Phase 1/2a Open-Label, Dose-Escalation, Multicenter, First-in-Human, Consecutive-Cohort, Clinical Trial of BI-1808, a Monoclonal Antibody to Tumor Necrosis Factor Receptor 2 (TNFR2), as a Single Agent and in Combination with Pembrolizumab in Subjects with Advanced Malignancies
- Conditions
- Advanced solid tumorsMedDRA version: 21.1Level: LLTClassification code: 10065147Term: Malignant solid tumor Class: 10029104Therapeutic area: Diseases [C] - Neoplasms [C04]
- Registration Number
- CTIS2023-509847-29-00
- Lead Sponsor
- BioInvent International AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 193
Is willing and able to provide written informed consent for the trial., Is =18 years of age on the day of signing informed consent., 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., Has received standard of care or is intolerant of, refuses, or is not eligible for standard antineoplastic therapy., Has at least 1 measurable disease lesion as defined by RECIST v 1.1., 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. The Screening biopsy, if required, must be performed prior to the first dose of BI-1808 (on non previously irradiated lesions only) and ?t 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., Has a life expectancy of =12 weeks., Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0–1., Has adequate organ function as confirmed by laboratory values.
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., 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 or pembrolizumab), are considered eligible., 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., Has had major surgery from which the subject has not yet recovered., Is at high medical risk because of nonmalignant systemic disease including severe active infections on treatment with antibiotics, antifungals, or antivirals., Has presence of chronic graft versus host disease., Has had an allogenic tissue/solid organ transplant., 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., Has a history of active tuberculosis (Bacillus tuberculosis)., 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., Has uncontrolled or significant cardiovascular disease as per protocol., 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., Has known or suspected hypersensitivity to BI-1808 (all subjects) or pembrolizumab (subjects in Phase 1, Part B and Phase 2a, Part B) or any of their excipients. Previous isolated infusion-related reactions are not to be considered a reason for exclusion unless Grade 4 in intensity., Has cardiac or renal amyloid light-chain amyloidosis., 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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method