Unecritinib Shows Efficacy as ROS1-Directed Therapy in NSCLC

Unecritinib (TTQ-B3101) monotherapy showed promising efficacy in the first line for patients with ROS1-positive non–small cell lung cancer (NSCLC). Shun Lu, MD, PhD, a professor at Shanghai Chest Hospital at Jiao Tong University and chief of Shanghai Lung Cancer Center in China, presented the findings at the European Lung Cancer Congress 2022.

The objective response rate (ORR) was 78.4% (95% CI, 69.6%-85.6%), according to investigators, and the disease control rate was 87.4% (95% CI, 79.7%-92.9%). Both rates were assessed by an independent review committee (IRC). The median duration of response (DOR) was 20.3 months (95% CI, 11.0-26.1). At the time of data cutoff, the median duration of follow-up was 12.1 months (95% CI, 11.9-17.4).

In this phase 2 study (NCT03972189), investigators evaluated 111 patients from 29 sites in China between November 2019 and January 2021. Patients received unecritinib at 300 mg twice a day until disease progression or intolerable toxicity. The primary end point was IRC-assessed ORR by RECIST 1.1 criteria and secondary end points were disease control rate, DOR, progression-free survival (PFS), overall survival (OS), and safety.

Median PFS was 15.6 months (95% CI, 10.2-27.0). At 3 months the PFS rate was 89.7% (95% CI, 82.2%-94.2%), at 6 months it was 82.7% (95% CI, 73.9%-88.7%), and at 12 months, 53.7% (95% CI, 42.0%-64.0%). OS at the data cutoff was not reached. However, at 12 months the OS rate was 98.1% (95% CI, 92.5%-99.5%) and at 24 months it was 88.1% (95% CI, 73.7%-94.9%).

The median age of patients was 52 years (range, 44-59), and 61.3% of patients were female (n=68). Most patients (71.2%) had an ECOG performance score of 1. Investigators recorded patients’ smoking history and found that 72.1% had never smoked, 25.2% had a past history of smoking, and 2.7% werecurrentlysmokers.Allbut1patient had adenocarcinoma as pathology. Most patients (92.8%) had stage IV disease and the remainder had stage III disease. Thirty-three patients (29.7%) had brain metastases. More than half the patient population (58.6%) had no previous chemotherapy treatment, 31.5% had received 1 prior line, and 9.9% had received 2 prior chemotherapy lines.

The entire patient population experienced any-grade treatment-emergent adverse events (TEAEs), and all but 1 patient experienced treatment-related AEs (TRAEs). Grade 3 or higher TEAEs occurred in 53.2% of patients, grade 3 or higher TRAEs were found in 45.1% of patients, and 14.4% experienced serious AEs (SAEs). Treatment related SAEs occurred in 3.6% of patients. TRAEs led to dose adjustment in 16.2% of patients, to dose disruption in 35.1% of patients, and to discontinuation in 16.2% of patients.

The most common any-grade TRAEs (TABLE1) were increased aspartate aminotransferase levels (73.9%), increased alanine aminotransferase levels (72.1%), vomiting (63.1%), and decreased neutrophil count (56.8%). The most common grade 3 or greater TRAEs were decreased neutrophil count (25.2%), decreased leukocyte count (7.2%), increased alanine aminotransferase levels (7.2%), and increased aspartate aminotransferase levels (3.6%). Lu noted that the occurrence of ocular organ disease was favorable, as this any-grade AE occurred in 26.1% of patients but was not found at grade 3 or higher.

With results offering promising efficacy data and a manageable safety profile, unecritinib can be regarded as a new first-line treatment option.

REFERENCE

Lu S, Pan H, Wu L, et al. The efficacy and safety of TQ-B3101 monother- apy in the first-line treatment in patients with ROS1-positive non-small cell lung cancer. Ann Oncol. 2022;33(suppl 2):S31. doi:10.1016/j. annonc.2022.02.017