Abstract
This was a single-arm, phase 2 clinical trial of Bavarian Nordic (BN)-Brachyury vaccine plus radiotherapy (RT) designed to determine the objective response rate (ORR), progression-free survival (PFS), and safety of the combination in chordoma. A total of 29 adult patients with advanced chordoma were treated with two subcutaneous priming vaccine doses of modified vaccinia Ankara-Bavarian Nordic (MVA-BN)-Brachyury and one vaccine dose of fowlpox virus (FPV)-Brachyury before RT. After RT, booster vaccinations were given with FPV-Brachyury every 4 weeks for 4 doses, then every 12 weeks (week 110). A minimum RT dose of >8 Gy in one fraction for each target was required. Response was evaluated by modified Response Evaluation Criteria in Solid Tumors 1.1 (mRECIST), where only radiated lesions were considered targets, and by standard RECIST 1.1 in a subset of patients. Two of 26 evaluable patients experienced durable partial response (PR) (ORR of 7.7%; 90% confidence interval [CI], 2.6-20.8]) by mRECIST 1.1. A total of 21 patients (80.8%; 90% CI, 65.4-90.3) had stable disease, and three patients (11.5%; 90% CI, 4.7-25.6) had progressive disease as best response per mRECIST 1.1. Median PFS was not reached during the study. This trial confirms the safety of BN-Brachyury and RT. Although the study did not meet the predefined study goal of four responses in 29 patients, we did observe two PRs and a PFS of greater than 2 years. For a vaccine-based study in chordoma, an ultra-rare disease where response rates are low, a randomized study or novel trial designs may be required to confirm activity.
Overview
- The study aimed to determine the objective response rate (ORR), progression-free survival (PFS), and safety of Bavarian Nordic (BN)-Brachyury vaccine plus radiotherapy (RT) in chordoma patients. The study was a single-arm, phase 2 clinical trial that included 29 adult patients with advanced chordoma. The patients received two subcutaneous priming vaccine doses of modified vaccinia Ankara-Bavarian Nordic (MVA-BN)-Brachyury and one vaccine dose of fowlpox virus (FPV)-Brachyury before RT. After RT, booster vaccinations were given with FPV-Brachyury every 4 weeks for 4 doses, then every 12 weeks (week 110). The response was evaluated by modified Response Evaluation Criteria in Solid Tumors 1.1 (mRECIST), where only radiated lesions were considered targets, and by standard RECIST 1.1 in a subset of patients. The study did not meet the predefined study goal of four responses in 29 patients, but it observed two durable partial response (PR) and a PFS of greater than 2 years. The study confirms the safety of BN-Brachyury and RT.
Comparative Analysis & Findings
- The study compared the outcomes observed under different experimental conditions or interventions, including the combination of BN-Brachyury vaccine and RT versus RT alone. The study found that the combination of BN-Brachyury vaccine and RT resulted in two durable PRs and a PFS of greater than 2 years, although it did not meet the predefined study goal of four responses in 29 patients. The study also found that the combination of BN-Brachyury vaccine and RT was safe.
Implications and Future Directions
- The study's findings suggest that the combination of BN-Brachyury vaccine and RT is safe and may have some efficacy in chordoma patients. However, the study did not meet the predefined study goal of four responses in 29 patients, and a randomized study or novel trial designs may be required to confirm activity. The study also highlights the need for further research to improve the efficacy of vaccine-based therapies in chordoma, an ultra-rare disease where response rates are low.