Phase 1, Parts A and Part B of the trial will recruit subjects with all types of malignancies whose tumors have progressed after standard anticancer treatment. Phase 2a, Parts A and Part B of the trial will recruit patients with NSCLC, OC, and CTCL (specifically MF or SS). MedDRA version: 21.1 Level: LLT Classification code 10065147 Term: Malignant solid tumor System Organ Class: 100000004864
Conditions
Sponsors
BioInvent International AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Is willing and able to provide written informed consent for the trial. 2. Is =18 years of age on the day of signing informed consent. 3. Has a histologically confirmed advanced malignancy. Subjects with CTCL [MF or SS] who satisfy the Phase 2a, Cohort 3-specific eligibility criteria may be enrolled into the Phase 1 part of the study. 4. Is intolerant of, refuses, or is not eligible for standard antineoplastic therapy. 5. Has at least 1 measurable disease lesion as defined by RECIST. 6. Is able to safely undergo a baseline tumor tissue biopsy prior to first dose of BI-1808 (on non previously irradiated lesions only). The biopsy must be performed at least 4 weeks following the last dose of tumor directed therapy. 7. Has a life expectancy of =12 weeks. 8. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0–1. 9. Has adequate organ function as confirmed by laboratory values. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 38 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 56
Exclusion criteria
Exclusion criteria: 1. 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. 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. 3. 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. 4. Has cardiac or renal amyloid light-chain amyloidosis. 5. 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. 6. 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. 7. Has had Grade =3 autoimmune manifestations of previous immune checkpoint inhibitor treatments (eg, anti-PD-1, anti-PD-L1, or anti-CTLA-4). 8. Has a history of (noninfectious) pneumonitis that required steroids or has current pneumonitis. 9. 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. 10. 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 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-1808, are considered eligible. 11. Is a male subject with partner(s) of childbearing potential (unless he agrees to take measures not to father children by using 1 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. 12. Has had major surgery from which the subject has not yet recovered. 13. Is at
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the safety and tolerability profile of increasing doses of BI-1808, as a single agent (Phase 1, Part A), and in combination with pembrolizumab (BI-1808 with pembrolizumab [Phase 1, Part B]) in subjects with advanced malignancies. To identify dose-limiting toxicities (DLTs), determine the maximum tolerated dose (MTD) and select a recommended Phase 2 dose (RP2D) of BI-1808, given via intravenous (IV) infusion, as a single agent (Phase 1, Part A), and in combination with pembrolizumab (Phase 1, Part B) in subjects with advanced malignancies.;Secondary Objective: To assess the pharmacokinetic (PK) profile of BI-1808 when administered every 3 weeks as a single agent (Phase 1, Part A), and in combination with pembrolizumab (Phase 1, Part B) in subjects with advanced malignancies. To assess the immunogenicity of BI-1808 in subjects with advanced malignancies. To evaluate the receptor occupancy of BI-1808 as a single agent and in combination with pembrolizumab on T-cells expressing TNFR2 in subjects with advanced malignancies.;Primary end point(s): 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), clinically significant laboratory parameters and physical findings and their causality to BI-1808, or BI 1808 in combination with pembrolizumab. Occurrence of dose-limiting toxicities (DLTs) of BI-1808 and in combination with pembrolizumab.;Timepoint(s) of evaluation of this end point: 1 year after start of treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Standard PK parameters for BI-1808 (including, but not limited to 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.;Timepoint(s) of evaluation of this end point: 1 year after start of treatment | — |
Countries
Denmark, Hungary, Russian Federation, Sweden
Contacts
Public ContactSusanne Gertsson
BioInvent International AB
Outcome results
None listed