Rolling FDA BLA Submission for OST-HER2 Begins for Fully Resected Pulmonary Metastatic Osteosarcoma

OS Therapies has initiated a rolling submission of a biologics license application (BLA) to the FDA seeking the approval of OST-HER2 (OST31-164) for the prevention or delay of recurrence in patients with fully resected pulmonary metastatic osteosarcoma.¹

The regulatory effort follows an October 2025 disclosure of final 2-year overall survival (OS) findings from a phase 2b study (NCT04974008). In evaluable patients (n = 36), the 2-year OS rate was 75%, exceeding a 40% historical control (P < .0001); the analysis did not include 5 patients lost to follow-up.² Patients who achieved event-free survival (EFS) of at least 12 months achieved a 2-year OS rate of 100%, whereas those who had an EFS event before 12 months had a 2-year OS rate of 59%.

According to the news release, the non-clinical and chemistry, manufacturing, and controls (CMC) modules have already been submitted to the FDA with a request for rolling review.¹ Following an FDA invitation after a December 2025 Type C meeting, OS Therapies—the developer of OST-HER2—has also requested a Type D meeting to review new comparative oncology biomarker data spanning the phase 2b human trial and a parallel canine osteosarcoma study.

The company expects to submit the clinical module by the end of March 2026, with an anticipated pathway that could support an FDA action timeline by September 30, 2026.

“We are delighted in the FDA's interest in reviewing OST-HER2 comparative oncology data,” Paul Romness, MPH, chairman and chief executive officer of OS Therapies, stated in a news release. “There is strong demand for compassionate use of OST-HER2 from the patient community, underscoring the urgent need for new therapies in human metastatic osteosarcoma. We remain committed to bringing OST-HER2 to market as expeditiously as possible and are grateful for [the] FDA's engagement as we finalize the biomarker data package that will be submitted as part of Type D meeting preparations to support our request for a BLA under the accelerated approval program."

How was the phase 2b trial evaluating OST-HER2 designed?

The phase 2b study was an open-label, multicenter, single-arm trial that enrolled patients 12 to 39 years of age with a body weight of at least 40 kg and histologically confirmed osteosarcoma who had experienced at least 1 pulmonary recurrence.³ There was no cap on the number of lung recurrences permitted for enrollment. Key eligibility requirements included surgical resection of all suspected pulmonary metastases with the intent to achieve complete remission within 8 weeks prior to enrollment, as well as pathologic confirmation of osteosarcoma from at least 1 resected tumor. Radiographic confirmation of complete remission was not required; however, patients were required to undergo a postoperative chest CT scan.

Additional inclusion criteria included a Karnofsky performance status (for patients over 16 years of age) or Lansky performance status (for patients 16 years of age or younger) corresponding to an ECOG performance status of 0 to 2; recovery from acute toxicities related to prior therapies; and adequate organ function. Patients were excluded if they had metastatic or recurrent disease beyond the lungs, concurrent pulmonary and local recurrence at the primary tumor site, primary refractory disease with progression on initial therapy, or central nervous system or other extrapulmonary involvement at the time of the most recent recurrence.

Patients received OST-HER2 at 1 × 10⁹ CFU every 3 weeks for 48 weeks, with 1 cycle defined as 12 weeks. Treatment continued through week 48 unless patients experienced disease progression, unacceptable toxicity, or met other discontinuation criteria. The primary end point was EFS, with OS and safety assessed as secondary end points.

References

1. OS Therapies initiates US FDA BLA filing for OST-HER2 in the prevention or delay of recurrent, fully resected, pulmonary metastatic osteosarcoma. News Release. February 2, 2026. Accessed February 6, 2026. https://ir.ostherapies.com/news-events/press-releases/detail/98/os-therapies-initiates-us-fda-bla-filing-for-ost-her2-in
2. 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. October 10, 2025. Accessed October 10, 2025. https://ir.ostherapies.com/news-events/press-releases/detail/85/os-therapies-announces-statistically-significant-positive
3. Osteosarcoma maintenance therapy with OST31-164 (OST-164-01). ClinicalTrials.gov. Updated January 22, 2025. Accessed February 6, 2025. https://clinicaltrials.gov/study/NCT04974008