OS Therapies Seeks RMAT Designation for OST-HER2 in Pediatric Lung-Metastatic Osteosarcoma

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OS Therapies has submitted a request to the FDA for regenerative medicine advanced therapy (RMAT) designation for OST-HER2 (OST31-164), an investigational immunotherapy being evaluated for the prevention of metastases in pediatric patients with recurrent, fully resected, lung-metastatic osteosarcoma.¹

RMAT designation is granted to regenerative medicine therapies intended to treat serious or life-threatening conditions and provides enhanced regulatory support, including eligibility for an accelerated biologics license application (BLA) review process.

This regulatory request follows positive findings from an ongoing phase 2b clinical trial (NCT04974008), which demonstrated that OST-HER2 met its primary end point by achieving a statistically significant improvement in 12-month event-free survival (EFS).² Patients treated with OST-HER2 experienced a 12-month EFS rate of 33% compared with 20% in a historical control cohort (P = .0158). Of note, the primary end point of 12-month EFS was assessed by evaluating patients who underwent imaging every 3 months, consistent with standard clinical surveillance protocols.

Moreover, all patients who achieved 12-month EFS with OST-HER2 remain alive. Interim overall survival (OS) data also favored OST-HER2, with a 1-year OS rate of 91% vs 81% with historical controls (P = .0700) and 2-year OS rates of 61% vs 40%, respectively (P = .0576).

OST-HER2 has previously received Rare Pediatric Disease Designation (RPDD), Orphan Drug Designation (ODD), and Fast Track Designation (FTD) from the FDA for the treatment of osteosarcoma.¹

OS Therapies anticipates receiving regulatory feedback from the FDA by mid-June 2025 following a Type D meeting focused on the statistical analysis plan for OST-HER2 in the prevention of metastases in recurrent, fully resected, lung-metastatic pediatric osteosarcoma.

Based on this feedback, the company plans to promptly initiate an end of phase 2 meeting with the agency, during which it will seek alignment on a pathway to begin a rolling BLA submission. Pending FDA agreement, OS Therapies aims to initiate the BLA filing process in the third quarter of 2025.

Phase 2 Study Design and Enrollment Criteria

The phase 2b study evaluating OST-HER2 was designed as a multicenter trial assessing the safety and efficacy of the investigational immunotherapy in patients with recurrent, fully resected, lung-only metastatic osteosarcoma.³

Eligible participants were between 12 and 39 years of age, weighed at least 40 kg at diagnosis, had an ECOG performance status of 0 to 2, and demonstrated adequate organ function. All patients were required to have fully recovered from prior therapies, including chemotherapy, immunotherapy, radiotherapy, or surgery, before study enrollment.

Key exclusion criteria included the presence of clinically evident metastatic or recurrent disease, concurrent pulmonary and local recurrence at the primary tumor site, primary refractory disease with progression during initial treatment, and evidence of central nervous system or extrapulmonary metastases at the time of most recent recurrence.

A total of 39 evaluable patients from 21 sites were included in the final analysis.² Patients received OST-HER2 monotherapy administered 16 times every 3 weeks for up to 48 weeks. The dosing regimen consisted of 4 doses per 12-week treatment cycle, with a total of 4 cycles permitted.³ The administered dose was 1 x 10⁹ colony-forming units (CFU) per infusion, continued until completion of the 48-week treatment period, disease progression, unacceptable toxicity, or fulfillment of other predefined discontinuation criteria.

The primary end point of 12-month EFS was assessed by evaluating patients who underwent imaging every 3 months, consistent with standard clinical surveillance protocols. A key secondary end point was OS at 3 years. Safety assessments included the incidence and characterization of treatment-emergent adverse events throughout OST-HER2 administration.

References

1. OS Therapies submits request for regenerative medicine advanced therapy (RMAT) designation to U.S. FDA for OST-HER2 in the prevention of metastases in recurrent, fully-resected, lung metastatic pediatric osteosarcoma. News release. OS Therapies, Inc. June 6, 2025. Accessed June 9, 2025. https://ir.ostherapies.com/news-events/press-releases/detail/63/os-therapies-submits-request-for-regenerative-medicine
2. OS Therapies announces phase 2b clinical trial of OST-HER2 achieves primary endpoint with statistical significance in the prevention of recurrent, fully resected, lung metastatic osteosarcoma. News release. OS Therapies, Inc. January 15, 2025. Accessed June 9, 2025. https://ir.ostherapies.com/news-events/press-releases/detail/41/os-therapies-announces-phase-2b-clinical-trial-of-ost-her2
3. Osteosarcoma maintenance therapy with OST31-164 (OST-164-01). ClinicalTrials.gov. Updated January 22, 2025. Accessed June 9, 2025. https://clinicaltrials.gov/study/NCT04974008