Clinical trial NCT05950165: 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
Official title: A Phase I/IIa, Open-label, Multicenter Study of the Safety and Efficacy of CHO-H01 As a Single Agent/Combined with Lenalidomide to Subjects with Refractory or Relapsed Non-Hodgkin's Lymphoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Non-Hodgkin Lymphoma
Keywords: CHO-H01
Anti-CD20 Antibodies
Large B-cell lymphoma
Follicular lymphoma
Glyco-engineered anti-CD20 antibody
Lead sponsor: Cho Pharma Inc.
Sponsor class: INDUSTRY
First posted: 2023-07-18
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: 3+3 sequential cohort design
Primary purpose: TREATMENT

Brief 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.

Detailed description: 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).

Primary outcomes:
measure: Number of subjects with adverse events (AE)
timeFrame: Through study completion, approximately 16 months
measure: Number of subjects with dose-limiting toxicities
timeFrame: Through study completion, approximately 16 months
measure: Objective Response Rate
timeFrame: Through study completion, approximately 16 months
measure: Best overall response
timeFrame: Through study completion, approximately 16 months
Secondary outcomes:
measure: Serum concentration of CHO-HO1
timeFrame: Through study completion, approximately 16 months
measure: Serum Antidrug antibody (ADA) concentration
timeFrame: Through study completion, approximately 16 months
measure: Clinical benefit rate
timeFrame: Through study completion, approximately 16 months
measure: Time to event endpoints of time to progression (TTP)
timeFrame: Through study completion, approximately 16 months
measure: Duration of stable disease
timeFrame: Through study completion, approximately 16 months
measure: Progression-free survival
timeFrame: Through study completion, approximately 16 months
measure: Duration of response
timeFrame: Through study completion, approximately 16 months
measure: Overall survival
timeFrame: Through study completion, approximately 16 months
Other outcomes:
Locations:
city: The Woodlands
country: United States
facility: Renovatio Clinical
state: Texas
city: New Taipei City
country: Taiwan
facility: Taipei Medical University - Shuang Ho Hospital - Oncology
state: Taipei Special Municipality
city: Kaohsiung
country: Taiwan
facility: Chang Gung Medical Foundation - Kaohsiung Chang Gung Memorial Hospital - Hemato-Oncology
city: Taichung City
country: Taiwan
facility: China Medical University Hospital - Hematology/Oncology - Taichung
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital - Internal Medicine
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital - Hematology And Oncology
city: Taipei
country: Taiwan
facility: Tri-Service General Hospital - Neihu Branch - Hematology
city: Taoyuan
country: Taiwan
facility: Chang Gung Medical Foundation - LinKou Chang Gung Memorial Hospital - Hematology and Oncology - Hematology and Oncology
Study officials:
References: