Clinical Trials /

A Study of STI-3031 (an Anti-PD-L1 Antibody) in Patients With Selected Relapsed/Refractory Malignancies

NCT03999658

Description:

This study evaluates the efficacy, as measured by the objective response rate, of STI-3031, an anti-PD-L1 antibody, in previously treated patients with selected advanced lymphomas or biliary tract cancer.

Related Conditions:
  • Biliary Tract Carcinoma
  • Diffuse Large B-Cell Lymphoma
  • Nasal Type Extranodal NK/T-Cell Lymphoma
  • Peripheral T-Cell Lymphoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of STI-3031 (an Anti-PD-L1 Antibody) in Patients With Selected Relapsed/Refractory Malignancies
  • Official Title: An Open-label, Multicenter, Global Phase 2 Basket Study to Investigate the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of STI-3031 in Patients With Selected Relapsed or Refractory Malignancies.

Clinical Trial IDs

  • ORG STUDY ID: STI-3031-001
  • NCT ID: NCT03999658

Conditions

  • Peripheral T Cell Lymphoma
  • Diffuse Large B Cell Lymphoma
  • Biliary Tract Cancer
  • Extranodal NK T Cell Lymphoma, Nasal

Interventions

DrugSynonymsArms
STI-3031IMC-001Extranodal NK/T-cell lymphoma (ENKTL)

Purpose

This study evaluates the efficacy, as measured by the objective response rate, of STI-3031, an anti-PD-L1 antibody, in previously treated patients with selected advanced lymphomas or biliary tract cancer.

Detailed Description

      This is an open-label, multicenter, global Phase 2 basket study to investigate the efficacy,
      safety, pharmacokinetics and pharmacodynamics of STI-3031 in patients with selected relapsed
      or refractory (R/R) malignancies. The study will be conducted as separate Phase 2, single arm
      substudies for each of the indications below:

        -  Extranodal NK/T-cell lymphoma (ENKTL)

        -  Peripheral T-cell lymphomas (PTCL)

        -  Diffuse large B-cell lymphoma (DLBCL) with PD-L1 gene translocation, copy gain,
           amplification, polysomy detectable by a fluorescence in situ hybridization (FISH) assay
           or Epstein-Barr virus positivity (EBV+) as assessed by EBV-encoded small RNA (EBER)
           testing

        -  Biliary tract cancers (BTC) (intrahepatic cholangiocarcinoma), extrahepatic
           cholangiocarcinoma or gallbladder cancer)

      All participants will receive the study intervention, STI-3031.
    

Trial Arms

NameTypeDescriptionInterventions
Extranodal NK/T-cell lymphoma (ENKTL)ExperimentalIntravenous STI-3031 (anti-PD-L1 antibody)
  • STI-3031
Peripheral T-cell lymphomas (PTCL)ExperimentalIntravenous STI-3031 (anti-PD-L1 antibody)
  • STI-3031
Diffuse large B-cell lymphoma (DLBCL)ExperimentalIntravenous STI-3031 (anti-PD-L1 antibody)
  • STI-3031
Biliary tract cancers (BTC)ExperimentalIntravenous STI-3031 (anti-PD-L1 antibody)
  • STI-3031

Eligibility Criteria

        Inclusion Criteria:

          -  Documented histologically confirmed diagnoses of Extranodal NK/T-cell lymphoma,
             Peripheral T-cell lymphoma, Diffuse Large B-cell lymphoma (with a PD-L1 gene
             abnormality or Epstein-Barr virus positivity, or biliary tract cancer.

          -  Prior treatment:

               -  Extranodal NK/T-cell lymphoma: Must have received at least 1 previous line of
                  systemic therapy including an asparaginase-based regimen.

               -  Peripheral T-cell lymphoma: must have received at least 1 previous line of
                  systemic multi-agent chemotherapy. Participants with anaplastic large cell
                  lymphoma (ALCL) must have received brentuximab vedotin

               -  Diffuse Large B-cell lymphoma: Must have received at least 2 previous lines of
                  systemic therapy including an anti-CD20 antibody

               -  Biliary Tract Cancer: Must have received at least 1 previous line of systemic
                  therapy including gemcitabine with or without platinum

          -  Documented disease progression during or after the last therapy

          -  If not previously treated with transplant, Investigator considers the participant
             ineligible for transplant

          -  Measurable disease

          -  Adult age (as defined by respective country) at time of signing informed consent form
             (ICF)

          -  Must be able to understand the nature of the study and provide a signed and dated,
             written ICF prior to any study-specific procedures, sample collections and analyses

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 or 1

          -  Prior radiotherapy is allowed if more than 14 days have elapsed since the end of
             treatment and radiopharmaceuticals are permitted if more than 8 weeks have elapsed
             since the end of treatment

          -  At least 14 days or 5 half-lives must have elapsed since the last chemotherapy,
             immunotherapy, biological or investigational therapy, and have recovered from
             toxicities associated with such treatment to < Grade 2

          -  Adequate hematologic, renal and hepatic function

          -  Females of childbearing potential (FCBP) must agree to use a reliable form of
             contraceptive during the study treatment period and for at least 90 days following the
             last dose of study intervention

          -  Male participants must agree to use barrier contraception (i.e., condoms) for the
             duration of the study and for at least 90 days after the last dose of study
             intervention

          -  Predicted life expectancy of at least 16 weeks

        Exclusion Criteria:

          -  Current participation in another therapeutic clinical trial

          -  Prior treatment with an anti-PD-L1 or anti-PD-1 antibody

          -  Patients with symptomatic central nervous system (CNS) metastases unless considered
             adequately treated and controlled for at least 2 weeks

          -  Prior hematopoietic stem cell transplantation

          -  History of other previous cancer that would interfere with the determination of safety
             or efficacy

          -  Any active autoimmune disease or a documented history of autoimmune disease, or
             history of syndrome that required systemic steroids or immunosuppressive medications,
             except for participants with vitiligo, hormone replacement therapy for stable thyroid
             diseases and Type 1 diabetes mellitus

          -  Apparent active or latent tuberculosis (TB) infection

          -  Seropositive for or have active infection with hepatitis C virus (HCV), unless HCV
             viral load is below the limit of quantification and participant is on concurrent viral
             suppressive therapy

          -  Seropositive for or have active viral infection with hepatitis B virus (HBV), unless
             HBV viral load is below the limit of quantification and participant is on concurrent
             viral suppressive therapy

          -  Seropositive for or active viral infection with HIV, unless the following are met:

               -  CD4+ T-cell (CD4+) counts ≥ 350 cells/uL; and

               -  Participant has been on established antiretroviral therapy (ART) for at least 4
                  weeks prior to screening and have HIV viral load < 400 copies/mL; and

               -  Participant has not had acquired immunodeficiency syndrome (AIDS)-defining
                  opportunistic infections within the past 12 months prior to screening

          -  Active infection (viral, bacterial, or fungal) requiring intravenous (IV) systemic
             therapy within 14 days

          -  Evidence of bleeding diathesis or coagulopathy.

          -  Significant proteinuria

          -  Conditions requiring chronic steroid use (> 10 mg/day of prednisone or equivalent).

          -  Recent history of attenuated viral vaccination within 30 days prior to the first dose
             of study intervention

          -  Herbal preparations/medications are not allowed throughout the treatment period unless
             first discussed with and approved by the Medical Monitor

          -  History of severe hypersensitivity reactions to other monoclonal antibodies or known
             hypersensitivity to the study intervention or its excipients.

          -  Known current drug or alcohol abuse

          -  Major surgical procedures ≤ 28 days prior to the first dose of study intervention, or
             minor surgical procedures ≤7 days prior to the first dose of study intervention

          -  Pregnant or lactating

          -  Any of the following cardiac diseases currently or within the last 6 months:

               -  QT interval corrected using Fridericia's formula >450 milliseconds in men and >
                  470 milliseconds in women (up to 480 milliseconds may be allowed after discussion
                  between the Investigator and the Medical Monitor).

               -  Left Ventricular Ejection Fraction (LVEF) <45% as determined by Multiple Gated
                  acquisition (MUGA) scan or echocardiogram (ECHO)

               -  Unstable angina pectoris

               -  Congestive heart failure (New York Heart Association ≥ Grade 2)

               -  Acute myocardial infarction

               -  Clinically significant conduction abnormality not controlled with pacemaker or
                  medication

               -  Significant ventricular or supraventricular arrhythmias (Participants with
                  chronic rate-controlled atrial fibrillation in the absence of other cardiac
                  abnormalities are eligible.)

          -  Underlying medical conditions that, in the opinion of the investigator and/or medical
             monitor, will render the administration of study drug hazardous or obscure the
             interpretation of safety or efficacy results
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective Response Rate
Time Frame:Approximately 24 months
Safety Issue:
Description:Percentage of participants achieving a Complete Response (CR) or Partial Response (PR) at any time during the study as assessed by an Independent Response Committee (IRC) per the Lugano criteria with LYRIC modification or RECIST 1.1

Secondary Outcome Measures

Measure:Objective Response Rate by treating physician
Time Frame:Approximately 24 months
Safety Issue:
Description:Percentage of participants achieving a CR or PR at any time during the study as assessed by the Investigator per the Lugano criteria with LYRIC modification or RECIST 1.1
Measure:Duration of Response
Time Frame:Approximately 24 months
Safety Issue:
Description:Time from the first documentation of response (CR or PR) to the first documentation of progressive disease (PD) as assessed by an IRC per the Lugano criteria with LYRIC modification or RECIST 1.1
Measure:Complete Response Rate
Time Frame:Approximately 24 months
Safety Issue:
Description:Percentage of participants achieving a CR at any time during the study as assessed by an IRC per the Lugano criteria with LYRIC modification or RECIST 1.1
Measure:Duration of Complete Response Rate
Time Frame:Approximately 24 months
Safety Issue:
Description:Time from the first documentation of CR to the first documentation of PD as assessed by an IRC per the Lugano criteria with LYRIC modification or RECIST 1.1
Measure:Progressive-free survival
Time Frame:Approximately 24 months
Safety Issue:
Description:Time from enrollment until PD or death as assessed by an IRC per the Lugano criteria with LYRIC modification or RECIST 1.1
Measure:12-month Progressive-free survival
Time Frame:Approximately 30 months (18 months for enrollment plus 12 months follow-up for the last participant enrolled)
Safety Issue:
Description:Percentage of participants without PD or death at 12 months after their first dose of study intervention as assessed by an IRC per the Lugano criteria with LYRIC modification or RECIST 1.1
Measure:Event free survival
Time Frame:Approximately 24 months
Safety Issue:
Description:Time from enrollment to PD, death, or start of new treatment as assessed by an IRC per the Lugano criteria with LYRIC modification or RECIST 1.1
Measure:Area Under the Curve (AUC) of the blood levels of STI-3031
Time Frame:Approximately 24 months
Safety Issue:
Description:Measure the actual body exposure to STI-3031
Measure:Maximum Plasma Concentration (Cmax) of STI-3031
Time Frame:Approximately 24 months
Safety Issue:
Description:Measure the maximum (or peak) blood concentration of STI-3031
Measure:Time of Maximum concentration observed (Tmax) of STI-3031
Time Frame:Approximately 24 months
Safety Issue:
Description:Measure the is the time at which the maximum blood concentration of STI-3031 is observed
Measure:Half-life (t1/2) of STI-3031
Time Frame:Approximately 24 months
Safety Issue:
Description:Measure the time it takes for the concentration of the drug in the blood to be reduced by 50%
Measure:Immunogenicity
Time Frame:Approximately 24 months
Safety Issue:
Description:Incidence of anti-drug antibody (ADA) (serum titers of anti-STI-3031 antibodies) and correlation with exposure and activity
Measure:Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of STI-3031
Time Frame:Approximately 24 months
Safety Issue:
Description:Terms, frequency, severity and seriousness of adverse events (AEs) and relationship of AEs to STI-3031 the actual body exposure to drug after administration

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Sorrento Therapeutics, Inc.

Trial Keywords

  • ENKTL
  • DLBCL
  • PTCL
  • cholangiocarcinoma
  • gall bladder cancer
  • relapsed
  • refractory
  • T/NK-cell
  • NK/T-cell
  • peripheral T-cell
  • PD-L1
  • anti-PD-L1 antibody

Last Updated

June 26, 2019