This is a multicenter, open-label, randomized controlled clinical trial designed to evaluate the efficacy and safety of combination therapy with Bojungikki-tang(BJIKT) and pembrolizumab monotherapy in patients with advanced non-small cell lung cancer whose tumors express PD-L1 positive with no EGFR or ALK genomic tumor aberrations. Based on prior pre-clinical studies, the combination of Bojungikki-tang and immune checkpoint inhibitors (ICIs) can be expected to improve survival and enhance the therapeutic efficacy of ICIs by modulating the systemic tumor-immune environment. Therefore, this clinical trial aims to assess the efficacy and safety of the combined therapy with BJIKT and pembrolizumab and establish clinical evidence for an integrative cancer treatment strategy by examining the survival rate and immune status following combined ICI and BJIKT treatment.
This is a multicenter, open-label, randomized controlled clinical trial to evaluate the efficacy and safety of combination therapy with Bojungikki-tang(BJIKT) and pembrolizumab monotherapy in patients with advanced non-small cell lung cancer whose tumors express PD-L1 positive with no EGFR or ALK genomic tumor aberrations. A total of 70 patients aged 19 or older will be enrolled in the study and progression-free survival (PFS) will be assessed as the primary endpoint. In a pre-clinical study, the combination of immune checkpoint inhibitors(ICIs) and Bojungikki-tang extended the survival of mice compared to the administration of ICIs or BJIKT alone and reduced tumor volume and weight. In addition, it was confirmed that various immune-related factors in the tumor microenvironment were controlled to improve the immunosuppressed microenvironment and to strengthen the tumor immune response by increasing major immune cytokines in the blood. Furthermore, the combination of ICIs and BJIKT did not cause pharmacodynamic and pharmacokinetic drug interactions, and significant side effects of Bojungikki-tang were not observed in most clinical reports on long-term administration of Bojungikki-tang. Based on the results, the combination of BJIKT and ICIs is expected to improve survival and enhance the therapeutic efficacy of ICIs by modulating the systemic tumor-immune environment. In order to evaluate efficacy, variables including PFS, disease control rate (DCR), overall survival (OS), and quality of life will be used. The incidence rate of adverse events (AEs) and AEs with CTCAE grade 3 or higher will be assessed for safety. Most variables will be followed up during and after 45-week treatment, and the safety of interventions will be monitored consistently. Immune profiling and multi-omics analyses, including transcriptomic, proteomic, and metabolomic evaluations of PBMCs, will be conducted for exploratory purposes. In addition, pattern identification, a traditional diagnostic method in East Asian medicine, will be utilized as an exploratory variable. A validated questionnaire assessing Cold-Heat patterns, tongue diagnosis data, and pulse diagnosis data will be used to investigate their correlation with clinical and laboratory data.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
26
Bojungikgitang, which is a classical formulation widely used in South Korea, China, and Japan for a long time, has been reported to have following anticancer activities. 1. Protective effect of intestine and hematopoietic organs against radiation damage 2. Improving localized radiotherapy-induced immune deterioration 3. Improving cancer-related fatigue and QOL 4. Reducing radiation or chemotherapy induced side effects
It is a humanized antibody used in cancer immunotherapy for various types of cancer, including lung cancer. It targets the programmed cell death protein 1 (PD-1) receptor of lymphocytes. It was approved for medical use in the U.S. in 2014.
Hallym University Medical Center
Anyang-si, Gyeonggi-do, South Korea
Pusan National University Yangsan Hospital
Yangsan, Gyeongsangnam-do, South Korea
Kyung Hee University Hospital
Seoul, South Korea
Hanyang University Seoul Hospital
Seoul, South Korea
Samsung medical center
Seoul, South Korea
Korea University Guro Hospital
Seoul, South Korea
The catholic university of Korea Seoul Saint. Mary's hospital
Seoul, South Korea
Progression-Free Survival (PFS)
Time frame: Every 9 weeks until PD(progressive disease), up to end of study (2 years from study initiation)
Disease Control Rate (DCR)
Time frame: Every 9 weeks until PD(progressive disease), up to end of study (2 years from study initiation)
Overall Survival (OS)
Time frame: Upon confirmation of death, end of the study (2 years from study initiation)
Object Response Rate (ORR)
Time frame: Every 9 weeks until PD(progressive disease), up to end of study (2 years from study initiation)
Time to Progression (TTP)
Time frame: Every 9 weeks until PD(progressive disease), up to end of study (2 years from study initiation)
Duration of Response (DoR)
Time frame: End of study (2 years from study initiation)
Time to Treatment Failure (TTF)
Time frame: Every 9 weeks until PD(progressive disease), up to end of study (2 years from study initiation)
Number of participants with hyper-progressive disease
Time frame: Up to end of study (2 years from study initiation)
Quality of Life (QoL)
Time frame: Baseline, Visit 4(week 10), End of Treatment(EOT) visit(week 46)
Correlation between immuno/omics data and clinical data
Time frame: Baseline, week 4, week 10, week 19, week 28, week 37, End of Treatment(EOT) visit(week 46)
Treatment response according to classification of the cold-heat pattern
Cold-heat pattern classification (Cold pattern, Non-cold pattern, Heat pattern, Non-heat) refers to pattern identification of traditional East Asian medicine diagnosed by experts (Doctors of Korean Medicine) based on validated questionnaire, digital tongue diagnosis system data, and digital pulse diagnosis system data
Time frame: End of study (2 years from study initiation)
Pulse waveform analysis of digital pulse diagnostic system
The Electric Radial Tonometry device complies with ISO 18615:2020.
Time frame: Baseline, Visit 4(week 10), End of Treatment(EOT) visit(week 46)
Data of digital tongue diagnosis system
Categorical scales including tongue colors of tongue body: pale, light pink, red, and continuous variables including the Commission Internationale del'Éclairage (CIE) L\*a\*b\* color values of tongue that represent the brightness, saturation of red and green, and saturation of blue and yellow, respectively. The equipment used in this study has an algorithm to increase repeatability and diagnostic accuracy by using indirect illumination and feedback gridlines. Also, it was designed to meet the international standards ISO 20498-1, 20498-2, 20498-3, 20498-4, and 20498-5.
Time frame: Baseline, Visit 4(week 10), End of Treatment(EOT) visit(week 46)
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