KEY POINTS
- Eclipse01 was a 3+3 phase I dose-escalation study enrolling nine men with stage IV NSCLC and tumors >5 cm who had failed standard treatment, were unsuitable for it or declined chemotherapy. Median age was 69 years, and all patients received treatment to a bulky primary lung tumor.
- EclipseRT deliberately created heterogeneous intratumoral dose. The entire bulky tumor received low-dose RT while a small internal subvolume received concurrent SBRT: level 1 used 2 Gy + 10 Gy in one fraction, level 2 4 Gy/2 + 20 Gy/2, and level 3 6 Gy/3 + 30 Gy/3, with three patients treated at each level.
- High-dose subvolumes were generally kept ≤3 cm in diameter and ≤14.1 cm³, positioned away from tumor edges, necrosis, atelectasis and major central structures. PD-1 blockade began within seven days of radiation, while the choice of checkpoint inhibitor and additional systemic therapy varied between patients.
- The primary safety endpoint was met: no dose-limiting toxicity occurred, no grade ≥3 treatment-related adverse event was reported, and there were no treatment-related deaths. 7/9 patients (77.8%) experienced treatment-related adverse events, all grade 1–2, while 6/9 (66.7%) experienced immune-related events.
- Despite the tiny cohort, activity was notable: 5/9 patients responded (55.6%). At median follow-up of 22.3 months, estimated median progression-free survival was 12.6 months and median overall survival 26.4 months.
- Several individual responses illustrate feasibility in very large tumors. One patient with a 278-cm³ lung mass and respiratory failure received 2-Gy whole-tumor RT plus a 10-Gy intratumoral SBRT region; dyspnea resolved within 3 days, and partial response persisted for 43.1 months with subsequent systemic therapy. Another patient had a whole-tumor volume of 607.6 cm³ and achieved partial response after the three-fraction regimen.
- Efficacy cannot be separated from systemic therapy in this design: patients received different PD-1 inhibitors, some also received chemotherapy, there were only three patients per radiation level, and there was no control arm. A randomized phase II study is therefore required to determine whether the deliberately heterogeneous dose distribution contributes meaningfully beyond immunotherapy and systemic treatment alone.
CLINICAL TAKEAWAY
The study demonstrates that partial intratumoral SBRT embedded inside whole-tumor low-dose RT can actually be delivered to very bulky NSCLC while continuing immunotherapy without an obvious early severe-toxicity signal. The response data are intriguing, but n=9 and heterogeneous systemic therapy make this a proof-of-concept, not evidence for routine EclipseRT.