OST-HER2 Shows Significant Final 3-Year OS Benefit in Osteosarcoma Trial

Treatment with OST-HER2 (daznelimgene lisbac; Herlystic) produced a statistically significant improvement in final 3-year overall survival (OS) compared with a combined published historical control in a phase 2b trial (NCT04974008) evaluating the agent in patients with fully resected, pulmonary metastatic osteosarcoma, according to a news release from the drug’s developer, OS Therapies.¹

What did the final 3-year OS analysis show?

The final 3-year OS rate among patients treated with OST-HER2 was 72.7% compared with 45.8% in the combined published historical control group (P = .0006). The analysis included 41 total enrolled patients, with 4 lost to follow-up. The final data follow a previously reported interim 3-year analysis, in which the OS rate was 71.2% with OST-HER2 vs 45.8% in the historical control cohort (P = .002).²

“I am encouraged by the 3-year [OS] results in this trial and am hopeful this could become a potential option for future patients,” said Peter Anderson, MD, a pediatric oncologist at Cleveland Clinic Children’s and a member of the scientific advisory board for OS Therapies, in the news release.¹

What is the regulatory path forward for OST-HER2?

Developers stated that they are working to complete regulatory submissions in the US, UK, Europe, and Australia to enable early market access, with plans to complete a biologics license application (BLA) submission under the accelerated approval program in the US and conditional marketing authorization applications (CMAAs) in Europe, the UK, and Australia in the fourth quarter of 2026. The company reported full alignment on the design of the confirmatory phase 3 trial across international regulatory agencies and said it is preparing to submit a Clinical Trial Authorisation to the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) as a precursor to trial initiation.

“Commencing the phase 3 study is a prerequisite to being granted accelerated approval of a [BLA] by the US [FDA], and [CMAAs] by MHRA, the European Medicines Agency [EMA], and the Australian Therapeutic Goods Administration,” said Craig Eagle, MD, chief medical advisor and a director of OS Therapies, in the news release.¹

What designations and incentives apply to OST-HER2?

OST-HER2 has received orphan drug, fast track, and rare pediatric disease designations from the FDA, as well as orphan drug, PRIME, and advanced therapy medicinal product designations from the EMA. Under the rare pediatric disease designation program, if the company is granted a BLA in the US, it would become eligible to receive a priority review voucher that it intends to sell. The company has also completed resubmission of a regenerative medicine advanced therapy request, and its letter of intent for a Commissioner’s National Priority Voucher has been accepted by the FDA. The World Health Organization recently accepted the proprietary brand name Herlystic for OST-HER2.

What is OST-HER2, and how was the trial designed?

OST-HER2 is a gene-edited, Listeria-based immunotherapy designed to elicit an immune response against the HER2 protein. The agent targets 2 mutated extracellular epitopes and 1 mutated intracellular epitope of the HER2 oncogene, requiring only 1 of the 3 epitopes to be present in a tumor or micrometastasis to trigger the intended response.

In the open-label, multicenter, single-arm phase 2b trial, patients 12 to 39 years of age with histologically confirmed osteosarcoma and at least 1 episode of disease recurrence in the lungs received OST-HER2 at 1 × 10⁹ colony-forming units every 3 weeks for 48 weeks, with 4 doses constituting a 12-week treatment cycle.³

The primary end point was 12-month event-free survival (EFS) vs historical controls. Secondary end points included OS and the incidence of treatment-emergent adverse events.

Previously reported data from the trial demonstrated a statistically significant improvement in the primary 12-month EFS end point, and earlier 2-year OS analyses also favored OST-HER2 over the pooled historical control.

References

1. OS Therapies achieves statistically significant final three-year overall survival benefit for Herlystic-treated patients in phase 2b pulmonary metastatic osteosarcoma trial. News release. OS Therapies, Inc. October 6, 2026. Accessed October 7, 2026. https://tinyurl.com/ms3jj9z6
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/d3xaez8r
3. Osteosarcoma maintenance therapy with OST31-164 (OST-164-01). ClinicalTrials.gov. Updated January 22, 2025. Accessed October 7, 2026. https://tinyurl.com/4vrvb4aj