Clinical Trials /

A Study of BI-1206 in Combination With Pembrolizumab in Subjects With Advanced Solid Tumors

NCT04219254

Description:

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

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Not yet recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of BI-1206 in Combination With Pembrolizumab in Subjects With Advanced Solid Tumors
  • 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

Clinical Trial IDs

  • ORG STUDY ID: 18-BI-1206-03
  • NCT ID: NCT04219254

Conditions

  • Solid Tumor, Adult

Interventions

DrugSynonymsArms
BI-1206pembrolizumabBI-1206

Purpose

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

Detailed Description

      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.
    

Trial Arms

NameTypeDescriptionInterventions
BI-1206ExperimentalBI-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.
  • BI-1206

Eligibility Criteria

        Inclusion Criteria:

          -  Is willing and able to provide written informed consent for the trial.

          -  Is ≥18 years of age on day of signing informed consent.

          -  Has a histologically confirmed advanced solid tumor. Subjects must have received at
             least 2 doses of an approved anti-PD-1/L1 mAb, and have documented progression on or
             within 12 weeks from the last dose of anti-PD-1/L1 mAb.

          -  Is intolerant of, refuses, or is not eligible for standard antineoplastic therapy.

          -  Has at least 1 measurable disease lesion as defined by Response Evaluation Criteria in
             Solid Tumors

          -  Is able to safely undergo a baseline tumor tissue biopsy prior to first dose of
             BI-1206

          -  Has a life expectancy of ≥12 weeks.

          -  Has an ECOG performance status of 0-1.

          -  Has adequate organ function as confirmed by laboratory values listed in the main body
             of the protocol

        Expansion Cohort-Specific Inclusion Criteria:

        In addition to the general inclusion criteria above, subjects must also meet the criteria
        for the specific cohort.

          -  Cohort 1 (Non-small cell lung cancer):

               -  For subjects whose tumor has PD-L1 ≥ 50%: Required prior therapies will include
                  anti-PD-1 therapy as monotherapy. Prior standard of care chemotherapy will be
                  allowed but not required.

               -  For tumors with unknown PD-L1 or PD-L1 < 50% , required prior therapies will
                  include anti-PD 1/PD-L1 therapy and SOC chemotherapy either combined with anti
                  PD-1/PD-L1 therapy or given separately.

               -  For subjects with known anaplastic lymphoma kinase, ROS1 or epidermal growth
                  factor receptor sensitizing molecular rearrangements, one line of targeted
                  therapy will be required in addition to anti-PD-1/PD-L1 therapy.

          -  Cohort 2 (Metastatic Melanoma):

               -  Required prior therapies will include anti-PD-1 therapy either as monotherapy or
                  as part of a combination regimen.

               -  For subjects with a known BRAF V600-activating mutation combination targeted
                  therapy will be required in addition to anti-PD-1/PD-L1 therapy.

          -  Cohort 3 (Other Tumor Types):

               -  All subjects will require prior anti-PD-1/PD-L1 therapy

        Exclusion Criteria:

          -  Needs doses of prednisolone >10 mg daily (or equipotent doses of other
             corticosteroids)

          -  Has known active central nervous system (CNS) metastases and/or carcinomatous
             meningitis.

          -  Has known or suspected hypersensitivity to pembrolizumab or BI-1206 or any of their
             excipients.

          -  Has cardiac or renal amyloid light-chain (AL) amyloidosis.

          -  Has received the following:

               -  Chemotherapy or small molecule products within 4 weeks of first dose of BI 1206.

               -  Radiotherapy within 2 weeks of first dose of BI-1206. A 1-week washout is
                  permitted for palliative radiation (≤2 weeks of radiotherapy) for non-CNS
                  disease. Subjects who have previously had radiation pneumonitis are not allowed.

               -  Immunotherapy within 4 weeks prior to the first dose of BI-1206.

          -  Has not recovered from AEs to at least Grade 1 by Common Terminology Criteria for
             Adverse Events v4.0 due to prior anti-cancer therapies.

          -  Has had Grade ≥3 autoimmune manifestations of previous immune checkpoint inhibitor
             treatments .

          -  Has a history of (non-infectious) pneumonitis that required steroids or has current
             pneumonitis.

          -  Has an active, known or suspected autoimmune disease.

          -  Is a female subject and has the ability to become pregnant (or already pregnant or
             lactating/ breastfeeding). o Intravaginal

          -  Is a male subject with partner(s) of child-bearing potential• Has had major surgery
             from which the subject has not yet recovered.

          -  Is at high medical risk because of non-malignant systemic disease including severe
             active infections on treatment with antibiotics, antifungals or antivirals.

          -  Has presence of chronic graft versus host disease.

          -  Has had an allogenic tissue/solid organ transplant.

          -  Has known human immunodeficiency virus (HIV) and / or history of hepatitis B or C
             infections, or has a positive test for HIV antibody, hepatitis B antigen / hepatitis B
             virus DNA or hepatitis C antibody or RNA.

          -  Has a history of active tuberculosis (bacillus tuberculosis).

          -  Has received a live vaccine within 30 days before the first dose of study treatment.

          -  Has uncontrolled or significant cardiovascular disease

          -  Has a known psychiatric or substance abuse disorder that would interfere with the
             subject's ability to cooperate with the requirements of the study.

          -  Has a history or current evidence of any condition, therapy, or laboratory abnormality
             that might confound the results of the study, interfere with the subject's
             participation for the full duration of the study, or is not in the best interest of
             the subject to participate, in the opinion of the treating investigator.

          -  Is participating or planning to participate in another interventional clinical trial,
             or has participated in a trial of an investigational agent or has used an
             investigational device within 4 weeks prior to first dose of study drug. Subjects who
             have entered the follow-up phase of an investigational study may participate as long
             as it has been 4 weeks after the last dose of the previous investigational agent.
             Participation in an observational trial is acceptable.

          -  Has a known additional malignancy of another type

          -  Has a diagnosis of primary or acquired immunodeficiency disorder or taking any other
             form of immunosuppressive therapy within 7 days prior the first dose of study drug.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Documenting AEs and SAEs and determining causality in relation to BI-1206 and/or pembrolizumab
Time Frame:Up to 2 year
Safety Issue:
Description: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

Secondary Outcome Measures

Measure:Evaluation of PK parameters for BI-1206. Maximum observed plasma concentration (Cmax)
Time Frame:Up to 2 year
Safety Issue:
Description:Study the PK profile of BI-1206 according to a non-compartmental analysis using a validated software
Measure:Evaluation of PK parameters for BI-1206. Area under the plasma concentration-time curve (AUC)
Time Frame:Up to 2 year
Safety Issue:
Description:Study the PK profile of BI-1206 according to a non-compartmental analysis using a validated software
Measure:Evaluation of ADA response to BI 1206
Time Frame:Up to 2 year
Safety Issue:
Description: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.
Measure:Measurement of CD32b receptor occupancy on B cells.
Time Frame:Up to 2 year
Safety Issue:
Description:Evaluate the effect of BI-1206 administered in combination with pembrolizumab on CD32b receptor occupancy on B cells in subjects with advanced solid tumors.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:BioInvent International AB

Last Updated

January 3, 2020