BI-1808 for Advanced solid tumors

Inclusion criteria

• {"criterion_text":"- 1. Is willing and able to provide written informed consent for the trial."}
• {"criterion_text":"- 2. Is ≥18 years of age on the day of signing informed consent."}
• {"criterion_text":"- 3. Has a histologically confirmed advanced malignancy. Subjects with TCL [MF or SS] who satisfy the Phase 2a, Cohort 3-specific eligibility criteria may be enrolled into the Phase 1 part of the study."}
• {"criterion_text":"- 4. Has received standard of care or is intolerant of, refuses, or is not eligible for standard antineoplastic therapy."}
• {"criterion_text":"- 5. Has at least 1 measurable disease lesion as defined by RECIST v 1.1 (not applicable for subjects with TCL)."}
• {"criterion_text":"- 6. Is willing to safely undergo tissue biopsies of involved tissue, if required. However, if the Investigator considers that a baseline tumor tissue biopsy is not safe and technically feasible, then the subject will not be required to undergo the biopsy. Note: for subjects with CTCL, skin punch biopsies are required, as specified in Cohort-specific inclusion criterion 2g, unless agreed otherwise with Sponsor a. The Screening biopsy, if required, must be performed prior to the first dose of BI-1808 (on non-previously irradiated lesions only), and at least 4 weeks following 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":"- 7. Has a life expectancy of ≥12 weeks."}
• {"criterion_text":"- 8. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0–1."}
• {"criterion_text":"- 9. Has adequate organ function as confirmed by laboratory values."}

Exclusion criteria

• {"criterion_text":"- 1. Needs doses of prednisolone >10 mg daily (or equipotent doses of other corticosteroids) while on the trial other than as premedication(except for subjects with TCL). 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(except for subjects with TCL). Steroids are allowed as premedication in subjects with allergies to contrast scans."}
• {"criterion_text":"- 19. 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 are allowed. COVID 19 vaccines based on live replicating viral or bacterial vectors (eg, adenoviruses, adeno-associated viruses, vesicular stomatitis virus, vaccinia viruses, or measles virus) are not allowed."}
• {"criterion_text":"- 20. Has uncontrolled or significant cardiovascular disease as per protocol."}
• {"criterion_text":"- 2. 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 [note that the repeat imaging should be performed during study 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":"- 3. Has symptomatic ascites or pleural effusion, requires surgical intervention of additional medication."}
• {"criterion_text":"- 5. Has cardiac or renal amyloid light-chain amyloidosis."}
• {"criterion_text":"- 6. Has received the following: a. Chemotherapy or small molecule products within 4 weeks of first dose of BI 1808. b. Radiotherapy within 2 weeks of first dose of BI-1808. 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. c. Immunotherapy within 4 weeks prior to the first dose of BI-1808."}
• {"criterion_text":"- 7. Has not recovered from AEs to at least Grade 1 by NCI CTCAE (version 5.0) due to prior anticancer therapies. Exceptions to this 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":"- 8. Has had Grade ≥3 autoimmune manifestations of previous immune checkpoint inhibitor treatments (eg, anti-PD-1, anti-PD-L1, or anti-CTLA4).Exceptions are adverse events with short duration, managed and resolved with adequate medical intervention, or where the subject could be rechallenged with immune checkpoint inhibitor treatment without further events. Exceptions must be agreed between the Investigator and Sponsor."}
• {"criterion_text":"- 9. Has a history of (noninfectious) pneumonitis that required steroids or has current pneumonitis."}
• {"criterion_text":"- 10. Has an active, known, or suspected autoimmune disease. However, 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":"- 11. Is a female subject and has the ability to become pregnant (or already pregnant or lactating/breastfeeding). However, those female subjects who have a negative serum or urine pregnancy test up to 72 hours prior to their first dose of study treatment 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 their last dose of study treatment (BI-1808, pembrolizumab or paclitaxel), are considered eligible."}
• {"criterion_text":"- 4. Has known or suspected hypersensitivity to BI-1808 (all subjects) or pembrolizumab (subjects in Phase 1, Part B and Phase 2a, Part B and C, or paclitaxel (subjects in Phase 2a, Part C) or any of their excipients. Previous isolated infusion-related reactions are not to be considered a reason for exclusion unless Grade 4 in intensity."}
• {"criterion_text":"- 12. Is a male subject with partner(s) of childbearing potential (unless he agrees to use a barrier method of contraception [condom plus spermicide gel] with the female partner(s) who are using one highly effective method of contraception 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":"- 13. Has had major surgery from which the subject has not yet recovered."}
• {"criterion_text":"- 14. Is at high medical risk because of nonmalignant systemic disease including severe active infections on treatment with antibiotics, antifungals, or antivirals."}
• {"criterion_text":"- 15. Has presence of chronic graft versus host disease."}
• {"criterion_text":"- 16. Has had an allogenic tissue/solid organ transplant."}
• {"criterion_text":"- 17. Has known human immunodeficiency (HIV) and/or history of hepatitis B or C infections, or has a positive test for HIV antibody, hepatitis B antigen/hepatitis B virus DNA or hepatitis C antibody or RNA."}
• {"criterion_text":"- 18. Has a history of active tuberculosis (Bacillus tuberculosis)."}

Primary endpoints

• {"endpoint_text":"- Phase 1:Adverse events (AEs) and serious adverse events (SAEs) (graded according to National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] version 5.0) or newer when applicable, clinically significant laboratory parameters and physical findings and their causality to BI1808, or BI 1808 in combination with pembrolizumab. Occurrence of dose-limiting toxicities (DLTs) of BI-1808 and in combination with pembrolizumab.","definition_or_measurement_approach":"AEs and SAEs graded per NCI CTCAE v5.0 (or newer); clinical labs and physical findings assessed and causality attributed to study drugs; DLT occurrence assessed per protocol-defined DLT criteria."}
• {"endpoint_text":"- Phase 2a: AEs and SAEs (graded according to CTCAE version 5.0 or newer when applicable, clinically significant laboratory parameters and physical findings and their causality to BI1808, or BI 1808 in combination with pembrolizumab or pembrolizumab and paclitaxel.","definition_or_measurement_approach":"AEs and SAEs graded per NCI CTCAE v5.0 (or newer); clinical labs and physical findings assessed and causality attributed to BI-1808 alone or in combination with pembrolizumab/paclitaxel."}

Secondary endpoints

• {"endpoint_text":"- Standard PK parameters for BI-1808 (including, but not limited to approximations of area under the serum concentration-time curve [AUC], maximum concentration [Cmax], and terminal half life [t½]). Antidrug antibodies (ADA) response to BI 1808. TNFR2 receptor occupancy on CD14+ and/or CD16+ cells.","definition_or_measurement_approach":"PK: measurement of serum BI-1808 concentrations to derive AUC, Cmax, t½, etc.; ADA: immunogenicity assays to detect antidrug antibodies; TNFR2 receptor occupancy measured on CD14+/CD16+ cells per pharmacodynamic assays."}

Denmark

Earliest CTIS Part Ii Submission Date

19-03-2024

Latest Decision Or Authorization Date

16-03-2026

Processing Time Days

728

Number Of Sites

2

Number Of Participants

47

Hungary

Earliest CTIS Part Ii Submission Date

19-03-2024

Latest Decision Or Authorization Date

19-03-2026

Processing Time Days

731

Number Of Sites

2

Number Of Participants

37

Spain

Earliest CTIS Part Ii Submission Date

29-07-2025

Latest Decision Or Authorization Date

23-03-2026

Processing Time Days

237

Number Of Sites

4

Number Of Participants

20

Sweden

Earliest CTIS Part Ii Submission Date

19-03-2024

Latest Decision Or Authorization Date

16-03-2026

Processing Time Days

728

Number Of Sites

3

Number Of Participants

37

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

codes: 1,11,12,13,2,5,8,9

Name

Pharmaceutical Research Associates Group B.V.

Responsibilities

"Pharmacodynamics, pharmacokinetics, ADA, tumor analysis"

Third parties

• {"country":"Netherlands","full_name":"Pharmaceutical Research Associates Group B.V.","duties_or_roles":"\"Pharmacodynamics, pharmacokinetics, ADA, tumor analysis\"","organisation_type":"Pharmaceutical company"}
• {"country":"Denmark","full_name":"Klifo A/S","duties_or_roles":"codes: 14; 15 (value: QP release for IMPs)","organisation_type":"Pharmaceutical company"}
• {"country":"Netherlands","full_name":"SkylineDx B.V.","duties_or_roles":"Tumor tissue analysis (mRNA); code: 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Personalis Inc.","duties_or_roles":"ctDNA in blood and DNA in tumor; code: 4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"codes: 1,11,12,13,2,5,8,9 (multiple clinical trial management responsibilities)","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"University Of Southampton","duties_or_roles":"Receptor occupancy; code: 4","organisation_type":"Educational Institution"}
• {"country":"United Kingdom","full_name":"University Of Southampton","duties_or_roles":"Single cell sequencing; code: 15","organisation_type":"Educational Institution"}
• {"country":"Denmark","full_name":"Unilabs A/S","duties_or_roles":"Lab kits supply, shipment to 3rd party labs","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Denmark","full_name":"KLIFO A/S","duties_or_roles":"codes: 14; 15 (value: QP release for IMPs)","organisation_type":"Pharmaceutical company"}
• {"country":"Sweden","full_name":"BioInvent International AB","duties_or_roles":"RO (receptor occupancy); code: 4","organisation_type":"Pharmaceutical company"}
• {"country":"Israel","full_name":"Bioforum C.D.M.C Ltd.","duties_or_roles":"codes: 10; 6","organisation_type":"Pharmaceutical company"}