NCT04219254招募中1 期
A Phase 1/2a Clinical Trial of BI-1206, a Monoclonal Antibody to CD32b (FcγRIIB), in Combination With Pembrolizumab in Subjects With Advanced Solid Tumors
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 197
- 试验地点
- 31
- 主要终点
- Documentation of AEs and SAEs, clinically significant laboratory parameters, and physical findings, as well as their causality to BI-1206 and/or pembrolizumab administration
研究概览
简要总结
Phase 1/2a Clinical Trial of BI-1206, a Monoclonal Antibody to CD32b (FcγRIIB), in Combination with Pembrolizumab in Subjects with Advanced Solid Tumors
详细描述
This is a Phase 1/2a, multicenter, dose-finding, consecutive-cohort, open-label trial of BI-1206 in combination with pembrolizumab in subjects with advanced solid tumors.
The trial will consist of 2 main parts:
Phase 1 with 2 different sets of cohorts assessing IV or SC dosing, with dose escalation of BI-1206 and selection of the RP2D of IV dosing (ivRP2D) and the RP2D of SC dosing (scRP2D).
Phase 2a with 2 parts: a signal seeking and a dose optimization part. In the signal seeking part, subjects with uveal melanoma and Non-Small Cellular Lung Cancer (NSCLC) will be treated with Pembrolizumab intravenously and BI-1206 at the scRP2D subcutaneously. In the dose optimization part, subjects with NSCLC will be randomized into one of 3 expansion arms and treated with pembrolizumab and BI-1206 at the scRP2D.
Subjects will initially receive 3 cycles of therapy with pembrolizumab in combination with BI-1206, either IV or SC.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
盲法说明
open label
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Is willing and able to provide written informed consent for the trial.
- •Is ≥18 years of age on day of signing informed consent.
- •Phase I only: Has a histologically confirmed advanced solid tumor. Subjects must have received at least 2 doses of an approved anti-PD-1/L1 mAb, and have documented progression on or within 12 weeks from the last dose of anti-PD-1/L1 mAb.
- •For patients with NSCLC (phase 2A SC cohorts):
- •Have a histologically confirmed diagnosis of advanced or metastatic NSCLC and not have an EGFR sensitizing (activating) mutation or an ALK translocation.
- •Have a PD-L1 positive (TPS≥50%) tumor as determined by IHC at a local laboratory.
- •Have not received prior systemic immunotherapy or chemotherapy treatment for their advanced/metastatic NSCLC.
- •Have 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.
- •For patients with uveal melanoma (phase 2A SC cohort): Have a histologically confirmed diagnosis of advanced or metastatic uveal melanoma
- •Have a PD-L1 positive (TPS≥1%) tumor as determined by IHC at a local laboratory.
- •Have 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.
- •Have 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.
- •Phase I only: Is intolerant of, refuses, or is not eligible for standard antineoplastic therapy.
- •Has at least 1 measurable disease lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST v1.1)
- •Phase IIa only: Is willing to provide an archival tumor tissue sample or newly obtained [core, incisional, OR excisional] biopsy of a tumor lesion not previously irradiated.
- •Is able to safely undergo a baseline tumor tissue biopsy prior to first dose of BI-
- •Has a life expectancy of ≥12 weeks.
- •Has an ECOG performance status of 0-
- •Has adequate organ function as confirmed by laboratory values listed in the main body of the protocol
- •Phase IIa only: 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 enrolment
- •Phase IIa only: Participants with history of HCV infection are eligible if HCV viral load is undetectable at Screening
- •Phase IIa only: Has adequate hematological and biochemical indices as listed in the main body of the protocol
排除标准
- •Needs doses of prednisolone >10 mg daily (or equipotent doses of other corticosteroids) while on the study, other than as premedication.
- •Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
- •Has known or suspected hypersensitivity to pembrolizumab or BI-1206 or any of their excipients.
- •Has cardiac or renal amyloid light-chain (AL) amyloidosis.
- •Has received radiotherapy within 2 weeks of the first dose of BI-
- •Has not recovered from AEs to at least Grade 1 by CTCAE v5.0 (or higher) due to prior anticancer therapies• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
- •Has an active, known or suspected autoimmune disease.
- •Is a female subject and has the ability to become pregnant (or already pregnant or lactating/breastfeeding)
- •Is a male subject with partner(s) of childbearing potential (unless he agrees to use a barrier method of contraception during the study and for 12 months after completing treatment)
- •Has had major surgery from which the subject has not yet recovered Is at high medical risk because of non-malignant 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 a known history of HIV infection
- •Has a history of active tuberculosis (Bacillus tuberculosis)
- •Has received a live vaccine within 30 days before the first dose of study treatment
- •Has uncontrolled or significant cardiovascular disease as listed in the main body of the protocol
- •Has a known psychiatric or substance abuse disorder that would interfere with the subject's ability to cooperate with the requirements of the study
- •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 treating Investigator.
- •Is participating or planning to participate in another interventional clinical study or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study drug
- •Has a known additional malignancy of another type, with the exception of adequately treated cone-biopsied carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) and basal or squamous cell carcinoma of the skin
- •Has a diagnosis of primary or acquired immunodeficiency disorder or has taken any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
- •Is unable to attend the study site to receive the study treatment
- •Additional exclusion criteria are described in the protocol.
研究组 & 干预措施
BI-1206 + Pembrolizumab 25mg/mL (MK-3475)
Experimental
BI-1206 administrated either IV or SC + Pembrolizumab 200mg administered IV every third week as a fixed dose will be used.
干预措施: BI1206 (Drug)
结局指标
主要结局
Documentation of AEs and SAEs, clinically significant laboratory parameters, and physical findings, as well as their causality to BI-1206 and/or pembrolizumab administration
时间窗: Up to 2 year
Assess the safety and tolerability profile of increasing doses of BI-1206, administered IV or SC, in combination with pembrolizumab in subjects with advanced solid tumors
DLT occurrence; determination of signal-seeking dose, the MTD or maximum administered dose of BI-1206 in Phase 1, based on the mTPI-2 design
时间窗: During the 42-day treatment period on induction therapy
In Phase 1, identify DLTs, determine the MTD, and select a signal-seeking Phase 2a dose of BI-1206 given via IV infusion or SC injection in combination with pembrolizumab (administered at the standard dose of 200 mg every 3 weeks) to subjects with advanced solid tumors who are experiencing disease progression and have been previously treated with anti-PD-1 or anti- PD-L1 antibodies
次要结局
- Measurement of CD32b receptor occupancy on B cells.(Up to 2 year)
- Determination of standard PK parameters (i.e., AUC, Cmax, Tmax, and terminal half-life [t½]) for BI-1206(Up to 2 year)
- Measurement of ADA response to BI-1206.(Up to 2 year)
研究者
研究点 (31)
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相关资讯
BioInvent Initiates Phase 2a Trial of BI-1206 Plus Pembrolizumab for Advanced NSCLC and Uveal Melanoma- BioInvent has launched a Phase 2a clinical trial evaluating BI-1206 in combination with pembrolizumab for first-line treatment of advanced or metastatic non-small cell lung cancer and uveal melanoma.
- The Phase 1 trial demonstrated promising clinical activity with one complete response, one partial response, and 11 patients achieving stable disease out of 36 evaluable heavily pre-treated patients.
- The Phase 2a study will enroll up to 30 NSCLC and 12 uveal melanoma patients across multiple international sites, with first data expected in the second half of 2026.
- BI-1206 targets FcγRIIB to overcome resistance mechanisms to anti-PD-1 therapy, potentially extending benefits to all pembrolizumab-approved indications.11 months agoBioInvent's BI-1206 Shows Promising Phase 1 Results in Combination with Pembrolizumab for Solid Tumors- BioInvent's Phase 1 study of BI-1206 combined with pembrolizumab demonstrated encouraging clinical activity in heavily pre-treated solid tumor patients, with one complete response and one partial response among 36 evaluable patients.
- The combination therapy was well-tolerated and showed potential to overcome resistance mechanisms to anti-PD-1 treatment by targeting FcγRIIB expressing immune cells.
- Based on these promising results, BioInvent plans to initiate Phase 2a expansion cohorts in H2 2025 for treatment-naïve patients with advanced NSCLC and uveal melanoma.
- The study supports transitioning from intravenous to subcutaneous formulation of BI-1206, which may enhance therapeutic impact and improve safety profiles.last year