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

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.

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:

• Low grade lymphoma: follicular lymphoma (Grades 1-3a), marginal zone lymphoma, small lymphocytic lymphoma;
• 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:

• At a daily dose higher than 15 mg prednisone or equivalent within 14 days prior to the first administration of CHO-H01;
• 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).