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

Indolent B-Cell Non-Hodgkin Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03571568
• Other study ID #: 17-BI-1206-02
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: May 16, 2018
• Est. completion date: September 22, 2025

Study information

• Verified date: January 2024
• Source: BioInvent International AB
• Contact: Erika Bågeman
• Phone: +46706126618
• Email: erika.bageman[@]bioinvent.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 98
• Est. completion date: September 22, 2025
• Est. primary completion date: September 22, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Indolent B-Cell Non-Hodgkin Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Non-Hodgkin

Intervention

Biological:
• BI-1206
375 mg/m2, as per SmPC

Locations

Country	Name	City	State
Brazil	Hospital de Clínicas de Porto Alegre	Porto Alegre	Rio Grande Do Sul
Brazil	Hospital São Rafael	Salvador	Bahia
Brazil	A.C. Camargo Cancer Center	São Paulo
Brazil	Hospital Israelita Albert Einstein	São Paulo
Brazil	Hospital Sírio-Libanês	São Paulo
Germany	Krankenhaus Nordwest Klinik für Onkologie und Hämatologie	Frankfurt	Hessen
Germany	Robert Bosch Hospital, Dep of Hematology, Oncology and Palliative care	Stuttgart
Poland	Szpital Specjlistyczny	Grudziadz
Poland	Malopolskie Centrum Medyczne	Krakow
Spain	Hospital ICO, Trias i Pujol	Badalona	Barcelona
Spain	Hospital de la Santa Creu i Sant Pau, Dep Hematologia	Barcelona
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Institut Català d'Oncologia, L'Hospitalet de Llobregat	Barcelona
Spain	Hospital General Universitario Gregorio Marañon-Oncología Médica	Madrid
Spain	Hospital Universitario HM San Chinarro	Madrid
Spain	University Hospital Fundacion Jimenez Diaz	Madrid
Spain	Hospital Universitario Virgen de la Arrixaca	Murcia
Spain	Hospital Virgen Macarene	Seville
Sweden	Department of Oncology, Skåne University Hospital	Lund
Sweden	Department of Oncology, Academical Hospital	Uppsala
United States	Emory University Hospital	Atlanta	Georgia
United States	Norton Cancer Institute - St. Matthews 3991 Dutchmans Lane Medical Plaza II, Suite 405	Louisville	Kentucky

Sponsors (1)

Lead Sponsor	Collaborator
BioInvent International AB

Countries where clinical trial is conducted

United States,  Brazil,  Germany,  Poland,  Spain,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Measurement of PROs using the PRO-CTCAE questionnaire.	Evaluate patient-reported outcomes (PROs)in subjects receiving BI-1206	Up to 1 year
Primary	Documenting AEs and SAEs and determining causality in relation to BI-1206 and/or rituximab	Assess the safety and tolerability profile of BI-1206 when administered intravenously (IV) or subcutaneously (SC) in combination with rituximab in subjects with relapsed or refractory B-cell non-Hodgkin lymphoma (NHL),subtypes follicular lymphoma (FL)(except FLgrade 3B), marginal zone lymphoma (MZL), and mantle cell lymphoma (MCL).	During the 28-day treatment period on induction therapy
Primary	Determining the MTD of BI-1206 at the same dose level experiencing a BI-1206 or Rituximab-related or possibly related dose-limiting toxicity (DLT)	Select the recommended Phase 2 dose (RP2D) by establishing the maximum tolerated dose (MTD) of BI-1206 given once weekly for 4 weeks, via IV infusion or SC injection in combination with rituximab.	During the 28-day treatment period on induction therapy
Secondary	Evaluation of PK parameters for BI-1206.	Study the PK profile of BI-1206 when administered IV or SC in combination with rituximab in subjects with relapsed or refractory B-cell NHL, subtypes FL (except FL grade 3B), MZL and MCL.	Up to 1 year
Secondary	Evaluation of PK parameters for rituximab during the BI-1206 treatment period.	Study the PK profile of rituximab when administered in combination with BI-1206 (IV or SC).	Up to 1 year
Secondary	Evaluation of ADA response to BI 1206.	Assess the immunogenicity of BI-1206 when administered IV or SC in combination with rituximab.	Up to 1 year
Secondary	Measurement of B cell depletion.	Evaluate the effect of BI-1206 administered IV or SC in combination with rituximab on the depletion of B-cells.	Up to 1 year
Secondary	Assessment of overall response rate (ORR) according to the response criteria for malignant lymphoma (Cheson, 2014).	Assess possible anti-tumor activity of BI-1206 administered IV or SC in combination with rituximab at Week 6 after first dose of BI-1206 and for subjects who continue during maintenance therapy.	Up to 1 year
Secondary	CD32b protein expression levels	Investigate CD32b protein expression levels; evaluate any potential correlation with clinical responses.	Up to 1 year