Phase 1/2a Open-label Clinical Trial of BI-1607, an Fc-Engineered Monoclonal Antibody to CD32b (FcγRIIB), in Combination with Trastuzumab in Subjects with HER2-positive Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 18
- 试验地点
- 6
- 主要终点
- Assessment of the safety and tolerability profile of BI-1607 in combination with trastuzumab
研究概览
简要总结
HER2+ breast and gastric cancer patients' survival is significantly improved by trastuzumab alone or in combination with chemotherapy. However, many patients remain uncured and develop resistance to trastuzumab resulting in relapse or progression of the disease. BI-1607, a human immunoglobulin G1 (IgG1) monoclonal antibody (mAb) targets CD32b (Fc Gamma Receptor IIB), it is intended to enhance the efficacy and overcome resistance to existing cancer treatments such as trastuzumab.
This is a Phase 1/2a, first-in-human, open-label, multicenter, dose-escalation, consecutive-cohort study of BI-1607 in combination with trastuzumab in subjects with HER2+ advanced solid tumors whose tumor has progressed after standard therapy.
详细描述
This is a Phase 1/2a, first-in-human, open-label, multicenter, dose-escalation, consecutive-cohort study of BI-1607 in combination with trastuzumab in subjects with HER2+ advanced solid tumors whose tumor has progressed after standard therapy.
The Phase 1 part of the trial is a dose escalation study of BI-1607 combined with trastuzumab in HER2+ advanced or metastatic solid tumors, the aim is to assess safety and tolerability and to determine the recommended phase II dose of BI-1607 in combination with trastuzumab.
The selected dose of BI-1607 will be studied in a subsequent Phase 2a part of the trial along with trastuzumab in 2 open-label, expansion cohorts of 15 evaluable subjects each. The first cohort will enroll subjects with locally advanced or metastatic HER2+ breast cancer, and the second will recruit subjects with HER2+ metastatic gastric or gastroesophageal junction adenocarcinoma. The aim of the phase 2a is to collect additional safety data to further support the recommended dose, and to detect early signs of clinical activity.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
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.
- •Has received standard of care or is intolerant to standard of care antineoplastic therapy. Subjects who are intolerant to trastuzumab cannot be enrolled in the study.
- •Has at least 1 measurable disease lesion as defined by RECIST v1.1 criteria.
- •Has a locally confirmed HER2+ tumor.
- •Must have progressive disease after the last line of treatment. In addition, subjects must have received the following previous lines of treatment:
- •Prior lines of treatment including trastuzumab and chemotherapy.
- •At least one prior line of treatment with an antibody-drug conjugate (ADC) (eg, trastuzumab-emtansine [TDM-1, or trastuzumab-deruxtecan]).
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.
- •Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
- •Has cardiac or renal amyloid light-chain amyloidosis.
- •Has had clinically significant lung disease requiring systemic corticosteroid treatment within the last 6 months of enrollment.
- •Has an active, known, or suspected autoimmune disease.
- •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 uncontrolled or significant cardiovascular disease.
- •Has a known additional malignancy of another type, except for adequately treated cone-biopsied carcinoma in situ (eg, breast carcinoma, cervical cancer in situ), adequately controlled superficial bladder cancer, and basal or squamous cell carcinoma of the skin.
- •Has a diagnosis of primary or acquired immunodeficiency disorder or is taking any other form of immunosuppressive therapy.
研究组 & 干预措施
Phase I -Dose escalation
Dose escalation study of BI-1607 combined with trastuzumab in HER2+ advanced or metastatic solid tumors.
干预措施: BI-1607 (Drug)
Phase I -Dose escalation
Dose escalation study of BI-1607 combined with trastuzumab in HER2+ advanced or metastatic solid tumors.
干预措施: Trastuzumab (Drug)
Phase 2a - Expansion cohorts
Dose expansion study of BI-1607 combined with trastuzumab in cohort 1: HER2 positive locally advanced or metastatic HER2+ breast cancer and cohort 2: metastatic gastric or gastroesophageal junction adenocarcinoma
干预措施: BI-1607 (Drug)
Phase 2a - Expansion cohorts
Dose expansion study of BI-1607 combined with trastuzumab in cohort 1: HER2 positive locally advanced or metastatic HER2+ breast cancer and cohort 2: metastatic gastric or gastroesophageal junction adenocarcinoma
干预措施: Trastuzumab (Drug)
结局指标
主要结局
Assessment of the safety and tolerability profile of BI-1607 in combination with trastuzumab
时间窗: End of treatment visit or 30 days after last dose of study drug.
Adverse events (AEs) and serious adverse events (SAEs) (graded according to the National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events \[CTCAE\] v5.0) and their causality in relation to BI-1607 or to the combination with trastuzumab
Identify Dose limiting toxicities, determine the maximum tolerate dose of BI-1607 and propose a recommended Phase 2 dose (RP2D) for evaluation of BI-1607 in combination with trastuzumab.
时间窗: 22 days
Occurrence of DLTs
次要结局
- Assessment of the pharmacokinetic (PK) profile of BI-1607 when administered every 3 weeks in combination with trastuzumab(90 days after the last dose of BI-1607)
- Assessment of the immunogenicity of BI-1607 when administered in combination with trastuzumab(90 days after the last dose of BI-1607)
- Assessment of the CD32b receptor occupancy (RO) of BI-1607 on B cells when administered in combination with trastuzumab(30 days after the last dose of BI-1607)
- Assessment of the possible antitumor activity of BI-1607 in combination with trastuzumab(1 year after the last treatment)