A Study of BI-1206 in Combination With Rituximab in Subjects With Indolent B-Cell Non-Hodgkin Lymphoma

BioInvent International

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Indolent B-Cell Non-Hodgkin Lymphoma

Treatments: Biological: BI-1206

Study type: Interventional

Funder types: Industry

Identifiers

NCT03571568

17-BI-1206-02

Details and patient eligibility

About

Phase 1/2a Clinical Trial of BI-1206, a Monoclonal Antibody to CD32b (FcyRIIB), in Combination with Rituximab in Subjects with Indolent B-Cell Non-Hodgkin Lymphoma That has Relapsed or is Refractory to Rituximab

Full description

This is a Phase 1/2a, dose escalation, consecutive-cohort, open-label trial of BI-1206 in combination with rituximab in subjects with indolent relapsed or refractory B-cell NHL, subtypes FL (except FL grade 3B), MZL, and MCL.

The trial consists of 2 main parts:

Phase 1 with two different Arms assessing IV or SC dosing of BI-1206,with dose escalation cohorts and selection of the RP2D of IV dosing (ivRP2D)and the RP2D of SC dosing (scRP2D) of BI-1206 in combination with rituximab (administered IV). Phase 2a with two expansion cohorts evaluating the ivRP2D and scRP2D of BI-1206 in combination with rituximab (administered IV).

Subjects in each phase (Phase 1 and 2a) and dosing Arms will receive 1 cycle of induction therapy with BI-1206 in combination with rituximab.

Subjects who show clinical benefit (complete response [CR], partial response [PR], or stable disease [SD]) at Week 6 will continue onto maintenance therapy and receive BI-1206 ( using the same dose and route of administration as induction therapy) and rituximab once every 8 weeks (relative to previous maintenance dose) for up to 6 maintenance cycles, or up to 1 year from first dose of BI-1206 (whichever occurs first).

Enrollment: 98 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Are ≥ 18 years of age by initiation of study treatment.
• Have B-cell NHL proven by histology, with histological subtypes limited to follicular lymphoma (FL) (except FL grade 3B), MCL and marginal zone lymphoma (MZL).
• Have measurable nodal disease
• Are willing to undergo lymph node biopsies or biopsies of other involved tissue
• Have relapsed disease or disease refractory to conventional treatment or for which no standard therapy exists.
• Have received at least one line of conventional previous therapy which must include at least one rituximab-based regimen.
• Have a life expectancy of at least 12 weeks
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
• Have CD20+ malignancy
• Have hematological and biochemical indices within prespecified ranges

Exclusion criteria

• Have had an allogenic bone marrow or stem cell transplant within 12 months
• Have presence of active chronic graft versus host disease
• Have current leptomeningeal lymphoma or compromise of the central nervous system.
• Have transformed lymphoma from a pre-existing indolent lymphoma.
• Have Waldenstrom's Macroglobulinemia or FL3B,
• Need systemic doses of prednisolone >10 mg daily (or equipotent doses of other corticosteroids) while on the study trial other than as pre-medication.
• Have known or suspected hypersensitivity to rituximab or BI-1206.
• Have cardiac or renal amyloid light-chain amyloidosis.
• Have received any of the following:
• Chemotherapy or small molecule products with 2 weeks of first dose of BI-1206
• Radiotherapy (except for focal symptomatic control of lymphadenopathy) within 4 weeks
• Immunotherapy within 8 weeks
• Have ongoing toxic manifestations of previous treatments.
• Have the ability to become pregnant (or already pregnant or lactating/breastfeeding).
• Have had major surgery from which the subject has not yet recovered.
• Are at high medical risk because of non-malignant systemic disease including active infection on treatment with antibiotics, antifungals or antivirals.
• Are serologically positive for hepatitis B, hepatitis C or human immunodeficiency virus (HIV).
• Have an active, known or suspected autoimmune disease.
• Have concurrent congestive heart failure, prior history of class III/ IV cardiac disease (New York Heart Association [NYHA]),
• Have current malignancies of other types

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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98 participants in 2 patient groups

BI-1206 IV

Experimental group

Description:

BI-1206 IV Standard 3+3 Dose-Escalation Design

Treatment:

Biological: BI-1206

BI-1206 SC

Experimental group

Description:

BI-1206 SC Adaptive Dose Escalation Design (Bayesian logistic regression model (BLRM)

Treatment:

Biological: BI-1206