safety and preliminary efficacy assessment of azd7789 in patients with relapsed or refractory classical hodgkin lymphoma

Conditions: Relapsed or Refractory Classical Hodgkin Lymphoma

Summary: the study is intended to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of sabestomig (azd7789) in patients with relapsed/refractory classical hodgkin lymphoma (r/r chl).

this is a phase i/ii, open-label multi-center study will have sabestomig administered via intravenous infusion on cycle 1 day 1 to adult/young adult patients with relapsed/refractory classical hodgkin lymphoma (r/r chl). this study will have 2 parts: phase 1 (part a) dose escalation and phase 2 (part b) dose expansion. patients will be treated with study intervention for a maximum of 35 cycles, or until disease progression, unacceptable toxicity, withdrawal of consent, or if other reasons to discontinue treatment occur. the trial was intended to be phase i/ii trial (but the trial never moved forward to phase 2). hence, the study phase was updated to phase i.

Eligibility criteria:
inclusion criteria: * ≥ 16 years of age at the time of obtaining informed consent * eastern cooperative oncology group performance status of 0 or 1 at screening * at least one positron emission tomography (pet)-avid measurable lesion according to modified lugano criteria after the last line of therapy. * confirmed histological diagnosis of active relapse/refractory chl * failed at least 2 prior lines of systemic therapy. * no previous treatment with anti-tim-3. * adequate organ and bone marrow function * non-pregnant women and willingness of female patients to avoid pregnancy or male participants willing to avoid fathering children through highly effective methods of contraception * minimum body weight ≥ 40 kg for all participants. exclusion criteria: * unresolved toxicities of ≥ grade 2 from prior therapy * any prior ≥ grade 3 imae while receiving prior checkpoint inhibitor immunotherapy * patients with central nervous system (cns) involvement or leptomeningeal disease. * history of allogeneic stem cell transplant or organ transplantation. * any venous or arterial thromboembolic event within ≤ 6 months prior to the first dose of study intervention. * active infection including tuberculosis (tb), human immunodeficiency virus (hiv), hepatitis a, chronic or active hepatitis b, chronic or active hepatitis c, active covid-19 infection * history of arrhythmia which is requires treatment, symptomatic or uncontrol led atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia * uncontrolled intercurrent illness. * active or prior documented pathologically confirmed autoimmune or inflammatory disorders. * past medical history of interstitial lung disease (ild), drug-induced ild, radiation pneumonitis requiring steroid treatment, or any evidence of clinically active ild * other invasive malignancy within 2 years prior to screening * congenital long qt syndrome or history of qt prolongation associated with other medications that cannot be changed or discontinued based on a cardiologist assessment * current or prior use of immunosuppressive medication within 14 days prior to the first dose of study intervention * any concurrent chemotherapy, radiotherapy, investigational, biologic, or hormonal therapy for cancer treatment.

Keywords: pharmacokinetics classical hodgkin lymphoma (chl) dose expansion dose escalation r/r chl programmed cell death protein-1 (pd-1) accelerated titration design (atd) t cell immunoglobulin and mucin domain-containing protein-3 (tim-3) modified toxicity probability interval-2 (mtpi-2) bispecific antibody immunotherapy