Study of SMT-NK Inj. Plus Pembrolizumab vs Pembrolizumab Monotherapy in Patients With Advanced Biliary Tract Cancer

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Brief Title

Study of SMT-NK Inj. Plus Pembrolizumab vs Pembrolizumab Monotherapy in Patients With Advanced Biliary Tract Cancer

Official Title

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

Brief Summary

      This study is designed to assess the antitumor activity of combination therapy of SMT-NK
      (allogeneic natural killer cells) and pembrolizumab versus pembrolizumab monotherapy in
      patients with advanced biliary tract cancer
    

Detailed Description

      The term of biliary tract cancer (BTC) refers to all tumors that arise from the biliary tract
      or the biliary drainage system, including the gallbladder.Biliary tract cancer is one of the
      most poorly prognosis cancers and the five-year survival rate remains at about 10% as it is
      difficult to expect long-term survival due to frequent local recurrence and remote metastasis
      after surgery.

      South Korea belongs to a country with a high number of biliary tract cancer patients, and the
      incidence of biliary tract cancer is actually increasing every year.According to the 2018
      National Cancer Registration Statistics, the number of 5-year biliary tract cancer patients
      was 13,967 (7,547 men and 6,420 women), which corresponds to about 2.9% of all cancersand the
      5-year survival rate of biliary tract cancer patients between 2014 and 2018 was 28.8%,
      showing a lower survival rate than other cancer species.

      Most of the long-term survival is due to early detection by screening, but advanced carcinoma
      is a refractory carcinoma with a 5-year survival rate of less than 5%.In addition to standard
      anticancer drugs, alternative anticancer drugs and targeted treatments can be developed for
      cancer with a large number of patients, but biliary tract cancer is difficult to find any
      more treatments if standard treatment fails and standard anticancer treatments cannot be
      continued due to resistance.

      Natural killer cells (NK cells) are innate lymphocyte cells with cell killing activity, and
      have the characteristic of destroying cells by secretion of and granzyme into cancer cells
      and abnormal cells that are reduced or deficient in expression of MHC class I.Clinical
      studies using natural killer cells as anticancer drugs have long been conducted on various
      cancers.

      Pembrolizumab is a monoclonal antibody designed to bind to a receptor called PD-1, which is
      expressed by immune cells such as T cells.Natural killer cells were also found to be
      expressing PD-1 in the same way as T cells, and in particular, PD-1 was found to be higher in
      cancer patients than in healthy people.

      Therefore, combined therapy with the immune-check point such as pembrolizumab can be useful
      in elevating the anticancer activity of NK cells.
    

Study Phase

Phase 2/Phase 3

Study Type

Interventional


Primary Outcome

Progression Free Survival

Secondary Outcome

 Object Response rate

Condition

Biliary Tract Cancer

Intervention

SMT-NK inj.+Pembrolizumab

Study Arms / Comparison Groups

 Pembrolizumab+SMT-NK inj.
Description:  Experimental:
Pembrolizumab + SMT-NK inj. Participants will be randomized to receive 200 mg pembrolizumab followed by 3*10^6cells/kg SMT-NK inj.
Interventions:
Drug: SMT-NK inj. Drug: Pembrolizumab

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

128

Start Date

June 9, 2022

Completion Date

June 8, 2026

Primary Completion Date

January 8, 2025

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
      

Gender

All

Ages

19 Years - 80 Years

Accepts Healthy Volunteers

No

Contacts

SEUNGWOO PARK, 82-10-8967-7358, [email protected]

Location Countries

Korea, Republic of

Location Countries

Korea, Republic of

Administrative Informations


NCT ID

NCT05429697

Organization ID

SNK-SIT-03


Responsible Party

Sponsor

Study Sponsor

SMT bio Co., Ltd.


Study Sponsor

SEUNGWOO PARK, Principal Investigator, Department of Internal Medicine, Yonsei University College of Medicine, Severance Hospital


Verification Date

June 2022