Alectinib Plus Cobimetinib for Alectinib-Naive Patients With ALK-Positive Lung Cancer
According to results from a multicohort, phase 1b study, the maximum tolerated dose was determined to be 600 mg alectinib twice daily plus 40 mg of cobimetinib twice daily for patients with ALK-positive lung cancer.
In cohort 1, 10 patients were enrolled irrespective of alectinib exposure to receive 600 mg of twice daily alectinib plus either 20 mg or 40 mg of cobimetinib on days 1 through 21 in 28-day cycles. At analysis, no dose-limiting toxicities were observed with alectinib plus 20 mg of cobimetinib (n = 4). With alectinib plus 40 mg of cobimetinib (n = 6) dose-limiting incidences of grade 3/4 creatine phosphokinase elevation and rash were observed in 2 alectinib-naive patients. The maximum tolerated dose was identified as 600 mg of alectinib plus 40 mg of cobimetinib.
In cohort 2, 6 treatment-naive patients were enrolled to receive 600 mg of twice daily alectinib plus 20 mg of cobimetinib on days 1 through 21 in 28-day cycles after a 2-week alectinib lead-in. With lead-in, no dose-limiting toxicities were observed. One patient discontinued cobimetinib due to grade 2 pneumonitis. The median progression-free survival was 2.2 months for alectinib-resistant patients and 49.2 months for alectinib-naive patients.
“Alectinib combined with cobimetinib demonstrated limited activity in alectinib-resistant tumors,” concluded study authors. They added that these results “suggest that ALK [plus] MEK blockade may lack broad efficacy in unselected alectinib-resistant disease and indicate that different dosing strategies may be needed in different therapeutic contexts.”
Source:
Dagogo-Jack I, Cooper AJ, Johnson BE, et al. Alectinib combined with cobimetinib in ALK-rearranged lung cancer: A phase IB study. Lung Can. Published online: November 1, 2024. doi: 10.1016/j.lungcan.2024.108003
