A phase II, multicenter study of lazertinib as consolidation therapy in patients with locally advanced, unresectable, EGFR mutation positive non-small cell lung cancer (stage III) who have not progressed following definitive, platinum-based, chemoradiation therapy (PLATINUM trial)

Abstract

Background The PACIFIC trial has demonstrated that durable progression free survival (PFS) and sustained overall survival (OS) benefit with durvalumab as consolidation therapy after concurrent chemoradiation therapy (CCRT). In a subgroup analysis, the effect was not proven in patients with EGFR mutation positive. There is an unmet need for consolidative therapy after CCRT in patients with unresectable stage III EGFR mutation positive. A recent ADAURA trial showed that osimertinib had a significant prolongation of PFS in the postoperative adjuvant treatment in EGFR mutation positive patients. Lazertinib is also 3rd generation EGFR TKI as osimertinib and shows good anti-cancer effect in EGFR sensitive mutations in preclinical data. And Lazertinib showed promising clinical activity in patients with NSCLC progressing after EGFR TKI therapy. Given these positive 3rd G EGFR TKI data in the adjuvant setting, and the preliminary data obtained in EGFR TKI therapies in the early disease setting, there is a strong rationale to suggest that Lazertinib may provide clinical benefit in the consolidative treatment after CCRT treatment.

Trial design This study is a phase II, multicenter study assessing the efficacy and safety of Lazertinib as consolidation therapy in patients with locally advanced, unresectable NSCLC (Stage III) who have not progressed following definitive, platinum based, CCRT.

Approximately 77 patients will be enrolled. The patients who have sensitizing EGFR mutation (e.g., exon 19 deletion or exon 21 L858R mutation) will be enrolled. Administration of Lazertinib will commence 1 to 42 days after the patients had received chemoradiotherapy and will continue a q4w schedule until clinical progression, confirmed radiological progression, initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study treatment occur.

The primary end point is PFS and 2ndary end points are OS, the objective response rate, the duration of response, the time to death or distant metastasis, and safety.