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

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.

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.

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.

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