The goals of the Taiwan Lung Cancer Clinical Trial Consortium (TALCC) 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 TALCC. We aim to form collaborative effort to perform clinical trials that benefit lung cancer patients. Moreover, TALCC 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 TALCC is to improve clinical trial activities and accrual efficacy. In addition, TALCC 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.

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.
• On March 27, 2020, the trial was initiated at National Taiwan University Hospital and gradually expanded to Taipei Veterans General Hospital, China Medical University Hospital, Tri-Service General Hospital, Kaohsiung Medical University Hospital, and Taichung Veterans General Hospital, and other hospitals. The study aimed to include 50 participants, and recruitment has been completed. The research result was presented at 2023 World Conference of Lung Cancer.

Every year, the consortium conducts over 30 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:

The genetic variations in lung cancer among Asians differ significantly from those in Western populations. Taking the example of Epidermal Growth Factor Receptor (EGFR) mutations, Asians have a much higher prevalence compared to Westerners. The collaboration among hospitals within the Taiwan Clinical Trial Consortium for Lung Cancer integrates medical resources and employs next-generation sequencing for lung cancer patients. This aims to precisely understand tumor characteristics, enabling the provision of precise medical care and effective treatment for patients.

• The bioinformatics databases study which is collaborated with TCOG:
  • Enrollment of participants began at National Taiwan University Hospital, Taipei Veterans General Hospital, China Medical University Hospital, Chung Shan Medical University Hospital, China Medical University Hospital, Dalin Tzu Chi Hospital and National Cheng Kung University Hospital in late 2021, with all participants recruited by March 2022. Total enrollment of 500 participants.
  • Currently, next-generation gene sequencing for cancer patients in Taiwan is expensive out-of-pocket expense, costing around NTD 100,000, which poses a significant financial burden for cancer patients engaged in long-term battles. This study provides participants with free next-generation genetic analysis of tumor samples, helping lung cancer patients confirm the presence of genetic mutations, offering clinical physicians diagnostic and treatment references, and establishing a local database for lung cancer genes in Taiwan.
  • This study can detect participants with rare genetic mutations and also assist other clinical trials in identifying potential candidates, thereby increasing the enrollment rate of clinical trials.
  • This study aims to establish a genetic database for lung cancer patients in Taiwan. The study has been completed, and the analysis finished. The findings were shared with other countries at the 2023 World Conference of Lung Cancer to present the genetic variations among lung cancer patients in Taiwan.

• We set up a co-constructed resource platform to gather hospitals
• By improving communication and execution, as well as data collection and storage, we establish a good platform for clinical trials initiated by investigators
• We have conducted a large number of clinical trials of lung cancer target therapies, such as afatinib and osimertinib. The clinical trials performed have become the main basis on which the drug can be launched.
• We have conducted many clinical trials for lung cancer immunotherapies, such as durvalumab, pembrolizumab, atezolizumab, and nivolumab. These drugs have also been approved in Taiwan.

Since its establishment in 2011, this consortium has conducted over 300 international clinical trials commissioned by pharmaceutical companies, with 7 cases commissioned by domestic pharmaceutical companies. Additionally, it has conducted 7 investigator-initiated trials and recruited more than 2,000 subjects. Currently, there are 65 ongoing clinical trials. Consortium members have also been invited to play crucial roles in these trials, including serving as principal investigators for 10 clinical trials and as members of advisory boards or steering committees for 38 clinical trials. These contributions demonstrate the outstanding commitment of consortium members to advancing clinical trials in the field of lung cancer.

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. Paik PK, Felip E, Veillon R, Sakai H, Cortot AB, Garassino MC, Mazieres J, Viteri S, Senellart H, Van Meerbeeck J, Raskin J, Reinmuth N, Conte P, Kowalski D, Cho BC, Patel JD, Horn L, Griesinger F, Han JY, Kim YC, Chang GC, Tsai CL, Yang JC, Chen YM, Smit EF, van der Wekken AJ, Kato T, Juraeva D, Stroh C, Bruns R, Straub J, Johne A, Scheele J, Heymach JV, Le X. Tepotinib in Non-Small-Cell Lung Cancer with MET Exon 14 Skipping Mutations. N Engl J Med. 2020 Sep 3;383:931-943.
2. Camidge DR, Kim HR, Ahn MJ, Yang JC, Han JY, Hochmair MJ, Lee KH, Delmonte A, Garcia Campelo MR, Kim DW, Griesinger F, Felip E, Califano R, Spira AI, Gettinger SN, Tiseo M, Lin HM, Liu Y, Vranceanu F, Niu H, Zhang P, Popat S. Brigatinib versus Crizotinib in Anaplastic Lymphoma Kinase (ALK) Inhibitor-Naive Advanced ALK-Positive Non-Small Cell Lung Cancer: Final Results of the Phase 3 ALTA-1L Trial. J Thorac Oncol. 2021 Aug 30:S1556-0864(21)02398-4.
3. Camidge DR, Kim HR, Ahn MJ, Yang JC, Han JY, Hochmair MJ, Lee KH, Delmonte A, Garcia Campelo MR, Kim DW, Griesinger F, Felip E, Califano R, Spira AI, Gettinger SN, Tiseo M, Lin HM, Liu Y, Vranceanu F, Niu H, Zhang P, Popat S. Brigatinib versus Crizotinib in Anaplastic Lymphoma Kinase (ALK) Inhibitor-Naive Advanced ALK-Positive Non-Small Cell Lung Cancer: Final Results of the Phase 3 ALTA-1L Trial. J Thorac Oncol. 2021 Aug 30:S1556-0864(21)02398-4.
4. Park K, Haura EB, Leighl NB, Mitchell P, Shu CA, Girard N, Viteri S, Han JY, Kim SW, Lee CK, Sabari JK, Spira AI, Yang TY, Kim DW, Lee KH, Sanborn RE, Trigo J, Goto K, Lee JS, Yang JC, Govindan R, Bauml JM, Garrido P, Krebs MG, Reckamp KL, Xie J, Curtin JC, Haddish-Berhane N, Roshak A, Millington D, Lorenzini P, Thayu M, Knoblauch RE, Cho BC. Amivantamab in EGFR Exon 20 Insertion-Mutated Non-Small-Cell Lung Cancer Progressing on Platinum Chemotherapy: Initial Results From the CHRYSALIS Phase I Study. J Clin Oncol. 2021 Oct 20;39(30):3391-3402.
5. Zhou C, Ramalingam SS, Kim TM, Kim SW, Yang JC, Riely GJ, Mekhail T, Nguyen D, Garcia Campelo MR, Felip E, Vincent S, Jin S, Griffin C, Bunn V, Lin J, Lin HM, Mehta M, Jänne PA. Treatment Outcomes and Safety of Mobocertinib in Platinum-Pretreated Patients With EGFR Exon 20 Insertion-Positive Metastatic Non-Small Cell Lung Cancer: A Phase 1/2 Open-label Nonrandomized Clinical Trial. JAMA Oncol. 2021 Dec 1;7(12):e214761.

Collaborating with international lung cancer experts to jointly author expert recommendations for lung cancer treatment, and publishing them in major international journals.

1. Passaro A, Leighl N, Blackhall F, Popat S, Kerr K, Ahn MJ, Arcila ME, Arrieta O, Planchard D, de Marinis F, Dingemans AM, Dziadziuszko R, Faivre-Finn C, Feldman J, Felip E, Curigliano G, Herbst R, Jänne PA, John T, Mitsudomi T, Mok T, Normanno N, Paz-Ares L, Ramalingam S, Sequist L, Vansteenkiste J, Wistuba II, Wolf J, Wu YL, Yang SR, Yang JCH, Yatabe Y, Pentheroudakis G, Peters S. ESMO expert consensus statements on the management of EGFR mutant non-small-cell lung cancer. Ann Oncol. 2022 May;33(5):466-487.
2. Ahn MJ, Mendoza MJL, Pavlakis N, Kato T, Soo RA, Kim DW, Liam CK, Hsia TC, Lee CK, Reungwetwattana T, Geater S, Chan OSH, Prasongsook N, Solomon BJ, Nguyen TTH, Kozuki T, Yang JC, Wu YL, Mok TSK, Tan DS, Yatabe Y. Asian Thoracic Oncology Research Group (ATORG) Expert Consensus Statement on MET Alterations in NSCLC: Diagnostic and Therapeutic Considerations. Clin Lung Cancer. 2022 Dec;23(8):670-685.