The goals of the Taiwan Clinical Trial Consortium for Lung Cancer (TLCC) are advancing lung cancer treatments and improving the treatment outcome of lung cancer patients. In 2011, we gathered lung cancer clinical trial experts from major hospitals in Taiwan to form TLCC. We aim to form collaborative effort to perform clinical trials that benefit lung cancer patients. Moreover, TLCC provides a platform for the pharmaceutical companies to promote new drugs and clinical trials from the laboratory to clinical applications.

One of the aims of TLCC is to improve clinical trial activities and accrual efficacy. In addition, TLCC members can share research activities and exchange experience in clinical trial. We hope that Taiwan continues to be a global leading country in lung cancer clinical trials and new drug development. Furthermore, we will be able to provide patients with effective new treatments.

Emerging trends in lung cancer clinical trial design

With the advancement of remote data transmission and information security storage technology, the rapid development of portable sensing components, and the widespread application of big data real clinical databases, how these novel scientific and technological achievements establish new model of clinical trial designs and provide benefits in clinical trial is a key issue. In order to meet the achievement, TLCC horizontally combines the professional experience of National Taiwan University Clinical Trial Center and relevant domestic guidelines. With the goal of accelerating the effectiveness of lung cancer clinical trials, TLCC will conduct of at least five new multi-center clinical trials with new model of clinical trial designs before 2027. Application models include “Decentralized clinical trials, DCT”, “Digital health technology, DHT”, and “Real-world data (RWD) to conduct real-world evidence (RWE)”.

As an example of "metaverse technology in clinical trial", through the combined use of digital sensing components, remote communications and databases, clinical trials are no longer limited to local centers. Digital data can be acquired remotely, and interpretation between experimenters and subjects is decentralized from a model that previously had to be conducted face-to-face in a medical center to a model that can be conducted remotely and on-site.

International collaboration aspects

The consortium made its inaugural attempt to collaborate with international academic institutions, jointly executing investigator-initiated academic projects. In 2018, it partnered with the University of Sydney in Australia to co-plan an investigator-initiated clinical trial for lung cancer. The trial was conducted across multiple hospitals in both countries, heralding the commencement of a new paradigm in cross-border cooperation.

• In Taiwan, our consortium collaborates with the National Health Research Institutes Taiwan Cooperative Oncology Group (TCOG), leveraging their extensive experience in conducting clinical trials, their backend clinical trial database, and administrative systems. This partnership allows our consortium to focus wholeheartedly on patient enrollment without any concerns and lays the foundation for future collaborations.

Every year, the consortium conducts over double digit new clinical trials, with many of them being registration trials. These trial results have also led to the successive approvals of numerous drugs domestically and internationally. During this program, the trials carried out by the Taiwan Clinical Trial Consortium for Lung Cancer have successfully led to the indication approval of the following medications:

■ Targeted drugs (based on corresponding gene types):

• EGFR exon 20 insertion:
  • The phase 1 clinical trial of amivantamab, conducted in collaboration between our consortium and an American pharma: The drug was approved in Taiwan in 2021 to treat the adult patients with locally advanced or metastatic non-small cell lung cancer with EGFR exon 20 insertion mutations whose disease has progressed on or after platinum-based chemotherapy.
  • The phase 1/2 clinical trial of mobocertinib, conducted in collaboration with Japanese pharma: The drug was approved in Taiwan in 2022. It is a kinase inhibitor indicated for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer with EGFR exon 20 insertion mutations whose disease has progressed on or after platinum-based chemotherapy.
• MET exon 14skipping:
  • The phase 2 clinical trial of tepotinib conducted in collaboration with German pharma: The drug was approved in USA in 2021 and approved in Taiwan in 2022. It is a kinase inhibitor indicated for the treatment of adult patients with metastatic non-small cell lung cancer harboring MET exon 14 skipping alterations. This medication is reimbursed by National Health Insurance (NHI) since 2023, leading to benefits for more patients and physicians.
  • The phase 2 clinical trial of capmatinibr conducted in collaboration with American pharma: The drug was approved in Taiwan in 2022. It is a kinase inhibitor indicated for the treatment of adult patients with metastatic non-small cell lung cancer harboring MET exon 14 skipping alterations.
• KRAS G12C mutation:
  • The phase 2 clinical trial of sotorasib conducted in collaboration with American pharma: The drug was approved in Taiwan in 2022. It is indicated for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer, who have received at least one prior systemic therapy.
• RET fusion:
  • The phase 1 clinical trial of selpercatinib conducted in collaboration with American pharma: The drug was approved in Taiwan in 2022. It is approved to treat adult patients with locally advanced or metastatic non-small cell lung cancer with RET gene fusion.
  • The phase 1 clinical trial of pralsetinib conducted in collaboration with American pharma: The drug was approved in Taiwan in 2022. It is a kinase inhibitor indicated for the treatment of adult patients with metastatic rearranged during RET fusion-positive non-small cell lung cancer.

■ Antibody Drug Conjugate (ADC): This represents a new direction in current cancer treatment, utilizing targeting specific to cancer cells membrane antigens to deliver chemotherapy drugs directly to tumor tissues, with the aim of enhancing the effectiveness of chemotherapy drugs. The consortium conducts numerous clinical trials of antibody-drug conjugates to achieve this goal.

• The phase 2 clinical trial of trastuzumab deruxtecan conducted in collaboration with Japanese pharma: The drug was approved in USA in 2022. It is approved to treat adult patients with unresectable or metastatic non-small cell lung cancer whose tumors have HER2 (ERBB2) mutations and have received a prior systemic therapy.

Economic aspects:

The trials conducted by this consortium are mostly funded by foreign manufacturers, which include substantial resources such as professionals (CRA, research nurse), operational costs, and the provision of expensive medications. The funding for each project often exceeds tens of millions of New Taiwan Dollars. By providing free high-cost medications, it compensates for the limitations of the health insurance, enabling Taiwanese patients to have the opportunity for early medication access and, consequently, extending the patients' survival periods.

This consortium has actively participated in and led numerous clinical trials sponsored by international pharmaceutical companies, as well as investigator-initiated research studies. By engaging in these phase I to III clinical trials, it has cultivated a pool of highly skilled professionals domestically, thereby generating numerous employment opportunities.

Social aspects:

Lung cancer has emerged as a critical health concern in Taiwan, ranking as the leading cause of cancer-related mortality. The paradigm shift of lung cancer therapy from late-stage to early stage is a global trend. The widespread adoption of LDCT led to a consistent increase in the number of lung cancer diagnoses accelerates this shift. The surgery plans a more important role than before in lung cancer control. How to speed up the development and commercialization of Taiwan biotechnology and medicine industries is the bottleneck for Taiwan being the Asia-Pacific biomedical research and development industry center. In response to this challenge, TLCC will consolidate medical centers from various regions across Taiwan, including core members such as National Taiwan University Hospital, Chung Shan Medical University Hospital, Tri-Service General Hospital, Taipei Veterans General Hospital, Linkou Chang Gung Memorial Hospital, and Far Eastern Memorial Hospital. The establishment of this consortium will streamline the operation of multi-center clinical trials, fostering collaborative efforts in both industry-sponsored trials and investigator-initiated research. Our ultimate goal is to expedite progress in lung cancer clinical trials and related translational research, ultimately enhancing the treatment and prognosis for lung cancer patients in Taiwan.

Important News:

The clinical trials conducted by the consortium are gradually being published in international prestigious journals, and the investigational drugs have also obtained relevant indications.

1. Gee-Chen Chang*, Chao-Hua Chiu*, Chong-Jen Yu* ", Low-dose CT screening among never-smokers with or without a family history of lung cancer in Taiwan: a prospective cohort study" Lancet Respir Med Volume:12 Issue: 2 Page:141-152 Published: Feb.2024
2. Gee-Chen Chang* " Low-Dose Computed Tomography screening in relatives with a family history of lung cancer", J Thorac Oncol. Volume: 18 Issue: 11 Page: 1492-1503 Published: Nov. 2023
3. Gee-Chen Chang* " A Randomized-Controlled Phase 2 Study of the MET Antibody Emibetuzumab in Combination with Erlotinib as First-Line Treatment for EGFR Mutation-Positive NSCLC Patients", J Thorac Oncol. Volume15 Issue: 1 Page:80-90 Published: Jan.2020
4. Mong-Wei Lin, Min-Shu Hsieh " Salvage Surgery for Advanced Lung Adenocarcinoma After Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Treatment", Ann Thorac Surg. Volume: 116 Issue: 1 Page: 111-119 Published: Jul. 2023
5. Gee-Chen Chang* "Evaluation of combination treatment with DS-1205c, an AXL kinase inhibitor, and osimertinib in metastatic or unresectable EGFR-mutant non-small cell lung cancer: results from a multicenter, open-label phase 1 study", Invest New Drugs. Volume: 41 Page: 306–316 Published: Mar. 2023
6. Gee-Chen Chang* " The Clinical Outcomes of Different First-Line EGFR-TKIs Plus Bevacizumab in Advanced EGFR-Mutant Lung Adenocarcinoma", Cancer Research and Treatment Volume: 54 Issue: 2 Pages: 434-444 Published: Apr. 2022