Clinical trial NCT03999658: 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.
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Peripheral T Cell Lymphoma
Diffuse Large B Cell Lymphoma
Biliary Tract Cancer
Extranodal NK T Cell Lymphoma, Nasal
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
Lead sponsor: Sorrento Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2019-06-27
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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

Primary outcomes:
measure: Objective Response Rate
timeFrame: Approximately 24 months
Secondary outcomes:
measure: Objective Response Rate by treating physician
timeFrame: Approximately 24 months
measure: Duration of Response
timeFrame: Approximately 24 months
measure: Complete Response Rate
timeFrame: Approximately 24 months
measure: Duration of Complete Response Rate
timeFrame: Approximately 24 months
measure: Progressive-free survival
timeFrame: Approximately 24 months
measure: 12-month Progressive-free survival
timeFrame: Approximately 30 months (18 months for enrollment plus 12 months follow-up for the last participant enrolled)
measure: Event free survival
timeFrame: Approximately 24 months
measure: Area Under the Curve (AUC) of the blood levels of STI-3031
timeFrame: Approximately 24 months
measure: Maximum Plasma Concentration (Cmax) of STI-3031
timeFrame: Approximately 24 months
measure: Time of Maximum concentration observed (Tmax) of STI-3031
timeFrame: Approximately 24 months
measure: Half-life (t1/2) of STI-3031
timeFrame: Approximately 24 months
measure: Immunogenicity
timeFrame: Approximately 24 months
measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of STI-3031
timeFrame: Approximately 24 months
Other outcomes:
Locations:
Study officials:
References: