| General information |
| Database: | DB00071 |
| Objective: | To establish the recommendedphase 2 dose of the drug and examine its activity in patients resistant or intolerant to crizotinib |
| Authors: | Gadgeel SM, et al |
| Title: | Safety and activity of alectinib against systemic disease and brain metastases in patients with crizotinibresistant ALKrearranged non small cell lung cancer (AF002JG): results from the dosefinding portion of a phase 1/2 study. |
| Journal: | Lancet Oncol. |
| Year: | 2014 |
| PMID: | 25153538 |
| Trial Design |
| Clinical Trial Id: | NCT01588028 |
| Agent: | alectinib
|
| Target: | ALK inhibition including activity againstL1196M, G1269A, C1156Y, and F1174Lmutations
|
| Cancer Type: | non small cell lung cancer |
| Cancer Subtype: | advanced ALKrearranged non small cell lung cancer |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | phase I/II, single arm, openlabel study |
| Key Patients Feature: | patients with ALKrearranged non small cell lung cancer who progressed on or were intolerant to crizotinib at six cancer treatment centres in the USA |
| Biomarker: | ALKpositive |
| Biomark Analysis: | Alectinib was well tolerated, with promising antitumour activity in patients with ALKrearranged non small cell lung cancer resistant to crizotinib, including those with CNS metastases. |
| Control Group Info: | single arm |
| Treatment Info: | they administered various oral doses of alectinib (300900 mg twice a day) during the doseescalation portion of the study (phase 1), to ascertain the recommended dose forphase 2. |
| Primary End Point: | safety and efficacy |
| Secondary End Point: | NA |
| Patients Number: | 55 |
| Trial Results |
| DLT_MTD: | Doselimiting toxic effects were recorded in two patients in the cohort receiving alectinib 900 mg twice a day; one individual had grade 3 headache and the other had grade 3 neutropenia. |
| Objective Response Rate: | 0.55 |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | grade 12:being fatigue 14 [30%], myalgia8[17%], peripheral oedema7[15%], 1[2%] grade 3). Grade34:increased levels of ¦Ãglutamyl transpeptidase (2[4%]), a reduction in the number of neutrophils (2[4%]), hypophosphataemia (2[4%]). |
| Conclusions: | Alectinib was well tolerated, with promising antitumour activity in patients with ALKrearranged non small cell lung cancer resistant to crizotinib, including those with CNS metastases. On the basis of activity, tolerability, and pharmacokinetic data, they chose alectinib 600 mg twice a day as the recommended dose forphase 2. |