Patients with fully resected pulmonary metastatic osteosarcoma treated with the investigational Listeria-based immunotherapy OST-HER2 had a reported 3-year overall survival rate of 71.2%, compared with 45.8% in a pooled historical control population (p = 0.002). The results come from an interim analysis of an ongoing Phase 2b trial in a disease setting where treatment options have changed little over several decades. OS Therapies, Inc. reported the findings on September 8, 2026. The company is now preparing for an FDA Type C meeting expected in mid-September to discuss whether the survival data, which are based on a pooled historical control rather than a randomized concurrent comparator, could support a Biologics License Application under the FDA’s Accelerated Approval Program. This regulatory discussion matters because the study is open-label and single-arm. While the reported survival difference reached statistical significance against the historical comparator, the study design does not provide the same level of evidence as a randomized trial with a concurrent control group.
Key Takeaways
- 71.2% vs 45.8%: The reported 3-year overall survival rate was 71.2% among patients treated with OST-HER2, compared with 45.8% in a pooled historical control population (p = 0.002).[1]
- Single-arm, historically controlled design: The trial is open-label and single-arm. Its efficacy comparisons rely on pooled, nonconcurrent historical data from previously published studies rather than a randomized control group.
- FDA review: An FDA Type C meeting scheduled for mid-September 2026 is expected to address whether the historical-control approach can support a BLA under the Accelerated Approval Program.[1]
- OST-HER2 is investigational and is not approved by the FDA, EMA, MHRA, or any other regulatory authority.
A Rare Disease With an Old Standard of Care
Osteosarcoma is the most common primary malignant bone tumor in children and young adults. For patients who develop pulmonary metastases after treatment of the primary tumor, surgery to remove recurrent lung nodules remains an important part of care. Treatment options for this group have changed little over the past several decades. There is currently no oncology drug specifically approved to prevent recurrence after complete resection of pulmonary metastatic osteosarcoma.
Craig Eagle, MD, chief medical advisor at OS Therapies, has described the interim findings in the context of the long-standing need for new treatment options in this population and the potential for earlier patient access.[1][2] That unmet need is separate from how the efficacy data should be interpreted. The OST-HER2 study is a single-arm trial and does not include a randomized concurrent control group.
Mechanism: A Gene-Edited Bacterial Vector Against HER2
OST-HER2, also designated OST31-164, is based on a live, gene-edited strain of Listeria monocytogenes. The investigational therapy is engineered to stimulate an immune response against three specific epitopes of the HER2 oncoprotein – two mutated extracellular epitopes and one mutated intracellular epitope. According to the reported study description, the presence of any one of the three epitopes in a tumor or micrometastasis is sufficient to trigger the intended immune response.[2][5] Patients in the trial received OST-HER2 intravenously at 1 × 10⁹ colony-forming units every three weeks for up to 48 weeks, or until disease progression, unacceptable toxicity, or another specified discontinuation criterion was reached.[1][2]
Trial Design and Patient Population
The Phase 2b study (ClinicalTrials.gov identifier NCT04974008) is an open-label, multicenter, single-arm trial. It enrolled patients 12 to 39 years of age with histologically confirmed osteosarcoma and at least one episode of pulmonary recurrence following complete surgical resection.[6][7] Patients were required to have an ECOG performance status of 0 to 2, adequate organ function, and recovery from the toxic effects of previous treatment. The researchers excluded patients with clinically evident metastatic or local recurrent disease at enrollment, concurrent pulmonary and local recurrence, or primary refractory disease.[6]
Disease surveillance was performed with imaging every three months, consistent with postsurgical monitoring in this patient population.[6] Because the study has no concurrent control group, efficacy comparisons are based on a pooled historical control assembled from five previously published trials. Those studies ranged from 10 to 339 patients and reported 3-year overall survival rates from 36.0% to 54.7%. Three of the five studies specifically examined recurrent, completely resected pulmonary metastatic disease. The other two included patients with resected metastatic disease but were not limited to pulmonary metastases.[6]
The use of these nonconcurrent historical data is an important part of the regulatory discussion surrounding OST-HER2. The FDA’s upcoming Type C meeting is expected to address whether this methodology is acceptable for evaluating the reported efficacy results.
Efficacy Results Across Endpoints
The study’s primary endpoint was 12-month event-free survival. The reported rate was 33% among patients treated with OST-HER2, compared with a 20% historical benchmark (p = 0.0156; reported elsewhere as p = 0.0158).[1][6] The company also reported that all patients who remained event-free at 12 months were alive at the time of subsequent analysis.[7] Overall survival, a secondary endpoint, has been reported at several interim timepoints as follow-up has continued.
In an August 2025 interim analysis, 2-year overall survival was reported at 66.6% (18 of 27 evaluable patients), compared with 40% in the historical control group (p = 0.0046).[1][6][7] A subsequent final 2-year analysis reported a 75% overall survival rate among 36 evaluable patients, compared with 40% in the historical controls (p <0.0001).[6][7] At a 2.5-year analysis reported in mid-2026, overall survival was 75%, compared with 47% in the historical comparator group (p = 0.003).[8]
The latest interim 3-year analysis reported overall survival of 71.2%, compared with 45.8% in the pooled historical control (p = 0.002; 90% CI, 11.9%-38.9%).[1][6][7] The trial enrolled 41 patients in total. At the time of the 3-year interim analysis, six patients had been recorded as lost to follow-up, while two had not yet reached the 3-year timepoint from enrollment. Monitoring visits for those patients were scheduled for September and early October 2026.[1][2]
Safety
Thirteen patients experienced serious adverse events during the study. Seven of those events were assessed as related to treatment.[6][7] All seven treatment-related serious adverse events were grade 3. No grade 4 or grade 5 treatment-related serious adverse events were reported, and no patient discontinued treatment because of a treatment-related serious adverse event.[6][7] A more detailed accounting of adverse events by system organ class and grade has not yet been made available beyond the company-reported summaries.
Regulatory Path and What Remains Unverified
OS Therapies has said it plans to pursue a BLA under the FDA’s Accelerated Approval Program. The company has also announced plans to submit Conditional Marketing Authorization Applications to the UK’s Medicines and Healthcare products Regulatory Agency, the European Medicines Agency, and Australia’s Therapeutic Goods Administration. The company has targeted submissions for the fourth quarter of 2026 and potential commercial availability in 2027.[1][2]
A rolling BLA submission reportedly began in January 2026. The company has requested rolling review pending the outcome of the Type C meeting with the FDA’s Center for Biologics Evaluation and Research, scheduled for mid-September 2026. The meeting is expected to focus specifically on whether the pooled historical-control methodology is acceptable for evaluating efficacy.[3][7]
OST-HER2 has received Orphan Drug, Fast Track, and Rare Pediatric Disease designations from the FDA. It also has Orphan Drug, Fast Track, and Advanced Therapy Medicinal Product designations from the EMA. The company has resubmitted a request for Regenerative Medicine Advanced Therapy designation and has had a letter of intent accepted for a Commissioner’s National Priority Review Voucher.[1][2]
Several aspects of the available evidence require caution.
To date, the reported efficacy and safety figures come from company press releases and secondary trade-press reports. As of this writing, the trial’s efficacy results do not appear to have been published in a peer-reviewed, PubMed-indexed publication. The reported findings therefore remain preliminary and have not yet undergone independent peer review. The lack of a randomized concurrent control group also limits conclusions from the survival comparison. The available study design cannot separate differences between the OST-HER2 trial population and the historical comparator populations—including differences in patient selection, treatment era, and surveillance—from the treatment effect. The FDA’s Type C meeting is expected to address this issue.
The study is also small, with 41 patients enrolled and six reported as lost to follow-up at the time of the interim 3-year analysis. These factors limit the precision of the reported survival estimates. The 71.2% versus 45.8% comparison should therefore be understood as a company-reported interim finding from an ongoing, single-arm study. It should not yet be presented as independently validated evidence of a survival benefit.
Clinical trials
Osteosarcoma Maintenance Therapy With OST31-164 (OST-164-01) – ClinicalTrials.gov ID NCT04974008
References
[1] OS Therapies, Inc. 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. Press release via Newsfile Corp. September 8, 2026.
[2] OS Therapies Inc. OS Therapies Provides OST-HER2 Metastatic Osteosarcoma Program Update and Announces Upcoming Conference Attendance. Press release via Newsfile Corp. September 2, 2026.
Editorial transparency note: Treat the survival and safety figures reported here as preliminary, company-reported data pending independent peer review and the outcome of the FDA’s Type C statistical methods meeting regarding the trial’s historical-control design. This article is intended for informational purposes for healthcare professionals and does not constitute medical advice.
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