OST-HER2 Meets Primary End Point of Phase 2b Trial in Lung-Only Metastatic Osteosarcoma

The investigational immunotherapy OST-HER2 (OST31-164) led to a statistically significant 12-month event-free survival (EFS) benefit in patients with recurrent, fully resected lung-only metastatic osteosarcoma, meeting the primary end point of an ongoing phase 2b trial (NCT04974008).1

OST-HER2 led to an EFS rate of 33% at 12 months compared with 20% with historical controls2 (P = .0158). All patients who achieved the primary end point of 12-month EFS remain alive. Moreover, data from an interim analysis of overall survival (OS), which continues to be evaluated, showed that the 1-year OS rate with OST-HER2 was 91% compared with 81% with the historical control (P = .0700); the respective OS rates at 2 years were 61% and 40% (P = .0576).

“We are extremely pleased with these results of our phase 2b clinical trial because they show that OST-HER2-treated patients achieved the primary endpoint of 12-month EFS in a statistically significantly higher ratio than comparable historical controls, in addition to increasing the likelihood of 1-year and 2-year survival as compared with comparable historical controls,” Robert Petit, MD, chief medical and scientific officer of OS Therapies, stated in a news release. “The strong safety profile shown in this study also supports the use of OST-HER2 in this incredibly difficult-to-treat population that has no currently approved therapies.”

The phase 2b study enrolled patients with recurred, fully resected, lung-only metastatic osteosarcoma between the ages of 12 and 39 years. They needed to weigh at least 40 kg at the time of diagnosis, have a performance status corresponding with an ECOG performance status ranging from 0 to 2, and have acceptable organ function.3 They also must have fully recovered from any acute adverse effects experienced with any prior chemotherapy, immunotherapy, radiotherapy, or surgery.

If patients had clinically evident metastatic or recurrent disease, concurrent pulmonary recurrence and local recurrence at the primary tumor site, primary refractory disease with progression of the primary tumor on initial treatment, or if they had central nervous system or extrapulmonary disease involvement at the time of the most recent recurrence before enrollment, they were excluded.

A total of 39 evaluable patients from 21 centers were included in the analysis.1 Patients received the immunotherapy as a monotherapy every 3 weeks for 48 weeks with 4 doses constituting 1 treatment cycle and 12 weeks per cycle.3 They received the agent at a dose of 1 x 109 CFU until week 48 or until progressive disease, intolerable toxicity, or other treatment discontinuation criteria were met.

The primary end point of the study was the relative proportion of patients experiencing EFS at 12 months vs historical controls. To do this, patients will be examined for recurrence every 3 months, which is consistent with standard of care. A key secondary end point is 3-year OS vs historical controls. Investigators are also examining the incidence of treatment-emergent adverse effects throughout the 48-week treatment period.

The historical control information was pulled from a prior retrospective analysis of outcomes for patients with recurrent or refractory osteosarcoma enrolled in 1 of 7 phase 2 trials that were done by the Children’s Oncology Group and predecessor groups from 1997 to 2007.2 The analysis leveraged information from a phase 2 study of patients with osteosarcoma who received inhaled granulocyte macrophage colony–stimulating factor with first pulmonary recurrence who had an EFS and biologic end point to identify the historical disease control rate for those with fully resected disease.

Additional findings from post-hoc analyses showed that the 12-month EFS rate with OST-HER2 in female patients (n = 19) was 47% vs 20% in male patients (n = 20; P = .0604).1 In patients who had 1 prior resection (n = 28), the 12-month EFS rate with the agent was 25%; in those with 2 or more prior resections (n = 11), this rate was 55% (P = .1366).

Using a non-concurrent control group (NCCG) from the only existing US osteosarcoma database with patients qualified for disease-free status after a fully resected, lung-only metastasis of osteosarcoma origin, investigators found that the 12-month EFS rate with OST-HER2 was 33% (n = 13/39); the 12-month EFS rate in the NCCG was 11% (n = 1/9; P = .1848).

Moreover, the time to recurrence in patients who did not achieve 12-month EFS was 5.9 months in evaluable patients who received OST-HER2 (n = 26) and 4.7 months in evaluable patients from the NCCG (n = 8; P = .1454).

In 2021, OST-HER2 received rare pediatric disease designation from the FDA.1 The agent also received fast track and orphan drug designations from both the FDA and the European Medicines Agency.

References

1. 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 January 15, 2025. https://ir.ostherapies.com/news-events/press-releases/detail/41/os-therapies-announces-phase-2b-clinical-trial-of-ost-her2
2. Lagmay JP, Krailo MD, Dang H, et al. Outcome of patients with recurrent osteosarcoma enrolled in seven phase II trials through Children’s Cancer Group, Pediatric Oncology Group, and Children’s Oncology Group: learning from the past to move forward. J Clin Oncol. 2016;34(25):3031-3038. doi:10.1200/JCO.2015.65.5381
3. Osteosarcoma maintenance therapy with OST31-164 (OST-164-01). ClinicalTrials.gov. Updated September 28, 2023. Accessed January 15, 2025. https://clinicaltrials.gov/study/NCT04974008