Relapsed/Refractory Multiple Myeloma
Conditions
Keywords
Amgen, Phase 1, Phase 2, Phase 1/2, Clinical Trial, Oncology/Hematology, Relapsed/Refractory Multiple Myeloma, Immunotherapy
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.
Interventions
DRUGAMG 701
Subjects will receive IV infusions of AMG 701.
DRUGPomalidomide
Subjects will receive oral capsules of pomalidomide.
DRUGDexamethasone
Subjects will receive IV injections or oral dexamethasone.
Sponsors
Amgen
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| 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
| Measure | Time frame | Description |
|---|---|---|
| Anti-tumor activity: Best overall response of partial response (PR) | 48 months | Efficacy parameter measured by International Myeloma Working Group (IMWG) response criteria. |
| Anti-tumor activity: Duration of response | 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 | 48 months | Efficacy parameter measured by International Myeloma Working Group (IMWG) response criteria. |
| Pharmacokinetic parameter of AMG 701: Maximum concentration (Cmax) | 12 weeks | — |
| Anti-tumor activity: Overall survival | 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 | 48 months | Efficacy parameter measured by International Myeloma Working Group (IMWG) response criteria. |
| Pharmacokinetic parameter of AMG 701: Trough concentration (Ctrough) | 12 weeks | — |
| Anti-tumor activity: Progression-free survival | 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. |
| 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 | 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) | 48 months | Efficacy parameter measured by International Myeloma Working Group (IMWG) response criteria. |
| Anti-tumor activity: Best overall response of complete response (CR) | 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) | 48 months | Efficacy parameter measured by International Myeloma Working Group (IMWG) response criteria. |
Countries
Australia, Canada, Germany, Japan, Netherlands, United States
Outcome results
None listed