A Study of BI-1206 in Combination With Pembrolizumab in Subjects With Advanced Solid Tumors (KEYNOTE-A04)
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|ClinicalTrials.gov Identifier: NCT04219254|
Recruitment Status : Recruiting
First Posted : January 7, 2020
Last Update Posted : October 5, 2020
|Condition or disease||Intervention/treatment||Phase|
|Solid Tumor, Adult||Drug: Pembrolizumab 25 MG/ML(MK-3475)||Phase 1 Phase 2|
This is a Phase 1/2a, multicenter, dose-finding, consecutive-cohort, open-label trial of BI-1206 in combination with pembrolizumab in subjects with advanced solid tumors who have previously received treatment with a PD-1/PD-L1 immune checkpoint inhibitor.
The trial will consist of 2 main parts: Phase 1 (with dose escalation cohorts and selection of the RP2D), and Phase 2a (with 3 expansion cohorts at the RP2D).
Subjects in each phase will initially receive 3 planned doses of therapy with BI-1206 in combination with pembrolizumab.
Subjects who show clinical benefit (CR, PR or SD) at the Week 9 Visit may continue on combination therapy. Starting at Week 10, these subjects will receive infusions every 3 weeks for up to 32 additional doses or up to 2 years from first dose of BI-1206 therapy or until progression.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||90 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||Phase 1/2a, dose escalation, consecutive-cohort, open-label study trial of BI-1206 in combination with pembrolizumab|
|Masking:||None (Open Label)|
|Masking Description:||open label|
|Official Title:||A Phase 1/2a Clinical Trial of BI-1206, a Monoclonal Antibody to CD32b (FcγRIIB), in Combination With Pembrolizumab in Subjects With Advanced Solid Tumors Previously Treated With Anti-PD-1 or Anti-PD-L1 Antibodies (KEYNOTE-A04)|
|Actual Study Start Date :||June 29, 2020|
|Estimated Primary Completion Date :||May 2024|
|Estimated Study Completion Date :||November 2024|
BI-1206 administrated IV with a starting dose of 1 mg/kg every third week using mTPI2 Design in escalation Phase I. RP2D to be used i Phase IIa.
Drug: Pembrolizumab 25 MG/ML(MK-3475)
Pembrolizumab 200mg administrated IV every third week as a fixed dose will be used in Phase I and IIa
- Documenting AEs and SAEs and determining causality in relation to BI-1206 and/or pembrolizumab [ Time Frame: Up to 2 year ]Assess the safety and tolerability profile of increasing doses of BI-1206 in combination with pembrolizumab, graded according to National Cancer Institute [NCI]-CTCAE version 4.0
- Determining the MTD of BI-1206 at the same dose level experiencing a BI-1206 or pembrolizumab-related or possibly related dose-limiting toxicity (DLT) [ Time Frame: During the 42-day treatment period on induction therapy ]Select the RP2D dose for BI-1206 using mTPI-2 design.
- Evaluation of PK parameters for BI-1206. Maximum observed plasma concentration (Cmax) [ Time Frame: Up to 2 year ]Study the PK profile of BI-1206 according to a non-compartmental analysis using a validated software
- Evaluation of PK parameters for BI-1206. Area under the plasma concentration-time curve (AUC) [ Time Frame: Up to 2 year ]Study the PK profile of BI-1206 according to a non-compartmental analysis using a validated software
- Evaluation of ADA response to BI 1206 [ Time Frame: Up to 2 year ]Assess the immunogenicity of BI-1206. Detection and characterization of antibodies to BI-1206 will be performed using a validated method and will be evaluated for BI-1206 serum concentration to enable interpretation of the antibody data.
- Measurement of CD32b receptor occupancy on B cells. [ Time Frame: Up to 2 year ]Evaluate the effect of BI-1206 administered in combination with pembrolizumab on CD32b receptor occupancy on B cells in subjects with advanced solid tumors.
- Assessment of best disease responses according to Immunological Response Evaluation Criteria in Solid Tumors (iRECIST). [ Time Frame: 8 weeks after first dose BI1206 and every 9 weeks for subjects who continue on therapy ]Initially assess possible anti-tumor activity of BI-1206 administered in combination with pembrolizumab 8 weeks after first dose of BI-1206 (i.e., the Week 9 Visit [including follow-up confirmation for progressive disease (PD)]) in subjects with advanced solid tumors. Anti-tumor activity will also be evaluated every 9 weeks for subjects whocontinue on therapy.
- Measurement of progression free survival. [ Time Frame: Up to 2 year ]Patients who complete a baseline and at least one post-treatment disease assessment will be evaluable.PFS will be measured from the date of administration of the first dose of BI-1206 to the first date of progression, date of death from any cause, or the last response assessment date, whichever comes first.
- Measurement of duration of objective response [ Time Frame: Up to 2 year ]Time-to-event estimates will be generated using the Kaplan-Meier method. In the context of this single arm study, these analyses will be only descriptive
- Measurement of objective response rate [ Time Frame: Up to 2 year ]ORR is defined as the percentage of subjects who achieved a response of CR or PR. ORR and the associated 2-sided 95% exact confidence limits will be provided
- Measurement of peripheral blood B-lymphocyte depletion. [ Time Frame: Up to 2 year ]Evaluate the effect of BI-1206 in combination with pembrolizumab measuring B Lymphocyutes CD19 in absolut value.
- Measurement of expression levels of immunological markers such as CD32b, PD-1 in tissue biopsies. [ Time Frame: Up to 2 year ]Study expression levels of immunological markers (e.g., CD32b, PD-1) in the tumor and study a potential correlation of levels of expression with clinical responses.
- Evaluate BI-1206 and pembrolizumab tumor penetrance in biopsies [ Time Frame: Up to 2 year ]Evaluate BI-1206 and pembrolizumab tumor penetrance in biopsies using immunohistochemistry
- Measurement of cytokine levels [ Time Frame: Up to 2 year ]Study the potential cause of infusion related reaction (IRR) by measure serum cytokine levels
- Measurement of serum cytokine levels and/or soluble CD32b. [ Time Frame: Up to 2 year ]• Study the potential cause of infusion related reaction (IRR), such as cytokine release and/or soluble CD32b
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04219254
|Contact: Susanne Gertsson||+46709 102 firstname.lastname@example.org|
|Contact: McAllister, PhDemail@example.com|
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