OST-HER2 Significantly Prevents Recurrent Lung Metastatic Osteosarcoma

Developers designed OST-HER2 to harness the immune-stimulatory effects of Listeria bacteria to facilitate strong immune responses targeting the HER2 protein.

Treatment with the investigational HER2-directed immunotherapy OST-HER2 (OST31-164) showed statistically significant event-free survival (EFS) in the prevention of recurrent, fully resected, lung metastatic osteosarcoma, according to a press release on findings from a phase 2b clinical trial (NCT04974008).¹

At 12 months, the EFS rate was 33% with OST-HER2 in the phase 2b trial compared with 20% in a peer-reviewed historical control cohort.² In an interim analysis of the secondary end point of overall survival (OS), the 1-year rates were 91% with OST-HER2 vs 80% in a historical population (P = .0700).³ The 2-year rates in each respective population were 61% vs 40% (P = .0576).

Post hoc analysis data show 12-month EFS rates of 47% among female patients (n = 19) and 20% among male patients (n = 20; P = .0604). Additionally, the 12-month EFS rates were 25% in patients with 1 prior lung resection (n = 28) and 55% for those with 2 or more prior resections (n = 11; P = .1366).

Investigators also compared findings from the phase 2b trial with those reported from a non-concurrent control group described as the only existing osteosarcoma database in the US that includes patients qualified for disease-free status after a fully resected lung metastasis of osteosarcoma origin. Overall, 33% (n = 13/39) of patients in the OST-HER2 cohort were EFS responders at 12 months compared with 11% (n = 1/9) in the control group (P = .1848). The time to recurrence in those who did not achieve EFS at 12 months was 5.9 months and 4.7 months in each respective group (P = .1454).

“We are extremely pleased with these results of our phase 2b clinical trial because they show that OST-HER2 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, PhD, chief medical & scientific officer at OS Therapies, the developer of OST-HER2, stated in the press release.¹ “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.”

Developers designed OST-HER2 to harness the immune-stimulatory effects of Listeria bacteria to facilitate strong immune responses targeting the HER2 protein.

In this open-label, multicenter, single-arm phase 2b study, patients were assigned to receive OST-HER2 at a dose of 1 x 10⁹ colony forming units every 3 weeks for 48 weeks or until progressive disease, unacceptable toxicity, or any other discontinuation criteria.⁴

The trial’s primary end point was EFS, with events defined as the recurrence of metastatic osteosarcoma. The trial’s secondary end point was OS; investigators also assessed the incidence of treatment-emergent adverse effects per CTCAE v5.0 criteria.

Patients 12 to 39 years old with a histologic confirmation of osteosarcoma and at least 1 instance of disease recurrence in the lungs were eligible for enrollment on the study. Additional eligibility criteria included having an ECOG performance status of 0 to 2 and adequate organ function.

“The achievement of the primary endpoint in the OST-HER2 phase 2b [study] is a tremendous success that opens the possibility, for the first time, of meaningful therapy for patients [who have] osteosarcoma with lung metastases after resection…With these positive data in hand, we are preparing to engage with US FDA on an accelerated pathway for approval in this extremely challenging indication,” Paul Romness, MHP, chair & chief executive officer at OS Therapies, concluded.¹

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 16, 2025. https://tinyurl.com/2acuznh5
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. AH Aljubran, A Griffin, M Pintilie, M Blackstein. Osteosarcoma in adolescents and adults: survival analysis with and without lung metastases. Ann Oncol. 2009;20(6):1136-1141. doi:10.1093/annonc/mdn731
4. Osteosarcoma maintenance therapy with OST31-164 (OST-164-01). ClinicalTrials.gov. Updated September 28, 2023. Accessed January 16, 2025. https://tinyurl.com/mr5amxz5