The IASLC 2024 World Conference on Lung Cancer (WCLC 2024) was held in San Diego, CA USA on September 7th. The mOS data from the INTELLECT study was disclosed at the conference on September 8th. Oncology Frontier has invited the lead principal investigator of the INTELLECT study, Dr. Yuankai Shi from the Cancer Hospital Chinese Academy of Medical Sciences, to share the latest findings from this groundbreaking research reported at the WCLC. This study highlights the promising outcomes of Iruplinakib treatment for advanced NSCLC patients resistant to crizotinib.

Yuankai Shi, MD, PhD

l    Professor of Oncology and Chief Physician, Department of Medical Oncology

l    Doctoral Supervisor, Cancer Hospital Chinese Academy of Medical Sciences

l    Professor, Peking Union Medical College (long-term appointment)

l    Founding President, First and Second Terms, Tumor Physician Branch, Chinese Medical Doctor Association

l    Chairman, Third and Fourth Terms, Tumor Clinical Chemotherapy Professional Committee, Chinese Anti-Cancer Association

l    Chairman, Fifth Term, Lymphoma Professional Committee, Chinese Anti-Cancer Association

l    Founding Chairman, First and Second Terms, Anti-tumor Drug Professional Committee, Chinese Pharmaceutical Association

l    Founding Chairman, Department of Medical Oncology, Chinese Medical Association

l    Member, Drug Evaluation Expert Advisory Committee, National Medical Products Administration (NMPA)

l    Member, First and Second Technology Innovation Advisory Committee, Shanghai Stock Exchange

l    President, Eighth Term, China Cancer Foundation

l    Founding President, Xiongan New Area Medical Association

China Leads in Lung Cancer Research, Showcasing Remarkable Expertise

Q1: The WCLC 2024 has officially commenced, with dozens of research outcomes from Chinese scholars being featured. Which studies are you particularly interested in?

Dr. Yuankai Shi: At the WCLC 2024, Chinese lung cancer experts have had over 70 studies selected for oral presentations, highlighting the exceptional academic achievements of China’s lung cancer research. I am particularly interested in new treatment strategies for NSCLC with driver mutations. For example:

1.                Abstract P1.12B.07: Iruplinalkib in Patients with ALK-Positive Crizotinib-Resistant NSCLC: Updated Efficacy and Safety Data from a Phase 2 Trial.

2.                Abstract PL04.10: Osimertinib with or without Savolitinib as 1L in De Novo MET Aberrant, EGFRm Advanced NSCLC (CTONG 2008): A Phase ll Trial.

3.                Abstract MA06.06: The phase II clinical trial on Lorlatinib for advanced ROS1+ NSCLC patients previously treated with crizotinib and platinum-based chemotherapy.

4.                Abstract PL04.13: Aumolertinib Maintenance after chemoradiotherapy in stage lll Non-Small-Cell Lung Cancer: Interim Results of the phase lll study (POLESTAR).

5.                Abstract OA09.05: Subcutaneous vs Intravenous Amivantamab: Patient Satisfaction and Resource Utilization Results from the PALOMA-3 Study.

I hope these new explorations led by Chinese scholars will make a significant contribution to the global clinical management of lung cancer.

Iruplinakib Offers Prolonged Survival for Crizotinib-Resistant Advanced NSCLC Patients

Q2: The INTELLECT study, which will be presented at this year’s conference, previously reported a median progression-free survival (mPFS) of 19.8 months. The updated data now show a median overall survival (mOS) of 41.8 months. Could you elaborate on these findings?

Dr. Yuankai Shi: The INTELLECT study is a single-arm, multicenter phase II clinical trial enrolling patients with advanced ALK-positive NSCLC who experienced disease progression after at least 12 weeks of crizotinib treatment. A total of 146 patients were enrolled. In 2023, BMC Medicine published the INTELLECT study results, revealing an mPFS of 19.8 months for Iruplinakib in treating crizotinib-resistant ALK-positive advanced NSCLC. Based on these findings, Iruplinakib was approved by the NMPA on June 27, 2023, for treating ALK-positive locally advanced or metastatic NSCLC patients who have progressed on or are intolerant to crizotinib.

At this year’s WCLC, we are presenting updated OS data. As of December 29, 2023, the median follow-up time reached 42.4 months. Among the 146 enrolled patients, 72 had died, and 16 were lost to follow-up. The mOS reached 41.8 months1. In comparison, the PROFILE 1014 study on crizotinib reported an mOS of only 20.8 months for patients treated with sequential chemotherapy after crizotinib resistance. This suggests that Iruplinakib may offer twice the OS benefit for patients with crizotinib-resistant ALK-positive advanced NSCLC.

Iruplinakib Shows Strong Efficacy in Brain Metastasis, Offering New Hope for Patients.

Q3: The updated INTELLECT study data also includes an analysis of patients with baseline brain metastases, showing encouraging efficacy results. Could you explain the significance of Iruplinakib’s ability to penetrate the brain for these patients?

Dr. Yuankai Shi: Brain metastases are a critical factor affecting patients’ quality of life and survival prognosis. Tumor-induced pressure and invasion can lead to intracranial hypertension, causing headaches, and result in severe central nervous system dysfunctions, such as seizures, behavioral changes, and speech difficulties. These complications significantly impact patients’ quality of life and place a heavy financial burden on patients and their families. For patients with advanced ALK-positive NSCLC initially treated with crizotinib, the drug’s molecular structure makes it difficult to cross the blood-brain barrier, leading to low intracranial drug concentrations and a high incidence of new intracranial lesions after crizotinib resistance.

The updated INTELLECT study results showed that among patients with baseline brain metastases treated with Iruplinakib, 42 had measurable intracranial lesions. The intracranial objective response rate (ORR) reached 64.3%, and the disease control rate (DCR) was 95.2%. The median intracranial duration of response (DoR) and PFS were 18.7 months and 17.3 months, respectively, indicating that Iruplinakib has strong brain-penetrating abilities, providing significant benefits for these patients.

China’s ALK-TKI Iruplinakib Advances Chronic Disease Management of ALK-Positive Advanced NSCLC

Q4: Novel ALK-TKIs are driving the chronic disease management of ALK-positive advanced NSCLC, making long-term drug safety management crucial. The safety data from the INTELLECT study presented at this conference are also noteworthy. How does this data contribute to improving patients’ quality of life?

Dr. Yuankai Shi: The ALK target, along with EGFR, has paved the way for precision treatment in lung cancer. Targeted therapies, represented by new-generation ALK-TKIs have significantly improved the survival of ALK-positive NSCLC patients and have become the treatment of choice for advanced ALK-positive NSCLC. However, ensuring patients receive standardized treatment throughout their disease course, extending survival while improving quality of life, is key to achieving chronic disease management for cancer. For advanced ALK-positive lung cancer patients, selecting an effective and safe targeted therapy is essential.

In recent years, new-generation ALK-TKIs have emerged, with Iruplinakib, developed in China, standing out due to its excellent efficacy and safety profile. The INTELLECT study showed that Iruplinakib achieved an mPFS of 19.8 months and an mOS of 41.8 months in crizotinib-resistant patients. The upcoming ESMO 2024 conference will feature the phase III INSPIRE study on Iruplinakib as a first-line treatment for ALK-positive NSCLC, with even more impressive median PFS data. This suggests that new-generation ALK-TKIs will further advance the chronic disease management of advanced ALK-positive NSCLC.

In clinical practice, both the efficacy and safety of a drug must be considered. For ALK-positive NSCLC patients, safety is particularly important, as this group tends to be younger and is an important participant in social activities. If safety issues significantly impact patients’ quality of life, it could also have negative consequences for social and economic development. Therefore, monitoring adverse drug reactions is a critical aspect of chronic disease management for advanced ALK-positive NSCLC.

The updated safety data from the INTELLECT study shows that the most common adverse reactions were elevated transaminases (45.2%) and hypercholesterolemia (37.7%), with grade 3-4 adverse reactions occurring in 30.8% of patients. The rate of treatment discontinuation due to adverse reactions was 3.4%. Additionally, a pooled analysis of 409 patients revealed that Iruplinakib had low incidences of muscle pain, constipation, and edema, with minimal impact on patients’ quality of life. These safety data suggest that Iruplinakib has a favorable safety profile, with few patients experiencing a decrease in quality of life due to adverse reactions, making it an ideal choice for the chronic management of advanced ALK-positive NSCLC. We also look forward to the availability of more safe and effective drugs in the future, providing additional benefits for patients with advanced ALK-positive NSCLC.

Reference

1. Shi Y, Chen J, Zhang H, et al. Iruplinakib in Patients with ALK-Positive Crizotinib-Resistant NSCLC: Updated Efficacy and Safety Data from a Phase 2 Trial. 2024 WCLC,Abstract 2049.

2. Shi Y, Chen J, Zhang H, et al. Efficacy and safety of Iruplinakib (WX-0593) in ALK-positive crizotinib-resistant advanced non-small cell lung cancer patients: a single-arm, multicenter phase II study (INTELLECT)[J]. BMC medicine, 2023, 21(1): 72 .

3. Solomon BJ, Kim DW, Wu YL, et al. Final Overall Survival Analysis From a Study Comparing First-Line Crizotinib Versus Chemotherapy in ALK-Mutation-Positive Non-Small-Cell Lung Cancer[J]. J Clin Oncol, 2018, 36(22): 2251–2258.

4. 陈雨晨, 韩寒, 魏晋攀等. ALK抑制剂在治疗NSCLC脑转移中的疗效及安全性研究进展. 中国肺癌杂志, 2023, 26(5): 400-406.