Single-center study to determine the safety and efficacy of CT-707 in Chinese patients with advanced anaplastic lymphoma kinase-rearranged non-small-cell lung cancer.

Publisher: Wiley Publishing Asia Pty Ltd Country of Publication: Singapore NLM ID: 101531441 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1759-7714 (Electronic) Linking ISSN: 17597706 NLM ISO Abbreviation: Thorac Cancer Subsets: MEDLINE

Publication: November 2012- : Singapore : Tianjin : Wiley Publishing Asia Pty Ltd ; Tianjin Lung Cancer Institute
Original Publication: Richmond, Vic. : Tianjin : Blackwell Pub. Asia Pty Ltd. ; Tianjin Lung Cancer Institute

Gene Rearrangement*; Adenocarcinoma of Lung/*drug therapy ; Anaplastic Lymphoma Kinase/*antagonists & inhibitors ; Anaplastic Lymphoma Kinase/*genetics ; Lung Neoplasms/*drug therapy ; Mesothelioma, Malignant/*drug therapy ; Protein Kinase Inhibitors/*therapeutic use ; Pyrimidines/*therapeutic use ; Pyrroles/*therapeutic use ; Sulfonamides/*therapeutic use; Adenocarcinoma of Lung/genetics ; Adenocarcinoma of Lung/pathology ; Adolescent ; Adult ; Aged ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms/genetics ; Lung Neoplasms/pathology ; Male ; Maximum Tolerated Dose ; Mesothelioma, Malignant/genetics ; Mesothelioma, Malignant/pathology ; Middle Aged ; Prognosis ; Survival Rate ; Young Adult

Introduction: It has been proven that ALK-rearranged non-small cell lung cancer (NSCLC) is sensitive to ALK inhibitors while the chemotherapy resistance is unavoidable. In this study, safety and antitumor activity of the novel ALK inhibitor (ALKi) CT-707 were evaluated in Chinese patients with advanced ALK-rearranged NSCLC.
Methods: This single-center, open-label phase I study recruited adult patients with ALK-rearrangement (confirmed by fluorescence in situ hybridization and/or immunohistochemistry) of locally advanced/metastatic malignancies including NSCLC. This study consisted of two parts: dose escalation and dose expansion. CT-707 was administered orally once a day for 21 days.
Results: A total of 13 patients who were treated with CT-707 from 450 to 600 mg (in the dose increasing phase) were enrolled in this trial (two patients were previously treated with crizotinib). There were 12 patients diagnosed with lung adenocarcinoma and one patient with malignant pleural mesothelioma. After treatment, grade 3 diarrhea (600 mg once a day) was found as dose-limiting toxicity (DLT).The most common adverse events included diarrhea (92%), elevated aspartate aminotransferase (61%), elevated alanine aminotransferase (54%), hair loss (38%), and vomiting (31%). The overall response rate was 77% (10/13). Among all patients, four of the five patients who did not receive any treatment, one of the two patients who had received treatments with crizotinib, and five of the six patients who received standard chemotherapy achieved partial response (PR). One patient reached a complete remission (CR).
Conclusions: This study indicated that CT-707 is clinically effective as a new antitumor drug for Chinese lung adenocarcinoma patients with ALK rearrangement. It is safe and reliable and the dose-expansion phase recruitment has started.
(© 2020 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

J Clin Oncol. 2009 Sep 10;27(26):4247-53. (PMID: 19667264)
Lancet Oncol. 2012 Oct;13(10):1011-9. (PMID: 22954507)
J Thorac Oncol. 2016 May;11(5):613-638. (PMID: 27013409)
Science. 1994 Mar 4;263(5151):1281-4. (PMID: 8122112)
Semin Oncol. 2014 Jun;41(3):297-9. (PMID: 25023344)
Sci Transl Med. 2012 Feb 8;4(120):120ra17. (PMID: 22277784)
J Hematol Oncol. 2016 Mar 08;9:19. (PMID: 26951079)
Eur J Cancer. 2009 Jan;45(2):228-47. (PMID: 19097774)
Nature. 2008 Oct 16;455(7215):930-5. (PMID: 18724359)
Mol Cancer Ther. 2016 Dec;15(12):2916-2925. (PMID: 27638856)
Lancet. 2017 Mar 4;389(10072):917-929. (PMID: 28126333)
N Engl J Med. 2017 Aug 31;377(9):829-838. (PMID: 28586279)
Proc Natl Acad Sci U S A. 2015 Sep 29;112(39):E5381-90. (PMID: 26372962)
N Engl J Med. 2013 Jun 20;368(25):2385-94. (PMID: 23724913)
Nature. 2007 Aug 2;448(7153):561-6. (PMID: 17625570)

Keywords: ALK; CT-707; NSCLC

0 (Protein Kinase Inhibitors)
0 (Pyrimidines)
0 (Pyrroles)
0 (Sulfonamides)
EC 2.7.10.1 (ALK protein, human)
EC 2.7.10.1 (Anaplastic Lymphoma Kinase)
URX2UMQ8XV (conteltinib)

Date Created: 20200318 Date Completed: 20210315 Latest Revision: 20210409

20250114

PMC7180692

10.1111/1759-7714.13376

32181989