Combination therapy for advanced biliary tract cancer

Randomized, Placebo-controlled, Open-label, Phase 2b Clinical Trial to Evaluate the Antitumor Activity of Combination Therapy of SMT-NK and Pembrolizumab vs Pembrolizumab Monotherapy in Patients With Advanced Biliary Tract Cancer

This study is testing if combining SMT-NK injections with pembrolizumab can help people with advanced biliary tract cancer do better than using pembrolizumab alone.

Quick facts

• Phase: PHASE2; PHASE3
• Study type: Interventional
• Enrollment: 128 (estimated)
• Ages: 19 Years to 80 Years
• Sex: All
• Sponsor: SMT bio Co., Ltd. (industry)
• Drugs / interventions: Pembrolizumab, chemotherapy, immunotherapy
• Locations: 3 sites (Goyang-si, Gyeonggi-do and 2 other locations)
• Trial ID: NCT05429697 on ClinicalTrials.gov

What this trial studies

This study evaluates the effectiveness of SMT-NK injections combined with pembrolizumab compared to pembrolizumab alone in patients with advanced biliary tract cancer. Biliary tract cancer is known for its poor prognosis and low survival rates, particularly in advanced stages. The trial aims to explore the potential of natural killer cells to enhance the antitumor activity of pembrolizumab, a checkpoint inhibitor. Patients will be monitored for tumor response using RECIST criteria, and the study is conducted in South Korea, where the incidence of biliary tract cancer is rising.

Who should consider this trial

Good fit: Ideal candidates include adults aged 19 to 80 with nonresectable advanced biliary tract carcinoma who have either refractory disease after chemotherapy or cannot continue chemotherapy due to side effects.

Not a fit: Patients with resectable biliary tract cancer or those who do not meet the eligibility criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve survival rates and outcomes for patients with advanced biliary tract cancer.

How similar studies have performed: While the combination of NK cell therapy and pembrolizumab is a novel approach, similar immunotherapy strategies have shown promise in other cancer types.

Eligibility criteria

Inclusion Criteria:

1. Patients who received a histopathological or cytologic diagnosis of nonresectable, advanced biliary tract carcinoma (intrahepatic or extrahepatic cholangiocarcinoma, gallbladder cancer) and patients with refractory disease after chemotherapy and/or patients who have difficulty with chemotherapy due to side effects of chemotherapy.
2. Patients who receives an explanation from the trial manager about the purpose, contents, and characteristics of the Investigational products for the clinical trial and is signed by the person, guardian or legal representative in the written informed consent.
3. 19 to 80 years old on day of signing informed consent.
4. Histopathological or cytologic diagnosis of advanced adenocarcinoma of the biliary tract and those with measurable lesions for RECIST evaluation

   * Tumor lesion: Must be accurately measured in at least one dimension (longest diameter in the plane of measurement is to be recorded) with a minimum size of 10mm by CT scan
   * Malignant lymph nodes: To be considered pathologically enlarged and measurable, a lymph node must be ≥15mm in short axis when assessed by CT scan
5. Have a performance status of ≤2 on the ECOG Performance Scale.
6. Patients who survival period is expected to be at least 3 months.
7. Demonstrate laboratory test results the following conditions:

   * ANC (Absolute Neutrophil Count) ≥ 1,500/μL
   * Hemoglobin≥ 9 g/dL
   * Platelet\> 80,000/μL
   * serum BUN \& Creatinine ≤ 2.0 x upper limit of normal (ULN)
   * AST \& ALT ≤ 5.0 x upper limit of normal (ULN)
   * Bilirubin ≤ 5mg/dL
   * Albumin ≥ 2.8g/dL
   * Prothrombin time (PT)% activity ≥ 70%
8. Patients or partners who has agreed to the appropriate use of contraceptives by two or more during the treatment period (including Survival follow-up period) (for men, those who have agreed not to provide sperm)
9. Patients who meet one or more of the following conditions:

   * Patients have at least 1% Combined Positive Score (\*CPS) PD-L1 expression detected on the tumor, as determined by \*\*immunohistochemistry performed by a central laboratory.

     * CPS = (number of PD-L1 positive tumor cells, lymphocytes, macrophage)/ (total number of viable tumor cells) X 100
     * Immunohistochemistry: IHC 22C3 pharmDx test

       ② Patients who have a positive MSI-H or dMMR test
       * MSI-high positive tumors analyzed by PCR
       * dMMR positive tumors analyzed by immunohistochemical staining
     * MSI-H was measured by PCR, and positive finding when two or more unstable markers were detected in PCR for 5 microsatellite markers, \*\*dMMR is analyzed by immunohistochemical staining and positive when the discovery of one or more genes in MLH1, MSH2, MSH6 and PMS2 staining is lost.

Exclusion Criteria:

1. Patients who have previous history

   * Immune deficiency or autoimmune disease that can be aggravated by immunotherapy (for example: Rheumatoid arthritis, systemic lupus erythematosus, vasculitis, multiple sclerosis, Crohn's disease, ulcerative colitis, adolescent-developed insulin-dependent diabetes mellitus).
   * Immune deficiency disease
   * Pneumonia, colitis, hepatitis, nephritis, endocrine diseases associated with immunodeficiency (hypophysis, thyroid dysfunction, Type 1 diabetes, etc.)
   * Obvious myocardial failure or uncontrolled arterial hypertension
   * Active central nervous system (CNS) metastases and/or carcinomatous meningitis.
   * Non-infectious pneumonia, interstitial lung disease
   * Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
   * Hepatitis B (defined as HBsAg reactive) or known active hepatitis C virus (defined as HCV ribonucleic acid (RNA) \[qualitative\] is detected) infection or active tuberculosis
   * Active infection (if systemic treatment is required)
2. Has a diagnosed and/or treated additional malignancy within 5 years prior to signing informed consent except for curatively treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin
3. Has a previous history of anti-angiogenic agent treatment before signing informed consent
4. Has a known serious allergic history
5. Has a known serious mental illness
6. Identified the following in Screening:

   * CRP ≥10 mg/dl and albumin ≤3.0 g/dl are suspected of cancer cachexia
   * Patients who have symptomatic ascites that is not controlled by medical treatment
7. Has received chemotherapy not less than 4 weeks old before randomization
8. Has received a live vaccine within 4 weeks before randomization
9. Is currently participating in or has participated in another clinical study within 4 weeks before randomization or the adverse event due to investigational drug administered remain before randomization
10. Has previously administrated Pembrolizumab and another anti-PD-1/PD-L1 agent
11. Has previously administrated immune-cell therapy (including natural killer cell etc.)
12. Female who are pregnant, breastfeeding or intending to become pregnant during the study period.
13. Has a history of any contraindication or has a severe hypersensitivity to any components of pembrolizumab
14. Has performed major surgery within 4 weeks prior to signing informed consent
15. Patients who are unsuitable to participate in clinical trials by investigator's decision

Where this trial is running

Goyang-si, Gyeonggi-do and 2 other locations

• National Cancer Center — Goyang-si, Gyeonggi-do, South Korea (RECRUITING)
• Severance Hospital — Seoul, South Korea (RECRUITING)
• Gangnam Severance Hospital — Seoul, South Korea (RECRUITING)

Study contacts

• Principal investigator: SEUNGWOO PARK — Department of Internal Medicine, Yonsei University College of Medicine, Severance Hospital
• Study coordinator: JUNGMIN IM

Conditions: Biliary Tract Cancer, BTC, Cholangiocarcinoma, Biliary tract cancer