a study of sti-3031 (an anti-pd-l1 antibody) in patients with selected relapsed/refractory malignancies

Conditions: Peripheral T Cell Lymphoma; Diffuse Large B Cell Lymphoma; Biliary Tract Cancer; Extranodal NK T Cell Lymphoma, Nasal

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.

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

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