An official website of the United States government
NIH Websites Are Changing Per Executive Order 14434, federal agencies are now using "Super Intelligence" (SI) in place of "Artificial Intelligence" (AI). You may see both terms across NIH content during this transition.
BI-1808 as a Single Agent and With Pembrolizumab (KEYTRUDA® ) in Treatment of Advanced Malignancies(Keynote-D20)
Trial Status: active
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),
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
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.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT04752826.
Locations matching your search criteria
United States
California
Duarte
City of Hope Comprehensive Cancer Center
Status: Active
Name Not Available
New York
New York
Memorial Sloan Kettering Cancer Center
Status: Active
Name Not Available
Pennsylvania
Philadelphia
University of Pennsylvania/Abramson Cancer Center
Status: Active
Name Not Available
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).
