BI-1808 as a Single Agent and With Pembrolizumab (KEYTRUDA® ) in Treatment of Advanced Malignancies(Keynote-D20)
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorBioInvent International AB
About this trial
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),
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
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.
Trial design
Design model
Sequential
Treatments tested in this trial
BI-1808
DrugBI-1808 administered as a flat-dose IV infusion once every 3 weeks
Pembrolizumab (KEYTRUDA® ) 25 Mg/mL Solution for Injection
DrugPembrolizumab administered as a flat-dose IV infusion once every 3 weeks.
Paclitaxel 80 mg/m2 weekly
DrugPaclitaxel administered as a flat-dose IV infusion weekly.
Treatment groups
250 Participants
are divided into 5 treatment groupsGroup A: Phase I, Part A - Dose escalation and safety of BI-1808 as single agentExperimental treatment 1 intervention
Group B: Phase I, Part B - Dose escalation and Safety of BI-1808 in combination with pembrolizumabExperimental treatment 2 interventions
Group C: Phase 2a - Part A dose expansion of BI-1808 as a single agentExperimental treatment 1 intervention
Group D: Phase 2a, Part B - Dose expansion of BI-1808 in combination with pembrolizumabExperimental treatment 2 interventions
Group E: Phase 2a, Part C - Dose expansion of BI-1808 in combination with pembrolizumab and paclitaxelExperimental treatment 3 interventions
Trial outcomes
Primary outcomes
1
Occurrence of adverse events (AEs)
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.
Time frame
From the start of the study treatment for up to 2 years and 90 days.2
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)
Determine the hypothesized RP2D dose for BI-1808 Phase 2a according to mTPI-2 design
Time frame
Up to 104 weeks (2 years)3
Occurrence of serious adverse events (SAEs)
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
Time frame
Up to 104 weeks (2 years)4
To identify the recommended Phase 2 dose (RP2D) of BI-1808,
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.
Time frame
up to 104 weeks (2 years)Secondary outcomes
1
Evaluation of PK parameters for BI-1808. Maximum observed plasma concentration (Cmax)
Study the PK profile of BI-1808 according to a non-compartmental analysis using a validated software
Time frame
Up to 104 weeks (2 years)2
Evaluation of ADA response to BI-1808 in serum with validated method
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
Time frame
Up to 104 weeks (2 years)3
Measurement of TNFR2 receptor occupancy on CD14+ and/CD16+ cells in serum with validated method
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
Time frame
Up to 104 weeks (2 years)Sponsors and contacts
Click on the lead sponsor to view all of their trials.
BioInvent International AB
Lead sponsor
Merck Sharp & Dohme LLC
Collaborator
Source ClinicalTrials.gov