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

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

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

Study Overview

• Status: Recruiting
• Conditions: Indolent B-Cell Non-Hodgkin Lymphoma
• Intervention / Treatment: Biological: BI-1206

Detailed 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).

• Study Type: Interventional
• Enrollment (Estimated): 98
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Erika Bågeman; Phone Number: +46706126618; Email: erika.bageman@bioinvent.com
• Study Contact Backup: Name: Andres McAllister, MD, PhD; Email: andres.mcallister@bioinvent.com

Study Locations

• Brazil
  • São Paulo, Brazil
    • Not yet recruiting
    • Hospital Sirio-Libanes
    • Principal Investigator: Ana Rita Da Fonseca, MD
  • São Paulo, Brazil
    • Not yet recruiting
    • Hospital Israelita Albert Einstein
    • Contact: RN
    • Principal Investigator: Guilherme Perini, MD
  • São Paulo, Brazil
    • Not yet recruiting
    • A.C. Camargo Cancer Center
    • Contact: RN
    • Principal Investigator: Ana Costa Cordeiro, MD
  • Bahia
    • Salvador, Bahia, Brazil
      • Not yet recruiting
      • Hospital Sao Rafael
      • Principal Investigator: Marco Aurelio Salvino De Araujo, MD
      • Contact: Cacilda
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil
      • Not yet recruiting
      • Hospital de Clinicas de Porto Alegre
      • Contact: Suellen
      • Principal Investigator: Laura Maria Fogliatto, MD
• Germany
  • Stuttgart, Germany
    • Not yet recruiting
    • Robert Bosch Hospital, Dep of Hematology, Oncology and Palliative care
    • Contact: RN
    • Principal Investigator: Nicola Giesen, MD
  • Hessen
    • Frankfurt, Hessen, Germany
      • Not yet recruiting
      • Krankenhaus Nordwest Klinik für Onkologie und Hämatologie
      • Principal Investigator: Eckhart Weidmann, MD
• Poland
  • Grudziadz, Poland, 86-300
    • Terminated
    • Szpital Specjlistyczny
  • Krakow, Poland
    • Terminated
    • Małopolskie Centrum Medyczne
• Spain
  • Barcelona, Spain
    • Recruiting
    • Hospital Universitari Vall d'Hebron
    • Principal Investigator: Pablo Abrisqueta Costa, MD
  • Barcelona, Spain
    • Recruiting
    • Hospital de la Santa Creu i Sant Pau, Dep Hematologia
    • Principal Investigator: Silvana Novelli, MD
  • Barcelona, Spain
    • Recruiting
    • Institut Català d'Oncologia, L'Hospitalet de Llobregat
    • Principal Investigator: Eva Domingo Domenech, MD
  • Madrid, Spain
    • Recruiting
    • University Hospital Fundacion Jimenez Diaz
    • Principal Investigator: Raul Cordoba Mascunano, MD
  • Madrid, Spain
    • Recruiting
    • Hospital General Universitario Gregorio Marañon-Oncología Médica
    • Principal Investigator: Mariana Bastos Oreiro, MD
  • Madrid, Spain
    • Not yet recruiting
    • Hospital Universitario HM San Chinarro
    • Principal Investigator: Jaime Perez de Oteyza, MD
  • Murcia, Spain
    • Not yet recruiting
    • Hospital Universitario Virgen de la Arrixaca
    • Principal Investigator: Joaquin Gomez Espuch, MD
  • Seville, Spain
    • Not yet recruiting
    • Hospital Virgen Macarene
    • Principal Investigator: Sergio Ortegón Alcaide, MD
  • Barcelona
    • Badalona, Barcelona, Spain
      • Recruiting
      • Hospital ICO, Trias i Pujol
      • Principal Investigator: Juan Manuel Sancho Cia, MA
• Sweden
  • Lund, Sweden, SE-22185
    • Recruiting
    • Department of Oncology, Skåne University Hospital
    • Contact: Mats Jerkeman, PI
    • Principal Investigator: Mats Jerkeman, MD, PhD
  • Uppsala, Sweden, 751 85
    • Terminated
    • Department of Oncology, Academical Hospital
• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Emory University Hospital
      • Contact: Jonathon Cohen, MD
  • Kentucky
    • Louisville, Kentucky, United States, 40207
      • Recruiting
      • Norton Cancer Institute - St. Matthews 3991 Dutchmans Lane Medical Plaza II, Suite 405
      • Principal Investigator: Don Stevens, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BI-1206 IV; BI-1206 IV Standard 3+3 Dose-Escalation Design	Biological: BI-1206; 375 mg/m2, as per SmPC; Other Names: Rituximab
Experimental: BI-1206 SC; BI-1206 SC Adaptive Dose Escalation Design (Bayesian logistic regression model (BLRM)	Biological: BI-1206; 375 mg/m2, as per SmPC; Other Names: Rituximab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
CD32b protein expression levels	Investigate CD32b protein expression levels; evaluate any potential correlation with clinical responses.	Up to 1 year
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measurement of PROs using the PRO-CTCAE questionnaire.	Evaluate patient-reported outcomes (PROs)in subjects receiving BI-1206	Up to 1 year

Collaborators and Investigators

• Sponsor: BioInvent International AB
• Investigators: Principal Investigator: Mats Jerkeman, MD PhD, Senior Consultant and Adjunct Professor, Skane Univ Hospital, Lund, Sweden

Study record dates

Study Major Dates

• Study Start (Actual): May 16, 2018
• Primary Completion (Estimated): September 22, 2025
• Study Completion (Estimated): September 22, 2025

Study Registration Dates

• First Submitted: May 17, 2018
• First Submitted That Met QC Criteria: June 18, 2018
• First Posted (Actual): June 27, 2018

Study Record Updates

• Last Update Posted (Actual): January 30, 2024
• Last Update Submitted That Met QC Criteria: January 29, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Rituximab
• Other Study ID Numbers: 17-BI-1206-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All information concerning the product as well as any matter concerning the operation of the Sponsor, such as clinical indications for the drug, its formula, methods of manufacture and other scientific data relating to it, that have been provided by the Sponsor and are unpublished, are confidential and must remain the sole property of the Sponsor. The Investigator will agree to use the information only for the purposes of carrying out this study and for no other purpose unless prior written permission from the Sponsor is obtained.
• IPD Sharing Time Frame: Within one year from end of study
• IPD Sharing Access Criteria: Paper copy of CSR
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No