ANTI-(FC FRAGMENT OF IGG RECEPTOR IIB) MONOCLONAL ANTIBODY BI-1206 for Advanced solid tumors

Inclusion criteria

• {"criterion_text":"- For Phase 1: Is willing and able to provide written informed consent for the trial."}
• {"criterion_text":"- Has at least 1 measurable disease lesion as defined by the Response Evaluation Criteria in Solid Tumors (RECIST)."}
• {"criterion_text":"- Is willing to provide an archival tumor tissue sample or newly obtained [core, incisional, OR excisional] biopsy of a tumor lesion not previously irradiated. If the Investigator considers that a tissue biopsy is not safe and/or not technically feasible, then the subject will not be required to undergo the biopsy. However, in SC cohorts of Phase 2a the tissue biopsy from Screening is mandatory. a. The Screening biopsy must be performed prior to the first dose of BI-1206 (on non-previously irradiated lesions only), and at least 4 weeks after the last dose of tumor-directed therapy. The biopsy at Screening can be replaced with a formalin- fixed archival tumor tissue sample collected from a previous standard of care biopsy, provided that the biopsy was performed after the subject's last tumor- directed therapy and prior to study entry. Subjects who do not have an archival tissue sample at Screening may still be enrolled in the study."}
• {"criterion_text":"- Has a life expectancy of ≥12 weeks."}
• {"criterion_text":"- Participants who are HBsAg positive are eligible if they have received HBV antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to enrollment."}
• {"criterion_text":"- Participants with history of HCV infection are eligible if HCV viral load is undetectable at Screening."}
• {"criterion_text":"- Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0–1."}
• {"criterion_text":"- Has adequate organ function as confirmed by laboratory values listed in the main body of the protocol."}
• {"criterion_text":"- Expansion Cohort-specific Inclusion Criteria: In addition to the general inclusion criteria above, subjects must also meet the criteria for the specific cohort. Additional requirements will be added based on learnings from subjects enrolled in the Phase 1 part of the trial. 3. Cohort 3 (Other Tumor Types): a. All subjects will require prior anti-PD-1/PD-L1 therapy."}
• {"criterion_text":"- For Phase 2a: Expansion Cohort-specific Inclusion Criteria: Note: Phase 2a will enroll subjects who are treatment-naïve. Inclusion criteria No.3, No.4 and No.6 do not apply to patients enrolled in the Phase 2a expansion cohorts. Subjects diagnosed with uveal melanoma who have received previous treatment with tebentafusp and/or liver directed therapy are allowed. In addition to the general inclusion criteria above (except for criteria n.3, n.4, and No.6), subjects must also meet the criteria for the tissue-specific cohort. 2. Cohort 2 (uveal Melanoma): a.Has a histologically confirmed diagnosis of advanced or metastatic uveal melanoma. b.Has a PD-L1 positive (TPS≥1%) tumor as determined by IHC at a local laboratory. c.Has not received prior systemic immunotherapy or chemotherapy treatment for their advanced/metastatic uveal melanoma. Subjects who have received previous treatment with tebentafusp and/or liver directed therapy are allowed. d.Has provided formalin-fixed tumor tissue sample from a biopsy of a tumor lesion either at the time of or after the diagnosis of advanced or metastatic disease has been made and from a site not previously irradiated to perform biomarker analysis"}
• {"criterion_text":"- For Phase 2a: Expansion Cohort-specific Inclusion Criteria: Note: Phase 2a will enroll subjects who are treatment-naïve. Inclusion criteria No.3, No.4 and No.6 do not apply to patients enrolled in the Phase 2a expansion cohorts. Subjects diagnosed with uveal melanoma who have received previous treatment with tebentafusp and/or liver directed therapy are allowed. In addition to the general inclusion criteria above (except for criteria n.3, n.4, and No.6), subjects must also meet the criteria for the tissue-specific cohort. 1. Cohort 1 (NSCLC): a.Have a histologically or cytologically confirmed diagnosis of advanced or metastatic NSCLC and not have an EGFR sensitizing (activating) mutation or an ALK translocation. b. Has a PD-L1 positive (TPS≥50%) tumor as determined by IHC at a local laboratory. c. Has not received prior systemic immunotherapy or chemotherapy treatment for their advanced/metastatic NSCLC. d. Has provided formalin-fixed tumor tissue sample from a biopsy of a tumor lesion either at the time of or after the diagnosis of advanced or metastatic disease has been made and from a lesion not previously irradiated to perform biomarker analysis."}
• {"criterion_text":"- Is at ≥ 18 years of age on the day of signing informed consent."}
• {"criterion_text":"- Has a histologically confirmed advanced solid tumor. Subjects must have received at least 2 doses of an approved anti-PD-1/PD-L1 monoclonal antibody (mAb) administered either as monotherapy, or in combination with other checkpoint inhibitors or other therapies, and must have documented progression on or within 12 weeks from the last dose of anti-PD-1/PD-L1 mAb."}
• {"criterion_text":"- Has received standard of care or is intolerant of, refuses, or is not eligible for standard of care antineoplastic therapy."}

Exclusion criteria

• {"criterion_text":"- Needs doses of prednisolone >10 mg daily (or equipotent doses of other corticosteroids) while on the trial 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 to the first dose of study drug. Steroids are allowed as premedication in subjects with allergies to contrast scans."}
• {"criterion_text":"- Has received a live vaccine within 30 days before the first dose of study treatment. COVID-19 vaccines based on viral RNA or protein fragments, or killed viruses, are allowed. COVID 19 vaccines based on live replicating viral or bacterial vectors are not allowed."}
• {"criterion_text":"- Has uncontrolled or significant cardiovascular disease as per protocol definition."}
• {"criterion_text":"- Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated CNS metastases may participate provided they are radiologically stable (without evidence of progression for at least 4 weeks by repeat imaging [performed during Screening]); have no newly-onset or worsening symptomatology of brain metastases; and have not required steroids for at least 14 days before study treatment."}
• {"criterion_text":"- Has a known psychiatric or substance abuse disorder that would interfere with the subject's ability to cooperate with the requirements of the study."}
• {"criterion_text":"- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or lead to participation not being in the best interest of the subject, in the opinion of the Investigator."}
• {"criterion_text":"- Is participating or planning to participate in another interventional clinical trial, or has participated in a trial of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study drug."}
• {"criterion_text":"- Has known or suspected hypersensitivity to pembrolizumab or BI1206 or any of their excipients. Previous isolated IRRs are not to be considered a reason for exclusion unless Grade 4 in intensity."}
• {"criterion_text":"- Has cardiac or renal amyloid light-chain amyloidosis."}
• {"criterion_text":"- Has received radiotherapy within 2 weeks of the first dose of BI-1206. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) for non-CNS disease. Subjects who have previously had radiation pneumonitis are not allowed."}
• {"criterion_text":"- Has not recovered from adverse events (AEs) to at least Grade 1 by CTCAE v5.0 (or higher) due to prior anti-cancer therapies. Exceptions are alopecia or certain Grade 1 toxicities, which in the opinion of the Investigator should not exclude the subject. Subjects with ≤Grade 2 neuropathy may be eligible, after discussion with the Medical Monitor."}
• {"criterion_text":"- Is a female subject and has the ability to become pregnancy (or already pregnant or lactating/ breastfeeding). Those female subjects who have a negative serum or urine 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 the last dose of BI-1206 are considered eligible. Highly effective methods of birth control are defined in protocol."}
• {"criterion_text":"- Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis."}
• {"criterion_text":"- Has an active, known or suspected autoimmune disease. Subjects with Type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, mild 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":"- Male subjects with partner(s) of childbearing potential are excluded unless the male partner agrees to use a barrier method of contraception (condom plus spermicidal gel) with the female partner(s) who are using one highly effective method of contraception during the study and for 12 months after completing treatment."}
• {"criterion_text":"- Has had major surgery from which the subject has not yet recovered."}
• {"criterion_text":"- Is at high medical risk because of non-malignant systemic disease including severe active infections on treatment with antibiotics, antifungals or antivirals."}
• {"criterion_text":"- Has presence of chronic graft versus host disease."}
• {"criterion_text":"- Has had an allogenic tissue/solid organ transplant."}
• {"criterion_text":"- Has known history of human immunodeficiency virus (HIV) infection. No HIV testing is required unless mandated by local health authority."}
• {"criterion_text":"- Has a history of active tuberculosis (bac. tuberculosis)."}

Primary endpoints

• {"endpoint_text":"- Documentation of AEs and SAEs (graded according to the NIH National Cancer Institute, Division of Cancer Treatment and Diagnosis: Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 or higher, clinically significant laboratory parameters and physical findings, as well as their causality to BI-1206 and/or pembrolizumab administration.","definition_or_measurement_approach":"Adverse events and serious adverse events will be recorded and graded per CTCAE v5.0 or higher; clinically significant laboratory parameters and physical findings will be documented and assessed for causality to BI-1206 and/or pembrolizumab."}
• {"endpoint_text":"- In Phase 1, identify DLT occurrence: Determination of signal-seeking dose and the MTD or maximum administered dose of BI-1206, based on the modified mTPI-2 design.","definition_or_measurement_approach":"Dose-limiting toxicities (DLTs) will be identified during Phase 1 and used within a modified mTPI-2 dose-escalation design to determine the signal-seeking dose and maximum tolerated or maximum administered dose."}
• {"endpoint_text":"- In Phase 2a: Determination of the RP2D","definition_or_measurement_approach":"Selection of a recommended Phase 2 dose (RP2D) for BI-1206 (SC) based on integrated review of safety, PK and pharmacodynamics, and possibly differing from the MTD."}

Secondary endpoints

• {"endpoint_text":"- Determination of standard PK parameters (i.e., AUC, Cmax, Tmax, and terminal half-life [t½]) for BI-1206.","definition_or_measurement_approach":"Standard PK parameters (AUC, Cmax, Tmax, terminal half-life) will be calculated from plasma concentration-time data for BI-1206."}
• {"endpoint_text":"- Measurement of ADA response to BI-1206.","definition_or_measurement_approach":"Assessment of anti-drug antibody (ADA) responses to BI-1206 using immunogenicity assays."}
• {"endpoint_text":"- Blood exploratory samples. Measurement of CD32b receptor occupancy on B cells.","definition_or_measurement_approach":"Exploratory blood biomarkers including measurement of CD32b receptor occupancy on B cells using flow cytometry or validated occupancy assays."}

Sweden

Earliest CTIS Part Ii Submission Date

14-02-2024

Latest Decision Or Authorization Date

09-10-2025

Processing Time Days

603

Number Of Sites

2

Number Of Participants

60

Romania

Earliest CTIS Part Ii Submission Date

15-08-2024

Latest Decision Or Authorization Date

27-10-2025

Processing Time Days

438

Number Of Sites

2

Number Of Participants

30

Poland

Earliest CTIS Part Ii Submission Date

16-10-2024

Latest Decision Or Authorization Date

28-11-2025

Processing Time Days

408

Number Of Sites

4

Number Of Participants

30

Spain

Earliest CTIS Part Ii Submission Date

03-12-2025

Latest Decision Or Authorization Date

18-12-2025

Processing Time Days

15

Number Of Sites

7

Number Of Participants

40

Germany

Earliest CTIS Part Ii Submission Date

14-01-2026

Latest Decision Or Authorization Date

29-01-2026

Processing Time Days

15

Number Of Sites

3

Number Of Participants

10

Primary sponsor

Full Name

BioInvent International AB

Organisation Type

Pharmaceutical company

Country Of Registered Address

Sweden

Contract research organisations

Name

Theradex (Europe) Limited

Responsibilities

Codes: 1,11,12,13,2,5

Name

Icon Clinical Research Limited

Responsibilities

Codes: 1,10,11,2,5,6,8,9

Name

Pharmaceutical Research Associates Group B.V.

Responsibilities

Codes: 4

Name

Charles River Laboratories Edinburgh Limited

Responsibilities

Site kit supply, reconciliation, shipment to 3rd party labs, tumor tissue storage (code 15); Code 4

Name

Neogenomics Laboratories Inc.

Responsibilities

Codes: 10,11,12,3,8,9

Third parties

• {"country":"United Kingdom","full_name":"Theradex (Europe) Limited","duties_or_roles":"Codes: 1,11,12,13,2,5","organisation_type":"Pharmaceutical company"}
• {"country":"Israel","full_name":"Bioforum C.D.M.C Ltd.","duties_or_roles":"Codes: 10,6","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"Codes: 1,10,11,2,5,6,8,9","organisation_type":"Pharmaceutical company"}
• {"country":"Netherlands","full_name":"Pharmaceutical Research Associates Group B.V.","duties_or_roles":"Codes: 4","organisation_type":"Pharmaceutical company"}
• {"country":"Sweden","full_name":"SVAR Life Science AB","duties_or_roles":"Codes: 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Neogenomics Laboratories Inc.","duties_or_roles":"Codes: 10,11,12,3,8,9","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"Codes: 7","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Netherlands","full_name":"SkylineDx B.V.","duties_or_roles":"Codes: 4","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Charles River Laboratories Edinburgh Limited","duties_or_roles":"Site kit supply, reconciliation, shipment to 3rd party labs, tumor tissue storage (code 15); Code 4","organisation_type":"Pharmaceutical company"}