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

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ClinicalTrials.gov Identifier: NCT03287908
Recruitment Status : Recruiting
First Posted : September 19, 2017
Last Update Posted : August 27, 2021
Sponsor:
Information provided by (Responsible Party):
Amgen

Tracking Information
First Submitted Date  ICMJE September 6, 2017
First Posted Date  ICMJE September 19, 2017
Last Update Posted Date August 27, 2021
Actual Study Start Date  ICMJE November 13, 2017
Estimated Primary Completion Date August 23, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 18, 2020)
  • Number of subjects with dose-limiting toxicities (DLTs) [ Time Frame: 28 days ]
  • Number of subjects with treatment emergent adverse events (TEAEs) [ Time Frame: 60 months ]
  • Number of subjects with treatment-related adverse events [ Time Frame: 60 months ]
  • Number of subjects with disease-related adverse events [ Time Frame: 60 months ]
  • Number of subjects with clinically-significant changes in vital signs [ Time Frame: 48 months ]
  • Number of subjects with clinically-significant changes in physical examination measurements [ Time Frame: 48 months ]
  • Number of subjects with clinically-significant changes in electrocardiogram (ECG) measurements [ Time Frame: 48 months ]
  • Number of subjects with clinically-significant changes in clinical laboratory tests [ Time Frame: 48 months ]
Original Primary Outcome Measures  ICMJE
 (submitted: September 15, 2017)
  • Subject incidence of adverse events as a Measure of Safety [ Time Frame: 48 months ]
  • Subject incidence of dose-limiting toxicities (DLTs) as a Measure of Safety [ Time Frame: 28 days ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 18, 2020)
  • Pharmacokinetic parameter of AMG 701: Maximum concentration (Cmax) [ Time Frame: 12 weeks ]
  • Pharmacokinetic parameter of AMG 701: Time of maximum concentration (Tmax) [ Time Frame: 12 weeks ]
  • Pharmacokinetic parameter of AMG 701: Area under the concentration-time curve (AUC) [ Time Frame: 12 weeks ]
  • Pharmacokinetic parameter of AMG 701: Steady state concentration (Css) [ Time Frame: 12 weeks ]
  • Anti-tumor activity: Overall response rate [ Time Frame: 48 months ]
    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).
  • Anti-tumor activity: Best overall response of stringent complete response (sCR) [ Time Frame: 48 months ]
    Efficacy parameter measured by International Myeloma Working Group (IMWG) response criteria.
  • Anti-tumor activity: Best overall response of complete response (CR) [ Time Frame: 48 months ]
    Efficacy parameter measured by International Myeloma Working Group (IMWG) response criteria.
  • Anti-tumor activity: Best overall response of very good partial response (VGPR) [ Time Frame: 48 months ]
    Efficacy parameter measured by International Myeloma Working Group (IMWG) response criteria.
  • Anti-tumor activity: Best overall response of partial response (PR) [ Time Frame: 48 months ]
    Efficacy parameter measured by International Myeloma Working Group (IMWG) response criteria.
  • Anti-tumor activity: Duration of response [ Time Frame: 48 months ]
    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.
  • Anti-tumor activity: Time to response [ Time Frame: 48 months ]
    Efficacy parameter measured by International Myeloma Working Group (IMWG) response criteria.
  • Anti-tumor activity: Progression-free survival [ Time Frame: 48 months ]
    Efficacy parameter measured by International Myeloma Working Group (IMWG) response criteria. Defined as time from start of treatment until disease progression or death.
  • Anti-tumor activity: Overall survival [ Time Frame: 60 months ]
    Defined as time from start of treatment until death due to any cause.
  • Anti-tumor activity: Number of subjects with minimum residual disease negative complete response [ Time Frame: 48 months ]
    Efficacy parameter measured by International Myeloma Working Group (IMWG) response criteria.
  • Pharmacokinetic parameter of AMG 701: Trough concentration (Ctrough) [ Time Frame: 12 weeks ]
Original Secondary Outcome Measures  ICMJE
 (submitted: September 15, 2017)
  • Anti-tumor activity [ Time Frame: 48 months ]
    Efficacy parameter measured by IMWG response criteria: stringent Complete Response (CR)
  • Anti-tumor activity [ Time Frame: 48 months ]
    Progression-free survival
  • Pharmacokinetic parameter of AMG 701 [ Time Frame: 12 weeks ]
    Maximum concentration (Cmax)
  • Pharmacokinetic parameter of AMG 701 [ Time Frame: 12 weeks ]
    Time of maximum concentration (Tmax)
  • Pharmacokinetic parameter of AMG 701 [ Time Frame: 12 weeks ]
    Area under the concentration-time curve (AUC)
  • Anti-tumor activity [ Time Frame: 48 months ]
    Efficacy parameter measured by IMWG response criteria: CR
  • Anti-tumor activity [ Time Frame: 48 months ]
    Efficacy parameter measured by IMWG response criteria: very good Partial Response (PR)
  • Anti-tumor activity [ Time Frame: 48 months ]
    Efficacy parameter measured by IMWG response criteria: PR
  • Anti-tumor activity [ Time Frame: 48 months ]
    Overall survival
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE 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)
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Relapsed/Refractory Multiple Myeloma
Intervention  ICMJE
  • Drug: AMG 701
    Subjects will receive IV infusions of AMG 701.
  • Drug: Pomalidomide
    Subjects will receive oral capsules of pomalidomide.
  • Drug: Dexamethasone
    Subjects will receive IV injections or oral dexamethasone.
Study Arms  ICMJE
  • Experimental: AMG 701
    Intervention: Drug: AMG 701
  • Experimental: AMG 701 + Pomalidomide
    Interventions:
    • Drug: AMG 701
    • Drug: Pomalidomide
  • Experimental: AMG 701 + Pomalidomide + Dexamethasone
    Interventions:
    • Drug: AMG 701
    • Drug: Pomalidomide
    • Drug: Dexamethasone
Publications * Cho SF, Lin L, Xing L, Li Y, Wen K, Yu T, Hsieh PA, Munshi N, Wahl J, Matthes K, Friedrich M, Arvedson T, Anderson KC, Tai YT. The immunomodulatory drugs lenalidomide and pomalidomide enhance the potency of AMG 701 in multiple myeloma preclinical models. Blood Adv. 2020 Sep 8;4(17):4195-4207. doi: 10.1182/bloodadvances.2020002524. Erratum in: Blood Adv. 2020 Nov 24;4(22):5772.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 27, 2021)
408
Original Estimated Enrollment  ICMJE
 (submitted: September 15, 2017)
115
Estimated Study Completion Date  ICMJE November 22, 2027
Estimated Primary Completion Date August 23, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 all approved and available therapies deemed eligible by the investigator, inclusing at a minimum of 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Amgen Call Center 866-572-6436 medinfo@amgen.com
Listed Location Countries  ICMJE Australia,   Canada,   Germany,   Japan,   Netherlands,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03287908
Other Study ID Numbers  ICMJE 20170122
2017-001997-41 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the link below.
URL: https://www.amgen.com/datasharing
Responsible Party Amgen
Study Sponsor  ICMJE Amgen
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: MD Amgen
PRS Account Amgen
Verification Date August 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP