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envonalkib (TQB3139 / envonalkib / CT 1139)

✓ Approved

Sino Biopharmaceutical Co., Ltd · ALK · Small Molecule

What is envonalkib?

envonalkib is a small molecule developed by Sino Biopharmaceutical Co., Ltd. It is approved for therapeutic indications via oral (po).

Drug Profile

Brand NamesTQB3139, envonalkib, CT 1139
CompanySino Biopharmaceutical Co., Ltd
Drug ClassSmall Molecule
Molecular TargetALK, MET
RouteOral (PO)
StatusApproved
Sources: ClinicalTrials.gov, Sino Biopharmaceutical Co., Ltd

Mechanism of Action

Molecular Targets

envonalkib acts on 2 molecular targets:

ALKALK receptor tyrosine kinase (CD246, NBLST3)
METMET proto-oncogene, receptor tyrosine kinase (c-Met, DFNB97)
Want deeper analysis?Noah AI can explain complex mechanisms and compare to similar drugs.

Therapeutic Indications

envonalkib is developed for 3 unique indications across 1 therapeutic area.

Therapeutic AreaConditionPhase
Neoplasms benign, malignant and unspecified (incl cysts and polyps)Non-small cell lung cancer stage IV✓ Approved
Neoplasms benign, malignant and unspecified (incl cysts and polyps)Non-small cell lung cancer metastatic✓ Approved
Neoplasms benign, malignant and unspecified (incl cysts and polyps)Rectosigmoid cancerPhase I

Related Research Articles

PubMedMedComm2026-10-05

Envonalkib Versus Crizotinib in Treatment-Naive ALK-Positive Non-Small Cell Lung Cancer: Final Efficacy and Biomarker Analyses of the Randomized Phase III Study.

Huang Jie J, Wang Yuanyuan Y, Sun Haishuang H, Min Jie J et al.

This study reports efficacy and biomarker results from a multicenter, randomized, open-label Phase III study (NCT04009317). Treatment-naive anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) patients were centrally randomized 1:1 to envonalkib or crizotinib, stratified by brain metastases and chemotherapy lines. The primary endpoint was progression-free survival (PFS) assessed by independent review committee. This analysis updated investigator-assessed PFS. A total of 264 patients were randomized (envonalkib: 131, crizotinib: 133). Median follow-up was 46.5 and 46.8 months for envonalkib and crizotinib, respectively. Envonalkib significantly improved PFS over crizotinib (median PFS: 30.4 vs. 12.0 months, p < 0.0001; hazard ratio [HR] = 0.48, 95% CI: 0.35-0.65). Overall survival (OS) data remained immature. In the envonalkib group, circulating tumor DNA (ctDNA) analysis revealed poor prognosis for patients with co-mutations in p53 pathway genes (TP53, CDKN2A, MDM2, MDM4) or other concurrent oncogenic drivers (median PFS: 15.7 and 8.3 months). Among 52 patients with post-progression ctDNA data, putative resistance mechanisms were identified in 14 (26.9%), including secondary ALK mutations (n = 9) and/or bypass pathway activations (n = 9). Final follow-up confirms the robust benefit of envonalkib over crizotinib, supporting its role as a first-line option for ALK-positive NSCLC. Biomarker analyses validate the prognostic impact of genomic co-alterations and delineate resistance mechanisms.

PMID 42830869
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PubMedDrug design, development and therapy2026-08-25

Clinical Evaluation of Anaplastic Lymphoma Kinase (ALK) Inhibitors for the First-Line Treatment of Advanced ALK-Positive Non-Small Cell Lung Cancer Based on the 2nd Edition of China's Drug Evaluation and Selection Guideline.

Guo Zhijun Z, Zhang Yunhui Y, Chen Haoyun H, Dong Xinyi X et al.

To provide a reference for healthcare organizations in the selection and rational use of ALK inhibitors, based on A Quick Guideline for Drug Evaluation and Selection in Chinese Medical Institutions (the Second Edition). According to the 2nd edition of China's drug evaluation and selection guideline released in 2023, relevant databases such as PubMed, Micromedex, and Medlive, drug labels, and clinical guidelines were searched for specific drug information. We systematically evaluated eight ALK inhibitors marketed in China for pharmacological properties, efficacy, safety, economy, and other attributes using a percentage scoring method. The ranking of ALK inhibitors was derived from a structured scoring framework based on the 2nd Edition of China's Drug Evaluation and Selection Guideline. The final assessment result scores from highest to lowest were alectinib (78.70 points), lorlatinib (78.70 points), brigatinib (78.50 points), ensartinib (73.30 points), iruplinalkib (72.55 points), ceritinib (71.50 points), envonalkib (71.15 points), crizotinib (70.60 points). Based on the second edition of China's drug evaluation and selection guideline and combined with the clinical application characteristics of ALK inhibitors, this study performed a multidimensional scoring of eight ALK inhibitors. The evaluation results could provide a reference for medical institutions in the introduction and elimination of ALK inhibitors.

PMID 42639549
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PubMedZhonghua zhong liu za zhi [Chinese journal of oncology]2026-07-26

[Expert consensus on iruplinalkib for the treatment of ALK-positive non-small cell lung cancer (2026 edition)].

Medical Oncology Branch of China International Exchange and Promotive Association for Medical and Health Care, Chinese Association for Clinical Oncologists

Anaplastic lymphoma kinase (ALK) fusion gene is one of the most common driver genes in non-small cell lung cancer (NSCLC). ALK-tyrosine kinase inhibitors (TKIs) have become the standard treatment option for patients with advanced ALK gene fusion positive NSCLC. Currently, the China National Medical Products Administration (NMPA) has approved ten ALK-TKIs, including crizotinib, ceritinib, alectinib, ensartinib, brigatinib, lorlatinib, iruplinalkib, envonalkib, dirozalkib and conteltinib. Iruplinalkib is a novel ALK-TKI independently developed in China. On June 27, 2023, the NMPA approved iruplinalkib for the treatment of patients with locally advanced or metastatic ALK-positive NSCLC who had progressed on or were intolerant to crizotinib. On January 16, 2024, the NMPA approved iruplinalkib for first-line treatment of patients with locally advanced or metastatic ALK-positive NSCLC patients. To help clinicians better understand the efficacy and safety of iruplinalkib and to facilitate its more rational clinical application, the Medical Oncology Branch of China International Exchange and Promotive Association for Medical and Health Care and the Chinese Association for Clinical Oncologists organized experts to develop the "Expert consensus on iruplinalkib for the treatment of ALK-positive non-small cell lung cancer (2026 edition)". This consensus provides systematic and comprehensive update of clinical research data on iruplinalkib published before June 25, 2026, based on the 2024 edition. It covers common clinical issues and provides corresponding recommendations for the use of iruplinalkib in the treatment of ALK-positive NSCLC.

PMID 42502071
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PubMedTranslational lung cancer research2026-06-15

Long-term outcomes of ALK inhibitors in metastatic ALK-positive non-small cell lung cancer: an updated indirect comparison using reconstructed patient-level data.

Ossato Andrea A, Damuzzo Vera V, Del Bono Luna L, Gasperoni Lorenzo L et al.

In metastatic ALK-positive non-small cell lung cancer (mNSCLC), ALK tyrosine kinase inhibitors (ALKi) represent the established standard of care. While second- and third-generation ALKi (including alectinib, brigatinib, ensartinib, envonalkib, and lorlatinib) have demonstrated superior efficacy compared with the first-generation inhibitor crizotinib in randomized trials, the absence of direct head-to-head comparisons limits the definition of their relative clinical benefit. We performed an updated indirect comparison of next-generation ALKi using data from pivotal randomized controlled trials. Seven first-line trials in ALK-positive mNSCLC were identified, and individual patient data were reconstructed from published Kaplan-Meier curves to estimate treatment effects using Cox proportional hazards models and restricted mean survival time (RMST) analyses, with crizotinib as a common comparator. All next-generation ALKi demonstrated significant progression-free survival (PFS) benefit versus crizotinib. In indirect comparisons, lorlatinib showed superior PFS compared with alectinib [hazard ratio (HR) 0.61; 95% confidence interval (CI): 0.43-0.85], brigatinib (HR 0.48; 95% CI: 0.33-0.71), ensartinib (HR 0.60; 95% CI: 0.40-0.90), and envonalkib (HR 0.42; 95% CI: 0.28-0.62). RMST analyses indicated increasing separation between lorlatinib and alectinib over time, suggesting a more sustained PFS benefit with lorlatinib. Among patients with baseline brain metastases (BMs), lorlatinib showed the strongest PFS effect compared with alectinib, brigatinib, ensartinib, and envonalkib. For overall survival (OS), alectinib demonstrated a statistically significant benefit versus crizotinib, while no significant differences were observed among next-generation ALKi. This indirect comparison indicates that lorlatinib provides the most durable PFS and the strongest intracranial disease control, although ALKis are characterized by distinct toxicity profiles. In the absence of clear OS differences at present, first-line treatment selection should integrate efficacy, intracranial activity, tolerability, and emerging molecular features within a personalized therapeutic framework.

PMID 42291358
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PubMedFrontiers in oncology2025-05-26

Treatment of metastatic ALK-positive non-small cell lung cancer: indirect comparison of different ALK inhibitors using reconstructed patient data.

Damuzzo Vera V, Gasperoni Lorenzo L, Del Bono Luna L, Ossato Andrea A et al.

Anaplastic lymphoma kinase (ALK) inhibitors (ALKi) are the standard treatment for metastatic, ALK-positive non-small cell lung cancer (NSCLC). Second- and third-generation ALKi, including alectinib, brigatinib, ensartinib, envonalkib, and lorlatinib, have shown better efficacy than crizotinib. However, due to the lack of direct head-to-head comparisons among these agents, the optimal treatment for metastatic ALK-positive NSCLC remains unclear. This study used the IPDfromKM (Individual Patient Data from Kaplan-Meier) method to reconstruct patient-level data from Kaplan-Meier curves of seven randomized phase III trials, involving a total of 3,850 patients. Crizotinib arms were pooled as the common comparator. Progression-free survival (PFS) was the primary endpoint, assessed using Cox proportional hazards models and restricted mean survival time (RMST). Subgroup analyses focused on patients with baseline central nervous system (CNS) metastases. All ALKi significantly improved PFS compared to crizotinib. Lorlatinib showed the most meaningful improvement, with the greatest benefit in both overall PFS (HR=0.28; 95% CI 0.21-0.38) and CNS PFS (HR=0.09; 95% CI 0.04-0.2). In direct comparisons, lorlatinib outperformed brigatinib (HR=0.59; 95% CI 0.39-0.87) and envonalkib (HR=0.52; 95% CI 0.35-0.77) in terms of PFS. While lorlatinib also showed improved PFS compared to alectinib (HR=0.72; 95% CI 0.50-1.04) and ensartinib (HR=0.73; 95% CI 0.48-1.10), these differences were not statistically significant. Lorlatinib demonstrated the greatest benefit in PFS among patients with baseline CNS metastases. In this indirect comparison using reconstructed patient data, lorlatinib emerged as the most effective ALKi, showed the most favorable HR for PFS compared to the other ALKi, although it did not reach statistical significance versus alectinib and ensartinib. Additionally, lorlatinib showed the highest efficacy in the control of CNS progression.

PMID 40416880
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PubMedTranslational lung cancer research2024-09-12

Efficacy of ALK inhibitors in Asian patients with ALK inhibitor-naïve advanced ALK-positive non-small cell lung cancer: a systematic review and network meta-analysis.

Li Xuchang X, Xia Yangchen Y, Wang Chengyan C, Huang Shanshan S et al.

A previous network meta-analysis (NMA) compared the efficacy of anaplastic lymphoma kinase (ALK) inhibitors in ALK-positive non-small cell lung cancer (NSCLC). The phase III INSPIRE study of iruplinalkib was published recently. The present study aimed to add the results related to iruplinalkib to the NMA. A systematic literature search was performed in PubMed, Embase, Cochrane Library, Google, and Baidu. Randomized controlled trials (RCTs) reporting the independent review committee-assessed progression-free survival (PFS), objective response rate (ORR), or disease control rate (DCR) results of Asian patients with ALK inhibitor-naïve advanced ALK-positive NSCLC were eligible for inclusion in the NMA. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool. Bayesian fixed-effect models were used for the direct and indirect pairwise comparisons. This study was registered with PROSPERO (CRD42024555299). Eight studies, involving 1,477 Asian patients and seven treatments (crizotinib, alectinib, brigatinib, ensartinib, envonalkib, iruplinalkib, and lorlatinib), were included in the NMA. In terms of the overall risks of bias, all of the studies had "some concerns". All the next-generation ALK inhibitors were statistically superior to crizotinib in terms of PFS. Iruplinalkib had the best surface under the cumulative ranking curve (74.0%), followed by brigatinib (69.1%) and ensartinib (63.7%). Most of the pairwise comparisons did not reveal significant differences in the ORR and DCR. In terms of both the ORR and DCR, alectinib ranked first, followed by lorlatinib. Next-generation ALK inhibitors had better efficacy than crizotinib in the treatment of Asian patients with ALK inhibitor-naïve advanced ALK-positive NSCLC. Iruplinalkib may have more favorable PFS benefit than other ALK inhibitors for Asians.

PMID 39263024
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