Clinical Trials List
Protocol Number20170122
NCT Number(ClinicalTrials.gov Identfier)NCT03287908
2021-05-10 - 2022-09-26
Phase II
Terminated3
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)
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Trial Applicant
IQVIA RDS Taiwan Ltd.
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Sponsor
Amgen Inc.
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Sheng-chieh Chou Division of General Internal Medicine
- CHENG-HONG TSAI Division of General Internal Medicine
- Shang-Ju Wu Division of General Internal Medicine
- Chieh-Lung Cheng Division of General Internal Medicine
- Chien-Chin Lin Division of Others -
- 劉家豪 Division of Hematology & Oncology
- MING YAO Division of General Internal Medicine
- 田豐銘 Division of Hematology & Oncology
- HSIN-AN HOU Division of General Internal Medicine
- - - Division of General Internal Medicine
- Huai-Hsuan Huang Division of General Internal Medicine
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Po-Shen Ko Division of Hematology & Oncology
- Jiun-I Lai Division of Radiation Therapy
- Yao-Chung Liu Division of Hematology & Oncology
- 陳玟均 Division of Hematology & Oncology
- Liang-Tsai Hsiao Division of Hematology & Oncology
- Ting-An Lin Division of Hematology & Oncology
- Jyh-Pyng Gau Division of Hematology & Oncology
- Hao-Yuan Wang Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Tung-Liang Lin Division of Hematology & Oncology
- HSUAN JEN SHIH Division of Hematology & Oncology
- Ming-Chung Kao Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Condition/Disease
Relapsed/Refractory Multiple Myeloma
Objectives
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.
Test Drug
AMG701
Active Ingredient
AMG701
Dosage Form
lyophilized powder for IV infusion
Dosage
1.5 mg
Endpoints
Primary Outcome Measures :
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 ]
Secondary Outcome Measures :
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 ]
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 ]
Secondary Outcome Measures :
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 ]
Inclution 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 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).
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
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.
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.
The Estimated Number of Participants
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Taiwan
8 participants
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Global
100 participants
