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

• ClinicalTrials.gov Identifier: NCT03571568
• Recruitment Status: Recruiting
• First Posted: June 27, 2018
• Last Update Posted: January 30, 2024
• Sponsor: BioInvent International AB
• Information provided by (Responsible Party): BioInvent International AB

Tracking Information

• First Submitted Date: May 17, 2018
• First Posted Date: June 27, 2018
• Last Update Posted Date: January 30, 2024
• Actual Study Start Date: May 16, 2018
• Estimated Primary Completion Date: September 22, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 7, 2023)

• Documenting AEs and SAEs and determining causality in relation to BI-1206 and/or rituximab [ 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 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).
• 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 ]
  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.

Original Primary Outcome Measures (submitted: June 18, 2018)

• Documenting AEs and SAEs and determining causality in relation to BI-1206 and/or rituximab [ Time Frame: During the 28-day treatment period on induction therapy ]
  Assess the safety and tolerability profile of BI-1206 when administered in combination with Rituximab
• 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 ]
  Select the RP2D

Current Secondary Outcome Measures (submitted: March 7, 2023)

• Evaluation of PK parameters for BI-1206. [ Time Frame: Up to 1 year ]
  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.
• Evaluation of PK parameters for rituximab during the BI-1206 treatment period. [ Time Frame: Up to 1 year ]
  Study the PK profile of rituximab when administered in combination with BI-1206 (IV or SC).
• Evaluation of ADA response to BI 1206. [ Time Frame: Up to 1 year ]
  Assess the immunogenicity of BI-1206 when administered IV or SC in combination with rituximab.
• Measurement of B cell depletion. [ Time Frame: Up to 1 year ]
  Evaluate the effect of BI-1206 administered IV or SC in combination with rituximab on the depletion of B-cells.
• 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 at Week 6 after first dose of BI-1206 and for subjects who continue during maintenance therapy.
• CD32b protein expression levels [ Time Frame: Up to 1 year ]
  Investigate CD32b protein expression levels; evaluate any potential correlation with clinical responses.

Original Secondary Outcome Measures (submitted: June 18, 2018)

• Evaluation of PK parameters for BI-1206. Maximum observed plasma concentration (Cmax) [ Time Frame: Up to 1 year ]
  Study the PK profile of BI-1206 together with Rituximab
• Evaluation of PK parameters for BI-1206. Area under the plasma concentration-time curve (AUC) [ Time Frame: Up to 1 year ]
  Study the PK profile of BI-1206 together with Rituximab
• Evaluation of PK parameters for Rituximab. Maximum observed plasma concentration (Cmax) [ Time Frame: Up to 1 year ]
  Study the PK profile of Rituximab together with BI-1206
• Evaluation of PK parameters for Rituximab. Area under the plasma concentration-time curve (AUC) [ Time Frame: Up to 1 year ]
  Study the PK profile of Rituximab together with BI-1206
• Evaluation of ADA response to BI 1206 [ Time Frame: Up to 1 year ]
  Assess the immunogenicity of BI-1206
• Measurement of B cell depletion [ Time Frame: Up to 1 year ]
  Evaluate the effect of BI-1206
• Assessment of overall response rate (response criteria for malignant lymphoma (Cheson, 2014). RR) [ Time Frame: Up to 1 year ]
  Assess possible anti-tumor activity of BI-1206

Current Other Pre-specified Outcome Measures (submitted: February 7, 2023)

Measurement of PROs using the PRO-CTCAE questionnaire. [ Time Frame: Up to 1 year ]

Evaluate patient-reported outcomes (PROs)in subjects receiving BI-1206

• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

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
• Study Phase: Phase 1; Phase 2

Study Design

Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Intervention Model Description:

Phase 1/2a, dose escalation, consecutive-cohort, open-label study trial of BI-1206 in combination with rituximab

Masking: None (Open Label)
Primary Purpose: Treatment

• Condition: Indolent B-Cell Non-Hodgkin Lymphoma

Intervention

Biological: BI-1206

375 mg/m2, as per SmPC

Other Name: Rituximab

Study Arms

• Experimental: BI-1206 IV
  BI-1206 IV Standard 3+3 Dose-Escalation Design
  Intervention: Biological: BI-1206
• Experimental: BI-1206 SC
  BI-1206 SC Adaptive Dose Escalation Design (Bayesian logistic regression model (BLRM)
  Intervention: Biological: BI-1206

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 7, 2023): 98
• Original Estimated Enrollment (submitted: June 18, 2018): 30
• Estimated Study Completion Date: September 22, 2025
• Estimated Primary Completion Date: September 22, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Erika Bågeman; +46706126618; erika.bageman@bioinvent.com

Contact: Andres McAllister, MD, PhD; andres.mcallister@bioinvent.com

• Listed Location Countries: Brazil, Germany, Poland, Spain, Sweden, United States

Administrative Information

• NCT Number: NCT03571568
• Other Study ID Numbers: 17-BI-1206-02
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: Yes
• 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.
• Supporting Materials: Study Protocol
• Supporting Materials: Clinical Study Report (CSR)
• Time Frame: Within one year from end of study
• Access Criteria: Paper copy of CSR

• Current Responsible Party: BioInvent International AB
• Original Responsible Party: Same as current
• Current Study Sponsor: BioInvent International AB
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: BioInvent International AB
• Verification Date: January 2024