ROS1 rearrangement-targeting unecritinib is a potential new first-line strategy

In a large, phase 2 trial, the novel ROS1 rearrangement-targeting tyrosine kinase inhibitor unecritinib showed promising efficacy and a manageable safety profile as first-line treatment in ROS1 rearrangement-positive, locally advanced or metastatic non-small cell lung cancer (NSCLC).

ROS1 rearrangement is present in 1–2% of patients with NSCLC. Initial treatment with crizotinib or entrectinib is recommended [1]. Unecritinib is a novel, small molecule receptor tyrosine kinase inhibitor targeting ALK, ROS1, and MET. Preclinical studies demonstrated a good tumor inhibition activity and duration. In a phase 1 trial, unecritinib achieved an objective response rate (ORR) of 62.5% at a recommended phase 2 dose of 300 mg twice daily [2]. Dr Shun Lu (Shanghai Chest Hospital, China) presented the results of the ensuing phase 2 trial (NCT03972189) [3].

A total of 111 patients with locally advanced/metastatic, ROS1 rearrangement-positive NSCLC (7% stage III, 93% stage IV; 30% had brain metastases) were enrolled and treated with unecritinib until disease progression or unacceptable toxicity.

At data cut-off, the median duration of follow-up was 12.1 months. ORR was 78.4%, disease control rate (DCR) was 87.4%, and median duration of response (DoR) was 20.3 months. ORR was irrespective of age, gender, ECOG performance status, brain metastases, and smoking history (see Figure). Median progression-free survival (PFS) was 15.6 months; median overall survival (OS) was not yet reached. The 12-month and 24-month OS rates was 98.1% and 88.1%, respectively.

Figure: Objective response rate in different subgroups [3]



Treatment-related adverse events (grade ≥3) were observed in 53% of participants; treatment-related adverse events led to discontinuation in 16.2%. Ocular organ disease was observed in 26.1% of participants; none of these events were grade ≥3.

“These results show that unecritinib has promising efficacy and a manageable safety profile as first-line treatment in ROS1 rearrangement-positive, locally advanced or metastatic NSCLC, offering a new potential first-line therapeutic strategy,” concluded Dr Lu.

1. Planchard D, et al. Ann Oncol. 2018 Oct;29 Suppl 4:iv192-iv237.
2. Fang Y, et al. Abstract e21705. ASCO Annual Meeting 2020, 29–31 May.
3. Lu S, et al. The phase II study of unecritinib (TQ-B3101) monotherapy in the first-line treatment in patients with ROS1-positive non-small cell lung cancer. Abstract 8MO. ELCC 2022 Virtual Meeting, 30 March–02 April.

 

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Posted on 25 May, 202222 February, 2024