ANTI-(FC FRAGMENT OF IGG RECEPTOR IIB) MONOCLONAL ANTIBODY (BI-1206) for Indolent B-cell non-Hodgkin lymphoma

Inclusion criteria

• {"criterion_text":"- Are ≥ 18 years of age by initiation of study treatment."}
• {"criterion_text":"- Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0–2."}
• {"criterion_text":"- Have CD20+ malignancy as demonstrated by IHC or flow cytometry prior to first dose of BI-1206. Analysis must have been performed on the most recent biopsy obtained and must be after anti-CD20 therapy."}
• {"criterion_text":"- Have hematological and biochemical indices within prespecified ranges, including hemoglobin (≥9.0 g/dL, red cell support is permissible); absolute neutrophil count (ANC) (≥1.0 × 109/L, or >0.5 × 109/L if due to lymphoma; granulocyte-colony stimulating factor support is not permissible at screening); and platelet count (≥100 × 109/L). These measurements must be performed within 1 week and assessed by the Investigator before their first dose of BI-1206."}
• {"criterion_text":"- Provide written (signed and dated) informed consent."}
• {"criterion_text":"- Are capable of cooperating with treatment and follow-up."}
• {"criterion_text":"- Have B-cell NHL proven by histology, with histological subtypes limited to FL (except FL3B), MCL and MZL."}
• {"criterion_text":"- Have measurable nodal disease, defined as the presence of ≥1 nodal lesion that measures ≥1.5 cm in a single dimension as assessed by computerized tomography (CT) or magnetic resonance imaging (MRI)."}
• {"criterion_text":"- Are willing to undergo lymph node biopsies or biopsies of other involved tissue (besides bone marrow). However, if a biopsy is not technically feasible, the sample can be omitted. If viable frozen tissue (not formalin-fixed) from a previous standard of care biopsy in the previous 8 weeks prior to consent is available, a new biopsy at screening is not required."}
• {"criterion_text":"- Have relapsed disease or disease refractory to conventional treatment or for which no standard therapy exists, the investigator judges available standard therapy as not being appropriate for the subject, or is declined by the subject. Rituximab refractory disease is defined as: • Lack of CR or PR during rituximab-containing treatment comprising ≥2 doses of ≥375 mg/m2, or • Occurrence of progressive disease up to one year after completion of a regimen of rituximab-containing therapy comprising ≥2 doses of ≥375 mg/m2, or • Occurrence of progressive disease during rituximab maintenance therapy or within 6 months of completion of rituximab maintenance therapy."}
• {"criterion_text":"- Have received at least one line of conventional previous therapy which must include at least one rituximab-based regimen."}
• {"criterion_text":"- Have a life expectancy of at least 12 weeks on the day of the first infusion of BI-1206."}

Exclusion criteria

• {"criterion_text":"- Have had an allogenic bone marrow or stem cell transplant within 12 months prior to the first dose of BI-1206."}
• {"criterion_text":"- Have ongoing toxic manifestations of previous treatments. Exceptions to this are alopecia or certain Grade 1 toxicities, which in the opinion of the Investigator should not exclude the subject."}
• {"criterion_text":"- Have the ability to become pregnant (or pregnant or lactating/breastfeeding). However, those female subjects who have a negative serum pregnancy test before enrollment and agree to use a highly effective method of birth control for 4 weeks before entering the trial, during the trial and for 12 months after last dose of BI 1206 are considered eligible. Highly effective methods of birth control include: • Combined (estrogen- and progestogen-containing) hormonal contraception associated with inhibition of ovulation • Progestogen-only hormonal contraception associated with inhibition of ovulation • Intrauterine device • Intrauterine hormone-releasing system • Bilateral tubal occlusion • Vasectomized partner • Sexual abstinence"}
• {"criterion_text":"- Are male subjects with partners of childbearing potential (unless they agree not to father children by using one form of highly effective contraception (condom plus spermicide gel) during the trial and for 12 months after completing treatment). Men with pregnant or lactating partners should be advised to use barrier method contraception (condom plus spermicidal gel) to prevent exposure to the fetus or neonate."}
• {"criterion_text":"- Have had major surgery from which the subject has not yet recovered."}
• {"criterion_text":"- Are at high medical risk because of non-malignant systemic disease including active infection on treatment with antibiotics, antifungals or antivirals."}
• {"criterion_text":"- Are serologically positive for hepatitis B, hepatitis C or human immunodeficiency virus (HIV)."}
• {"criterion_text":"- Have an active, known or suspected autoimmune disease. However, subjects with Type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia not requiring systemic treatment), or conditions not expected to recur in the absence of an external trigger will be permitted to participate."}
• {"criterion_text":"- Have concurrent congestive heart failure, prior history of class III/ IV cardiac disease (New York Heart Association [NYHA]), history of clinically significant cardiac ischemia or cardiac arrhythmia in the past 6 months."}
• {"criterion_text":"- Have ongoing alcohol or drug addiction, as judged by the Investigator."}
• {"criterion_text":"- Have any other condition which in the Investigator's opinion would not make the subject a good candidate for the clinical trial."}
• {"criterion_text":"- Have presence of active chronic graft versus host disease of any grade/severity."}
• {"criterion_text":"- Are participating or plan to participate in another interventional clinical study, while taking part in this Phase 1/2a study of BI-1206. Participation in an observational non-interventional study is acceptable."}
• {"criterion_text":"- Have current malignancies of other types, with the exception of: • adequately treated cone-biopsied in situ carcinoma of the cervix uteri • basal or squamous cell carcinoma of the skin • asymptomatic prostate cancer without known metastatic disease and with no requirement for therapy or requiring only hormonal therapy and with normal prostate-specific antigen for >1 year prior to start of study therapy. Cancer survivors, who have undergone potentially curative therapy, have no evidence of that disease for ≥ 3 years and are deemed at negligible risk for recurrence, are also eligible for the trial."}
• {"criterion_text":"- Have current leptomeningeal lymphoma or compromise of the central nervous system."}
• {"criterion_text":"- Have transformed lymphoma from a pre-existing indolent lymphoma. Subjects with a previous history of transformation, but on this disease episode have a biopsy proven indolent recurrence, may be included. Subjects with proven or suspected Richter transformation are not eligible."}
• {"criterion_text":"- Have Waldenstrom's Macroglobulinemia or FL3B, due to the high risk of transformation while on study."}
• {"criterion_text":"- Need systemic doses of prednisolone >10 mg daily (or equipotent doses of other corticosteroids) while on the study other than as premedication. During the screening period, doses of up to 20 mg/day may be given but the dose must be reduced to 10 mg/day within 7 days prior the first dose of study drug. Inhaled or intranasal steroids are permissible."}
• {"criterion_text":"- Have known or suspected hypersensitivity to rituximab or BI-1206. Previous isolated IRRs are not to be considered a reason for exclusion."}
• {"criterion_text":"- Have cardiac or renal amyloid light-chain amyloidosis."}
• {"criterion_text":"- Have received any of the following: • Chemotherapy or small molecule products with 2 weeks of first dose of BI- 1206 and/or • Radiotherapy (except for focal symptomatic control of lymphadenopathy) within 4 weeks of first dose of BI-1206 and/or • Immunotherapy within 8 weeks prior to the first dose of BI-1206. Subjects receiving BI-1206 with rituximab and acalabrutinib: previous lines of treatment containing BTK inhibitors."}

Primary endpoints

• {"endpoint_text":"- • Documenting AEs and SAEs (graded according to National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events CTCAE, and determining causality in relation to BI 1206, rituximab or acalabrutinib.. Causality of AEs/SAEs will be assessed by the Investigator.","definition_or_measurement_approach":"AEs/SAEs graded per NCI CTCAE; causality assessed by the Investigator."}
• {"endpoint_text":"- Phase 1: • Determining the MTD of BI-1206, with no more than 1 of up to 6 subjects at the same dose level experiencing DLT during the 28-day treatment period on induction therapy (i.e., by Day 29/Week 5). If pharmacokinetic (PK) and pharmacodynamic (PD) data suggest an optimal therapeutic dose, the escalation may be halted by the Cohort Review Committee (CRC) prior to reaching the MTD, and the RP2D will be based off the PK, PD, safety tolerability and efficacy data.","definition_or_measurement_approach":"MTD determined by DLT occurrence during the 28-day induction period (by Day 29/Week 5), with rule: no more than 1 of up to 6 subjects at same dose level experiencing DLT. PK/PD and CRC review may halt escalation; RP2D chosen based on PK, PD, safety, tolerability and efficacy."}
• {"endpoint_text":"- Phase 2a, BI-1206 in Combination with Rituximab and Acalabrutinib: The recommended dose will be derived from totality of PK, PD, clinical response, safety, and tolerability observed.","definition_or_measurement_approach":"Recommended Phase 2 dose derived from integrated assessment of PK, PD, clinical response, safety and tolerability."}

Secondary endpoints

• {"endpoint_text":"- Evaluation of PK parameters for BI-1206 during the BI-1206 treatment period.","definition_or_measurement_approach":"PK parameters of BI-1206 assessed during treatment period (sampling and PK analysis as per protocol)."}
• {"endpoint_text":"- Evaluation of ADA response to BI 1206.","definition_or_measurement_approach":"Assessment of anti-drug antibody (ADA) response to BI-1206 (immunogenicity testing)."}
• {"endpoint_text":"- Measurement of B cell depletion.","definition_or_measurement_approach":"Measurement of B-cell counts/depletion (flow cytometry or equivalent) as specified in protocol."}
• {"endpoint_text":"- Assessment of overall response rate (ORR) according to the response criteria for malignant lymphoma (Cheson, 2014). Other endpoints will include time to objective response, duration of response, PFS, and OS.","definition_or_measurement_approach":"ORR assessed per Cheson 2014 response criteria; additional outcomes include time to objective response, duration of response, progression-free survival (PFS), and overall survival (OS)."}
• {"endpoint_text":"- CD32b protein expression levels.","definition_or_measurement_approach":"Assessment of CD32b protein expression levels (e.g., by IHC or other assay as defined in protocol)."}
• {"endpoint_text":"- Expression levels of CD32b and/or other immunological markers.","definition_or_measurement_approach":"Measurement of CD32b and other immunological marker expression levels (assay methodology per protocol)."}

Germany

Earliest CTIS Part Ii Submission Date

30-06-2024

Latest Decision Or Authorization Date

17-04-2026

Processing Time Days

656

Number Of Sites

2

Number Of Participants

8

Spain

Earliest CTIS Part Ii Submission Date

30-06-2024

Latest Decision Or Authorization Date

17-04-2026

Processing Time Days

656

Number Of Sites

9

Number Of Participants

15

Primary sponsor

Full Name

BioInvent International AB

Organisation Type

Pharmaceutical company

Country Of Registered Address

Sweden

Contract research organisations

Name

Icon Clinical Research Limited

Responsibilities

Sponsor duties codes: [1,10,11,12,13,2,5,6,7,8] (as listed in CTIS record)

Name

Klifo A/S

Responsibilities

IMP labeling, storage and QP release

Name

Charles River Laboratories Edinburgh Limited

Responsibilities

PD analysis and other lab/PD responsibilities

Name

SkylineDx B.V.

Responsibilities

Whole-transcriptome analysis

Name

SVAR Life Science AB

Responsibilities

PK and ADA Analysis

Third parties

• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"Sponsor duties codes: [1,10,11,12,13,2,5,6,7,8] (as listed in CTIS record)","organisation_type":"Pharmaceutical company"}
• {"country":"Denmark","full_name":"Klifo A/S","duties_or_roles":"IMP labeling, storage and QP release","organisation_type":"Pharmaceutical company"}
• {"country":"Sweden","full_name":"BioInvent International AB","duties_or_roles":"Genetic Analysis","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Charles River Laboratories Edinburgh Limited","duties_or_roles":"PD analysis; other duties codes include code 4","organisation_type":"Pharmaceutical company"}
• {"country":"Netherlands","full_name":"SkylineDx B.V.","duties_or_roles":"Whole-transcriptome analysis","organisation_type":"Pharmaceutical company"}
• {"country":"Sweden","full_name":"SVAR Life Science AB","duties_or_roles":"PK and ADA Analysis","organisation_type":"Pharmaceutical company"}