Clinical Trials /

A Study to Assess AMG 701 Montherapy, or in Combination With Pomalidomide, With or Without, Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma

NCT03287908

Description:

The primary purpose of the phase 1 part of the study is to evaluate safety and tolerability of AMG 701 monotherapy to identify the RP2D for AMG 701 monotherapy followed by a dose-confirmation part to gather further safety data for AMG 701 monotherapy at the RP2D in adult subjects with relapsed/refractory multiple myeloma (RRMM). In addition, this study will include a sequential dose exploration part to identify the RP2D of AMG 701 in combination with pomalidomide, with and without dexamethasone (AMG 701-P+/-d). Phase 2 will consist of the dose-expansion part to gain further efficacy and safety experience with AMG 701 monotherapy in adult subjects with RRMM.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study to Assess AMG 701 Montherapy, or in Combination With Pomalidomide, With or Without, Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma
  • Official Title: A Phase 1/2 Open-label Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of AMG 701 Monotherapy, or in Combination With Pomalidomide, With and Without Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma (ParadigMM-1B)

Clinical Trial IDs

  • ORG STUDY ID: 20170122
  • SECONDARY ID: 2017-001997-41
  • NCT ID: NCT03287908

Conditions

  • Relapsed/Refractory Multiple Myeloma

Interventions

DrugSynonymsArms
AMG 701AMG 701
PomalidomideAMG 701 + Pomalidomide
DexamethasoneAMG 701 + Pomalidomide + Dexamethasone

Purpose

The primary purpose of the phase 1 part of the study is to evaluate safety and tolerability of AMG 701 monotherapy to identify the RP2D for AMG 701 monotherapy followed by a dose-confirmation part to gather further safety data for AMG 701 monotherapy at the RP2D in adult subjects with relapsed/refractory multiple myeloma (RRMM). In addition, this study will include a sequential dose exploration part to identify the RP2D of AMG 701 in combination with pomalidomide, with and without dexamethasone (AMG 701-P+/-d). Phase 2 will consist of the dose-expansion part to gain further efficacy and safety experience with AMG 701 monotherapy in adult subjects with RRMM.

Trial Arms

NameTypeDescriptionInterventions
AMG 701Experimental
  • AMG 701
AMG 701 + PomalidomideExperimental
  • AMG 701
  • Pomalidomide
AMG 701 + Pomalidomide + DexamethasoneExperimental
  • AMG 701
  • Pomalidomide
  • Dexamethasone

Eligibility Criteria

        Inclusion Criteria:

          -  Multiple myeloma meeting the following criteria:

               -  Pathologically-documented diagnosis of multiple myeloma that is relapsed or is
                  refractory as defined by the following:

                    -  Relapsed after > or = 3 lines of prior therapy that must include a
                       proteasome inhibitor (PI), an immunomodulatory drug (IMiD), and, where
                       approved and available, a CD38-directed cytolytic antibody in combination in
                       the same line or separate lines of treatment OR refractory to PI, IMiD, and
                       CD38- directed cytolytic antibody,

                    -  Subjects who could not tolerate a PI, IMiDs, or a CD38-directed cytolytic
                       antibody are eligible to enroll in the study.

               -  Measurable disease as per IMWG response criteria

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2

        Inclusion criteria specific to AMG 701-P±d include:

          -  Subjects must have received ≥ 2 lines of prior therapy that must include a proteasome
             inhibitor (PI), lenalidomide, and where approved and available a CD38-directed
             antibody. These therapies may be in the same line or separate lines of treatment.

          -  Subjects must have responded to at least 1 prior line with at least a PR.

          -  Subjects that have previously received pomalidomide must not have been removed from
             therapy due to toxicity attributable to pomalidomide and must be at least 6 months
             from their last dose of pomalidomide.

          -  Subjects must not have known intolerance to doses of dexamethasone up to 40 mg weekly
             (20 mg weekly if > 75 years).

        Exclusion Criteria:

          -  Known extramedullary relapse in the absence of any measurable medullary involvement

          -  Known central nervous system involvement by multiple myeloma

          -  Autologous stem cell transplantation less than 90 days prior to study day 1

          -  Recent history of primary plasma cell leukemia (within last 6 months prior to
             enrollment) or evidence of primary or secondary plasma cell leukemia at the time of
             screening

          -  Waldenstrom's macroglobulinemia

          -  Prior amyloidosis (subjects with multiple myeloma with asymptomatic deposition of
             amyloid plaques found on biopsy would be eligible if all other criteria are met)

          -  Treatment with systemic immune modulators including, but not limited to, nontopical
             systemic corticosteroids (unless the dose is ≤ 10 mg/day prednisone or equivalent),
             cyclosporine, and tacrolimus within 2 weeks before study day 1

          -  Last anticancer treatment (chemotherapy, IMiD, PI, molecular targeted therapy) < 2
             weeks prior to study day 1 or treatment with a therapeutic antibody less than 4 weeks
             prior to study day 1 as well as systemic radiation therapy within 28 days prior to
             study day 1 or focal radiotherapy within 14 days prior to study day 1.

          -  Prior treatment with any drug or construct that targets BCMA on tumor cells (eg, other
             bispecific antibody constructs, antibody drug conjugates, or CAR-T cells), other than
             Group C where prior treatment with GSK2857916 (belantamab mafodotin) is required.

        Exclusion criteria specific to AMG 701-P±d include:

          -  History of serious hypersensitivity associated with thalidomide, pomalidomide, or
             lenalidomide (> grade 3).

          -  Multiple myeloma with IgM subtype.

          -  POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and
             skin changes).

          -  Contraindication to pomalidomide or dexamethasone.

          -  Glucocorticoid therapy within 14 days prior to randomization that exceeds a cumulative
             dose of 160 mg of dexamethasone or equivalent dose of other corticosteroids.

          -  Treatment with systemic immune modulators including, but not limited to, non-topical
             systemic corticosteroids (unless the dose is ≤ 10 mg/day prednisone or equivalent),
             cyclosporine, and tacrolimus within 2 weeks before study day 1 or 4 weeks before study
             day 1 for Phase 1 dose-confirmation.

          -  Female subjects of childbearing potential with a positive pregnancy test assessed
             within 14 days prior to first dose of study drugs and/or a positive urine pregnancy
             test within 24 hours prior to first dose. In addition, females of childbearing
             potential unwilling to undergo pregnancy testing weekly during the first 4 weeks of
             pomalidomide use followed by pregnancy testing every 4 weeks in females with regular
             menses or every 2 weeks in females with irregular menstrual cycles.

          -  Male subjects with a female partner of childbearing potential and female subjects of
             childbearing potential who are unwilling to use 2 methods of contraception (1 of which
             must be highly effective during the study and for an additional 75 days (females) and
             135 days (males) after receiving the last dose of AMG 701, or 28 days after the last
             dose pomalidomide (males and females) or dexamethasone (females), whichever occurs
             later.

          -  Females who are lactating/breastfeeding or who plan to breastfeed while on study
             through 75 days after receiving the last dose of AMG 701, or 28 days after the last
             dose pomalidomide or dexamethasone, whichever occurs later.

          -  Females planning to become pregnant while on study through 75 days after receiving the
             last dose of AMG 701 or 28 days after the last dose pomalidomide or dexamethasone,
             whichever occurs later.

          -  Male subjects with a pregnant partner who are unwilling to practice abstinence or use
             a latex or synthetic condom (even if they have had a vasectomy with medical
             confirmation of surgical success) during treatment (including during dose
             interruptions) and for an additional 135 days after the last dose of AMG 701, or 28
             days after the last dose pomalidomide, whichever occurs later.

          -  Males who are unwilling to abstain from sperm donation while on study through 135 days
             after receiving the last dose of AMG 701 or 28 days after the last dose pomalidomide,
             whichever occurs later.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of subjects with dose-limiting toxicities (DLTs)
Time Frame:28 days
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Pharmacokinetic parameter of AMG 701: Maximum concentration (Cmax)
Time Frame:12 weeks
Safety Issue:
Description:
Measure:Pharmacokinetic parameter of AMG 701: Time of maximum concentration (Tmax)
Time Frame:12 weeks
Safety Issue:
Description:
Measure:Pharmacokinetic parameter of AMG 701: Area under the concentration-time curve (AUC)
Time Frame:12 weeks
Safety Issue:
Description:
Measure:Pharmacokinetic parameter of AMG 701: Steady state concentration (Css)
Time Frame:12 weeks
Safety Issue:
Description:
Measure:Anti-tumor activity: Overall response rate
Time Frame:48 months
Safety Issue:
Description:Efficacy parameter measured by International Myeloma Working Group (IMWG) response criteria. Best overall response of stringent CR (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR).
Measure:Anti-tumor activity: Best overall response of stringent complete response (sCR)
Time Frame:48 months
Safety Issue:
Description:Efficacy parameter measured by International Myeloma Working Group (IMWG) response criteria.
Measure:Anti-tumor activity: Best overall response of complete response (CR)
Time Frame:48 months
Safety Issue:
Description:Efficacy parameter measured by International Myeloma Working Group (IMWG) response criteria.
Measure:Anti-tumor activity: Best overall response of very good partial response (VGPR)
Time Frame:48 months
Safety Issue:
Description:Efficacy parameter measured by International Myeloma Working Group (IMWG) response criteria.
Measure:Anti-tumor activity: Best overall response of partial response (PR)
Time Frame:48 months
Safety Issue:
Description:Efficacy parameter measured by International Myeloma Working Group (IMWG) response criteria.
Measure:Anti-tumor activity: Duration of response
Time Frame:48 months
Safety Issue:
Description:Efficacy parameter measured by International Myeloma Working Group (IMWG) response criteria. Defined as time from the first PR or better to disease progression or death.
Measure:Anti-tumor activity: Time to response
Time Frame:48 months
Safety Issue:
Description:Efficacy parameter measured by International Myeloma Working Group (IMWG) response criteria.
Measure:Anti-tumor activity: Progression-free survival
Time Frame:48 months
Safety Issue:
Description:Efficacy parameter measured by International Myeloma Working Group (IMWG) response criteria. Defined as time from start of treatment until disease progression or death.
Measure:Anti-tumor activity: Overall survival
Time Frame:60 months
Safety Issue:
Description:Defined as time from start of treatment until death due to any cause.
Measure:Anti-tumor activity: Number of subjects with minimum residual disease negative complete response
Time Frame:48 months
Safety Issue:
Description:Efficacy parameter measured by International Myeloma Working Group (IMWG) response criteria.
Measure:Pharmacokinetic parameter of AMG 701: Trough concentration (Ctrough)
Time Frame:12 weeks
Safety Issue:
Description:

Details

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

Trial Keywords

  • Amgen
  • Phase 1
  • Phase 2
  • Phase 1/2
  • Clinical Trial
  • Oncology/Hematology
  • Relapsed/Refractory Multiple Myeloma
  • Immunotherapy

Last Updated

September 18, 2020