419O - Safety of alectinib in non-small cell lung cancer patients with RET fusion gene (ALL-RET): results from the dose-finding portion of a phase 1/2 stu...

Date 19 November 2017
Event ESMO Asia 2017 Congress
Session Thoracic malignancies 2
Topics Anti-Cancer Agents & Biologic Therapy
Non-Small-Cell Lung Cancer, Metastatic
Lung and other Thoracic Tumours
Translational Research
Presenter Kaname Nosaki
Citation Annals of Oncology (2017) 28 (suppl_10): x124-x143. 10.1093/annonc/mdx671
Authors K. Nosaki1, S. Takeuchi2, S. Takahara3, T. Kawakami3, K. Yoh4, Y. Kono5, A. Horiike6, T. Seto1, K. Goto7, K. Yoshimura3, Y. Imai3, T. Murayama3, S. Yano2
  • 1Department Of Thoracic Oncology, National Kyushu Cancer Center, 811-1395 - FUKUOKA/JP
  • 2Division Of Medical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa/JP
  • 3Innovative Clinical Research Center (icrek), Kanazawa University Hospital, Kanazawa/JP
  • 4Department Of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa/JP
  • 5Department Of Thoracic Oncology, Hyogo Cancer Center, Akashi/JP
  • 6Department Of Thoracic Medical Oncology, Cancer Institute Hospital of JFCR, 135-8550 - Tokyo/JP
  • 7Department Of Thoracic Oncology, National Cancer Center Hospital East, 277-8577 - Kashiwa/JP



The rearranged during transfection (RET) fusion gene was discovered as a driver oncogene in 1–2% of non-small cell lung cancer (NSCLC). Alectinib (300 mg BID) has been approved for the treatment of anaplastic lymphoma kinase (ALK) fusion-positive NSCLC in Japan; it also has a high activity against RET in vitro. A global trial showed the efficacy and safety of alectinib (600 mg BID) in ALK fusion-positive NSCLC patients. Therefore, we conducted a phase 1/2 study of alectinib to establish the recommended dose and examine its activity in RET fusion-positive NSCLC patients.


This study is a single-arm, open-label, multi-institutional phase I/II trial. RET fusion-positive NSCLC patients treated with at least one regimen of chemotherapy were recruited. In the phase 1 portion (step 1) using 3 + 3 design to establish the recommended dose, alectinib (cohort 1/2: 600 mg/450 mg BID) was orally administered in a 21-day cycle. Dose-limiting toxicity (DLT) was evaluated during the first cycle. Here, we present data for the phase 1 portion of the study; phase 2 is ongoing. This study is registered at the UMIN Clinical Trials Registry (UMIN000020628).


We enrolled 10 patients (2 patients previously treated with RET-TKIs, vandetanib and/or lenvatinib) in step 1, and 9 patients could be evaluated. In cohort 1, we observed 5 DLTs (grade 3 rash, increased aspartate aminotransferase, erythema multiforme, thromboembolic event, and increased CPK) in 3 of 6 patients. In accordance with the protocol, we moved to cohort 2 and observed no DLTs in 3 patients. The most commonly reported adverse events (occurring in ≥ 30% of patients) in step 1 were constipation, increased creatinine, increased CPK, and myalgia. Serious adverse events reported in one patient in cohort 1 were grade 3 biliary tract infection and grade 2 lower limb muscle weakness.


On the basis of DLTs, we determined alectinib 450 mg BID as the recommended dose for phase 2. Phase 2 is ongoing.

Clinical trial identification


Legal entity responsible for the study

Seiji Yano


the Japan Agency for Medical Research and Development, AMED


T. Seto, K. Goto, S. Yano: Speaker honoraria and research funding from Chugai Pharmaceutical Co, Ltd.

All other authors have declared no conflicts of interest.