Final 3-Year OS Reported for OST-HER2 in Lung-Metastatic Osteosarcoma

Daznelimgene lisbac (Herlystic; OST-HER2) was associated with a statistically significant improvement in final 3-year overall survival (OS) over a pooled historical control in patients with fully resected, pulmonary metastatic osteosarcoma.¹

The final analysis of the phase 2b OST31-164-01 trial (NCT04974008) showed a 3-year OS rate of 72.7% (90% CI, 58.3%-82.8%) with daznelimgene lisbac compared with 45.8% (90% CI, 41.6%-50.0%) in a historical control group. The absolute difference was 26.9 percentage points (90% CI, 14.0%-39.7%; P = .0006). Of the 41 patients enrolled, 4 were lost to follow-up.

"I am encouraged by the 3-year overall survival results in this trial and am hopeful this could become a potential option for future patients," said Peter Anderson, MD, pediatric oncologist at Cleveland Clinic Children's in Cleveland, Ohio, and a member of the scientific advisory board for OS Therapies, stated in a news release.

Trial Design and Updated Results

OST31-164-01 is an open-label study in patients aged 12 to 39 years whose osteosarcoma recurred in the lungs and was surgically resected. Daznelimgene lisbac was infused every 3 weeks for 48 weeks, a total of 16 doses, with the goal of preventing or delaying another recurrence.

The primary end point was 12-month event-free survival (EFS), and OS was a secondary end point. OS Therapies previously reported that the trial met the primary end point, with a 12-month EFS rate of 33% vs 20% in a historical control (P = .0158). The final OS results align closely with the interim results previously reportedwhich included a 71.2% 3-year OS rate when 2 of 41 enrolled patients had not yet reached the 3-year follow-up timepoint and 6 were considered lost to follow-up.^1,2

Historical Control Comparison

The historical control was drawn from 5 published studies that together included 467 patients combined on a weighted basis. In the individual studies, 3-year OS estimates ranged from 36.0% to 54.7%. Three of the studies with a total of 90 patients enrolled recurrent, completely resected, pulmonary disease, whereas the other 2 studies, which contributed 377 of the 467 control patients, enrolled patients with recurrent, completely resected disease without restriction on site of metastasis.¹

Mechanism and Regulatory Status

Daznelimgene lisbac is an immunotherapy that uses gene-edited Listeria monocytogenes to provoke an immune response against HER2. According to the company, the agent is directed at 3 mutated HER2 epitopes, 2 extracellular and 1 intracellular, and a tumor or micrometastasis needs to carry only 1 of them for the response to be triggered.

The agent holds FDA orphan drug, fast track, and rare pediatric disease designations, and the company said it has resubmitted a request for regenerative medicine advanced therapy designation. From the European Medicines Agency, it holds orphan drug and fast track designations and is classified as an advanced therapy medicinal product.

OS Therapies said it intends to complete a biologics license application under the accelerated approval pathway in the US in the fourth quarter of 2026, along with conditional marketing authorization applications in Europe, the United Kingdom, and Australia. A confirmatory phase 3 trial is also planned; the company stated that it has aligned with regulators on the phase 3 trial design.

REFERENCES

1. OS Therapies Achieves Statistically Significant Final Three-Year Overall Survival Benefit for Herlystic(TM)-Treated Patients in Phase 2b Pulmonary Metastatic Osteosarcoma Trial. News release. OS Therapies, Inc. October 6, 2026. Accessed October 7, 2026. https://tinyurl.com/47r6yw4w

2. OS Therapies Achieves Statistically Significant Benefit for OST-HER2-Treated Patients in Interim 3-Year Overall Survival Analysis of Phase 2b Pulmonary Metastatic Osteosarcoma Trial. News release. OS Therapies, Inc. September 8, 2026. Accessed October 7, 2026. https://tinyurl.com/44khsb2c