Lazertinib, an investigational third-generation oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), has good safety and antitumor activity in patients with EGFR-mutated advanced non–small cell lung cancer (NSCLC), finds a phase 1/2 trial.
Only about one in six patients experienced a grade 3 or 4 adverse event when given the drug at various doses, according to results reported in.
Meanwhile, 54% of patients achieved a response, with a higher rate seen among those whose tumors were positive versus negative for the T790M resistance mutation. Notably, 44% of the subgroup with brain metastases had an intracranial response.
“[O]ur results show that lazertinib is well tolerated, with responses frequently observed in patients with NSCLC harbouring both activating EGFR mutations and EGFR T790M TKI resistance mutations. Intracranial responses were also frequently seen, indicating effective blood-brain barrier penetration,” wrote senior investigator Byoung Chul Cho, MD, PhD, Cancer Center, Yonsei University College of Medicine, Seoul, South Korea, and coinvestigators.
“Lazertinib has a potential therapeutic role in the treatment of NSCLC harbouring EGFR T790M mutations, either alone or in combination with other drugs,” they concluded.
The trial was conducted in Korea among adults having advanced NSCLC with an activating EGFR mutation who experienced progression after treatment with a first- or second-generation EGFR TKI. All were treated on an open-label basis with lazertinib at dose levels from 20 mg to 320 mg once daily, continuously in 21-day cycles.
Dr. Cho and coinvestigators reported results for 127 patients (38 in a dose escalation cohort and 89 in a dose expansion cohort).
Results showed that there were no dose-limiting toxicities and no dose-dependent increases in adverse events. The leading adverse events were grade 1 or 2 rash or acne (30%) and pruritus (27%). Overall, 16% of patients experienced grade 3 or grade 4 adverse events, most commonly grade 3 pneumonia (3%). Only 3% of patients had treatment-related grade 3 or 4 adverse events, while 5% had treatment-related serious adverse events. None experienced adverse events leading to death or treatment-related death.
On independent central review, 54% of patients overall had an objective response (52% had a partial response, 2% had a complete response). The response rate was 57% in patients with T790M-positive tumors compared with 37% in patients with T790M-negative tumors.
The median duration of response was 15.2 months. With a median follow-up of 11.0 months, the median progression-free survival was 9.5 months for the whole study cohort; it was longer in patients whose tumors were positive versus negative for the T790M resistance mutations (9.7 months vs 5.4 months).
Among evaluable patients with brain metastases, the intracranial response rate was 44%, and median intracranial progression-free survival was not reached.
Dr. Cho disclosed relationships with numerous pharmaceutical companies, including Yuhan Corporation, which funded the trial.
SOURCE: Cho BC et al. Lancet Oncol. 2019 Oct 3. .