OST-HER2 Extends 12-Month EFS in Osteosarcoma With Lung Metastases

Sarcoma Cells: Developing in connective tissues like bones and muscles, these spindle-shaped cells are known for their aggressiveness and rapid spread: © BEST - stock.adobe.com

OST-HER2 (OST31-164), a HER2-targeted immunotherapy candidate, led to statistically significant 12-month event-free survival (EFS) results when given to patients with recurrent, fully resected osteosarcoma with lung metastases, according to findings from a phase 2b trial (NCT04974008).¹

EFS at 12 months, the primary end point of the phase 2b trial, was 33.3% among patients treated with OST-HER2 vs the peer-reviewed comparable historical control of 20% (P =.0158).

The most recent follow-up data demonstrate a favorable trend for patients treated with OST-HER2 compared with the historical control. At the 1-year interim timepoint, overall survival (OS) was 91% for OST-HER2 vs 80% for the historical control (P =.0700). At the 2-year interim timepoint, OS was 61% for OST-HER2 vs 40% for the historical control (P =.0576). Notably, all patients who achieved the primary 12-month EFS end point remain alive.

“We are extremely pleased with these results of our phase 2b clinical trial because they show that OST-HER2-treated patients achieved the primary end point 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,” said Robert Petit, PhD, chief medical & scientific officer of OS Therapies, in a press 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 2, open-label, multicenter, single-arm study enrolled patients between the ages of 12 and 39 years old with recurred, fully resected lung-only metastatic osteosarcoma.² Patients were treated with OST-HER2 infusions every 3 weeks over 48 weeks. They were then followed for 3 years after.

A total of 39 evaluable patients were enrolled at 21 centers and included in the single treatment arm. According to the 12-months EFS subgroup analysis in the OST-HER2 arm, 19 (47%) patients were female, 28 (25%) patients had 1 prior resection, and 11 (55%) patients had 2 or more prior resections.¹

Using a non-concurrent control group (NCCG) from the only existing US osteosarcoma database with patients qualified for disease-free status following fully resected lung-only metastasis of osteosarcoma origin, 12-month EFS rates were assessed. Among patients treated with OST-HER2, 33% of patients achieved 12-month EFS, compared with 11% in the NCCG group (P =.1848).

For patients who did not achieve 12-month EFS, the median time to recurrence was longer in the OST-HER2 group, at 5.9 months (n = 26), compared with 4.7 months in the NCCG group (n = 8; P =.1454).

“The achievement of the primary end point in the OST-HER2 phase 2b is a tremendous success that opens the possibility, for the first time, of meaningful therapy for patients suffering from osteosarcoma with lung metastases after resection. This is a leap forward in the development of OST-HER2 and we are pleased that our regulatory strategy is consistent with the FDA’s recent draft guidance update for accelerated approvals. With these positive data in hand, we are preparing to engage with the US FDA on an accelerated pathway for approval in this extremely challenging indication,” said Paul Romness, MHP, chair & chief executive officer of OS Therapies, in the press release.¹ “We do not expect to have to treat additional patients as part of this process with FDA.”

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/mx2tsvdk

2. Osteosarcoma maintenance therapy with OST31-164 (OST-164-01). ClinicalTrials.gov. Updated September 28, 2023. Accessed January 16, 2025. https://clinicaltrials.gov/study/NCT04974008