Efficacy and Safety of Combination Therapy With Bojungikki-tang and Pembrolizumab Monotherapy in Patients With Advanced Non-small Cell Lung Cancer

NCT06249854 | Recruiting Phase 2

• 1 other identifier: KIOM-NSCLC-ICT-01
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 7

Brief Summary

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.

Conditions

Non-small Cell Lung Cancer

Keywords

Bojungikki-tang; Buzhong Yiqi decoction; Hochu-ekki-to

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS)

  Every 9 weeks until PD(progressive disease), up to end of study (2 years from study initiation)

Secondary Outcomes (12)

• Disease Control Rate (DCR)

  Every 9 weeks until PD(progressive disease), up to end of study (2 years from study initiation)

• Overall Survival (OS)

  Upon confirmation of death, end of the study (2 years from study initiation)

• Object Response Rate (ORR)

  Every 9 weeks until PD(progressive disease), up to end of study (2 years from study initiation)

• Time to Progression (TTP)

  Every 9 weeks until PD(progressive disease), up to end of study (2 years from study initiation)

• Duration of Response (DoR)

  End of study (2 years from study initiation)

Study Arms (2)

Bojungikkitang & Pembrolizumab combination treatment group

EXPERIMENTAL

Pembrolizumab is administered intravenously every 3 weeks for 45 weeks according to standard procedures until disease progression (PD) or unacceptable toxicity occurs. Bojungikgitang is used in combination with immune checkpoint inhibitor treatment(Pembrolizumab) and is taken 1 bag twice a day before or between meals.

Drug: Bojungikki-tang(BJIKT); Drug: Pembrolizumab

Pembrolizumab monotherapy group

ACTIVE COMPARATOR

Pembrolizumab is administered intravenously every 3-week for 45 weeks according to routine practice until disease progression (PD) or unacceptable toxicity occurs.

Drug: Pembrolizumab

Interventions

Bojungikki-tang(BJIKT) DRUG

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

Also known as: Buzhong Yiqi Decoction, Hochu-ekki-to

Bojungikkitang & Pembrolizumab combination treatment group

Pembrolizumab DRUG

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.

Bojungikkitang & Pembrolizumab combination treatment group; Pembrolizumab monotherapy group

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients who voluntarily decided to participate and provided written consent, after listening and understanding the detailed explanation about the clinical trial
• Adult male or female aged 19 years or older
• Patients with histologically or cytologically confirmed advanced (stage IV) non-small cell lung cancer \[according to TNM 8th edition\] In case of recurrence, only extra-thoracic metastasis is allowed.
• Patients planned for immune checkpoint inhibitor (Pembrolizumab) monotherapy as first-line treatment (Patients with PD-L1 tumor proportion score(TPS) ≥ 50% and no EGFR or ALK genomic tumor aberrations)
• Life expectancy ≥ 3 months
• ECOG (Eastern Cooperative Oncology Group) Performance Status score of 0\~2
• Patients with at least 1 measurable lesion as defined in RECIST V1.1
• Patients with adequate bone marrow reserve or organ function as follows:
• Hemoglobin ≥ 9.0 g/dL
• Absolute neutrophil count (ANC) ≥ 1,500/㎕
• Platelet count ≥100× 10\^3/㎕
• Serum creatinine ≤ 1.5x ULN or creatinine clearance ≥ 45 ml/min (measured using standard methods at the study site)
• ALT and AST ≤ 2.5× ULN Patients with liver metastasis: ALT and AST ≤ 5× ULN
• Total bilirubin ≤ 1.5× ULN Patients with liver metastasis or known Gilbert syndrome(unconjugated hyperbilirubinemia): Total bilirubin ≤ 3× ULN

You may not qualify if:

• Active brain metastases accompanied by clinically significant neurological symptoms or signs
• Patients who diagnosed with another primary malignancy that affect non-small cell lung cancer in the last 5 years However, effectively treated non-melanoma skin cancer, carcinoma in situ of cervix, ductal carcinoma in situ of breast, thyroid cancer, or malignancies which were remained in remission during more than 3 years after being treated effectively and considered cured are permitted.
• Patients who treated with immune checkpoint inhibitor or anti-CTLA-4 within the last 6 weeks or systemic immunosuppressive medications within the last 2 weeks However, low-dose corticosteroids (prednisone ≤ 10 mg/day or an equivalent dose of corticosteroid within 7 consecutive days) are permitted at the investigator's discretion.
• Patients receiving thiazide or loop diuretics
• Hypokalemia (less than 3.0 mEq/L)
• Active interstitial lung disease requiring oral or intravenous steroid treatment
• Patients with autoimmune disease requiring systemic treatment at the time of enrollment
• Uncontrolled diabetes mellitus at the time of enrollment (Uncontrolled with insulin and oral medications, HbA1c ≥ 8.0% or fasting blood sugar ≥ 200 mg/dL)
• Patients with uncontrolled hypertension at the time of enrollment (systolic pressure \> 150 mmHg or diastolic pressure \>100 mmHg) despite use of antihypertensive agent
• Patients with uncontrolled heart disease (severe heart failure, unstable angina, uncontrolled arrhythmia, or history of life-threatening arrhythmia, etc.)
• Patients with hereditary problems such as galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption, etc.
• Patient with known active or uncontrolled HIV, tuberculosis, hepatitis B, or hepatitis C infection
• Pregnant or lactating women
• Patients who do not agree to use effective contraception during treatment period and for at least 5 months after the end of IP administration
• Patients who received herbal medicine within 4 weeks before the first administration of IP (Bojungikgitang) and been decided that such intake affect the trial or safety of the subject at the investigator's discretion

Sponsors & Collaborators

• Korea Institute of Oriental Medicine: lead

Study Sites (7)

Hallym University Medical Center

Anyang-si, Gyeonggi-do, 14068, South Korea

RECRUITING

Pusan National University Yangsan Hospital

Yangsan, Gyeongsangnam-do, 50612, South Korea

RECRUITING

Kyung Hee University Hospital

Seoul, 02447, South Korea

RECRUITING

Hanyang University Seoul Hospital

Seoul, 04763, South Korea

RECRUITING

Samsung medical center

Seoul, 06351, South Korea

RECRUITING

Korea University Guro Hospital

Seoul, 08308, South Korea

RECRUITING

The catholic university of Korea Seoul Saint. Mary's hospital

Seoul, South Korea

RECRUITING

Related Publications (7)

• Pai-Scherf L, Blumenthal GM, Li H, Subramaniam S, Mishra-Kalyani PS, He K, Zhao H, Yu J, Paciga M, Goldberg KB, McKee AE, Keegan P, Pazdur R. FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. Oncologist. 2017 Nov;22(11):1392-1399. doi: 10.1634/theoncologist.2017-0078. Epub 2017 Aug 23.

  PMID: 28835513 BACKGROUND

• Postow MA, Sidlow R, Hellmann MD. Immune-Related Adverse Events Associated with Immune Checkpoint Blockade. N Engl J Med. 2018 Jan 11;378(2):158-168. doi: 10.1056/NEJMra1703481. No abstract available.

  PMID: 29320654 BACKGROUND

• Sharma P, Hu-Lieskovan S, Wargo JA, Ribas A. Primary, Adaptive, and Acquired Resistance to Cancer Immunotherapy. Cell. 2017 Feb 9;168(4):707-723. doi: 10.1016/j.cell.2017.01.017.

  PMID: 28187290 BACKGROUND

• Pishvar M, Amirkhosravi M, Altan MC. Magnet Assisted Composite Manufacturing: A Flexible New Technique for Achieving High Consolidation Pressure in Vacuum Bag/Lay-Up Processes. J Vis Exp. 2018 May 17;(135):57254. doi: 10.3791/57254.

  PMID: 29863655 BACKGROUND

• Kimura M, Sasada T, Kanai M, Kawai Y, Yoshida Y, Hayashi E, Iwata S, Takabayashi A. Preventive effect of a traditional herbal medicine, Hochu-ekki-to, on immunosuppression induced by surgical stress. Surg Today. 2008;38(4):316-22. doi: 10.1007/s00595-007-3631-4. Epub 2008 Mar 27.

  PMID: 18368320 BACKGROUND

• Peng M, Li X, Lei G, Weng YM, Hu MX, Song QB. The efficacy and safety of immune checkpoint inhibitor combination therapy in lung cancer: a systematic review and meta-analysis. Onco Targets Ther. 2018 Oct 24;11:7369-7383. doi: 10.2147/OTT.S177318. eCollection 2018.

  PMID: 30425525 BACKGROUND

• Qi F, Zhao L, Zhou A, Zhang B, Li A, Wang Z, Han J. The advantages of using traditional Chinese medicine as an adjunctive therapy in the whole course of cancer treatment instead of only terminal stage of cancer. Biosci Trends. 2015 Feb;9(1):16-34. doi: 10.5582/bst.2015.01019.

  PMID: 25787906 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Buzhong Yiqi decoction; bu-zhong-yi-qi-tang; pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Sung Yong Lee, Ph.D

  Koera University Guro Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mi-Kyung Jeong, Ph.D

CONTACT

042-868-9475; oiny2000@kiom.re.kr

Eunbyul Cho

CONTACT

042-869-2779; eunbc@kiom.re.kr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal researcher

Study Record Dates

• First Submitted: January 9, 2024
• First Posted: February 8, 2024
• Study Start: February 8, 2024
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: October 1, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

KR (7)