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

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)

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.

Study Overview

• Status: Terminated
• Conditions: Relapsed/Refractory Multiple Myeloma
• Intervention / Treatment: Drug: AMG 701; Drug: Pomalidomide; Drug: Dexamethasone

• Study Type: Interventional
• Enrollment (Actual): 174
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Queensland
    • Woolloongabba, Queensland, Australia, 4102
      • Princess Alexandra Hospital
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • The Alfred Hospital
    • Melbourne, Victoria, Australia, 3000
      • Peter MacCallum Cancer Centre
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X6
      • University Health Network-Princess Margaret Cancer Centre
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • McGill University Health Centre Glen Site
• Germany
  • Heidelberg, Germany, 69120
    • Universitätsklinikum Heidelberg
  • Kiel, Germany, 24105
    • Universitatsklinikum Schleswig Holstein Campus Kiel
  • Würzburg, Germany, 97080
    • Universitaetsklinikum Wuerzburg
• Japan
  • Aichi-ken
    • Nagoya, Aichi-ken, Japan, 467-8602
      • Nagoya City University Hospital
  • Gunma
    • Maebashi, Gunma, Japan, 371-8511
      • Gunma University Hospital
  • Hyōgo
    • Kobe, Hyōgo, Japan, 650-0047
      • Kobe City Medical Center General Hospital
  • Ishikawa-ken
    • Kanazawa, Ishikawa-ken, Japan, 920-8641
      • Kanazawa University Hospital
  • Okayama-ken
    • Okayama, Okayama-ken, Japan, 701-1192
      • National Hospital Organization Okayama Medical Center
  • Tokyo
    • Koto-ku, Tokyo, Japan, 135-8550
      • The Cancer Institute Hospital of Japanese Foundation for Cancer Research
• Netherlands
  • Groningen, Netherlands, 9713 GZ
    • Universitair Medisch Centrum Groningen
  • Maastricht, Netherlands, 6229 HX
    • Maastricht Universitair Medisch Centrum
  • Utrecht, Netherlands, 3584 CX
    • Universitair Medisch Centrum Utrecht
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic - Arizona
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas for Medical Sciences Myeloma Institute Slot 816
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic Florida
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Winship Cancer Institute Emory U
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center - Multiple Myeloma Research Consortium
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
    • Hackensack, New Jersey, United States, 07601
      • ICAHN School of Medicine at Mount Sinai
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • New York, New York, United States, 10065
      • New York Presbyterian Hospital, Weill Cornell Medical College
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Levine Cancer Institute
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Health
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas MD Anderson Cancer Center
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • University of Utah Huntsman Cancer Institute
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • The Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AMG 701	Drug: AMG 701; Subjects will receive IV infusions of AMG 701.
Experimental: AMG 701 + Pomalidomide	Drug: AMG 701; Subjects will receive IV infusions of AMG 701.; Drug: Pomalidomide; Subjects will receive oral capsules of pomalidomide.
Experimental: AMG 701 + Pomalidomide + Dexamethasone	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of subjects with dose-limiting toxicities (DLTs)	28 days
Number of subjects with treatment emergent adverse events (TEAEs)	60 months
Number of subjects with treatment-related adverse events	60 months
Number of subjects with disease-related adverse events	60 months
Number of subjects with clinically-significant changes in vital signs	48 months
Number of subjects with clinically-significant changes in physical examination measurements	48 months
Number of subjects with clinically-significant changes in electrocardiogram (ECG) measurements	48 months
Number of subjects with clinically-significant changes in clinical laboratory tests	48 months

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Amgen
• Investigators: Study Director: MD, Amgen

Publications and helpful links

General 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.

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): November 13, 2017
• Primary Completion (Actual): June 30, 2023
• Study Completion (Actual): June 30, 2023

Study Registration Dates

• First Submitted: September 6, 2017
• First Submitted That Met QC Criteria: September 15, 2017
• First Posted (Actual): September 19, 2017

Study Record Updates

• Last Update Posted (Estimated): October 8, 2025
• Last Update Submitted That Met QC Criteria: October 7, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: Immunotherapy; Phase 1; Clinical Trial; Relapsed/Refractory Multiple Myeloma; Phase 2; Amgen; Phase 1/2; Oncology/Hematology
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms, Plasma Cell; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Hemic and Lymphatic Diseases; Neoplasms; Multiple Myeloma; Polycyclic Compounds; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated; Pregnadienetriols; Dexamethasone; pomalidomide
• Other Study ID Numbers: 20170122; 2017-001997-41 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
• IPD Sharing 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.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No