BI-1808 단일 제제 및 진행성 악성 종양 치료에 Pembrolizumab 병용(Keynote-D20)
1/2a상 오픈 라벨, 용량 증량, 다기관, FIH, 연속 코호트, 단일 제제로서 TNFR 2에 대한 단일 클론 항체인 BI-1808의 임상 시험 및 진행성 악성종양(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),
연구 개요
상태
상세 설명
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).
연구 유형
등록 (추정된)
단계
- 2 단계
- 1단계
연락처 및 위치
연구 연락처
- 이름: Susanne Gertsson
- 전화번호: +46462868550
- 이메일: susanne.gertsson@bioinvent.com
연구 연락처 백업
- 이름: Mona Welschof, PhD
- 전화번호: +47 97088721
- 이메일: mona.welschof@bioinvent.com
연구 장소
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Copenhagen, 덴마크
- 모병
- Rigshospitalet
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수석 연구원:
- Kristoffer Staal Rohrberg
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Herlev, 덴마크, 2730
- 모병
- Herlev Hospital
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수석 연구원:
- Rikke Løvendahl Eefsen
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Omsk, 러시아 제국, 644013
- 종료됨
- Byudzhetnoye Uchrezhdeniye Zdravookhraneniya Omskoy Oblasti - Klinicheskiy Onkologicheskiy Dispanser
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Saint Petersburg, 러시아 제국, 197022
- 빼는
- National Medical Research Center VA Almazov
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Saint Petersburg, 러시아 제국, 197758
- 빼는
- N.N. Petrov National Medical Research Center of Oncology
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California
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Duarte, California, 미국, 91010
- 모병
- City of Hope National Medical Center
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수석 연구원:
- Christiane Querfeld
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New York
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New York, New York, 미국, 10021
- 모병
- Memorial Sloan Kettering Cancer Center
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연락하다:
- Jasmine Zain
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Pennsylvania
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Philadelphia, Pennsylvania, 미국, 19104
- 모병
- University of Pennsylvania
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수석 연구원:
- Stefan Barta
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Gothenburg, 스웨덴, 41345
- 모병
- Sahlgrenska University Hospital
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수석 연구원:
- Edvard Abel
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Lund, 스웨덴, 223 70
- 모병
- Skanes University Hospital
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수석 연구원:
- Ana Carnerio
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Stockholm, 스웨덴, 17176
- 모병
- Karolinska University Hospital, Solna
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수석 연구원:
- Jeffrey Yachnin
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Barcelona, 스페인, 08907
- 아직 모집하지 않음
- Institut Catala d'oncologia. Hospital Duran I Reynals
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Madrid, 스페인, 28041
- 모병
- Hospital Universitario 12 de Octubre
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Madrid, 스페인, 28040
- 모병
- START Madrid - Hospital Universitario Fundación Jiménez Díaz
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Madrid, 스페인, 28007
- 아직 모집하지 않음
- Hospital Universitario Puerta de Hierro-Majadahonda, Madrid,
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Birmingham, 영국
- 모병
- University Hospital Birmingham
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연락하다:
- Julia Scarisbrick, Prof.
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Leicester, 영국, LE1 5WW
- 모병
- University Hospitals of Leicester NHS Trust
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수석 연구원:
- Harriet Walter
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London, 영국, W1G 6AD
- 모병
- Sarah Cannon Research Institute UK
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수석 연구원:
- Anja Williams
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London, 영국, SE1 9RT
- 모병
- Guy's and Saint Thomas' NHS Foundation Trust
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수석 연구원:
- Stephen Morris
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London, 영국
- 모병
- The Royal Marsden Hospital NHS Foundation Trust
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수석 연구원:
- Juanita Lopez
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Manchester, 영국, M20 4BX
- 모병
- The Christie NHS Foundation Trust
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수석 연구원:
- Richard Cowan
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Southampton, 영국, SO16 6YD
- 모병
- Southampton General Hospital
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수석 연구원:
- Sean Lim
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Budapest, 헝가리, 1134
- 모병
- Magyar Honvédség-Egészségügyi Központ
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수석 연구원:
- Zsuzsanna Pápai
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Budapest, 헝가리, 1077
- 모집하지 않고 적극적으로
- PRA Health Sciences - Hungary
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Debrecen, 헝가리, 4032
- 빼는
- Debreceni Egyetem Klinikai Központ
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참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
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.
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위화되지 않음
- 중재 모델: 순차적 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
|---|---|
|
실험적: Phase I, Part A - Dose escalation and safety of BI-1808 as single agent
Dose escalation of BI-1808 administrated a single agent |
BI-1808 administered as a flat-dose IV infusion once every 3 weeks |
|
실험적: Phase I, Part B - Dose escalation and Safety of BI-1808 in combination with pembrolizumab
Dose escalation of BI-1808 in combination with pembrolizumab. |
BI-1808 administered as a flat-dose IV infusion once every 3 weeks Pembrolizumab administered as a flat-dose IV infusion once every 3 weeks. |
|
실험적: 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 |
BI-1808 administered as a flat-dose IV infusion once every 3 weeks |
|
실험적: 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 |
BI-1808 administered as a flat-dose IV infusion once every 3 weeks Pembrolizumab administered as a flat-dose IV infusion once every 3 weeks. |
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실험적: 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. |
BI-1808 administered as a flat-dose IV infusion once every 3 weeks Pembrolizumab administered as a flat-dose IV infusion once every 3 weeks. Paclitaxel administered as a flat-dose IV infusion weekly. |
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Occurrence of adverse events (AEs)
기간: From the start of the study treatment for up to 2 years and 90 days.
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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.
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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)
기간: Up to 104 weeks (2 years)
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Determine the hypothesized RP2D dose for BI-1808 Phase 2a according to mTPI-2 design |
Up to 104 weeks (2 years)
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Occurrence of serious adverse events (SAEs)
기간: Up to 104 weeks (2 years)
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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)
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To identify the recommended Phase 2 dose (RP2D) of BI-1808,
기간: up to 104 weeks (2 years)
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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)
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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Evaluation of PK parameters for BI-1808. Maximum observed plasma concentration (Cmax)
기간: Up to 104 weeks (2 years)
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Study the PK profile of BI-1808 according to a non-compartmental analysis using a validated software |
Up to 104 weeks (2 years)
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Evaluation of ADA response to BI-1808 in serum with validated method
기간: Up to 104 weeks (2 years)
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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)
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Measurement of TNFR2 receptor occupancy on CD14+ and/CD16+ cells in serum with validated method
기간: Up to 104 weeks (2 years)
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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)
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공동 작업자 및 조사자
수사관
- 연구 책임자: Andres McAllister, PhD, BioInvent International AB
연구 기록 날짜
연구 주요 날짜
연구 시작 (실제)
기본 완료 (추정된)
연구 완료 (추정된)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (실제)
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
- 비뇨생식기 질환
- 생식기 질환
- 내분비계 질환
- 비뇨생식기 신생물
- 부위별 신생물
- 신생물
- 여성 비뇨 생식기 질환
- 여성 비뇨 생식기 질환 및 임신 합병증
- 면역계 질환
- 조직학적 유형에 따른 신생물
- 생식기 질환, 여성
- 내분비샘 신생물
- 난소 질환
- 부속기 질환
- 생식기 신생물, 여성
- 생식선 장애
- 피부병
- 림프계 질환
- 림프 증식 장애
- 면역증식성 장애
- 림프종, 비호지킨
- 신경외배엽 종양
- 신생물, 생식 세포 및 배아
- 신생물, 신경 조직
- 림프종
- 신경내분비종양
- 모반과 흑색종
- 피부 신생물
- 피부 및 결합 조직 질환
- 헴 및 림프병
- 난소 신생물
- 흑색종
- 림프종, T 세포
- 유기 화학 물질
- 제약 준비
- 치료학
- 의약품 경로
- 약물 요법
- 탄화수소
- 사이클로 파라핀
- 탄화수소, alicyclic
- 탄화수소, 순환
- 테르펜
- 박습니다
- 사이클로 데카네
- Diterpenes
- 파클리탁셀
- 주사
- 펨브 롤리 주맙
- 솔루션
기타 연구 ID 번호
- 19-BI-1808-01
- MK3475-D20 (기타 식별자: Merck Sharp & Dohme Corp)
- 2023-509847-29-00 (씨티스)
- 2023 (미국 NIH 보조금/계약)
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
미국 FDA 규제 기기 제품 연구
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