Qi Xinke (iruplinalkib)

After failure of gemcitabine/docetaxel chemotherapy, next-generation sequencing identified an IGFBP5-ALK fusion (breakpoint: IGFBP5 exon 1 - ALK exon 19), a TERT promoter mutation, and a homozygous CDKN2A/CDKN2B/MTAP deletion. This case highlights the first documented response to an ALK inhibitor in ALK-rearranged HG-ESS. The findings underscore the importance of comprehensive molecular profiling in identifying targetable alterations in rare sarcomas and support the use of iruplinalkib as an effective therapeutic option in this setting.

Specifically, lorlatinib demonstrated superior efficacy in the Non-Asian subgroup (86.8%), patients without brain metastasis (84.7%), those with Eastern Cooperative Oncology Group performance status (ECOG PS) 0/1 (78.5%), males (71.2%), females (83.9%), patients aged < 65 years (74.3%), and never-smoking patients (89.7%)...Ensartinib achieved the optimal PFS in the Asian subgroup (71.8%)...Alectinib had the lowest hepatic and gastrointestinal AEs risk, while iruplinalkib had the lowest hematological AEs risk. https://www.crd.york.ac.uk/prospero/, identifier CRD42023495527.

P=N/A, N=20, Recruiting, Peking University Shenzhen Hospital

P=N/A, N=10, Not yet recruiting, Peking University Shenzhen Hospital; Peking University Shenzhen Hospital

P=N/A, N=200, Not yet recruiting, Shandong First Medical University and Shandong Academy of Medical Sciences (Shandong Cancer Hospital ＆Institute); Shandong First Medical University

P2, N=28, Not yet recruiting, Tianjin Medical University Cancer Institute and Hospital

From the probabilistic sensitivity analysis (PSA), iruplinalkib had a 100% probability of being cost-effective at a willingness-to-pay threshold of $13,447.89/QALY. Compared to crizotinib, iruplinalkib is a cost-effective therapy for treatment-naïve patients with ALK-positive NSCLC.

Systemic SAEs exhibited greater variability across agents, ranging from 29% to 47%: crizotinib, 43% (95% CI, 36%-49%); ceritinib, 41% (95% CI, 37%-45%); lorlatinib, 39% (95% CI, 25%-55%); entrectinib, 32% (95% CI, 28%-36%); repotrectinib, 29% (95% CI, 24%-33%); iruplinalkib, 44% (95% CI, 38%-50%); and unecritinib, 47% (95% CI, 38%-56%)...Taletrectinib and unecritinib were notably associated with hepatotoxicity...These findings will guide drug selection and safety monitoring, emphasizing the necessity of considering patients' health status, potential risk factors, and the characteristics of ROS1-TKI-related adverse reactions. https://www.crd.york.ac.uk/PROSPERO/view/CRD42024551353, identifier CRD42024551353.

This case underscores the potential of Iruplinalkib, which is currently not available outside of China, to induce rapid and profound tumor regression in ALK-positive NSCLC, particularly in adolescent patients with aggressive clinical presentations. We hope that the anticancer efficacy of Iruplinalkib will be recognized globally and that it will become accessible to ALK-positive lung cancer patients worldwide.

A translational model-based approach using integrated preclinical PK/PD and PopPK modeling in patients with non-small cell lung cancer is a reliable method to predict RP2D. Trial Registration: ChiCTR.org.cn number: ChiCTR20170871; ClinicalTrials.gov identifier: NCT03389815; ChinaDrugTrials.org.cn number: CTR20190737.

P2, N=26, Recruiting, Pingping Song | Trial completion date: Apr 2028 --> Mar 2029 | Trial primary completion date: Jan 2026 --> Mar 2027

In December 2023, a needle biopsy of a metastasis in the left lower lobe of the lung showed a positive SDC4-ROS1 fusion. Subsequent treatment with the oral ALK TKI iruplinalkib was initiated based on the patient's preference, which exhibited a promising response over the next 2 months.