a study to assess safety and efficacy of cho-h01 as a single agent/combined with lenalidomide in subjects with refractory or relapsed non-hodgkin's lymphoma

Conditions: Non-Hodgkin Lymphoma

Summary: this is a 2-part study. part 1/phase 1 of the study will be conducted to determine the safety and tolerability of cho-h01 in subjects with relapsed/refractory cd20+ non-hodgkin's lymphoma. it will also determine maximum tolerated dose (mtd) and recommended phase ii dose (rp2d). part 2/phase 2a will assess the anticancer activity and safety of cho-h01 plus lenalidomide in subjects with low-grade relapsed/refractory cd20+ non-hodgkin's lymphoma.

phase i fih study includes subjects with relapsed/refractory cd20 + non-hodgkin's lymphoma, who may benefit from treatment with cho-h01. in phase i of the study, the first 2 cohorts will follow a 2-step modified accelerated titration dose escalation design and subsequent cohorts will follow a standard 3+3 dose escalation design. the investigational medicinal product, cho-h01, will be administered via iv infusion once weekly for 4 weeks in cycle 1 and then once only (on day 1) in each subsequent 21-day cycle until disease progression or for up to 6 cycles (19 weeks) of treatment. once the mtd/rp2d has been confirmed, phase iia of the study will be initiated. the purpose of phase iia is to assess anticancer activity and safety of cho-h01 plus lenalidomide in low-grade relapsed/refractory cd20 + non hodgkin's lymphoma, including follicular lymphoma (grades 1-3a), marginal zone lymphoma, and small lymphocytic lymphoma.

Eligibility criteria:
inclusion criteria: * life expectancy of \>12 weeks. * body mass index of 18 to 32 kg/m2. * eastern cooperative oncology group (ecog) performance status of 0 to 2. * phase i: have histologically (laboratory test) confirmed cd20 + non-hodgkin's lymphoma according to the world health organization's 2016 classification: 1. low grade lymphoma: follicular lymphoma (grades 1-3a), marginal zone lymphoma, small lymphocytic lymphoma; 2. other lymphoma: dlbcl (nos: to include germinal center b-cell-like \[gcb\] and activated b-cell-like \[abc\]), follicular lymphoma grade 3b, mantle cell lymphoma; primary mediastinal large b-cell lymphoma. * phase iia: histologically confirmed cd20 + non-hodgkin's lymphoma according to the world health organization's 2016 classification, only low grade lymphoma: follicular lymphoma (grades 1-3a), marginal zone lymphoma, small lymphocytic lymphoma. * have at least one measurable lesion that is at least 1.5 cm in its largest dimension. * off treatment for 30 days from last anti-cd20 infusion until planned administration of cho-h01. * if no original sample is available, is willing and able to provide an adequate tumor biopsy sample at screening. * have adequate cardiac function: without clinically significant and/or uncontrolled heart disease. * must be sterile, or have a monogamous partner who is surgically sterile, or at least 2 years postmenopausal, or be committed to use an acceptable form of birth control for the duration of the study (male), and for the duration of the study and for 3 months following the last cho-h01 administration (female). exclusion criteria: * must not have a history of egg allergy or allergic reactions to any component of cho-h01. * must not have any known or current illnesses (such as autoimmune disease, unless well controlled or resolved), infection, or other condition that could limit study compliance or interfere with assessments. * subjects who have received anti-programmed death-ligand 1 (pd-l1), programmed cell death 1 (pd-1), or cytotoxic t-lymphocyte associated protein 4 (ctla-4) therapy. * subjects who have completed an autologous stem cell transplant within 100 days prior to cho-h01 therapy or an allogeneic stem cell transplant. * subjects with known hepatitis b surface antigen (hbsag) seropositive or known or suspected active hepatitis c infection with detectable viral load. * subjects with known human immunodeficiency virus (hiv) infection * subjects who have had radiation therapy, major surgical procedure or live vaccinations within 28 days prior to cho-h01 administration. * subjects with a history of type i hypersensitivity or anaphylactic reactions to murine proteins or to previous infusions of cd20 monoclonal antibodies. * subjects who have received (or are receiving) systemic corticosteroids: 1. at a daily dose higher than 15 mg prednisone or equivalent within 14 days prior to the first administration of cho-h01; 2. topical, inhaled, nasal, and ophthalmic steroids are allowed. * inadequate bone marrow, hepatic or renal function. * subjects with a history of seizure disorder. * subjects who are pregnant or breast feeding. * subjects with any contraindications to lenalidomide (only for phase iia).

Keywords: cho-h01 anti-cd20 antibodies large b-cell lymphoma follicular lymphoma glyco-engineered anti-cd20 antibody