A Study of BI-1206 in Combination With Rituximab With or Without Acalabrutinib in Subjects With Indolent B-Cell NHL

April 23, 2025 updated by: BioInvent International AB

Phase 1/2a Trial of BI-1206, a Monoclonal Antibody to CD32b (FcyRIIB), in Combination With Rituximab With or Without Acalabrutinib 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 with or without Acalabrutinib in Subjects with Indolent B-Cell Non-Hodgkin Lymphoma That has Relapsed or is Refractory to Rituximab

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a Phase 1/2a, multicenter, dose escalation, consecutive-cohort, open-label trial of BI-1206 in combination with rituximab with or without acalabrutinib in subjects with indolent relapsed or refractory B-cell NHL, sub-types FL (except FL grade 3B), MZL, and MCL.

Phase 2a, consists of signal seeking cohorts followed by a randomized, parallel, two-arm dose optimization.

The trial consists of 2 main parts:

Phase 1

- Dose Escalation, with two different Arms assessing IV or SC dosing of BI-1206 in combination with rituximab, with dose escalation cohorts and selection of the IV and SC doses of BI-1206 for Phase 2a

Phase 2a

  • Dose Expansion, with one expansion cohort evaluating the selected IV dose of BI-1206 in combination with rituximab
  • Signal Seeking, assessing IV and SC dosing of BI-1206 in combination with rituximab and acalabrutinib. The Signal Seeking will consist of a Safety Run-in and an Expansion
  • Dose Optimization to select the recommended dose of BI-1206 in combination with rituximab and acalabrutinib

Study Type

Interventional

Enrollment (Estimated)

140

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Brazil
      • Curitiba, Brazil
        • Not yet recruiting
        • Hospital Erasto Gaertner - Liga Paranaense de Combate ao Cancer
        • Contact:
        • Principal Investigator:
          • Eduardo Munhoz, MD
      • Rio De Janeiro, Brazil
      • Sao Paulo, Brazil
      • São Paulo, Brazil
      • São Paulo, Brazil
        • Not yet recruiting
        • Hospital Sírio-Libanês
        • Principal Investigator:
          • Ana Rita Da Fonseca, MD
        • Contact:
      • São Paulo, Brazil
        • Not yet recruiting
        • Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
        • Contact:
        • Principal Investigator:
          • Juliana Pereira, MD
      • São Paulo, Brazil
        • Recruiting
        • Hospital israelita Albert Einstein
        • Principal Investigator:
          • Guilherme Perini, MD
        • Contact:
      • São Paulo, Brazil
    • Bahia
      • Salvador, Bahia, Brazil
    • Rio Grande Do Sul
      • Porto Alegre, Rio Grande Do Sul, Brazil
        • Recruiting
        • Hospital de Clinicas de Porto Alegre
        • Principal Investigator:
          • Laura Maria Fogliatto, MD
        • Contact:
  • Germany
      • Stuttgart, Germany
        • Withdrawn
        • Robert Bosch Hospital, Dep of Hematology, Oncology and Palliative care
    • Hessen
      • Frankfurt, Hessen, Germany
        • Not yet recruiting
        • Krankenhaus Nordwest Klinik für Onkologie und Hämatologie
        • Principal Investigator:
          • Eckhart Weidmann, MD
        • Contact:
  • 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
        • Contact:
      • Barcelona, Spain
        • Recruiting
        • Hospital de la Santa Creu i Sant Pau, Dep Hematologia
        • Contact:
        • Principal Investigator:
          • Sara Miqueleiz Alamos, MD
      • Barcelona, Spain
        • Recruiting
        • Institut Català d'Oncologia, L'Hospitalet de Llobregat
        • Principal Investigator:
          • Eva Domingo Domenech, MD
        • Contact:
      • Madrid, Spain
        • Recruiting
        • Hospital Universitario HM Sanchinarro
        • Contact:
        • Principal Investigator:
          • Augustin Penedo Coello, MD
      • Madrid, Spain
        • Recruiting
        • University Hospital Fundación Jiménez Díaz
        • Principal Investigator:
          • Raul Cordoba Mascunano, MD
        • Contact:
      • Madrid, Spain
        • Recruiting
        • Hospital General Universitario Gregorio Marañon-Oncología Médica
        • Principal Investigator:
          • Mariana Bastos Oreiro, MD
        • Contact:
      • Murcia, Spain
        • Not yet recruiting
        • Hospital Universitario Virgen de la Arrixaca
        • Principal Investigator:
          • Joaquin Gomez Espuch, MD
        • Contact:
      • Seville, Spain
        • Recruiting
        • Hospital University Virgen Macarene
        • Principal Investigator:
          • Sergio Ortegon Alcaide, MD
        • Contact:
    • Barcelona
      • Badalona, Barcelona, Spain
        • Recruiting
        • Hospital ICO, Trias i Pujol
        • Principal Investigator:
          • Juan Manuel Sancho Cia, MA
        • Contact:
  • Sweden
      • Lund, Sweden, SE-22185
        • Terminated
        • Department of Oncology, Skåne University Hospital
      • Uppsala, Sweden, 751 85
        • Terminated
        • Department of Oncology, Academical Hospital
  • United States
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Active, not recruiting
        • Emory University Hospital
    • 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

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Are ≥ 18 years of age by initiation of study treatment.
  2. 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)
  3. Have measurable nodal disease
  4. Are willing to undergo lymph node biopsies or biopsies of other involved tissue
  5. Have relapsed disease or disease refractory to conventional treatment or for which no standard therapy exists
  6. Have received at least one line of conventional previous therapy which must include at least one rituximab-based regimen
  7. Have a life expectancy of at least 12 weeks
  8. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
  9. Have CD20+ malignancy
  10. Have hematological and biochemical indices within prespecified ranges

Exclusion Criteria:

  1. Have had an allogenic bone marrow or stem cell transplant within 12 months
  2. Have presence of active chronic graft versus host disease
  3. Have current leptomeningeal lymphoma or compromise of the central nervous system
  4. Have transformed lymphoma from a pre-existing indolent lymphoma
  5. Have Waldenstrom's Macroglobulinemia or FL grade 3B,
  6. Need systemic doses of prednisolone >10 mg daily (or equipotent doses of other corticosteroids) while on the study trial other than as pre-medication.
  7. Have known or suspected hypersensitivity to rituximab or BI-1206
  8. Have cardiac or renal amyloid light-chain amyloidosis

  9. Have received any of the following:

    1. Chemotherapy or small molecule products with 2 weeks of first dose of BI-1206
    2. Radiotherapy (except for focal symptomatic control of lymphadenopathy) within 4 weeks
    3. Immunotherapy within 8 weeks
    4. Previous lines of treatment containing BTK inhibitors for Subjects receiving BI-1206 in combination with rituximab and acalabrutinib
  10. Have ongoing toxic manifestations of previous treatments.
  11. Have the ability to become pregnant (or already pregnant or lactating/breastfeeding).
  12. Have had major surgery from which the subject has not yet recovered.
  13. Are at high medical risk because of non-malignant systemic disease including active infection on treatment with antibiotics, antifungals or antivirals.
  14. Are serologically positive for hepatitis B, hepatitis C or human immunodeficiency virus (HIV).
  15. Have an active, known or suspected autoimmune disease.
  16. Have concurrent congestive heart failure, prior history of class III/ IV cardiac disease (New York Heart Association [NYHA])
  17. Have current malignancies of other types

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: BI-1206 IV Dose Escalation
Standard 3+3 Dose-Escalation of BI-1206 IV in combination with Rituximab
Biological: BI-1206

BI-1206 150 mg / 225 mg Subcutaneous injection

BI-1206 50 mg /100 mg Intravenous infusion

Biological: Rituximab
Rituximab 375 mg/m2, as per SmPC
Other Names:
  • Ruxience
Experimental: BI-1206 SC Dose Escalation
Adaptive Dose Escalation of BI-1206 SC (Bayesian logistic regression model (BLRM) in combination with Rituximab
Biological: BI-1206

BI-1206 150 mg / 225 mg Subcutaneous injection

BI-1206 50 mg /100 mg Intravenous infusion

Biological: Rituximab
Rituximab 375 mg/m2, as per SmPC
Other Names:
  • Ruxience
Experimental: Phase 2a IV Dose expansion
BI-1206 IV in Combination with Rituximab
Biological: BI-1206

BI-1206 150 mg / 225 mg Subcutaneous injection

BI-1206 50 mg /100 mg Intravenous infusion

Biological: Rituximab
Rituximab 375 mg/m2, as per SmPC
Other Names:
  • Ruxience
Experimental: Phase 2a SC Signal seeking
SC Arm, BI-1206 in Combination with Rituximab and Acalabrutinib
Biological: BI-1206

BI-1206 150 mg / 225 mg Subcutaneous injection

BI-1206 50 mg /100 mg Intravenous infusion

Biological: Rituximab
Rituximab 375 mg/m2, as per SmPC
Other Names:
  • Ruxience
Biological: Acalabrutinib
Acalabrutinib 100 mg orally as per SmPC
Other Names:
  • Calquence
Experimental: Phase 2a IV Signal Seeking
IV Arm, BI-1206 in Combination with Rituximab and Acalabrutinib
Biological: BI-1206

BI-1206 150 mg / 225 mg Subcutaneous injection

BI-1206 50 mg /100 mg Intravenous infusion

Biological: Rituximab
Rituximab 375 mg/m2, as per SmPC
Other Names:
  • Ruxience
Biological: Acalabrutinib
Acalabrutinib 100 mg orally as per SmPC
Other Names:
  • Calquence

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 and/or acalabrutinib
Time Frame: During the 28-day treatment period on induction therapy
Assess the safety and tolerability profile of BI-1206 when administered intravenously (IV) or subcutaneously (SC) in combination with rituximab or rituximab and acalabrutinib in subjects with relapsed or refractory B-cell non-Hodgkin lymphoma (NHL), subtypes follicular lymphoma (FL)(except FL grade 3B), marginal zone lymphoma (MZL), and mantle cell lymphoma (MCL). Assessment will be done according to National Cancer Institute (NCI-CTCAE) criteria v. 5.0.
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)
Time Frame: During the 28-day treatment period on induction therapy

Phase 1:

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
Determine the recommended dose of BI-1206 in combination with rituximab and acalabrutinib
Time Frame: During the 28-day treatment period on induction therapy

Phase 2a:

Select the recommended dose of BI-1206 in combination with rituximab and acalabrutinib.
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
Time Frame: Up to 1 year
PK parameters assessed will include AUC, Cmax, time to Cmax and t1/2 of BI-1206 when administered IV or SC
Up to 1 year
Evaluation of ADA (immunogenicity) response to BI-1206
Time Frame: Up to 1 year
Assess the incidence and titre of antidrug antibodies of BI-1206 in serum when administered IV or SC in combination with rituximab or rituximab and acalabrutinib.
Up to 1 year
Measurement of peripheral blood B-lymphocytes depletion
Time Frame: Up to 1 year
Evaluate the effect of BI-1206 administered IV or SC in combination with rituximab or rituximab and acalabrutinib measuring B Lymphocytes CD19+ (absolute value) as part of hematology assessment to determine the level of peripheral blood B lymphocyte depletion.
Up to 1 year
Assessment of overall response rate (ORR) according to the response criteria for malignant lymphoma (Cheson, 2014).
Time Frame: Up to 1 year
Assess possible anti-tumor activity of BI-1206 administered IV or SC in combination with rituximab or rituximab and acalabrutinib at Week 6 after first dose of BI-1206 and for subjects who continue during maintenance therapy.
Up to 1 year

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Expression levels of CD32b protein
Time Frame: Up to 1 year
To investigate CD32b protein expression levels using flow cytometry to evaluate any potential correlation with clinical responses. Change from baseline expression levels will be summarized descriptively by dose cohort and/or response to treatment.
Up to 1 year
Assessment of Patient Reported Outcomes using the NCI PRO-CTCAE questionnaire
Time Frame: Up to 1 year

The NCI PRO-CTCAE will be used to evaluate symptomatic toxicities reported by patients. The questionnaire characterizes the frequency, severity, interference, and presence/absence of symptomatic toxicities, all toxicities that can be meaningfully reported from the patient perspective.

Responses are scored from 0 to 4 (or 0/1 for absent/present). Scores for each attribute (frequency, severity and/or interference) will be presented descriptively (e.g. summary statistics or graphical presentations).
Up to 1 year
Expression levels of CD32b and/or other immunological markers
Time Frame: Up to 1 year
Perform whole-transcriptome, quantitative polymerase chain reaction (qPCR) and/or IHC analysis of lymph node biopsies to evaluate potential correlation with clinical responses.
Up to 1 year
Measurement of serum cytokines levels and/or soluble CD32b.
Time Frame: Up to 1 year
Study the potential cause of infusion related reactions (IRRs), such as cytokine release signs, C-reactive protein (CRP) and/or soluble CD32b.
Up to 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

BioInvent International AB

Investigators

  • Principal Investigator: Mats Jerkeman, MD PhD, Senior Consultant and Adjunct Professor, Skane Univ Hospital, Lund, Sweden

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 16, 2018

Primary Completion (Estimated)

September 30, 2026

Study Completion (Estimated)

September 30, 2026

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)

April 24, 2025

Last Update Submitted That Met QC Criteria

April 23, 2025

Last Verified

April 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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