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
概览
- 阶段
- 1/2 期
- 状态
- 招募中
- 入组人数
- 231
- 试验地点
- 11
- 主要终点
- 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.
概览
简要总结
Phase 1: To assess the safety and tolerability profile of increasing doses of BI1808, 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. Phase 1: To identify dose-limiting toxicities (DLTs), determine the maximum tolerated dose (MTD) and select a signal- seeking Phase 2 dose 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. Phase 2a: To assess the safety and tolerability profile of BI-1808, as a single agent (Phase 2a, Part A), in combination with pembrolizumab (Phase 2a, Part B), and in combination with pembrolizumab and paclitaxel (Phase 2a, Part C), in subjects with advanced malignancies.
研究设计
- 分配方式
- Randomized
- 主要目的
- Phase 2a Part C
- 盲法
- None
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 是
入选标准
- •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 (not applicable for subjects with TCL).
- •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.
- •Has a life expectancy of ≥12 weeks.
- •Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0–
- •Has adequate organ function as confirmed by laboratory values.
排除标准
- •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.
- •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 symptomatic ascites or pleural effusion, requires surgical intervention of additional medication.
- •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
- •b. Radiotherapy within 2 weeks of first dose of BI-
- •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-
- •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.
结局指标
主要结局
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.
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.
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.
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.
次要结局
- 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.
研究者
Ingunn Munch Lindvig
Scientific
BioInvent International AB