A Phase 1 interventional study of Immediate Release (IR) Formulation and Gastro-Retentive (GR) Formulation in Relapsed or Refractory Multiple Myeloma, sponsored by Amgen. Completed at 20 sites in 4 countries. Open to participants aged 18 Years to 100 Years. Per ClinicalTrials.gov, last updated 2024-09-26.
Sponsored by Amgen · Phase 1, Interventional, and Treatment
A study evaluating two new formulations of oprozomib plus pomalidomide and dexamethasone in participants with relapsed refractory multiple myeloma.
A multicenter, non-randomized, open-label, dose-exploration study evaluating two new formulations of oprozomib plus pomalidomide and dexamethasone in participants with relapsed refractory multiple myeloma. The study will be conducted in two parts. Part 1 will evaluate the formulations of oprozomib in combination with dexamethasone only. Part 2 will evaluate the formulations of oprozomib administered at increasing dose levels (dose escalation) in combination with pomalidomide and dexamethasone.
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Exclusion Criteria
Oprozomib IR plus dexamethasone
Drug: Immediate Release (IR) Formulation · Drug: Dexamethasone
Oprozomib GR plus dexamethasone
Drug: Gastro-Retentive (GR) Formulation · Drug: Dexamethasone
Oprozomib IR plus pomalidomide and dexamethasone
Drug: Immediate Release (IR) Formulation · Drug: Dexamethasone · Drug: Pomalidomide
Oprozomib GR plus pomalidomide and dexamethasone
Drug: Gastro-Retentive (GR) Formulation · Drug: Dexamethasone · Drug: Pomalidomide
Oprozomib GR monotherapy, or oprozomib GR plus dexamethasone
Drug: Gastro-Retentive (GR) Formulation · Drug: Dexamethasone
Immediate Release (IR) Formulation
Gastro-Retentive (GR) Formulation
Dexamethasone
Pomalidomide
Number of Participants Who Experienced Dose-Limiting Toxcity (DLT)
DLTs were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 and included the below, if judged by the investigator/medical monitor to be possibly related to study treatment: Non-hematologic DLTs were any ≥ Grade 3 toxicity, except: Grade 3 asymptomatic electrolyte abnormalities (except hypophosphatemia \> 24 hours); Grade 3 nausea, vomiting and diarrhea \< 3 days; Grade 3 fatigue \< 14 days; ≥ Grade 3 hyperglycemia/toxicity due to dexamethasone; ≥ Grade 3 rash due to pomalidomide. Hematologic DLTs included: Grade 4 neutropenia if absolute neutrophil count \< 0.5 x 10\^9/L ≥ 7 days; febrile neutropenia; Grade 4 thrombocytopenia ≥ 7 days; Grade ≥ 3 with ≥ Grade 2 bleeding/requiring platelet transfusion.
Time frame: Day 1 to day 28 of cycle 1, where each cycle was 28 days
Maximum Tolerated Dose (MTD) of Each Formulation of Oprozomib in Combination With Pomolidomide and Dexamethasone
The MTD was the dose with the highest posterior probability of having a DLT rate within the target toxicity interval (15% to 25%), while the posterior probability of excessive/unacceptable toxicity (\>25% to 100%) is \<40%. DLTs were graded using CTCAE version 4.03 and included the below, if judged by the investigator/medical monitor to be possibly related to study treatment: Non-hematologic DLTs were any ≥ Grade 3 toxicity, except: Grade 3 asymptomatic electrolyte abnormalities (except hypophosphatemia \> 24 hours); Grade 3 nausea, vomiting and diarrhea \< 3 days; Grade 3 fatigue \< 14 days; ≥ Grade 3 hyperglycemia/toxicity due to dexamethasone; ≥ Grade 3 rash due to pomalidomide. Hematologic DLTs included: Grade 4 neutropenia if absolute neutrophil count \< 0.5 x 10\^9/L ≥ 7 days; febrile neutropenia; Grade 4 thrombocytopenia ≥ 7 days; Grade ≥ 3 with ≥ Grade 2 bleeding/requiring platelet transfusion.
Time frame: Day 1 to Day 28 of cycle 1, where each cycle was 28 days
Number of Participants With Treatment-emergent Adverse Events (TEAEs) (Oprozomib in Combination With Dexamethasone and/or Pomalidomide)
An adverse event (AE) is defined as any untoward medical occurrence in a clinical trial participant. TEAEs were any AE that started on or after receiving the first dose of investigational product and up to and including 30 days after the last dose of investigational product or the end of study date, whichever is earlier. Treatment-related TEAEs were those considered related to study treatment by the investigator. Any clinically significant changes in electrocardiograms, vital signs, physical examination with a neurological assessment and clinical laboratory tests were recorded as TEAEs.
Time frame: Day 1 of cycle 1 to 30 (+7) days after the last dose of study treatment or end of study date, whichever is earlier (where each cycle was 28 days). Median treatment duration in Part 1 was 11.43 weeks and in Part 2 was 28 weeks
Number of Participants With TEAEs and Treatment-emergent Serious AEs (Open-label Roll-over)
TEAEs were any AE that started on or after receiving the first dose of investigational product and up to and including 30 days after the last dose of investigational product or the end of study date, whichever is earlier. Treatment-related TEAEs were those considered related to study treatment by the investigator. Serious TEAEs were any AE meeting at least 1 of the following criteria: fatal; life-threatening; required in-patient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; congenital anomaly/birth defect; other medically important serious event.
Time frame: Day 1 to 30 (+7) days after the last dose of study treatment or end of study date, whichever is earlier (where each cycle was 28 days). Median treatment duration for the open-label roll-over arm was 75.14 weeks
Maximum Observed Concentration (Cmax) of Oprozomib
The mean Cmax of oprozomib is presented following dosing on cycle 1 day 8 and cycle 1 day 22 for the IR and GR oprozomib formulations.
Time frame: Cycle 1 days 8 and 22: pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose. GR only: cycle 1 day 8: 8 hours post-dose
Time to Cmax (Tmax) of Oprozomib
The median Tmax of oprozomib is presented following dosing on cycle 1 day 8 and cycle 1 day 22 for the IR and GR oprozomib formulations.
Time frame: Cycle 1 days 8 and 22: pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose. GR only: cycle 1 day 8: 8 hours post-dose
Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of Oprozomib
The mean AUClast of oprozomib is presented following dosing on cycle 1 day 8 and cycle 1 day 22 for the IR and GR oprozomib formulations.
Time frame: Cycle 1 days 8 and 22: pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose. GR only: cycle 1 day 8: 8 hours post-dose
Best Overall Response (BOR) According to Revised International Myeloma Working Group Uniform Response Criteria (IMWG-URC)
BOR was the best response per IMWG-URC from best to worst: stringent complete response (sCR; complete response \[CR\], normal serum free light chain ratio, no clonal cells in bone marrow \[BM\]), CR (negative immunofixation on serum and urine, soft tissue plasmacytomas disappearance, \< 5% plasma cells in BM), very good partial response (VGPR; serum and urine M-protein detectable by immunofixation or ≥ 90% reduction in serum M-protein \[urine M-protein level \< 100 mg/24-h\]), partial response (PR; ≥ 50% reduction of serum M-protein and 24-h urinary M-protein by ≥ 90% or \< 200 mg/24-h), minimal response (MR; 25-49% reduction of serum M-protein and 50-89% in 24-h urinary M-protein, exceeding 200 mg/24-h), stable disease (SD; not CR, VGPR, PR or progressive disease \[PD\]), and PD (≥ 25% increase in serum or urine M-component, development of new or increased size of existing bone lesions or soft tissue plasmacytomas, hypercalcemia attributed to the plasma cell proliferative disorder).
Time frame: Day 1 of cycle 1 up to the end of study visit (where each cycle was 28 days); median treatment duration in Part 1 was 11.43 weeks and in Part 2 was 28 weeks
Overall Response Rate (ORR) According to IMWG-URC
The ORR was defined as the percentage of participants with a BOR of sCR, CR, VGPR, and PR per the IMWG-URC. Complete response (CR): Negative immunofixation on serum and urine, soft tissue plasmacytomas disappearance, \< 5% plasma cells in bone marrow (BM). Stringent CR (sCR): CR and normal serum free light chain ratio and no clonal cells in BM. Very Good Partial Response (VGPR): Serum and urine M-protein detectable by immunofixation or ≥ 90% reduction in serum M-protein (urine M-protein level \< 100 mg/24-h). PR: ≥ 50% reduction of serum M-protein and 24-h urinary M-protein by ≥ 90% or to \< 200 mg/24-h. The 95% confidence intervals (CIs) were estimated using the Clopper-Pearson method.
Time frame: Day 1 of cycle 1 up to the end of study visit (where each cycle was 28 days); median treatment duration in Part 1 was 11.43 weeks and in Part 2 was 28 weeks
Number of Participants With Progression Free Survival (PFS) Events
PFS was defined as the number of months from a participant's first dose of study treatment to the earlier of disease progression or death due to any cause. The number of participants who had a PFS event or who were censored are presented. PFS events were an assessment of progressive disease according to the IMWG-URC or death due to any cause. PFS data was censored: participants alive and no documented disease progression at time of analysis were censored at date of last disease assessment; participants alive with no disease assessment were censored at the first study dose date; participants alive without documented disease progression, with withdrawn consent were censored at date of last disease assessment before consent withdrawal; and for participants who started anti-cancer therapy other than study treatment prior to documentation of disease progression were censored at date of last disease assessment prior to starting new therapy.
Time frame: Day 1 of cycle 1 up to the end of study visit (where each cycle was 28 days); median treatment duration in Part 1 was 11.43 weeks and in Part 2 was 28 weeks
Kaplan-Meier Estimate of PFS
PFS was defined as the number of months from a participant's first dose of study treatment to the earlier of disease progression or death due to any cause. Median PFS was estimated using the Kaplan-Meier method. 95% CIs were estimated using the method by Klein and Moeschberger (1997) with log-log transformation. PFS data was censored: participants alive and no documented disease progression at time of analysis were censored at date of last disease assessment; participants alive with no disease assessment were censored at the first study dose date; participants alive without documented disease progression, with withdrawn consent were censored at date of last disease assessment before consent withdrawal; and for participants who started anti-cancer therapy other than study treatment prior to documentation of disease progression were censored at date of last disease assessment prior to starting new therapy.
Time frame: Day 1 of cycle 1 up to the end of study visit (where each cycle was 28 days); median treatment duration in Part 1 was 11.43 weeks and in Part 2 was 28 weeks
Kaplan-Meier Estimate of Duration of Response (DOR)
DOR, presented in months, was defined as the number of days between the date of the first tumor assessment indicating an objective response (PR or better) through to the subsequent date of progression or death due to any cause, or where applicable date of censoring (date of first progressive disease assessment or death or date of censoring - date of the first objective response result + 1/30.4). Median PFS was estimated using the Kaplan-Meier method. 95% confidence intervals were estimated using the method by Klein and Moeschberger (1997) with log-log transformation.
Time frame: Day 1 of cycle 1 up to the end of study visit (where each cycle was 28 days); median treatment duration in Part 1 was 11.43 weeks and in Part 2 was 28 weeks
Participants were enrolled at 26 research centers in Australia, Canada, Spain, and the United States, and participated from 17 January 2017 to 06 October 2022.
| Milestone | Oprozomib IR 150 mg/Day + Dexamethsone | Oprozomib GR 150 mg/Day + Dexamethasone | Oprozomib IR 150 mg/Day + Pomalidomide + Dexamethasone | Oprozomib GR 150 mg/Day + Pomalidomide + Dexamethasone | Oprozomib IR 200 mg/Day + Pomalidomide + Dexamethasone | Oprozomib GR 200 mg/Day + Pomalidomide + Dexamethasone | Oprozomib IR 225 mg/Day + Pomalidomide + Dexamethasone | Oprozomib IR 250 mg/Day + Pomalidomide + Dexamethasone | Open-label Roll-over |
|---|---|---|---|---|---|---|---|---|---|
| Started | 5 | 8 | 3 | 5 | 9 | 5 | 11 | 8 | 7 |
| Received oprozomib | 5 | 8 | 3 | 4 | 9 | 5 | 10 | 8 | 7 |
| Completed | 5 | 5 | 2 | 2 | 7 | 3 | 4 | 5 | 1 |
| Not completed | 0 | 3 | 1 | 3 | 2 | 2 | 7 | 3 | 6 |
| Withdrew: Death | 0 | 0 | 1 | 0 | 0 | 2 | 1 | 0 | 0 |
| Withdrew: Sponsor decision | 0 | 1 | 0 | 1 | 2 | 0 | 3 | 1 | 4 |
| Withdrew: Withdrawal by subject | 0 | 2 | 0 | 1 | 0 | 0 | 2 | 2 | 2 |
| Withdrew: Not treated due to adverse event | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 |
DLTs were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 and included the below, if judged by the investigator/medical monitor to be possibly related to study treatment: Non-hematologic DLTs were any ≥ Grade 3 toxicity, except: Grade 3 asymptomatic electrolyte abnormalities (except hypophosphatemia \> 24 hours); Grade 3 nausea, vomiting and diarrhea \< 3 days; Grade 3 fatigue \< 14 days; ≥ Grade 3 hyperglycemia/toxicity due to dexamethasone; ≥ Grade 3 rash due to pomalidomide. Hematologic DLTs included: Grade 4 neutropenia if absolute neutrophil count \< 0.5 x 10\^9/L ≥ 7 days; febrile neutropenia; Grade 4 thrombocytopenia ≥ 7 days; Grade ≥ 3 with ≥ Grade 2 bleeding/requiring platelet transfusion.
| Participants | Oprozomib IR 150 mg/Day + Dexamethsone | Oprozomib GR 150 mg/Day + Dexamethasone | Oprozomib IR 150 mg/Day + Pomalidomide + Dexamethasone | Oprozomib GR 150 mg/Day + Pomalidomide + Dexamethasone | Oprozomib IR 200 mg/Day + Pomalidomide + Dexamethasone | Oprozomib GR 200 mg/Day + Pomalidomide + Dexamethasone | Oprozomib IR 225 mg/Day + Pomalidomide + Dexamethasone | Oprozomib IR 250 mg/Day + Pomalidomide + Dexamethasone |
|---|---|---|---|---|---|---|---|---|
| Number of Participants Who Experienced Dose-Limiting Toxcity (DLT) | 0 | 0 | 1 | 1 | 1 | 1 | 0 | 2 |
The MTD was the dose with the highest posterior probability of having a DLT rate within the target toxicity interval (15% to 25%), while the posterior probability of excessive/unacceptable toxicity (\>25% to 100%) is \<40%. DLTs were graded using CTCAE version 4.03 and included the below, if judged by the investigator/medical monitor to be possibly related to study treatment: Non-hematologic DLTs were any ≥ Grade 3 toxicity, except: Grade 3 asymptomatic electrolyte abnormalities (except hypophosphatemia \> 24 hours); Grade 3 nausea, vomiting and diarrhea \< 3 days; Grade 3 fatigue \< 14 days; ≥ Grade 3 hyperglycemia/toxicity due to dexamethasone; ≥ Grade 3 rash due to pomalidomide. Hematologic DLTs included: Grade 4 neutropenia if absolute neutrophil count \< 0.5 x 10\^9/L ≥ 7 days; febrile neutropenia; Grade 4 thrombocytopenia ≥ 7 days; Grade ≥ 3 with ≥ Grade 2 bleeding/requiring platelet transfusion.
| mg/day | All Doses Oprozomib IR + Pomalidomide + Dexamethasone | All Doses Oprozomib GR + Pomalidomide + Dexamethasone |
|---|---|---|
| Maximum Tolerated Dose (MTD) of Each Formulation of Oprozomib in Combination With Pomolidomide and Dexamethasone | 250 | NA |
An adverse event (AE) is defined as any untoward medical occurrence in a clinical trial participant. TEAEs were any AE that started on or after receiving the first dose of investigational product and up to and including 30 days after the last dose of investigational product or the end of study date, whichever is earlier. Treatment-related TEAEs were those considered related to study treatment by the investigator. Any clinically significant changes in electrocardiograms, vital signs, physical examination with a neurological assessment and clinical laboratory tests were recorded as TEAEs.
| Participants | Oprozomib IR 150 mg/Day + Dexamethsone | Oprozomib GR 150 mg/Day + Dexamethasone | Oprozomib IR 150 mg/Day + Pomalidomide + Dexamethasone | Oprozomib GR 150 mg/Day + Pomalidomide + Dexamethasone | Oprozomib IR 200 mg/Day + Pomalidomide + Dexamethasone | Oprozomib GR 200 mg/Day + Pomalidomide + Dexamethasone | Oprozomib IR 225 mg/Day + Pomalidomide + Dexamethasone | Oprozomib IR 250 mg/Day + Pomalidomide + Dexamethasone |
|---|---|---|---|---|---|---|---|---|
| Any TEAE | 4 | 8 | 4 | 4 | 8 | 5 | 10 | 8 |
| Any Treatment-related TEAE | 4 | 8 | 4 | 4 | 8 | 5 | 10 | 8 |
TEAEs were any AE that started on or after receiving the first dose of investigational product and up to and including 30 days after the last dose of investigational product or the end of study date, whichever is earlier. Treatment-related TEAEs were those considered related to study treatment by the investigator. Serious TEAEs were any AE meeting at least 1 of the following criteria: fatal; life-threatening; required in-patient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; congenital anomaly/birth defect; other medically important serious event.
| Participants | Open-label Roll-over |
|---|---|
| Any TEAE | 7 |
| Any Serious TEAE | 4 |
The mean Cmax of oprozomib is presented following dosing on cycle 1 day 8 and cycle 1 day 22 for the IR and GR oprozomib formulations.
| ng/mL | Oprozomib IR 150 mg/Day + Dexamethsone | Oprozomib GR 150 mg/Day + Dexamethasone | Oprozomib IR 150 mg/Day + Pomalidomide + Dexamethasone | Oprozomib GR 150 mg/Day + Pomalidomide + Dexamethasone | Oprozomib IR 200 mg/Day + Pomalidomide + Dexamethasone | Oprozomib GR 200 mg/Day + Pomalidomide + Dexamethasone | Oprozomib IR 225 mg/Day + Pomalidomide + Dexamethasone | Oprozomib IR 250 mg/Day + Pomalidomide + Dexamethasone |
|---|---|---|---|---|---|---|---|---|
| Cycle 1 Day 8 | 321 ± 89.2 | 118 ± 90.3 | 349 ± 195 | 119 ± 77.7 | 694 ± 479 | 367 ± 429 | 1020 ± 911 | 800 ± 703 |
| Cycle 1 Day 22 | 453 ± 48.0 | 209 ± 185 | 305 ± NA | 191 ± 99.2 | 1040 ± 941 | 137 ± 81.1 | 1580 ± 672 | 1420 ± 1250 |
The median Tmax of oprozomib is presented following dosing on cycle 1 day 8 and cycle 1 day 22 for the IR and GR oprozomib formulations.
| hours | Oprozomib IR 150 mg/Day + Dexamethsone | Oprozomib GR 150 mg/Day + Dexamethasone | Oprozomib IR 150 mg/Day + Pomalidomide + Dexamethasone | Oprozomib GR 150 mg/Day + Pomalidomide + Dexamethasone | Oprozomib IR 200 mg/Day + Pomalidomide + Dexamethasone | Oprozomib GR 200 mg/Day + Pomalidomide + Dexamethasone | Oprozomib IR 225 mg/Day + Pomalidomide + Dexamethasone | Oprozomib IR 250 mg/Day + Pomalidomide + Dexamethasone |
|---|---|---|---|---|---|---|---|---|
| Cycle 1 Day 8 | 1.0 (0.93 to 1.9) | 2.0 (2.0 to 4.0) | 2.0 (0.50 to 2.0) | 5.8 (3.9 to 6.0) | 2.0 (0.45 to 6.0) | 2.0 (1.1 to 5.8) | 1.5 (0.47 to 4.2) | 1.3 (0.42 to 5.8) |
| Cycle 1 Day 22 | 1.0 (0.98 to 2.0) | 3.0 (1.9 to 6.0) | 1.0 (1.0 to 1.0) | 4.1 (3.7 to 6.0) | 1.3 (0.45 to 2.0) | 4.8 (2.0 to 6.0) | 0.98 (0.42 to 2.2) | 0.75 (0.50 to 1.1) |
The mean AUClast of oprozomib is presented following dosing on cycle 1 day 8 and cycle 1 day 22 for the IR and GR oprozomib formulations.
| hour*ng/mL | Oprozomib IR 150 mg/Day + Dexamethsone | Oprozomib GR 150 mg/Day + Dexamethasone | Oprozomib IR 150 mg/Day + Pomalidomide + Dexamethasone | Oprozomib GR 150 mg/Day + Pomalidomide + Dexamethasone | Oprozomib IR 200 mg/Day + Pomalidomide + Dexamethasone | Oprozomib GR 200 mg/Day + Pomalidomide + Dexamethasone | Oprozomib IR 225 mg/Day + Pomalidomide + Dexamethasone | Oprozomib IR 250 mg/Day + Pomalidomide + Dexamethasone |
|---|---|---|---|---|---|---|---|---|
| Cycle 1 Day 8 | 656 ± 77.6 | 357 ± 252 | 869 ± 449 | 655 ± 73.5 | 1210 ± 658 | 1880 ± 2190 | 1730 ± 1160 | 1710 ± 1560 |
| Cycle 1 Day 22 | 1020 ± 281 | 1380 ± 1090 | 681 ± NA | 839 ± 544 | 1420 ± 659 | 888 ± 1200 | 2050 ± 722 | 2030 ± 1070 |
BOR was the best response per IMWG-URC from best to worst: stringent complete response (sCR; complete response \[CR\], normal serum free light chain ratio, no clonal cells in bone marrow \[BM\]), CR (negative immunofixation on serum and urine, soft tissue plasmacytomas disappearance, \< 5% plasma cells in BM), very good partial response (VGPR; serum and urine M-protein detectable by immunofixation or ≥ 90% reduction in serum M-protein \[urine M-protein level \< 100 mg/24-h\]), partial response (PR; ≥ 50% reduction of serum M-protein and 24-h urinary M-protein by ≥ 90% or \< 200 mg/24-h), minimal response (MR; 25-49% reduction of serum M-protein and 50-89% in 24-h urinary M-protein, exceeding 200 mg/24-h), stable disease (SD; not CR, VGPR, PR or progressive disease \[PD\]), and PD (≥ 25% increase in serum or urine M-component, development of new or increased size of existing bone lesions or soft tissue plasmacytomas, hypercalcemia attributed to the plasma cell proliferative disorder).
| Participants | Oprozomib IR 150 mg/Day + Dexamethsone | Oprozomib GR 150 mg/Day + Dexamethasone | Oprozomib IR 150 mg/Day + Pomalidomide + Dexamethasone | Oprozomib GR 150 mg/Day + Pomalidomide + Dexamethasone | Oprozomib IR 200 mg/Day + Pomalidomide + Dexamethasone | Oprozomib GR 200 mg/Day + Pomalidomide + Dexamethasone | Oprozomib IR 225 mg/Day + Pomalidomide + Dexamethasone | Oprozomib IR 250 mg/Day + Pomalidomide + Dexamethasone |
|---|---|---|---|---|---|---|---|---|
| sCR | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 |
| CR | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| VGPR | 1 | 0 | 0 | 0 | 3 | 0 | 2 | 3 |
| PR | 1 | 1 | 1 | 0 | 3 | 2 | 3 | 3 |
| MR | 0 | 0 | 2 | 1 | 0 | 0 | 0 | 0 |
| SD | 0 | 4 | 0 | 1 | 0 | 0 | 4 | 0 |
| PD | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Unconfirmed response | 1 | 1 | 0 | 1 | 1 | 2 | 0 | 1 |
The ORR was defined as the percentage of participants with a BOR of sCR, CR, VGPR, and PR per the IMWG-URC. Complete response (CR): Negative immunofixation on serum and urine, soft tissue plasmacytomas disappearance, \< 5% plasma cells in bone marrow (BM). Stringent CR (sCR): CR and normal serum free light chain ratio and no clonal cells in BM. Very Good Partial Response (VGPR): Serum and urine M-protein detectable by immunofixation or ≥ 90% reduction in serum M-protein (urine M-protein level \< 100 mg/24-h). PR: ≥ 50% reduction of serum M-protein and 24-h urinary M-protein by ≥ 90% or to \< 200 mg/24-h. The 95% confidence intervals (CIs) were estimated using the Clopper-Pearson method.
| percentage of participants | Oprozomib IR 150 mg/Day + Dexamethsone | Oprozomib GR 150 mg/Day + Dexamethasone | Oprozomib IR 150 mg/Day + Pomalidomide + Dexamethasone | Oprozomib GR 150 mg/Day + Pomalidomide + Dexamethasone | Oprozomib IR 200 mg/Day + Pomalidomide + Dexamethasone | Oprozomib GR 200 mg/Day + Pomalidomide + Dexamethasone | Oprozomib IR 225 mg/Day + Pomalidomide + Dexamethasone | Oprozomib IR 250 mg/Day + Pomalidomide + Dexamethasone |
|---|---|---|---|---|---|---|---|---|
| Overall Response Rate (ORR) According to IMWG-URC | 66.7 (9.4 to 99.2) | 16.7 (0.4 to 64.1) | 33.3 (0.8 to 90.6) | 0.0 (NA to NA) | 85.7 (42.1 to 99.6) | 60.0 (14.7 to 94.7) | 60.0 (26.2 to 87.8) | 87.5 (47.3 to 99.7) |
PFS was defined as the number of months from a participant's first dose of study treatment to the earlier of disease progression or death due to any cause. The number of participants who had a PFS event or who were censored are presented. PFS events were an assessment of progressive disease according to the IMWG-URC or death due to any cause. PFS data was censored: participants alive and no documented disease progression at time of analysis were censored at date of last disease assessment; participants alive with no disease assessment were censored at the first study dose date; participants alive without documented disease progression, with withdrawn consent were censored at date of last disease assessment before consent withdrawal; and for participants who started anti-cancer therapy other than study treatment prior to documentation of disease progression were censored at date of last disease assessment prior to starting new therapy.
| Participants | Oprozomib IR 150 mg/Day + Dexamethsone | Oprozomib GR 150 mg/Day + Dexamethasone | Oprozomib IR 150 mg/Day + Pomalidomide + Dexamethasone | Oprozomib GR 150 mg/Day + Pomalidomide + Dexamethasone | Oprozomib IR 200 mg/Day + Pomalidomide + Dexamethasone | Oprozomib GR 200 mg/Day + Pomalidomide + Dexamethasone | Oprozomib IR 225 mg/Day + Pomalidomide + Dexamethasone | Oprozomib IR 250 mg/Day + Pomalidomide + Dexamethasone |
|---|---|---|---|---|---|---|---|---|
| Participants with PFS events | 0 | 1 | 1 | 0 | 0 | 2 | 4 | 1 |
| Participants who were censored | 3 | 5 | 2 | 3 | 7 | 3 | 6 | 7 |
PFS was defined as the number of months from a participant's first dose of study treatment to the earlier of disease progression or death due to any cause. Median PFS was estimated using the Kaplan-Meier method. 95% CIs were estimated using the method by Klein and Moeschberger (1997) with log-log transformation. PFS data was censored: participants alive and no documented disease progression at time of analysis were censored at date of last disease assessment; participants alive with no disease assessment were censored at the first study dose date; participants alive without documented disease progression, with withdrawn consent were censored at date of last disease assessment before consent withdrawal; and for participants who started anti-cancer therapy other than study treatment prior to documentation of disease progression were censored at date of last disease assessment prior to starting new therapy.
| months | Oprozomib IR 150 mg/Day + Dexamethsone | Oprozomib GR 150 mg/Day + Dexamethasone | Oprozomib IR 150 mg/Day + Pomalidomide + Dexamethasone | Oprozomib GR 150 mg/Day + Pomalidomide + Dexamethasone | Oprozomib IR 200 mg/Day + Pomalidomide + Dexamethasone | Oprozomib GR 200 mg/Day + Pomalidomide + Dexamethasone | Oprozomib IR 225 mg/Day + Pomalidomide + Dexamethasone | Oprozomib IR 250 mg/Day + Pomalidomide + Dexamethasone |
|---|---|---|---|---|---|---|---|---|
| Kaplan-Meier Estimate of PFS | NA (NA to NA) | NA (2.7 to NA) | 14.24 (NA to NA) | NA (NA to NA) | NA (NA to NA) | NA (1.5 to NA) | 17.50 (5.6 to NA) | NA (29.5 to NA) |
DOR, presented in months, was defined as the number of days between the date of the first tumor assessment indicating an objective response (PR or better) through to the subsequent date of progression or death due to any cause, or where applicable date of censoring (date of first progressive disease assessment or death or date of censoring - date of the first objective response result + 1/30.4). Median PFS was estimated using the Kaplan-Meier method. 95% confidence intervals were estimated using the method by Klein and Moeschberger (1997) with log-log transformation.
| months | Oprozomib IR 150 mg/Day + Dexamethsone | Oprozomib GR 150 mg/Day + Dexamethasone | Oprozomib IR 150 mg/Day + Pomalidomide + Dexamethasone | Oprozomib GR 150 mg/Day + Pomalidomide + Dexamethasone | Oprozomib IR 200 mg/Day + Pomalidomide + Dexamethasone | Oprozomib GR 200 mg/Day + Pomalidomide + Dexamethasone | Oprozomib IR 225 mg/Day + Pomalidomide + Dexamethasone | Oprozomib IR 250 mg/Day + Pomalidomide + Dexamethasone |
|---|---|---|---|---|---|---|---|---|
| Kaplan-Meier Estimate of Duration of Response (DOR) | NA (NA to NA) | NA (NA to NA) | NA (NA to NA) | — | NA (NA to NA) | NA (NA to NA) | 16.6 (3.7 to NA) | NA (28.6 to NA) |
Collected over Treatment-emergent adverse events were collected from the first dose of study treatment until the last dose + 30 days; median treatment duration in Part 1 was 11.43 weeks, in Part 2 was 28 weeks, and in the open-label roll-over arm was 75.14 weeks. All-cause mortality was collected from enrollment to end of study visit; median overall duration on study was 259.00 days.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Oprozomib IR 150 mg/Day + Dexamethsone | 0/5 (0%) | 2/5 (40%) | 4/5 (80%) |
| Oprozomib GR 150 mg/Day + Dexamethasone | 0/8 (0%) | 2/8 (25%) | 8/8 (100%) |
| Oprozomib IR 150 mg/Day + Pomalidomide + Dexamethasone | 1/3 (33.3%) | 2/4 (50%) | 4/4 (100%) |
| Oprozomib GR 150 mg/Day + Pomalidomide + Dexamethasone | 0/5 (0%) | 4/4 (100%) | 4/4 (100%) |
| Oprozomib IR 200 mg/Day + Pomalidomide + Dexamethasone | 0/9 (0%) | 6/8 (75%) | 8/8 (100%) |
| Oprozomib GR 200 mg/Day + Pomalidomide + Dexamethasone | 2/5 (40%) | 5/5 (100%) | 5/5 (100%) |
| Oprozomib IR 225 mg/Day + Pomalidomide + Dexamethasone | 1/11 (9.1%) | 3/10 (30%) | 10/10 (100%) |
| Oprozomib IR 250 mg/Day + Pomalidomide + Dexamethasone | 0/8 (0%) | 4/8 (50%) | 8/8 (100%) |
| Open-label Roll-over | 0/7 (0%) | 4/7 (57.1%) | 7/7 (100%) |
| Event | Oprozomib IR 150 mg/Day + Dexamethsone | Oprozomib GR 150 mg/Day + Dexamethasone | Oprozomib IR 150 mg/Day + Pomalidomide + Dexamethasone | Oprozomib GR 150 mg/Day + Pomalidomide + Dexamethasone | Oprozomib IR 200 mg/Day + Pomalidomide + Dexamethasone | Oprozomib GR 200 mg/Day + Pomalidomide + Dexamethasone | Oprozomib IR 225 mg/Day + Pomalidomide + Dexamethasone | Oprozomib IR 250 mg/Day + Pomalidomide + Dexamethasone | Open-label Roll-over |
|---|---|---|---|---|---|---|---|---|---|
| PneumoniaInfections and infestations | 1/5 | 1/8 | 1/4 | 3/4 | 1/8 | 2/5 | 1/10 | 2/8 | 1/7 |
| Splenic infarctionBlood and lymphatic system disorders | 0/5 | 0/8 | 0/4 | 1/4 | 0/8 | 0/5 | 0/10 | 0/8 | 0/7 |
| DiarrhoeaGastrointestinal disorders | 0/5 | 0/8 | 0/4 | 0/4 | 1/8 | 0/5 | 0/10 | 2/8 | 0/7 |
| GastritisGastrointestinal disorders | 0/5 | 0/8 | 0/4 | 1/4 | 0/8 | 0/5 | 0/10 | 0/8 | 0/7 |
| Small intestinal obstructionGastrointestinal disorders | 0/5 | 0/8 | 1/4 | 0/4 | 0/8 | 0/5 | 0/10 | 0/8 | 0/7 |
| BronchitisInfections and infestations | 0/5 | 0/8 | 0/4 | 1/4 | 0/8 | 0/5 | 2/10 | 0/8 | 0/7 |
| DiverticulitisInfections and infestations | 0/5 | 0/8 | 0/4 | 0/4 | 2/8 | 0/5 | 0/10 | 0/8 | 0/7 |
| Lower respiratory tract infectionInfections and infestations | 1/5 | 0/8 | 0/4 | 1/4 | 1/8 | 0/5 | 0/10 | 0/8 | 0/7 |
| Pneumonia respiratory syncytial viralInfections and infestations | 0/5 | 1/8 | 1/4 | 0/4 | 0/8 | 0/5 | 0/10 | 0/8 | 0/7 |
| Pathological fractureMusculoskeletal and connective tissue disorders | 0/5 | 0/8 | 0/4 | 1/4 | 0/8 | 0/5 | 0/10 | 0/8 | 0/7 |
| Event | Oprozomib IR 150 mg/Day + Dexamethsone | Oprozomib GR 150 mg/Day + Dexamethasone | Oprozomib IR 150 mg/Day + Pomalidomide + Dexamethasone | Oprozomib GR 150 mg/Day + Pomalidomide + Dexamethasone | Oprozomib IR 200 mg/Day + Pomalidomide + Dexamethasone | Oprozomib GR 200 mg/Day + Pomalidomide + Dexamethasone | Oprozomib IR 225 mg/Day + Pomalidomide + Dexamethasone | Oprozomib IR 250 mg/Day + Pomalidomide + Dexamethasone | Open-label Roll-over |
|---|---|---|---|---|---|---|---|---|---|
| DiarrhoeaGastrointestinal disorders | 2/5 | 5/8 | 3/4 | 2/4 | 5/8 | 4/5 | 8/10 | 8/8 | 2/7 |
| NauseaGastrointestinal disorders | 4/5 | 7/8 | 3/4 | 3/4 | 6/8 | 3/5 | 8/10 | 8/8 | 2/7 |
| VomitingGastrointestinal disorders | 3/5 | 3/8 | 2/4 | 1/4 | 6/8 | 3/5 | 7/10 | 7/8 | 1/7 |
| ConstipationGastrointestinal disorders | 4/5 | 3/8 | 2/4 | 1/4 | 4/8 | 3/5 | 3/10 | 6/8 | 1/7 |
| AnaemiaBlood and lymphatic system disorders | 1/5 | 2/8 | 3/4 | 1/4 | 2/8 | 2/5 | 3/10 | 0/8 | 2/7 |
| FatigueGeneral disorders | 3/5 | 4/8 | 2/4 | 3/4 | 3/8 | 2/5 | 6/10 | 5/8 | 0/7 |
| Upper respiratory tract infectionInfections and infestations | 2/5 | 2/8 | 1/4 | 0/4 | 3/8 | 2/5 | 1/10 | 5/8 | 0/7 |
| Oedema peripheralGeneral disorders | 1/5 | 0/8 | 1/4 | 1/4 | 3/8 | 3/5 | 5/10 | 1/8 | 0/7 |
| HypokalaemiaMetabolism and nutrition disorders | 1/5 | 1/8 | 1/4 | 1/4 | 3/8 | 3/5 | 0/10 | 3/8 | 0/7 |
| HypomagnesaemiaMetabolism and nutrition disorders | 0/5 | 1/8 | 0/4 | 1/4 | 1/8 | 3/5 | 0/10 | 1/8 | 0/7 |
The safety analysis set included all participants who received any amount of oprozomib, pomalidomide and/or dexamethasone. One participant in arm Oprozomib IR 200 mg/day + pomalidomide + dexamethasone received oprozomib IR 150 mg + pomalidomide + dexamethasone, and their baseline characteristics data were included in the Oprozomib IR 150 mg + pomalidomide + dexamethasone arm. Participants enrolled from other Amgen studies were included in a single roll-over arm, as pre-specified in the SAP.
| Age, Continuous(years) | Oprozomib IR 150 mg/Day + Dexamethsone | Oprozomib GR 150 mg/Day + Dexamethasone | Oprozomib IR 150 mg/Day + Pomalidomide + Dexamethasone | Oprozomib GR 150 mg/Day + Pomalidomide + Dexamethasone | Oprozomib IR 200 mg/Day + Pomalidomide + Dexamethasone | Oprozomib GR 200 mg/Day + Pomalidomide + Dexamethasone | Oprozomib IR 225 mg/Day + Pomalidomide + Dexamethasone | Oprozomib IR 250 mg/Day + Pomalidomide + Dexamethasone | Open-label Roll-over | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| Mean | 69.0 ± 17.2 | 59.6 ± 8.1 | 62.5 ± 8.7 | 63.5 ± 5.9 | 64.3 ± 9.8 | 62.0 ± 8.2 | 63.1 ± 10.2 | 65.9 ± 10.5 | 70.4 ± 8.7 | 63.6 ± 9.9 |
| Sex: Female, Male(Participants) | Oprozomib IR 150 mg/Day + Dexamethsone | Oprozomib GR 150 mg/Day + Dexamethasone | Oprozomib IR 150 mg/Day + Pomalidomide + Dexamethasone | Oprozomib GR 150 mg/Day + Pomalidomide + Dexamethasone | Oprozomib IR 200 mg/Day + Pomalidomide + Dexamethasone | Oprozomib GR 200 mg/Day + Pomalidomide + Dexamethasone | Oprozomib IR 225 mg/Day + Pomalidomide + Dexamethasone | Oprozomib IR 250 mg/Day + Pomalidomide + Dexamethasone | Open-label Roll-over | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| Female | 1 | 4 | 2 | 1 | 3 | 3 | 3 | 1 | 1 | 19 |
| Male | 4 | 4 | 2 | 3 | 5 | 2 | 7 | 7 | 6 | 40 |
| Ethnicity (NIH/OMB)(Participants) | Oprozomib IR 150 mg/Day + Dexamethsone | Oprozomib GR 150 mg/Day + Dexamethasone | Oprozomib IR 150 mg/Day + Pomalidomide + Dexamethasone | Oprozomib GR 150 mg/Day + Pomalidomide + Dexamethasone | Oprozomib IR 200 mg/Day + Pomalidomide + Dexamethasone | Oprozomib GR 200 mg/Day + Pomalidomide + Dexamethasone | Oprozomib IR 225 mg/Day + Pomalidomide + Dexamethasone | Oprozomib IR 250 mg/Day + Pomalidomide + Dexamethasone | Open-label Roll-over | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| Hispanic or Latino | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Not Hispanic or Latino | 5 | 8 | 4 | 4 | 8 | 5 | 7 | 8 | 7 | 56 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 0 | 0 | 3 |
| Race/Ethnicity, Customized(Participants) | Oprozomib IR 150 mg/Day + Dexamethsone | Oprozomib GR 150 mg/Day + Dexamethasone | Oprozomib IR 150 mg/Day + Pomalidomide + Dexamethasone | Oprozomib GR 150 mg/Day + Pomalidomide + Dexamethasone | Oprozomib IR 200 mg/Day + Pomalidomide + Dexamethasone | Oprozomib GR 200 mg/Day + Pomalidomide + Dexamethasone | Oprozomib IR 225 mg/Day + Pomalidomide + Dexamethasone | Oprozomib IR 250 mg/Day + Pomalidomide + Dexamethasone | Open-label Roll-over | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| Black (or African American) | 1 | 1 | 2 | 0 | 1 | 2 | 2 | 1 | 0 | 10 |
| White | 4 | 7 | 2 | 4 | 6 | 3 | 7 | 7 | 6 | 46 |
| Other | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 1 | 3 |
Documents are hosted by the registry — open the source record to download them.
Plan to share: Yes — De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
Supporting information: Study protocol, Statistical analysis plan, Informed consent form, Clinical study report
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 URL below.
Data sharing details ↗ · www.amgen.com
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Studies of the drug tested here: Pomalidomide