Clinical Trials /

Phase 1 Study Of PF-06863135, A BCMA- CD3 Bispecific Ab, As A Single Agent And In Combination With Either PF-06801591 Or Lenalidomide In Relapse/ Refractory Multiple Myeloma

NCT03269136

Description:

To assess the safety and tolerability at increasing dose levels of PF-06863135 in patients with relapse/ refractory multiple myeloma in order to determine the maximum tolerated dose and select the recommended Phase 2 dose.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Phase 1 Study Of PF-06863135, A BCMA- CD3 Bispecific Ab, As A Single Agent And In Combination With Either PF-06801591 Or Lenalidomide In Relapse/ Refractory Multiple Myeloma
  • Official Title: A PHASE I, OPEN LABEL STUDY TO EVALUATE THE SAFETY, PHARMACOKINETIC, PHARMACODYNAMIC AND CLINICAL ACTIVITY OF PF-06863135, A B-CELL MATURATION ANTIGEN (BCMA) - CD3 BISPECIFIC ANTIBODY, AS A SINGLE AGENT AND IN COMBINATION WITH EITHER PF-06801591 OR LENALIDOMIDE IN PATIENTS WITH RELAPSED/REFRACTORY ADVANCED MULTIPLE MYELOMA (MM)

Clinical Trial IDs

  • ORG STUDY ID: C1071001
  • NCT ID: NCT03269136

Conditions

  • Multiple Myeloma

Interventions

DrugSynonymsArms
PF-06863135 monotherapy IV or SCPF-06863135
PF-06863135 + PF-06801591PF-06863135 + PF-06801591
PF-06863135 + lenalidomidePF-06863135 + lenalidomide

Purpose

To assess the safety and tolerability at increasing dose levels of PF-06863135 in patients with relapse/ refractory multiple myeloma in order to determine the maximum tolerated dose and select the recommended Phase 2 dose.

Detailed Description

      Study C1071001 is a Phase 1, open label, multi dose, multi center, dose escalation, safety,
      pharmacokinetic (PK) and pharmacodynamic study of PF-06863135 in adult patients with advanced
      multiple myeloma who have relapsed from or are refractory to standard therapy. This two part
      study will assess the safety and tolerability of increasing dose levels of PF-06863135 in
      Part 1, and establish the recommended Phase 2 dose (RP2D) in Part 2.
    

Trial Arms

NameTypeDescriptionInterventions
PF-06863135ExperimentalBCMA-CD3 bispecific antibody
  • PF-06863135 monotherapy IV or SC
PF-06863135 + PF-06801591ExperimentalBCMA-CD3 bispecific antibody + anti-PD-1
  • PF-06863135 + PF-06801591
PF-06863135 + lenalidomideExperimentalBCMA-CD3 bispecific antibody + lenalidomide
  • PF-06863135 + lenalidomide

Eligibility Criteria

        Inclusion Criteria:

          -  Relapsed/refractory multiple myeloma

          -  Progressed or are intolerant of established therapies including proteasome inhibitor,
             immunomodulatory drug, and anti-CD38 antibody

          -  Performance Status of 0- 2 (unless due to bone pain)

          -  Adequate bone marrow, hematological, kidney and liver function

          -  Resolved acute effects of any prior therapy to baseline severity

          -  Not pregnant

        Exclusion Criteria:

          -  Recent history of other malignancies

          -  History of active autoimmune disorders

          -  Any form of primary immunodeficiency

          -  Active and clinically significant bacterial, fungal, or viral infection

          -  Evidence of active mucosal or internal bleeding

          -  History of severe immune-mediated adverse event with prior immunomodulatory treatment

          -  Major surgery within 4 weeks of study treatment start

          -  Radiation therapy within 2 weeks of study treatment start

          -  History of stem cell transplant (autologous or allogeneic) within 100 days prior to
             study enrollment

          -  Donor Lymphocyte Infusion (DLI) within 30 days prior to study entry

          -  Less than 30 days since last dose of antibody based therapies or less than 5
             half-lives since last dose of previous therapy

          -  Requirement for systemic immune suppressive medication

          -  Current requirement for chronic blood product support
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose Escalation: Number of participants with Dose-limiting toxicities (DLT)
Time Frame:21 or 28 days
Safety Issue:
Description:Number of participants with DLTs, which are typically Grade 3 or higher adverse events

Secondary Outcome Measures

Measure:To evaluate incidence of treatment emergent adverse events and laboratory abnormalities
Time Frame:From baseline until end of study treatment or study completion (approximately 2 years)
Safety Issue:
Description:Type, incidence, severity, timing, seriousness and relationship to study treatment of adverse events and any laboratory abnormalities
Measure:To evaluate anti-myeloma activity by objective response rate (ORR) in dose escalation
Time Frame:From baseline and every 3-4 weeks through disease progression or study completion (approximately 2 years)
Safety Issue:
Description:Percentage of participants that have a best response of partial response or better using IMWG criteria
Measure:To evaluate anti-myeloma activity by time to event endpoints
Time Frame:From baseline through time to event on study or study completion (approximately 2 years)
Safety Issue:
Description:Time from start date to date of first documentation of event (response or progression by IMWG criteria or death)
Measure:To evaluate anti-myeloma activity by duration of event endpoints
Time Frame:From start of event endpoint to end of event endpoint or study completion (approximately 2 years)
Safety Issue:
Description:Time from first assessment of event endpoint (response or stable disease) to last assessment of (response or stable disease) by IMWG criteria
Measure:Impact of treatment on systemic soluble immune factors
Time Frame:9 months on treatment
Safety Issue:
Description:Pre and post dose quantification of soluble cytokines in serum.
Measure:Maximum plasma concentration (Cmax) of PF-06863135
Time Frame:Cycle 1 Day 1 and Cycle 2 Day 1 (3 to 4 weeks)
Safety Issue:
Description:Peak concentration of PF-06863135 during first cycle
Measure:Trough serum concentrations of PF-06863135 and PF-06801591
Time Frame:From start of treatment until end of treatment or study completion (approximately 2 years)
Safety Issue:
Description:Trough serum concentrations of PF-06863135 and PF-06801591 at selected cycles
Measure:Area under the concentration versus time curve from time zero to the last quantifiable time point prior to the next dose (AUClast) of PF-06863135
Time Frame:From start of treatment until end of treatment or study completion (approximately 2 years)
Safety Issue:
Description:AUC of PF-06863135 will be calculated at selected cycles
Measure:Incidence and titers of anti-drug antibodies and neutralizing antibodies against PF-06863135 and PF-06801591 when combined with PF-06863135
Time Frame:From baseline and scheduled timepoints post dose through study completion (approximately 2 years)
Safety Issue:
Description:Number of participants with the presence of anti-PF-06863135 antibodies and PF-06801591 when combined with PF-06863135

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Pfizer

Trial Keywords

  • Multiple Myeloma
  • relapse/ refractory multiple myeloma
  • bispecific antibody
  • bispecific
  • BCMA
  • BCMA- CD3 bispecific
  • Phase 1
  • PF-06863135
  • PF-06801591
  • lenalidomide

Last Updated

June 19, 2020