Phase I/IIa 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 Identifier:
17-BI-1206-02
CT.gov Identifier:
NCT03571568
EudraCT Identifier:
201800000000
EU Trial (CTIS) Number:
2024-512972-36-00
Study Contact Information:
(210) 593-5651 or [email protected]
Recruiting

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Study Summary

To assess the safety and tolerability of BI-1206 in combination with rituximab, as well as early signs of efficacy. During the clinical trials, biomarkers that may predict patients’ responses to treatment will also be monitored. Assessments: The assessment of the pharmacokinetics (PK) of BI-1206 included non-compartmental analysis (NCA), and the assessment of the pharmacodynamics (PD) included receptor occupancy (RO%). PK modelling was conducted to further characterize the PK behavior and to provide predictions of upcoming dose levels. In addition, the effect of BI-1206 on the PK of rituximab was investigated by comparing PK parameters of rituximab to literature values of rituximab monotherapy. In Phase 2a, BI-1206 will be evaluated in combination with rituximab and acalabrutinib, with a Safety Run-infollowed by an Expansion of up to 30 patients The Phase 2a study arm will combine the subcutaneous formulation of BI-1206 and rituximab with Calquence® (acalabrutinib), a selective inhibitor of Bruton's tyrosine kinase (BTK). To investigate the safety and efficacy of BI-1206 in combination with rituximab and acalabrutinib in R/R NHL (FL, MZL, and MCL).

To investigate the safety and efficacy of BI-1206 in combination with rituximab and acalabrutinib in R/R NHL with a focus on FL.

To evaluate BI-1206, an anti-FcγRIIB antibody, in combination with rituximab and Calquence® (acalabrutinib) for the treatment of non-Hodgkin's lymphoma (NHL)

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
  • Lymphoma, Non-Hodgkin's
    • Phase
    The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
    I/II
    Sex
    Female & Male
    Age
    18+ years
    Study Drug
  • Drug: Experimental: BI-1206 IV Dose Escalation Standard 3+3 Dose-Escalation of BI-1206 IV in combination with Rituximab Experimental: BI-1206 SC Dose Escalation Adaptive Dose Escalation of BI-1206 SC (Bayesian logistic regression model (BLRM) in combination with Rituximab Experimental: Phase 2a IV Dose expansion BI-1206 IV in Combination with Rituximab Intervention/Treatment 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 Experimental: Phase 2a SC Signal seeking SC Arm, BI-1206 in Combination with Rituximab and Acalabrutinib 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 Biological: Acalabrutinib Acalabrutinib 100 mg orally as per SmPC ICML 2023 Ph2a of the trial will consist of cohorts of at minimum 6 and maximum 12 subjects each, receiving ivRP2D, scRP2D, and potential additional dose levels of interest. During induction therapy, patients receive one dose of single-agent rituximab (375 mg/m2) followed by dosing of BI-1206 with subsequent rituximab on weeks 2, 3, and 4. Patients showing clinical benefit (complete response [CR], partial response [PR], or stable disease [SD]) at week 6 are eligible for continued maintenance therapy with dosing of BI-1206 and rituximab every 8 weeks for up to 7 cycles. Patients will receive BI-1206, in combination with rituximab and Calquence. A corticosteroid pretreatment schedule using two doses of corticosteroids prior to IV administration (16-24h and 1h) was implemented after first three cohorts. During induction therapy, patients receive one dose of single-agent rituximab (375 mg/m2) followed by dosingof BI-1206 with rituximab on weeks 2, 3, and 4. Patients showing clinical benefit at week 6 are eligible for maintenance therapy with dosing of BI-1206 and rituximab every 8 weeks for up to 6 cycles EHA 2025: BI-1206 will be administered SC in combination with rituximab IV, QW for a 4 week induction period. Acalabrutinib will be dosed daily throughout study duration (1 year). Patients exhibiting disease control at week 6 are eligible for an additional induction period, followed by maintenance therapy with dosing of BI-1206 and rituximab every 8 weeks for up to 6 cycles.
    • Study Status
    Indicates the current recruitment status or the expanded access status
    Recruiting

    Requirements information
    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 FL grade 3B,
    • 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
    • Previous lines of treatment containing BTK inhibitors for Subjects receiving BI-1206 in combination with rituximab and acalabrutinib
    • 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

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    Study Locations

    Location
    Investigator
    Status
    Condition(s) Treated at Site
    Location
    START Madrid, Spain (FJD)
    Madrid, Spain, 28040
    Investigator
    Daniel Morillo Giles
    Status
    Recruiting
    Condition(s) Treated at Site
    Lymphoma, Non-Hodgkin's
    Location
    START Madrid, Spain (CIOCC)
    Madrid, Spain, 28050
    Investigator
    Status
    Recruitment Complete
    Condition(s) Treated at Site
    Lymphoma, Non-Hodgkin's