Missing content? – Request curation!
Request curation for specific Genes, Variants, or PubMed publications.
Have questions, comments, or suggestions? - Let us know!
Email us at : ckbsupport@genomenon.com
| Ref Type | Journal Article | ||||||||||||
| PMID | (37574511) | ||||||||||||
| Authors | Yang Y, Min J, Yang N, Yu Q, Cheng Y, Zhao Y, Li M, Chen H, Ren S, Zhou J, Zhuang W, Qin X, Cao L, Yu Y, Zhang J, He J, Feng J, Yu H, Zhang L, Fang W | ||||||||||||
| Title | Envonalkib versus crizotinib for treatment-naive ALK-positive non-small cell lung cancer: a randomized, multicenter, open-label, phase III trial. | ||||||||||||
|
|||||||||||||
| URL | |||||||||||||
| Abstract Text | Anaplastic lymphoma kinase (ALK) rearrangements are present in about 5-6% of non-small cell lung cancer (NSCLC) cases and associated with increased risks of central nervous system (CNS) involvement. Envonalkib, a novel ALK inhibitor, demonstrated promising anti-tumor activity and safety in advanced ALK-positive NSCLC in the first-in-human phase I study. This phase III trial (ClinicalTrials.gov NCT04009317) investigated the efficacy and safety of first-line envonalkib in advanced ALK-positive NSCLC cases. Totally 264 participants were randomized 1:1 to receive envonalkib (n = 131) or crizotinib (n = 133). Median independent review committee (IRC)-assessed progression-free survival (PFS) times were 24.87 (95% confidence interval [CI]: 15.64-30.36) and 11.60 (95% CI: 8.28-13.73) months in the envonalkib and crizotinib groups, respectively (hazard ratio [HR] = 0.47, 95% CI: 0.34-0.64, p < 0.0001). IRC-assessed confirmed objective response rate (ORR) was higher (81.68% vs. 70.68%, p = 0.056) and duration of response was longer (median, 25.79 [95% CI, 16.53-29.47] vs. 11.14 [95% CI, 9.23-16.59] months, p = 0.0003) in the envonalkib group compared with the crizotinib group. In participants with baseline brain target lesions, IRC-assessed CNS-ORR was improved with envonalkib compared with crizotinib (78.95% vs. 23.81%). Overall survival (OS) data were immature, and median OS was not reached in either group (HR = 0.84, 95% CI: 0.48-1.47, p = 0.5741). The 12-month OS rates were 90.6% (95% CI, 84.0%-94.5%) and 89.4% (95% CI, 82.8%-93.6%) in the envonalkib and crizotinib groups, respectively. Grade ≥3 treatment-related adverse events were observed in 55.73% and 42.86% of participants in the envonalkib and crizotinib groups, respectively. Envonalkib significantly improved PFS and delayed brain metastasis progression in advanced ALK-positive NSCLC. | ||||||||||||
| 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 |
|---|---|---|---|---|---|---|---|
| ALK rearrange | lung non-small cell carcinoma | sensitive | TQ-B3139 | Phase III | Actionable | In a Phase III trial, TQ-B3139 (CT-711) improved median progression-free survival (24.87 vs 11.60 mo; HR=0.47, p<0.0001), objective response rate (ORR) (81.68% vs 70.68%, p=0.056), and median duration of response (DOR) (25.79 vs 11.14 mo; HR=0.50, p=0.0003) compared to Xalkori (crizotinib) in ALK-rearranged non-small cell lung cancer patients, and also improved CNS ORR (78.95% vs 23.81%) and CNS DOR (25.82 vs 7.39 mo, p=0.0030) in patients with baseline brain lesions (PMID: 37574511; NCT04009317). | 37574511 |