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 | Terminated Phase 1 FDA Drug

• 2 other identifiers: 201701222017-001997-41
• Study Type: interventional
• Target: 174
• Locations: 6 countries
• Sites: 34

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.

Conditions

Relapsed/Refractory Multiple Myeloma

Keywords

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

Outcome Measures

Primary Outcomes (8)

• 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 Outcomes (15)

• 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

  48 months

Study Arms (3)

AMG 701

EXPERIMENTAL

Drug: AMG 701

AMG 701 + Pomalidomide

EXPERIMENTAL

Drug: AMG 701; Drug: Pomalidomide

AMG 701 + Pomalidomide + Dexamethasone

EXPERIMENTAL

Drug: AMG 701; Drug: Pomalidomide; Drug: Dexamethasone

Interventions

AMG 701 DRUG

Subjects will receive IV infusions of AMG 701.

AMG 701; AMG 701 + Pomalidomide; AMG 701 + Pomalidomide + Dexamethasone

Pomalidomide DRUG

Subjects will receive oral capsules of pomalidomide.

AMG 701 + Pomalidomide; AMG 701 + Pomalidomide + Dexamethasone

Dexamethasone DRUG

Subjects will receive IV injections or oral dexamethasone.

AMG 701 + Pomalidomide + Dexamethasone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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).

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Amgen: lead

Study Sites (34)

Mayo Clinic - Arizona

Scottsdale, Arizona, 85259, United States

Location

University of Arkansas for Medical Sciences Myeloma Institute Slot 816

Little Rock, Arkansas, 72205, United States

Location

Mayo Clinic Florida

Jacksonville, Florida, 32224, United States

Location

Winship Cancer Institute Emory U

Atlanta, Georgia, 30322, United States

Location

University of Chicago Medical Center - Multiple Myeloma Research Consortium

Chicago, Illinois, 60637, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Icahn School of Medicine at Mount Sinai

Hackensack, New Jersey, 07601, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

New York Presbyterian Hospital, Weill Cornell Medical College

New York, New York, 10065, United States

Location

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

Location

Wake Forest Baptist Health

Winston-Salem, North Carolina, 27157, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University of Utah Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

The Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Princess Alexandra Hospital

Woolloongabba, Queensland, 4102, Australia

Location

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

Location

The Alfred Hospital

Melbourne, Victoria, 3004, Australia

Location

University Health Network-Princess Margaret Cancer Centre

Toronto, Ontario, M5G 1X6, Canada

Location

McGill University Health Centre Glen Site

Montreal, Quebec, H4A 3J1, Canada

Location

Universitätsklinikum Heidelberg

Heidelberg, 69120, Germany

Location

Universitätsklinikum Schleswig Holstein Campus Kiel

Kiel, 24105, Germany

Location

Universitaetsklinikum Wuerzburg

Würzburg, 97080, Germany

Location

Nagoya City University Hospital

Nagoya, Aichi-ken, 467-8602, Japan

Location

Gunma University Hospital

Maebashi, Gunma, 371-8511, Japan

Location

Kobe City Medical Center General Hospital

Kobe, Hyōgo, 650-0047, Japan

Location

Kanazawa University Hospital

Kanazawa, Ishikawa-ken, 920-8641, Japan

Location

National Hospital Organization Okayama Medical Center

Okayama, Okayama-ken, 701-1192, Japan

Location

The Cancer Institute Hospital of Japanese Foundation for Cancer Research

Koto-ku, Tokyo, 135-8550, Japan

Location

Universitair Medisch Centrum Groningen

Groningen, 9713 GZ, Netherlands

Location

Maastricht Universitair Medisch Centrum

Maastricht, 6229 HX, Netherlands

Location

Universitair Medisch Centrum Utrecht

Utrecht, 3584 CX, Netherlands

Location

Related Publications (1)

• 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.

  PMID: 32898244 DERIVED

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Multiple Myeloma; Neoplasms

Interventions

pomalidomide; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 6, 2017
• First Posted: September 19, 2017
• Study Start: November 13, 2017
• Primary Completion: June 30, 2023
• Study Completion: June 30, 2023
• Last Updated: October 8, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, 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.

Locations

AU (3); CA (2); JP (6); NL (3); US (17); DE (3)