First-in-human phase I study of TQ-B3139 (CT-711) in advanced non-small cell lung cancer patients with ALK and ROS1 rearrangements

Eur J Cancer. 2022 Sep;173:238-249. doi: 10.1016/j.ejca.2022.06.037. Epub 2022 Aug 5.


Background: TQ-B3139 is a novel ALK tyrosine kinase inhibitor (TKI) against a broad range of ALK mutations. The aim of this first-in-human phase I trial was to investigate the safety, tolerability, pharmacokinetics, and clinical efficacy of TQ-B3139 in ALK or ROS1 positive advanced NSCLC patients.

Methods: Following a 3 + 3 design, patients received escalating daily dose of TQ-B3139 (50-800 mg) continuously in 28-day cycles. Expansion stage started at dose of 200 mg twice daily (BID). The primary objectives were the safety, dose-limited toxicities (DLT) and recommended phase II dose (RP2D); secondary objectives included pharmacokinetics and antitumor activity. Non-obligatory tumor samples at baseline were collected and sequenced.

Results: The study enrolled 63 patients. Fifty-nine (93.4%) patients experienced treatment-related adverse events (TRAEs), mostly grade 1-2 vomiting (79.3%), diarrhea (76.1%) or nausea (68.2%). 1 (1/6) DLT occurred at 600 mg BID and 1 (1/3) at 800 mg BID. Based on safety and pharmacokinetics data, the RP2D was selected as 600 mg BID. At a dose level ≥200 mg BID, the overall response rate (ORR) was 76.7% (33/43), and the median progression free survival (mPFS) was 25.2 months (95%CI 11.9-NR) for TKI-naive patients. For TKI-treated patients, the ORR was 37.5% (6/16), and the mPFS was 5.4 months (95%CI 3.6-9.1). The ORR was 66.7% (2/3) in patients with ROS1 fusion at dose level ≥200 mg BID. In patients with measurable brain metastases, the intracranial ORR was 70% (7/10), with median intracranial PFS of 15.9 months. In TKI-treated patients, variant 3 and TP53 alteration were associated with poor PFS.

Conclusions: TQ-B3139 was well-tolerated and exhibited promising anti-tumor activities in patients with ALK and ROS1 positive advanced NSCLC.

Clinical trial number: NCT03099330.

Keywords: ALK rearrangement; Efficacy; Next-generation sequencing; Safety; TQ-B3139.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anaplastic Lymphoma Kinase / genetics
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • Enzyme Inhibitors / therapeutic use
  • Humans
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / pathology
  • Protein Kinase Inhibitors / adverse effects
  • Protein-Tyrosine Kinases / genetics
  • Proto-Oncogene Proteins / genetics
  • Tomography, X-Ray Computed


  • Enzyme Inhibitors
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins
  • Anaplastic Lymphoma Kinase
  • Protein-Tyrosine Kinases
  • ROS1 protein, human

Associated data