Qi Xinke (iruplinalkib)

P2, N=12, Not yet recruiting, Tianjin Medical University Cancer Institute and Hospital

P=N/A, N=1000, Not yet recruiting, Qilu Pharmaceutical Co., Ltd.

P4, N=105, Not yet recruiting, Jiangsu Provincial Hospital; Jiangsu Province Hospital

P2, N=165, Recruiting, Shanghai Chest Hospital; Shanghai Chest Hospital

Eight studies, involving 1,477 Asian patients and seven treatments (crizotinib, alectinib, brigatinib, ensartinib, envonalkib, iruplinalkib, and lorlatinib), were included in the NMA. 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.

P1, N=39, Recruiting, Henan Cancer Hospital

From the PSA, iruplinalkib had a 90% probability of being cost-effective at a willingness-to-pay threshold of $37,863.56/QALY. Compared to alectinib, iruplinalkib is a cost-effective therapy for patients with ALK-positive crizotinib-resistant advanced NSCLC.

Seven different ALK-TKIs have been approved by the National Medical Products Administration (NMPA) of China, including crizotinib, ceritinib, alectinib, ensartinib, brigatinib, lorlatinib, and iruplinalkib. On January 16, 2024, the NMPA approved iruplinalkib for the first-line treatment of locally advanced or metastatic ALK-positive NSCLC patients. In order to better understand the efficacy and safety of iruplinalkib, and facilitate more rationally clinical application of iruplinalkib, the Medical Oncology Branch of China International Exchange and Promotive Association for Medical and Health Care and the Chinese Association for Clinical Oncologists co-organized experts to compile the "Chinese expert consensus on iruplinalkib for the treatment of locally advanced or metastatic ALK-positive non-small cell lung cancer (2024 edition)".

As of June 27, 2023, seven ALK-TKI, including crizotinib, ceritinib, alectinib, ensartinib, brigatinib, lorlatinib, and iruplinalkib, have garnered approval from the China National Medical Products Administration (NMPA)(ranking according to the approval time for marketing by NMPA), providing individualized treatment modalities for ALK-positive NSCLC patients. To standardize the application of ALK-TKI, the Chinese Association for Clinical Oncologists and the Medical Oncology Branch of China International Exchange and Promotive Association for Medical and Health Care has organized experts to compile the " China expert recommendations on anaplastic lymphoma kinase-tyrosine kinase inhibitors treatment for advanced non-small cell lung cancer (2024 edition)". This treatment expert recommendation provides recommendations in four aspects, encompassing ALK fusion testing, ALK-TKI targeted therapy, ALK-TKI adverse events management, and patient post-treatment follow-up, thus serving as a valuable reference for the standardized treatment of Chinese advanced ALK fusion-positive NSCLC.

Iruplinalkib demonstrated significantly improved PFS and improved intracranial antitumor activity versus crizotinib. Iruplinalkib may be a new treatment option for patients with advanced ALK positive and ALK TKI-naïve NSCLC.

Iruplinalkib is a novel anaplastic lymphoma kinase (ALK) inhibitor for the treatment of ALK-positive crizotinib-resistant NSCLC. Iruplinalkib was well tolerated at the study dose. The trial is registered at ClinicalTrials.gov (Identifier: Anonymized).

P3, N=292, Active, not recruiting, Qilu Pharmaceutical Co., Ltd. | Unknown status --> Active, not recruiting | Trial completion date: Dec 2021 --> Dec 2024 | Trial primary completion date: Jun 2021 --> Dec 2024

In June 2023, iruplinalkib was approved in China for the treatment of patients with locally advanced or metastatic ALK+ NSCLC who have progressed after prior crizotinib therapy or are intolerant to crizotinib. This article summarizes the milestones in the development of iruplinalkib leading to this first approval for the treatment of patients with locally advanced or metastatic ALK+ NSCLC.

Other endpoints were shown in the table. Conclusions Iruplinalkib demonstrated promising efficacy and acceptable toxicity in ALK-positive advanced NSCLC patients previously treated with second-generation ALK TKIs.

P=N/A, N=5000, Recruiting, Jinming Yu

Iruplinalkib demonstrated significantly improved PFS versus crizotinib and higher ORR and iORR. Iruplinalkib may be a new treatment option for pts with advanced ALK+ and ALK TKI-naïve NSCLC.

Moreover, iruplinalkib showed robust antitumor effects in BALB/c nude mice xenograft models with ALK-/ROS1-positive tumors implanted subcutaneously, and the tumor suppressive effects in crizotinib-resistant model was significantly better than that of brigatinib. Iruplinalkib did not induce CYP1A2, CYP2B6 and CYP3A4 at therapeutic concentration, and was also a strong inhibitor of MATE1 and MATE2K transporters, as well as P-gp and BCRP. In conclusion, iruplinalkib, a highly active and selective ALK/ROS1 inhibitor, exhibited strong antitumor effects in vitro and in crizotinib-resistant models.

P2, N=26, Not yet recruiting, Pingping Song

In this study, iruplinalkib (WX-0593) demonstrated favorable efficacy and manageable safety profiles in patients with ALK-positive crizotinib-resistant advanced NSCLC. Iruplinalkib could be a new treatment option for this patient population.

To evaluate the safety and therapeutic efficacy of WX-0593, a newly developed potent anaplastic lymphoma kinase (ALK) inhibitor, in combination with an epithelial growth factor receptor (EGFR) monoclonal antibody (QL1203 or Vectibix) for the treatment of xenograft tumors carrying mutant EGFR and osimertinib-resistant mutations (EGFR/T790M/C797S). WX-0593 exhibited a synergetic effect with an EGFR monoclonal antibody on osimertinib-resistant EGFR-mutant non-small cell lung cancer (NSCLC) both in vitro and in vivo. Their combination showed potent antitumor efficacy and an acceptable safety profile, which may be a promising strategy for the treatment of patients with EGFR triple-mutant NSCLC resistant to osimertinib.

P2, N=40, Recruiting, Jinming Yu

WX-0593 showed promising activity against ALK-positive NSCLC after crizotinib resistance and favorable safety profile, demonstrating WX-0593 could be a new treatment option for this patient population.

For patients who were ALK-rearranged and ALK TKI naive, the ORR were 81.0% (17 of 21) in the dose-escalation phase and 76.3% (29 of 38) in the dose-expansion phase, and for patients who previously received crizotinib as the only ALK TKI, the ORR were 38.1% (8 of 21) and 45.7% (21 of 46) for the two phases, respectively. For patients who were ROS1-rearranged, the ORR were 30.0% (3 of 10) in the dose-escalation phase and 44.4% (4 of 9) in the dose-expansion phase. WX-0593 showed favorable safety and promising antitumor activity in advanced NSCLC patients with ALK or ROS1 rearrangement.

The combination of WX-0593 and bevacizumab biosimilar had obvious synergistic effect and showed potent tumor suppressive activity, which was significantly better than WX-0593 or bevacizumab biosimilar alone at the same dose. There was no drug-related toxicity in all groups, and no increase in toxicity after combined administration.

The data from the study suggested that WX-0593 and panitumumab had a promising synergistic effect on osimertinib-resistant EGFR-mutant NSCLC both in vitro and in vivo. The combination regimen may have important clinical implications for the future treatment of patients with EGFR triple-mutant NSCLC resistant to osimertinib.

P2, N=176, Recruiting, Qilu Pharmaceutical Co., Ltd.