% range. In addition, we found that sarcomas, which were enriched in this cohort, also derived benefit.

Were there any adverse events observed?

What was cool about this particular combination is that we found no serious adverse events or dose-limiting toxicities that were directly related to AdAPT-001by itself. 

In general with oncolytic therapies, are they associated with any specific adverse events? Or do they typically have a safer profile than other therapies?

I would say compared with cellular therapies or immune checkpoint blockade, what we typically see is that most patients will have flu-like symptoms. In this particular study, 84% of patients had grade 1 or grade 2 flu-like symptoms that usually resolved within 24 to 48 hours. Importantly, when we inject the tumors, we do not see any surrounding tissue damage.

What would be the main takeaways from this study?

I think this study helps to show that oncolytic viruses can have potent activity and can augment the responsiveness that we see with immune checkpoint inhibitors, and the activity is broad. It is not limited to 1particular type of tumor, but it seems to be seen across the board from rare diseases like sarcomas to more common diseases like triple-negative breast cancer.

What are the next steps for this research?

I think the next plans are basically to expand out and see where there are specific areas of interest in both rare diseases like sarcomas, but also in other disease types, like I said earlier, such as triple-negative breast cancer [and] hepatocellular carcinoma, and there are plans to do different types of infusions, not just intratumoral infusions, but also intraarterial infusions. There is a lot to be learned, and we are excited about seeing how we can potentially use this to help patients with their cancer care.

REFERENCES:

Conley A, Ravi V, Roland C, et al. Phase 1/2 study of the TGF-β-trap-enhanced oncolytic adenovirus, AdAPT-001, plus an immune checkpoint inhibitor for patients with immune refractory cancers. Presented at: 2024 American Society of Clinical Oncology Annual Meeting; May 31-June 4, 2024; Chicago, IL. Abstract 2506.