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|Ref Type||Journal Article|
|Authors||Ma Y, Zhao H, Xue J, Liu L, Yang N, Zhang Y, Yang H, Hong S, Xiong Y, Zhang Z, Zeng L, Pan H, Zhou C, Zhang Y, Wang X, Han X, Wan X, Shao Y, Liu J, Yang Y, Huang Y, Zhao Y, Fang W, Li S, Zhang L|
|Title||First-in-human phase I study of TQ-B3139 (CT-711) in advanced non-small cell lung cancer patients with ALK and ROS1 rearrangements.|
|Journal||European journal of cancer (Oxford, England : 1990)|
|Date||2022 Aug 05|
|Abstract Text||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.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.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.TQ-B3139 was well-tolerated and exhibited promising anti-tumor activities in patients with ALK and ROS1 positive advanced NSCLC.NCT03099330.|
|Molecular Profile||Treatment Approach|
|Gene Name||Source||Synonyms||Protein Domains||Gene Description||Gene Role|
|Therapy Name||Drugs||Efficacy Evidence||Clinical Trials|
|Drug Name||Trade Name||Synonyms||Drug Classes||Drug Description|
|Gene||Variant||Impact||Protein Effect||Variant Description||Associated with drug Resistance|
|Molecular Profile||Indication/Tumor Type||Response Type||Therapy Name||Approval Status||Evidence Type||Efficacy Evidence||References|
|ROS1 E539*||lung non-small cell carcinoma||predicted - sensitive||TQ-B3139||Case Reports/Case Series||Actionable||In a Phase I trial, TQ-B3139 (CT-711) treatment demonstrated safety and resulted in an overall response rate (ORR) of 61.9% (39/63), intracranial ORR of 70% (7/10), disease control rate of 84.1% (53/63), and median progression-free survival (mPFS) of 19.0 mo in non-small cell lung cancer patients harboring an ALK or ROS1 fusion, with longer mPFS in TKI-naive patients (25.2 mo vs 5.4 mo), and an ORR of 66.7% (2/3), including 1 complete response, in patients with ROS1 fusions (PMID: 35940055; NCT03099330).||35940055|
|ALK fusion||lung non-small cell carcinoma||sensitive||TQ-B3139||Phase I||Actionable||In a Phase I trial, TQ-B3139 (CT-711) treatment demonstrated safety and resulted in an overall response rate (ORR) of 61.9% (39/63), an intracranial ORR of 70% (7/10), disease control rate of 84.1% (53/63), and median progression-free survival (PFS) of 19.0 months in patients with non-small cell lung cancer harboring an ALK fusion or ROS1 fusion, with TKI-naive patients demonstrating a longer PFS (25.2 mo vs 5.4 mo, p=0.02) (PMID: 35940055; NCT03099330).||35940055|