OST-HER2 Yields Significant 3-Year Survival in Pulmonary Osteosarcoma

Treatment with OST-HER2 (OST31-164) produced a statistically significant improvement in 3-year overall survival (OS) compared with a combined published historical control in an interim analysis of 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

The interim 3-year OS rate among patients who received OST-HER2 was 71.2% vs 45.8% in the comparable combined historical control group (P = .002). The analysis included 41 enrolled patients, 6 of whom were lost to follow-up. The 2 remaining patients who have not yet reached the 3-year time point from enrollment have trial monitoring visits scheduled for September 2026 and early October 2026.

“We believe the increasing survival benefit as time goes on for [patients treated with] OST-HER2 when compared with any and all available published literature in [patients with] fully resected metastatic osteosarcoma, including data published as recently as 2026, presents a compelling case for early market access for [patients with] osteosarcoma who have not seen a new drug approved in the last 40 years,” Craig Eagle, MD, chief medical advisor and member of the OS Therapies Board of Directors, said in the news release.¹

Developers intend to complete regulatory submissions to the FDA, MHRA, EMA, and Australia’s Therapeutic Goods Administration in the months ahead, with the goal of making OST-HER2 commercially available in 2027. The company is seeking a biologics license application (BLA) under the accelerated approval program in the US and conditional marketing authorization applications in Europe, the UK, and Australia in the fourth quarter of 2026.¹

OS Therapies plans to request rolling review of the BLA submission that began in January 2026 following its FDA Type C Statistical Methods Meeting, which is scheduled for mid-September 2026.^1,2 The company has also completed resubmission of a regenerative medicine advanced therapy (RMAT) designation request, and its letter of intent for a Commissioner’s National Priority Review Voucher has been accepted by the FDA. OST-HER2 previously received orphan drug, fast track, and rare pediatric disease designations from the FDA, as well as orphan drug, fast track, and advanced therapy medicinal product designations from the EMA.

Additionally, the company reported receiving $3.15 million in value-added tax refunds through its OS Therapies UK subsidiary, with at least $7.2 million in additional refundable tax credits pending. Those funds are earmarked to initiate a confirmatory phase 3 trial in the UK, which must begin before an FDA decision on a BLA under the accelerated approval program.¹

“The opening of that confirmatory trial following the upcoming MHRA meeting will initially be limited to the UK because of MHRA allowing the company to use existing phase 2 drug product to open that confirmatory phase 3 trial,” Paul Romness, MPH, chair and chief executive officer of OS Therapies, said in the news release.¹

The 3-year findings build on the 2.5-year OS data that prompted the FDA to grant the Type C meeting in August 2026. At that time point, the OS rate was 75% with OST-HER2 vs 47% with the pooled historical control (P = .003), with no new patient deaths reported between the 2- and 2.5-year analyses.^2,3

In October 2025, final 2-year OS data showed that 27 of 36 patients (75%) evaluable for efficacy were alive as measured from the most recent pulmonary resection compared with 40% of historical control patients (P <.0001).⁴ All patients who achieved 12-month event-free survival (EFS) reached 2-year OS vs 59% of those who did not. An earlier interim analysis in August 2025 reported a 2-year OS rate of 66.6% (n = 18/27) vs 40% in the historical control cohort (P = .0046).⁵

Data presented at the 2025 MIB Factor Osteosarcoma Conference showed that 14 of 40 patients (35%) treated with OST-HER2 achieved 1-year EFS compared with a historical rate of 20% (P = .0194).⁶ Thirteen patients experienced serious adverse effects (SAEs), 7 of which were related to the study drug. All 7 treatment-related SAEs were grade 3 in severity, with no grade 4 or 5 events and no discontinuations attributed to treatment-related SAEs.

In the open-label, multicenter, single-arm trial, patients 12 to 39 years old with histologically confirmed osteosarcoma and at least 1 episode of disease recurrence in the lungs received OST-HER2 at 1 x 10⁹ colony-forming units every 3 weeks for 48 weeks, with 4 doses constituting a 12-week treatment cycle.⁷ Treatment continued until disease progression, unacceptable toxicity, or other discontinuation criteria were met. The primary end point was 12-month EFS vs historical controls; secondary end points included OS and the incidence of treatment-emergent AEs. Examinations for recurrence occurred every 3 months, consistent with standard of care.

Eligible patients had an ECOG performance status of 0 to 2, adequate organ function, and full recovery from acute toxicity associated with prior therapy. Those with clinically evident metastatic or recurrent disease, concurrent pulmonary and local recurrence, or primary refractory disease were excluded.

OST-HER2 is a gene-edited, Listeria-based immunotherapy designed to elicit an immune response against HER2. 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.

References

1. 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 September 9, 2026. https://tinyurl.com/d3xaez8r
2. OS Therapies granted U.S. FDA Type C Statistical Methods meeting to review 2.5-year overall survival data for OST-HER2 in the prevention or delay of recurrence in fully resected, pulmonary metastatic osteosarcoma. News release. OS Therapies, Inc. August 13, 2026. Accessed September 9, 2026. https://tinyurl.com/3vszsft7
3. OS Therapies achieves statistically significant 2.5-year overall survival in phase 2b trial of OST-HER2 in fully resected pulmonary metastatic osteosarcoma. News release. OS Therapies, Inc. June 2, 2026. Accessed September 9, 2026. https://tinyurl.com/5ykcab3y
4. OS Therapies announces statistically significant positive final 2-year overall survival data from phase 2b trial of OST-HER2 in the prevention or delay of recurrent, fully-resected, pulmonary metastatic osteosarcoma. News release. OS Therapies, Inc. October 10, 2025. Accessed September 9, 2026. https://tinyurl.com/3nzbtpky
5. 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 September 9, 2026. https://tinyurl.com/2f8d62ct
6. 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 September 9, 2026. https://tinyurl.com/ysmsw7pp
7. Osteosarcoma maintenance therapy with OST31-164 (OST-164-01). ClinicalTrials.gov. Updated January 22, 2025. Accessed September 9, 2026. https://tinyurl.com/4vrvb4aj