OST-HER2 Yields Significant Survival in Pulmonary Metastatic Osteosarcoma

In June 2025, investigators presented findings from the phase 2b trial at the 2025 MIB Factor Osteosarcoma Conference, demonstrating an EFS rate of 35% (n = 14/40) among evaluable patients

Treatment with OST-HER2 (OST31-164) produced a statistically significant improvement in overall survival (OS) among a small cohort of patients with recurrent, fully resected, pulmonary metastatic osteosarcoma, according to a press release on updated interim findings from a phase 2b trial (NCT04974008).¹

The 2-year OS rate among patients who received OST-HER2 was 66.6% (n = 18/27). This outcome exceeded a 2-year OS rate of 40% in a historical control cohort of patients with osteosarcoma (P = .0046).²

The FDA has also issued a biologics license application (BLA) number for OST-HER2 to receive an application submission after an End of Phase 2 Meeting slated for August 27, 2025. Additionally, developers have responded to the agency’s correspondence, aiming to align on approval metrics for regenerative medicine advanced therapy designation, breakthrough therapy designation, and the BLA based on the accelerated approval program.

“We are seeking to bring this novel immunotherapy to market to improve the survival rates in pulmonary metastatic osteosarcoma, and today’s updated interim [OS] data continue to show a statistically significant benefit for OST-HER2–treated patients compared with control,” Paul Romness, MPH, chairman and chief executive officer at OS Therapies, the developers of OST-HER2, stated in the press release.¹ “We believe that continued statistically significant outperformance in [OS] of OST-HER2–treated patients compared with historical control, together with the statistically significant positive 12-month event- free survival [EFS] data presented at MIB Factor in June 2025, will provide the necessary scientific and medical basis to support a BLA under the FDA's accelerated approval program.”

In June 2025, investigators presented findings from the phase 2b trial at the 2025 MIB Factor Osteosarcoma Conference, demonstrating an EFS rate of 35% (n = 14/40) among evaluable patients.³ Safety findings showed that 13 patients had severe adverse effects (AEs), including 7 that were related to treatment with OST-HER2. All 7 treatment-related toxicities were grade 3 in severity; no grade 4/5 AEs occurred. Additionally, no patients discontinued treatment with OST-HER2 at the time of analysis.

“The updated OST-HER2 data presented at MIB Factor…showed EFS data statistically significantly favoring [patients who received] OST-HER2 when compared with the leading peer-reviewed publications on historical [EFS] outcomes in this subset of the pulmonary metastatic osteosarcoma patient population. The favorable safety profile of OST-HER2 compared with standard of care is also an important quality of life factor when assessing potential new treatment options for this difficult-to-treat patient population,” Robert Petit, PhD, chief medical and scientific officer of OS Therapies, said in a prior press release.³

In the open-label, multi-center, single-arm trial, patients received OST-HER2 at 1 x10⁹ colony-forming units every 3 weeks for 48 weeks.⁴ Treatment continued until progressive disease, unacceptable toxicity, or fulfillment of any other discontinuation criteria.

The trial’s primary end point was EFS. Other end points included OS and incidence of treatment-emergent AEs.

Patients 12 to 39 years old with a histologic confirmation of osteosarcoma at diagnosis and at least 1 episode of disease recurrence in the lungs were eligible for enrollment on the trial. Other eligibility criteria included having an ECOG performance status of 0 to 2; full recovery from acute toxicity associated with any prior chemotherapy, immunotherapy, radiotherapy, or surgery; and adequate organ function.

Those with clinically evident metastatic or recurrent disease, concurrent pulmonary recurrence and local recurrence at the primary tumor site, or primary refractory disease with progression of the primary tumor on initial treatment were ineligible for study entry.

References

1. OS Therapies announces statistically significant positive interim 2-year overall survival data from phase 2b clinical trial of OST-HER2 in the prevention or delay of recurrent, fully resected, pulmonary metastatic osteosarcoma. News release. OS Therapies, Inc. August 7, 2025. Accessed August 7, 2025. https://tinyurl.com/2f8d62ct
2. Aljubran AH, Griffin A, Pintilie M, Blackstein M. Osteosarcoma in adolescents and adults: survival analysis with and without lung metastases. Ann Oncol. 2009;20(6):1136-41. doi:10.1093/annonc/mdn731. Erratum in: Ann Oncol. 2021;32(3):424. doi: 10.1016/j.annonc.2020.12.011
3. OS Therapies presents statistically significantly positive 1-Year event free survival, overall survival and safety clinical data updates for OST-HER2 at the MIB Agents Factor Osteosarcoma Conference. News release. OS Therapies, Inc. June 30, 2025. Accessed August 7, 2025. https://tinyurl.com/ysmsw7pp
4. Osteosarcoma maintenance therapy with OST31-164 (OST-164-01). ClinicalTrials.gov. Updated January 22, 2025. Accessed July 1, 2025. https://tinyurl.com/mptma4ub