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BI-1808 单药联合派姆单抗治疗晚期恶性肿瘤(Keynote-D20)

2026年9月15日更新者：BioInvent International AB

1/2a 期开放标签、剂量递增、多中心、FIH、连续队列、BI-1808 的临床试验，一种针对 TNFR 2 的单克隆抗体作为单一药物并与 Pembrolizumab (MK-3475) 联合用于患有以下疾病的受试者晚期恶性肿瘤 (Keynote-D20)

The goal of this first in human clinical trial is to test BI-1808 administered as single agent and in combination with pembrolizumab in subjects with advanced malignancies whose disease has progressed after standard therapy.

The main questions it aims to answer are:

how safe and tolerable is BI-1808
what is maximum tolerated or administrated dose
to determine recommended dose for further clinical trials. Participants will receive infusions of with BI-1808 as a single agent, BI-1808 in combination with pembrolizumab and BI-1808 in combination with pembrolizumab and paclitaxel every 3 weeks.

For the purpose of this study, subjects with advanced malignancies includes subjects with advanced solid tumors and subjects with T-cell lymphoma (TCL),

研究概览

地位

招聘中

条件

干预/治疗

详细说明

This is a Phase 1/2a, dose-escalation, multicenter, first-in-human, consecutive-cohort, open-label study of BI-1808, as a single agent, in combination with pembrolizumab, and in BI-1808 in combination with pembrolizumab and paclitaxel in subjects with advanced malignancies, whose disease has progressed after standard therapy.

The study will consist of 2 phases: a Phase 1 with Parts A and B, and a Phase 2a with Parts A , B and C.

Phase 1 Part A consists of a dose escalation of BI-1808 as a single agent to evaluate safety and tolerability and to determine the RP2D as a single agent (sRP2D) in subjects with advanced malignancies whose disease has progressed after standard therapy.

Phase 1 Part B consists of a dose escalation of BI-1808 in combination with pembrolizumab to evaluate the safety and tolerability of the combination treatment and to allow selection of the RP2D for BI-1808 in combination with pembrolizumab (cRP2D) in subjects with advanced malignancies whose disease has progressed after standard therapy.

Phase 2a will assess BI-1808 administered as a single agent (Part A), in combination with pembrolizumab (Part B), and in combination with pembrolizumab and paclitaxel (Part C) at the respective hypothesized RP2D(s) determined in Phase 1. Phase 2a expansion will be conducted in indication specific signal seeking cohorts and indication specific Dose Optimization Cohorts) of subjects. The Phase 2a study aims to further evaluate the safety and tolerability of BI-1808 as monotherapy (Part A), in combination with pembrolizumab (Part B), and in combination with pembrolizumab and paclitaxel (Part C). Including characterization of the PK and PD profiles of BI-1808, evaluation of preliminary antitumor activity based on ORR, DoR, and progression-free survival (PFS) as assessed by RECIST v1.1 and iRECIST, and determination of the recommended Phase 2 dose (RP2D).

研究类型

介入性

注册 (估计的)

250

阶段

阶段2
阶段1

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习联系方式

姓名：Susanne Gertsson
电话号码：+46462868550
邮箱：susanne.gertsson@bioinvent.com

研究联系人备份

姓名：Mona Welschof, PhD
电话号码：+47 97088721
邮箱：mona.welschof@bioinvent.com

学习地点

丹麦
- - Copenhagen、丹麦
    - 招聘中
    - Rigshospitalet
    - 首席研究员：
      
      Kristoffer Staal Rohrberg
  - Herlev、丹麦、2730
    - 招聘中
    - Herlev Hospital
    - 首席研究员：
      
      Rikke Løvendahl Eefsen
俄罗斯
- - Omsk、俄罗斯、644013
    - 终止
    - Byudzhetnoye Uchrezhdeniye Zdravookhraneniya Omskoy Oblasti - Klinicheskiy Onkologicheskiy Dispanser
  - Saint Petersburg、俄罗斯、197022
    - 撤销
    - National Medical Research Center VA Almazov
  - Saint Petersburg、俄罗斯、197758
    - 撤销
    - N.N. Petrov National Medical Research Center of Oncology
匈牙利
- - Budapest、匈牙利、1134
    - 招聘中
    - Magyar Honvédség-Egészségügyi Központ
    - 首席研究员：
      
      Zsuzsanna Pápai
  - Budapest、匈牙利、1077
    - 主动，不招人
    - PRA Health Sciences - Hungary
  - Debrecen、匈牙利、4032
    - 撤销
    - Debreceni Egyetem Klinikai Központ
瑞典
- - Gothenburg、瑞典、41345
    - 招聘中
    - Sahlgrenska University Hospital
    - 首席研究员：
      
      Edvard Abel
  - Lund、瑞典、223 70
    - 招聘中
    - Skanes University Hospital
    - 首席研究员：
      
      Ana Carnerio
  - Stockholm、瑞典、17176
    - 招聘中
    - Karolinska University Hospital, Solna
    - 首席研究员：
      
      Jeffrey Yachnin
美国
- California
  - Duarte、California、美国、91010
    - 招聘中
    - City of Hope National Medical Center
    - 首席研究员：
      
      Christiane Querfeld
- New York
  - New York、New York、美国、10021
    - 招聘中
    - Memorial Sloan Kettering Cancer Center
    - 接触：
      
      Jasmine Zain
- Pennsylvania
  - Philadelphia、Pennsylvania、美国、19104
    - 招聘中
    - University of Pennsylvania
    - 首席研究员：
      
      Stefan Barta
英国
- - Birmingham、英国
    - 招聘中
    - University Hospital Birmingham
    - 接触：
      
      Julia Scarisbrick, Prof.
  - Leicester、英国、LE1 5WW
    - 招聘中
    - University Hospitals of Leicester NHS Trust
    - 首席研究员：
      
      Harriet Walter
  - London、英国、W1G 6AD
    - 招聘中
    - Sarah Cannon Research Institute UK
    - 首席研究员：
      
      Anja Williams
  - London、英国、SE1 9RT
    - 招聘中
    - Guy's and Saint Thomas' NHS Foundation Trust
    - 首席研究员：
      
      Stephen Morris
  - London、英国
    - 招聘中
    - The Royal Marsden Hospital NHS Foundation Trust
    - 首席研究员：
      
      Juanita Lopez
  - Manchester、英国、M20 4BX
    - 招聘中
    - The Christie NHS Foundation Trust
    - 首席研究员：
      
      Richard Cowan
  - Southampton、英国、SO16 6YD
    - 招聘中
    - Southampton General Hospital
    - 首席研究员：
      
      Sean Lim
西班牙
- - Barcelona、西班牙、08907
    - 尚未招聘
    - Institut Catala d'oncologia. Hospital Duran I Reynals
  - Madrid、西班牙、28041
    - 招聘中
    - Hospital Universitario 12 de Octubre
  - Madrid、西班牙、28040
    - 招聘中
    - START Madrid - Hospital Universitario Fundación Jiménez Díaz
  - Madrid、西班牙、28007
    - 尚未招聘
    - Hospital Universitario Puerta de Hierro-Majadahonda, Madrid,

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

18年及以上 (成人、年长者)

接受健康志愿者

不

有资格学习的性别

全部

描述

Inclusion Criteria:

Able and willing to provide written informed consent.
Aged 18 years or older.
Histologically confirmed advanced or metastatic malignancy eligible for an enrolling study cohort.
Disease progression following, intolerance of, ineligibility for, or refusal of applicable standard therapy.
At least one measurable lesion according to the response criteria specified in the protocol.
Eastern Cooperative Oncology Group performance status of 0 or 1.
Life expectancy of at least 12 weeks.
Adequate organ function.
Willing and medically suitable to provide required tumor or skin biopsies.
Meets the disease-specific and treatment-history requirements of the applicable Phase 2a cohort.
For Phase 2a Part C: Histologically confirmed platinum-resistant high-grade serous or clear-cell ovarian carcinoma, prior platinum-based treatment as specified in the protocol, and suitability for paclitaxel treatment.

Exclusion Criteria:

1. Active central nervous system metastases or carcinomatous meningitis.

Active or clinically significant autoimmune disease, immunodeficiency, or use of prohibited immunosuppressive treatment.
Prior treatment-related toxicity not recovered to the level specified in the protocol.
Prior anticancer therapy, radiotherapy, immunotherapy, investigational treatment, or live vaccine within the protocol-defined washout period.
History of clinically significant immune-mediated toxicity, including pneumonitis, associated with previous immune-checkpoint inhibitor treatment.
Uncontrolled or clinically significant cardiovascular disease, serious infection, or another condition that could compromise safety or study participation.
Major surgery without adequate recovery.
Prior allogeneic tissue or solid-organ transplantation or active graft-versus-host disease.
Pregnancy or breastfeeding, or unwillingness to comply with protocol-defined contraceptive requirements.
Known hypersensitivity to a study treatment or its components.
Another active malignancy, except for protocol-defined permitted malignancies.
Participation in another interventional clinical trial that conflicts with this study.
Unable or unlikely to comply with study procedures and requirements.
For Phase 2a Part C: Receipt of prohibited colony-stimulating factors within the protocol-defined period before treatment.

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

主要用途：治疗
分配：非随机化
介入模型：顺序分配
屏蔽：无（打开标签）

手臂数量

武器和干预

参与者组/臂	干预/治疗
实验性的：Phase I, Part A - Dose escalation and safety of BI-1808 as single agent Dose escalation of BI-1808 administrated a single agent	药品：BI-1808 BI-1808 administered as a flat-dose IV infusion once every 3 weeks
实验性的：Phase I, Part B - Dose escalation and Safety of BI-1808 in combination with pembrolizumab Dose escalation of BI-1808 in combination with pembrolizumab.	药品：BI-1808 BI-1808 administered as a flat-dose IV infusion once every 3 weeks 药品：Pembrolizumab (KEYTRUDA® ) 25 Mg/mL Solution for Injection Pembrolizumab administered as a flat-dose IV infusion once every 3 weeks.
实验性的：Phase 2a - Part A dose expansion of BI-1808 as a single agent BI-1808 administered as a single agent at the hypothesized recommended phase 2 dose determined in Phase 1	药品：BI-1808 BI-1808 administered as a flat-dose IV infusion once every 3 weeks
实验性的：Phase 2a, Part B - Dose expansion of BI-1808 in combination with pembrolizumab BI-1808 administered in combination with pembrolizumab at the respective hypothesized recommended phase 2 doses determined in Phase 1	药品：BI-1808 BI-1808 administered as a flat-dose IV infusion once every 3 weeks 药品：Pembrolizumab (KEYTRUDA® ) 25 Mg/mL Solution for Injection Pembrolizumab administered as a flat-dose IV infusion once every 3 weeks.
实验性的：Phase 2a, Part C - Dose expansion of BI-1808 in combination with pembrolizumab and paclitaxel BI-1808 administered in combination with pembrolizumab and paclitaxel at the respective hypothesized recommended phase 2 doses determined in Phase 1.	药品：BI-1808 BI-1808 administered as a flat-dose IV infusion once every 3 weeks 药品：Pembrolizumab (KEYTRUDA® ) 25 Mg/mL Solution for Injection Pembrolizumab administered as a flat-dose IV infusion once every 3 weeks. 药品：Paclitaxel 80 mg/m2 weekly Paclitaxel administered as a flat-dose IV infusion weekly.

研究衡量的是什么？

主要结果指标

结果测量	措施说明	大体时间
Occurrence of adverse events (AEs) 大体时间：From the start of the study treatment for up to 2 years and 90 days.	AEs will be assessed by the investigators by severity and will be graded according to the NCI CTCAE v5.0 or higher and causality between AEs and the exposure to the study treatment.	From the start of the study treatment for up to 2 years and 90 days.
Identify DLTs, determine the maximum tolerated dose 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) 大体时间：Up to 104 weeks (2 years)	Determine the hypothesized RP2D dose for BI-1808 Phase 2a according to mTPI-2 design	Up to 104 weeks (2 years)
Occurrence of serious adverse events (SAEs) 大体时间：Up to 104 weeks (2 years)	SAEs will be assessed by the investigators by severity and will be graded according to the NCI CTCAE v5.0 or higher and causality between SAEs and the exposure to the study treatment	Up to 104 weeks (2 years)
To identify the recommended Phase 2 dose (RP2D) of BI-1808, 大体时间：up to 104 weeks (2 years)	Select the RP2D dose for BI-1808 derived from the totality of PK, PD, clinical response, safety,and tolerability observed in signal seeking and dose optimization cohorts.	up to 104 weeks (2 years)

次要结果测量

结果测量	措施说明	大体时间
Evaluation of PK parameters for BI-1808. Maximum observed plasma concentration (Cmax) 大体时间：Up to 104 weeks (2 years)	Study the PK profile of BI-1808 according to a non-compartmental analysis using a validated software	Up to 104 weeks (2 years)
Evaluation of ADA response to BI-1808 in serum with validated method 大体时间：Up to 104 weeks (2 years)	The detection and characterization of antibodies to BI-1808 will be performed using a validated method and will be evaluated for BI-1808 serum concentration to enable interpretation of the antibody data	Up to 104 weeks (2 years)
Measurement of TNFR2 receptor occupancy on CD14+ and/CD16+ cells in serum with validated method 大体时间：Up to 104 weeks (2 years)	evaluate the receptor occupancy of BI-1808 as a single agent and in combination with pembrolizumab or pembrolizumab and paclitaxel on T-cells expressing TNFR2 in absolute value	Up to 104 weeks (2 years)

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

BioInvent International AB

合作者

Merck Sharp & Dohme LLC

调查人员

研究主任：Andres McAllister, PhD、BioInvent International AB

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (实际的)

2021年1月25日

初级完成 (估计的)

2028年1月31日

研究完成 (估计的)

2028年12月31日

研究注册日期

首次提交

2020年12月15日

首先提交符合 QC 标准的

2021年2月11日

首次发布 (实际的)

2021年2月12日

研究记录更新

最后更新发布 (实际的)

2026年9月18日

上次提交的符合 QC 标准的更新

2026年9月15日

最后验证

2026年9月1日

BI-1808 单药联合派姆单抗治疗晚期恶性肿瘤(Keynote-D20)

1/2a 期开放标签、剂量递增、多中心、FIH、连续队列、BI-1808 的临床试验，一种针对 TNFR 2 的单克隆抗体作为单一药物并与 Pembrolizumab (MK-3475) 联合用于患有以下疾病的受试者晚期恶性肿瘤 (Keynote-D20)

研究概览

地位

条件

干预/治疗

详细说明

研究类型

注册 (估计的)

阶段

联系人和位置

学习联系方式

研究联系人备份

学习地点

参与标准

资格标准

适合学习的年龄

接受健康志愿者

有资格学习的性别

描述

学习计划

研究是如何设计的？

设计细节

手臂数量

武器和干预

参与者组/臂

干预/治疗

研究衡量的是什么？

主要结果指标

结果测量

措施说明

大体时间

次要结果测量

结果测量

措施说明

大体时间

合作者和调查者

赞助

合作者

调查人员

研究记录日期

研究主要日期

学习开始 (实际的)

初级完成 (估计的)

研究完成 (估计的)

研究注册日期

首次提交

首先提交符合 QC 标准的

首次发布 (实际的)

研究记录更新

最后更新发布 (实际的)

上次提交的符合 QC 标准的更新

最后验证

更多信息

与本研究相关的术语

关键字

其他相关的 MeSH 术语

其他研究编号

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)？

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