Multiple Myeloma
Conditions
Keywords
multiple myeloma, oprozomib, OPZ, ONX 0912, Onyx, proteasome inhibitor, oprozomib tablets
Brief summary
The primary objectives are: Phase 1b: * To determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of oprozomib given orally, once daily, on 2 different schedules. * To evaluate safety and tolerability Phase 2: * To estimate the overall response rate (ORR). * To evaluate safety and tolerability
Detailed description
The purpose of the Phase 1b portion of the study was to determine the maximum tolerated dose (MTD), the recommended phase 2 dose (RP2D), safety, and pharmacokinetics (PK) of oprozomib administered orally once daily in combination with dexamethasone, in participants with relapsed and/or refractory multiple myeloma, using a 3 + 3 dose-escalation scheme with and without step-up dosing. The MTD was defined as the highest dose level at which fewer than 33% of participants had a dose-limiting toxicity (DLT).
Interventions
DRUGOprozomib
Oprozomib tablets were supplied containing 60, 90, or 120 mg of oprozomib. Oprozomib extended release tablets were supplied containing 150, 180, 210, 240, or 270 mg of oprozomib. Both formulations were administered in a single dose on dosing days. The tablet formulation required multiple tablets to reach each dose on dosing days.
DRUGDexamethasone
Dexamethasone was administered as 20 mg tablets in strengths of 4 and 6 mg taken orally. If a participant could not tolerate tablets or tablets were unavailable, 20 mg administered intravenously was substituted.
Sponsors
Amgen
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Diagnosis of multiple myeloma with measureable disease as indicated by 1 or more of the following: * a. Serum M-protein ≥ 500 mg/dL * b. Urine M-protein ≥ 200 mg/24 hours * c. Only for subjects without measurable serum and urine M-protein, serum free light chain: Involved free light chain (FLC) level ≥ 10 mg/dL, provided serum FLC ratio is abnormal 2. Patients requiring therapy who have relapsed and/or are refractory to their last therapy and have been treated with at least 1, but not more than 5, lines of multiple myeloma therapy. Prior therapy must have consisted of at least 1 regimen that included lenalidomide and/or bortezomib. Patients should be considered to be appropriate candidates for a clinical study by their treating physicians. Relapsed patients must have previously achieved ≥ minimal response (MR) on at least 1 line of therapy, as assessed by the treating physician. Refractory patients are allowed, but it is not required that patients be refractory to their last therapy. Primary refractory patients are allowed in the Phase 1b portion of the study only. 3. Males and females ≥ 18 years of age 4. Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-2 5. Adequate hepatic function, with bilirubin ≤ 1.5 times the upper limit of normal (ULN) in the absence of Gilbert's disease or hemolysis, aspartate aminotransferase (AST) ≤ 3 times ULN, and alanine aminotransferase (ALT) ≤ 3 times ULN 6. Absolute neutrophil count (ANC) ≥ 1000 cells/mcL, hemoglobin ≥ 7.0 g/dL, and platelet count ≥ 30,000 cells/mcL: * a. Patients must not have received platelet transfusions for at least 1 week prior to Screening. * b. Screening ANC must be independent of granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor (G-CSF and GM-CSF) support for at least 1 week and of pegylated G-CSF for ≥ 2 weeks prior to first dose. * c. Patients may receive red blood cell (RBC) transfusions or receive supportive care with erythropoietin or darbepoetin in accordance with institutional guidelines. 7. Calculated or measured creatinine clearance (CrCl) of ≥ 30 mL/minute calculated using the formula of Cockcroft and Gault (\[140 - Age\] \* Mass (kg) / \[72 \* creatinine mg/mL\]). Multiply result by 0.85 if female. 8. Uric acid, if elevated, must be corrected to within laboratory normal range before dosing. 9. Patients must sign a written informed consent form in accordance with federal, local, and institutional guidelines. 10. Female patients of childbearing potential must have a negative serum or urine pregnancy test within 3 days prior to receiving the first dose of study drug and agree to use effective methods of contraception during the study and for 3 months following the last dose of study drug. Postmenopausal females (\> 45 years old and without menses for \> 1 year) and surgically sterilized females are exempt from these requirements. Male patients must use an effective barrier method of contraception during the study and for 3 months following the last dose if sexually active with a female of childbearing potential. 11. Prior carfilzomib is not required but is allowed if a patient had at least 2 cycles of carfilzomib alone or in combination with a dose of at least 20/27 mg/m\^2, as long as the patient: * a. Had at least a partial response to prior carfilzomib therapy * b. Was not removed from carfilzomib therapy due to toxicity, unless approved by the medical monitor * c. Was not removed from carfilzomib therapy for progressive disease nor experienced progressive disease within 6 months after any prior carfilzomib therapy. Key
Exclusion criteria
1. Radiation therapy within 2 weeks prior to first dose; localized radiation therapy within 1 week prior to first dose 2. Immunotherapy/standard myeloma therapy within 2 weeks prior to first dose (except for antibody therapy, where 6 weeks are required, and alkylator therapy, where 3 weeks are required); prior stem cell transplant (SCT) therapy (autologous SCT within the prior 8 weeks; allogeneic SCT within the prior 16 weeks). Patients with prior allogeneic SCT should not have evidence of moderate-to-severe graft-versus-host disease (GvHD). 3. Plasmapheresis is not permitted at any time during the Screening period or while the subject is receiving study treatment. If a subject has started screening procedures requiring plasmapheresis, or is anticipated to require plasmapheresis during or after the Screening period, this patient will be considered ineligible and should not be enrolled. 4. Glucocorticoid therapy within 14 days prior to enrollment that exceeds a cumulative dose of 160 mg of dexamethasone or equivalent 5. Participation in an investigational therapeutic study within 3 weeks prior to first dose 6. Prior oprozomib exposure 7. Known hypersensitivity/toxicity or intolerance to dexamethasone 8. Major surgery within 3 weeks prior to first dose 9. Congestive heart failure (\[CHF\] New York Heart Association Class III to IV), symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention, or myocardial infarction within 6 months prior to first dose 10. Uncontrolled hypertension or uncontrolled diabetes 11. Active infection requiring systemic antibiotics, antivirals, or antifungals within 2 weeks prior to first dose 12. Known or suspected human immunodeficiency virus (HIV) infection or patients who are HIV seropositive 13. Active hepatitis A, B, or C infection 14. History of previous clinically significant GI bleed in the last 6 months prior to first dose 15. Significant neuropathy (Grade 3, Grade 4, or Grade 2 with pain) at the time of the first dose 16. Other malignancy within the past 3 years, with the exception of adequately treated basal cell carcinoma of the skin, squamous cell skin cancer, thyroid cancer, carcinoma in situ of the cervix, carcinoma in situ of the breast, prostate cancer of Gleason Score of 6 or less with stable prostate specific antigen levels, or cancer considered cured by surgical resection 17. Plasma cell leukemia 18. Female patients who are pregnant or nursing 19. Inability to swallow medication, inability or unwillingness to comply with the drug administration requirements, or GI condition that could interfere with the oral absorption or tolerance of treatment 20. Any contraindication to oral hydration (e.g., significant preexisting comorbidity or fluid restriction) 21. Any clinically significant psychiatric or medical condition that in the opinion of the investigator could increase patient risk or interfere with protocol adherence or a patient's ability to give informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Participants With Dose-Limiting Toxicities (DLT) | Day 1 to Day 14 (Cycle 1) for continous dosing and Day 15 to Day 28 (Cycle 2) for step-up dosing | Toxicities (graded per the Common Terminology Criteria for Adverse Events v 4.03) were considered DLTs if judged by the investigator to be related to oprozomib and occurred in the first 14 days of treatment, with treatment at the dose to be studied (i.e., Cycle 1 for continuous dosing or Cycle 2 for step-up dosing). A DLT was categorized as nonhematologic or hematologic. Examples include: * Any ≥ Grade 3 nonhematologic AE, with exceptions or qualifications such as Grade 3 nausea, vomiting, diarrhea, or constipation were considered a DLT only if lasting for \> 7 days despite optimal supportive care * Grade 3 fatigue lasting \> 14 days * Grade 4 neutropenia: absolute neutrophil count (ANC) \< 500 cells/mcL lasting ≥ 7 days * Febrile neutropenia: Any single temperature ≥ 38.3°C or a sustained temperature of ≥ 38.0°C for over 1 hour with ≥ Grade 3 neutropenia (ANC \< 1000 cells/mcL) * Grade 3/4 thrombocytopenia * Others specified in the protocol |
| Participants With Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | Day 1 up to Week 282 | AE defined as any untoward medical occurrence in a clinical trial participant. Treatment-emergent adverse events were defined as adverse events that start on or after the first day of study treatment and within 30 days of the last day of study treatment. An adverse event that was present before the first administration of study treatment and subsequently worsens in severity during treatment was also considered to be treatment-emergent. Serious AE defined as AE that is fatal, life threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or other significant medical hazard. Severity of AEs assessed according to Common Terminology Criteria for Adverse Events (CTCAE, v4.03) based on the general guideline: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening or disabling; Grade 5: Death related to AE. IP=investigational product |
| Participants With Treatment-Related, Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | Day 1 up to Week 282 | AE defined as any untoward medical occurrence in a clinical trial participant. TEAEs were defined as AEs that start on or after the first day of study treatment and within 30 days of the last day of study treatment. An AE that was present before the first administration of study treatment and subsequently worsens in severity during treatment was also considered a TEAE. Investigator assessed AEs for relatedness to study drug. Serious AE defined as AE that is fatal, life threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or other significant medical hazard. Severity of AEs assessed according to Common Terminology Criteria for Adverse Events (CTCAE, v4.03) based on the general guideline: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening or disabling; Grade 5: Death related to AE. IP=investigational product |
| Best Overall Response in Phase 2 as Assessed by Investigator | Screening: Day 14 to Day -1; During study: Day 1 up to 13.16 months | Disease response and progression were determined using the International Myeloma Working Group-Uniform Response Criteria (IMWG-URC), except for minimal response (MR) and near complete response (nCR) which was based on the European Group for Blood and Marrow Transplantation (EBMT) criteria. Evaluations reported were assessed by the investigator for participants in Phase 2. |
| Percentage of Participants Who Achieved an Overall Response As Assessed by Investigator During Phase 2 | Screening: Day 14 to Day -1; During study: Day 1 up to 13.16 months | The overall response rate (ORR) was defined as the percentage of participants with the best overall response of stringent complete response (sCR), complete response (CR), near complete response (nCR), very good partial response (VGPR), and partial response (PR) as defined by the International Myeloma Working Group-Uniform Response Criteria (IMWG-URC) and modified European Group for Blood and Marrow Transplantation (EBMT) criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic (PK) Parameter for Oprozomib, Tablet and ER Formulation: Apparent Drug Clearance After Oral Administration (CL/F) on Cycle 1, Day 1 | Day 1 | The apparent drug clearance after oral administration (CL/F) was calculated as the dose divided by AUCinf. PK samples obtained on the following schedule: Phase 1b Continuous Dosing, Cycles 1 and 2: Day 1: pre-dose, post-dose at 15 and 30 minutes, 1, 2, 4, 6, and 8 hours post-dose plus pre-dose on Day 2 Phase 1b Step-up Dosing, Day 1: pre-dose, post-dose at 15 and 30 minutes, 1, 2, 4, 6, and 7 hours post-dose plus pre-dose on Day 2 Phase 2, Day 1: pre-dose, post-dose at 15 and 30 minutes, 1, 2, 4, 6, and 7 hours post-dose plus pre-dose on Day 2 |
| Pharmacokinetic (PK) Parameter for Oprozomib, Tablet and ER Formulation: Apparent Volume of Distribution After Oral Administration (Vz/F) on Cycle 1, Day 1 | Day 1 | The apparent volume of distribution after oral administration (Vz/F) calculated as the dose divided by AUCinf times ƒz, where ƒz was the first-order terminal rate constant estimated via linear regression of the terminal log-linear phase. PK samples obtained on the following schedule: Phase 1b Continuous Dosing, Cycles 1 and 2: Day 1: pre-dose, post-dose at 15 and 30 minutes, 1, 2, 4, 6, and 8 hours post-dose plus pre-dose on Day 2 Phase 1b Step-up Dosing, Day 1: pre-dose, post-dose at 15 and 30 minutes, 1, 2, 4, 6, and 7 hours post-dose plus pre-dose on Day 2 Phase 2, Day 1: pre-dose, post-dose at 15 and 30 minutes, 1, 2, 4, 6, and 7 hours post-dose plus pre-dose on Day 2 |
| Percentage of Participants Who Achieved a Clinical Benefit Response As Assessed by Investigator During Phase 2 | Screening: Day 14 to Day -1; During study: Day 1 up to 13.16 months | The clinical benefit rate (CBR) was defined as Overall Response Rate (ORR) plus Minimal Response (MR) as defined by the European Group for Blood and Marrow Transplantation (EBMT) criteria. |
| Pharmacokinetic (PK) Parameter for Oprozomib, Tablet and ER Formulation: Time to Maximum Serum Concentration (Tmax) on Cycle 1, Day 1 | Day 1 | PK samples obtained on the following schedule: Phase 1b Continuous Dosing, Cycles 1 and 2: Day 1: pre-dose, post-dose at 15 and 30 minutes, 1, 2, 4, 6, and 8 hours post-dose plus pre-dose on Day 2 Phase 1b Step-up Dosing, Day 1: pre-dose, post-dose at 15 and 30 minutes, 1, 2, 4, 6, and 7 hours post-dose plus pre-dose on Day 2 Phase 2, Day 1: pre-dose, post-dose at 15 and 30 minutes, 1, 2, 4, 6, and 7 hours post-dose plus pre-dose on Day 2 |
| Kaplan-Meier Estimates for Progression-free Survival (PFS) as Assessed by Investigator During Phase 2 | Day 1 up to 14.1 months | Progression-free survival (PFS) was defined as number of months between start of treatment and first evidence of documented disease progression or death (due to any cause), whichever occurs first. Disease progression was determined using IMWG-URC per investigator. The duration of PFS was right-censored for participants who met 1 of the following conditions: * 1\) starting a new anticancer therapy before documentation of disease progression or death; * 2\) death or disease progression immediately after more than 1 consecutively missed disease assessment visit or; * 3\) alive without documentation of disease progression before the data cutoff date. 95% CIs for medians were estimated using the method by Klein and Moeschberger (1997) with log-log transformation. |
| Kaplan-Meier Estimate for Time to Progression (TTP) as Assessed by Investigator During Phase 2 | Day 1 up to 14.1 months | Time to progression (TTP) was defined as the number of months between the start of treatment to the first documentation of disease progression. Disease progression was determined using IMWG-URC as assessed by the investigator. The same censoring rules, except for death, as in analysis of PFS were applied in the calculation of TTP. Participants who died prior to progressive disease were censored at the date of last evaluable response assessment. |
| Kaplan-Meier Estimates for Duration of Response (DOR) as Assessed by Investigator During Phase 2 | Day 1 up to 13.16 months | Duration of response was defined as the time from first evidence of partial response (PR) or better (i.e. best overall response) to confirmation of disease progression or death due to any cause. Durations were calculated for responders only. Medians and percentiles were estimated using the Kaplan-Meier method. 95% confidence intervals for medians and percentiles were estimated using the method by Klein and Moeschberger (1997) with log-log transformation. |
| Pharmacokinetic (PK) Parameter for Oprozomib, Tablet and ER Formulation: Maximum Serum Concentration (Cmax) on Cycle 1, Day 1 | Day 1 | PK samples obtained on the following schedule: Phase 1b Continuous Dosing, Cycles 1 and 2: Day 1: pre-dose, post-dose at 15 and 30 minutes, 1, 2, 4, 6, and 8 hours post-dose plus pre-dose on Day 2 Phase 1b Step-up Dosing, Day 1: pre-dose, post-dose at 15 and 30 minutes, 1, 2, 4, 6, and 7 hours post-dose plus pre-dose on Day 2 Phase 2, Day 1: pre-dose, post-dose at 15 and 30 minutes, 1, 2, 4, 6, and 7 hours post-dose plus pre-dose on Day 2 |
| Pharmacokinetic (PK) Parameter for Oprozomib, Tablet and ER Formulation: Area Under the Curve at the Last Measurable Time Point (AUClast) on Cycle 1, Day 1 | Day 1 | The area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration (AUClast) was estimated using the linear trapezoidal method. PK samples obtained on the following schedule: Phase 1b Continuous Dosing, Cycles 1 and 2: Day 1: pre-dose, post-dose at 15 and 30 minutes, 1, 2, 4, 6, and 8 hours post-dose plus pre-dose on Day 2 Phase 1b Step-up Dosing, Day 1: pre-dose, post-dose at 15 and 30 minutes, 1, 2, 4, 6, and 7 hours post-dose plus pre-dose on Day 2 Phase 2, Day 1: pre-dose, post-dose at 15 and 30 minutes, 1, 2, 4, 6, and 7 hours post-dose plus pre-dose on Day 2 |
| Pharmacokinetic (PK) Parameter for Oprozomib, Tablet and ER Formulation: Area Under the Curve From Time 0 to Time Infinity (AUCinf) on Cycle 1, Day 1 | Day 1 | The area under the plasma concentration-curve from time 0 to time infinity (AUCinf) was estimated using the linear trapezoidal method PK samples obtained on the following schedule: Phase 1b Continuous Dosing, Cycles 1 and 2: Day 1: pre-dose, post-dose at 15 and 30 minutes, 1, 2, 4, 6, and 8 hours post-dose plus pre-dose on Day 2 Phase 1b Step-up Dosing, Day 1: pre-dose, post-dose at 15 and 30 minutes, 1, 2, 4, 6, and 7 hours post-dose plus pre-dose on Day 2 Phase 2, Day 1: pre-dose, post-dose at 15 and 30 minutes, 1, 2, 4, 6, and 7 hours post-dose plus pre-dose on Day 2 |
| Pharmacokinetic (PK) Parameter for Oprozomib, Tablet and ER Formulation: Terminal Half-Life (t1/2,z) on Cycle 1, Day 1 | Day 1 | PK samples obtained on the following schedule: Phase 1b Continuous Dosing, Cycles 1 and 2: Day 1: pre-dose, post-dose at 15 and 30 minutes, 1, 2, 4, 6, and 8 hours post-dose plus pre-dose on Day 2 Phase 1b Step-up Dosing, Day 1: pre-dose, post-dose at 15 and 30 minutes, 1, 2, 4, 6, and 7 hours post-dose plus pre-dose on Day 2 Phase 2, Day 1: pre-dose, post-dose at 15 and 30 minutes, 1, 2, 4, 6, and 7 hours post-dose plus pre-dose on Day 2 |
Countries
France, United States
Participant flow
Recruitment details
This study was conducted at 18 centers in the United States and France.
Pre-assignment details
Eighty-one subjects were screened; sixteen were not enrolled due to entry criteria violations.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 180 mg 5/14 Schedule (Phase 1b) Oprozomib 180 mg treatment once daily for 5 consecutive days bimonthly (days 1, 2, 3, 4, and 5 of a 14-day cycle) with 20 mg dexamethasone once daily on days 1, 2, 8, and 9 (referred to as the 5/14 schedule). Treatment was administered in 14-day cycles until disease progression, unacceptable toxicity, or study treatment discontinuation for any reason. | 9 |
| Cohort 210 mg 5/14 Schedule (Phase 1b) Oprozomib 210 mg treatment once daily for 5 consecutive days bimonthly (days 1, 2, 3, 4, and 5 of a 14-day cycle) with 20 mg dexamethasone once daily on days 1, 2, 8, and 9 (referred to as the 5/14 schedule). Treatment was administered in 14-day cycles until disease progression, unacceptable toxicity, or study treatment discontinuation for any reason.
This was the first cohort to enroll participants into the 5/14 schedule. The Cohort Safety Review Committee (CSRC) reviewed safety data and made dose adjustments for oprozomib in 30 mg increments for all cohorts. | 7 |
| Cohort 150/180 mg 5/14 Schedule (Phase 1b) Oprozomib 150 mg once daily treatment for 5 consecutive days (days 1, 2, 3, 4, and 5 of a 14-day cycle) followed by a step-up in oprozomib once daily dose to 180 mg starting in cycle 2 and moving forward. Dexamethasone 20 mg once daily was administered on days 1, 2, 8, and 9 of each 14-day cycle. Treatment was administered in 14-day cycles until disease progression, unacceptable toxicity, or study treatment discontinuation for any reason. | 3 |
| Cohort 210 mg 2/7 Schedule (Phase 1b) Oprozomib 210 mg once daily on Days 1, 2, 8, and 9 of a 14-day treatment cycle in combination with 20 mg dexamethasone once daily on Days 1, 2, 8, and 9 of a 14-day cycle. Treatment was administered in 14-day cycles until disease progression, unacceptable toxicity, or study treatment discontinuation for any reason.
This was the first cohort to enroll participants into the 2/7 schedule. The Cohort Safety Review Committee (CSRC) reviewed safety data and made dose adjustments for oprozomib in 30 mg increments for all cohorts. | 4 |
| Cohort 240 mg 2/7 Schedule (Phase 1b) Oprozomib 240 mg once daily on Days 1, 2, 8, and 9 of a 14-day treatment cycle in combination with 20 mg dexamethasone once daily on Days 1, 2, 8, and 9 of a 14-day cycle. Treatment was administered in 14-day cycles until disease progression, unacceptable toxicity, or study treatment discontinuation for any reason. | 4 |
| Cohort 270 mg 2/7 Schedule (Phase 1b) Oprozomib 270 mg once daily on Days 1, 2, 8, and 9 of a 14-day treatment cycle in combination with 20 mg dexamethasone once daily on Days 1, 2, 8, and 9 of a 14-day cycle. Treatment was administered in 14-day cycles until disease progression, unacceptable toxicity, or study treatment discontinuation for any reason. | 6 |
| Cohort 300 mg 2/7 Schedule (Phase 1b) Oprozomib 300 mg once daily on Days 1, 2, 8, and 9 of a 14-day treatment cycle in combination with 20 mg dexamethasone once daily on Days 1, 2, 8, and 9 of a 14-day cycle. Treatment was administered in 14-day cycles until disease progression, unacceptable toxicity, or study treatment discontinuation for any reason. | 8 |
| Cohort 330 mg 2/7 Schedule (Phase 1b) Oprozomib 330 mg once daily on Days 1, 2, 8, and 9 of a 14-day treatment cycle in combination with 20 mg dexamethasone once daily on Days 1, 2, 8, and 9 of a 14-day cycle. Treatment was administered in 14-day cycles until disease progression, unacceptable toxicity, or study treatment discontinuation for any reason. | 6 |
| Phase 2 300 mg 2/7 Schedule The Cohort Safety Review Committee (CSRC) determined this dose as the recommended phase 2 dose (RP2D). Oprozomib 300 mg once daily on Days 1, 2, 8, and 9 of a 14-day treatment cycle in combination with 20 mg dexamethasone once daily on Days 1, 2, 8, and 9 of a 14-day cycle. Treatment was administered in 14-day cycles until disease progression, unacceptable toxicity, or study treatment discontinuation for any reason. | 18 |
| Total | 65 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 4 | 6 | 1 | 0 | 1 | 1 | 2 | 1 | 9 |
| Overall Study | Disease progression | 3 | 0 | 2 | 1 | 3 | 3 | 6 | 2 | 7 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Physician Decision | 1 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Study terminated by sponsor | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 1 | 0 | 1 | 0 | 1 | 0 | 2 | 1 |
Baseline characteristics
| Characteristic | Phase 2 300 mg 2/7 Schedule | Cohort 180 mg 5/14 Schedule (Phase 1b) | Cohort 210 mg 5/14 Schedule (Phase 1b) | Cohort 150/180 mg 5/14 Schedule (Phase 1b) | Cohort 210 mg 2/7 Schedule (Phase 1b) | Cohort 240 mg 2/7 Schedule (Phase 1b) | Cohort 270 mg 2/7 Schedule (Phase 1b) | Cohort 300 mg 2/7 Schedule (Phase 1b) | Cohort 330 mg 2/7 Schedule (Phase 1b) | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized 65 - <75 years | 7 Participants | 2 Participants | 3 Participants | 0 Participants | 2 Participants | 0 Participants | 3 Participants | 3 Participants | 0 Participants | 20 Participants |
| Age, Customized <65 years | 6 Participants | 5 Participants | 4 Participants | 2 Participants | 1 Participants | 4 Participants | 2 Participants | 4 Participants | 5 Participants | 33 Participants |
| Age, Customized >=75 years | 5 Participants | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants | 9 Participants | 7 Participants | 3 Participants | 4 Participants | 2 Participants | 6 Participants | 8 Participants | 5 Participants | 55 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 7 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 8 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 1 Participants | 1 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 7 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 9 Participants |
| Race (NIH/OMB) White | 10 Participants | 8 Participants | 7 Participants | 2 Participants | 3 Participants | 2 Participants | 4 Participants | 7 Participants | 4 Participants | 47 Participants |
| Sex: Female, Male Female | 9 Participants | 3 Participants | 4 Participants | 1 Participants | 2 Participants | 1 Participants | 2 Participants | 3 Participants | 2 Participants | 27 Participants |
| Sex: Female, Male Male | 9 Participants | 6 Participants | 3 Participants | 2 Participants | 2 Participants | 3 Participants | 4 Participants | 5 Participants | 4 Participants | 38 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 1 / 7 | 0 / 3 | 0 / 4 | 1 / 4 | 0 / 6 | 0 / 8 | 0 / 6 | 0 / 18 |
| other Total, other adverse events | 9 / 9 | 7 / 7 | 3 / 3 | 4 / 4 | 4 / 4 | 6 / 6 | 8 / 8 | 6 / 6 | 18 / 18 |
| serious Total, serious adverse events | 4 / 9 | 2 / 7 | 2 / 3 | 2 / 4 | 1 / 4 | 1 / 6 | 3 / 8 | 0 / 6 | 9 / 18 |
Outcome results
Primary
Best Overall Response in Phase 2 as Assessed by Investigator
Disease response and progression were determined using the International Myeloma Working Group-Uniform Response Criteria (IMWG-URC), except for minimal response (MR) and near complete response (nCR) which was based on the European Group for Blood and Marrow Transplantation (EBMT) criteria. Evaluations reported were assessed by the investigator for participants in Phase 2.
Time frame: Screening: Day 14 to Day -1; During study: Day 1 up to 13.16 months
Population: Safety Population
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 180 mg 5/14 Schedule (Phase 1b) | Best Overall Response in Phase 2 as Assessed by Investigator | Stringent Complete Response (sCR) | 0 Participants |
| Cohort 180 mg 5/14 Schedule (Phase 1b) | Best Overall Response in Phase 2 as Assessed by Investigator | Complete Response (CR) | 1 Participants |
| Cohort 180 mg 5/14 Schedule (Phase 1b) | Best Overall Response in Phase 2 as Assessed by Investigator | Stable Disease (SD) | 2 Participants |
| Cohort 180 mg 5/14 Schedule (Phase 1b) | Best Overall Response in Phase 2 as Assessed by Investigator | Progressive Disease (PD) | 1 Participants |
| Cohort 180 mg 5/14 Schedule (Phase 1b) | Best Overall Response in Phase 2 as Assessed by Investigator | Not Evaluable (NE) | 2 Participants |
| Cohort 180 mg 5/14 Schedule (Phase 1b) | Best Overall Response in Phase 2 as Assessed by Investigator | Near Complete Response (nCR) | 0 Participants |
| Cohort 180 mg 5/14 Schedule (Phase 1b) | Best Overall Response in Phase 2 as Assessed by Investigator | Very Good Partial Response (VGPR) | 2 Participants |
| Cohort 180 mg 5/14 Schedule (Phase 1b) | Best Overall Response in Phase 2 as Assessed by Investigator | Partial Response (PR) | 9 Participants |
| Cohort 180 mg 5/14 Schedule (Phase 1b) | Best Overall Response in Phase 2 as Assessed by Investigator | Minimal Response (MR) | 1 Participants |
| Cohort 180 mg 5/14 Schedule (Phase 1b) | Best Overall Response in Phase 2 as Assessed by Investigator | Unknown | 0 Participants |
Primary
Participants With Dose-Limiting Toxicities (DLT)
Toxicities (graded per the Common Terminology Criteria for Adverse Events v 4.03) were considered DLTs if judged by the investigator to be related to oprozomib and occurred in the first 14 days of treatment, with treatment at the dose to be studied (i.e., Cycle 1 for continuous dosing or Cycle 2 for step-up dosing). A DLT was categorized as nonhematologic or hematologic. Examples include: * Any ≥ Grade 3 nonhematologic AE, with exceptions or qualifications such as Grade 3 nausea, vomiting, diarrhea, or constipation were considered a DLT only if lasting for \> 7 days despite optimal supportive care * Grade 3 fatigue lasting \> 14 days * Grade 4 neutropenia: absolute neutrophil count (ANC) \< 500 cells/mcL lasting ≥ 7 days * Febrile neutropenia: Any single temperature ≥ 38.3°C or a sustained temperature of ≥ 38.0°C for over 1 hour with ≥ Grade 3 neutropenia (ANC \< 1000 cells/mcL) * Grade 3/4 thrombocytopenia * Others specified in the protocol
Time frame: Day 1 to Day 14 (Cycle 1) for continous dosing and Day 15 to Day 28 (Cycle 2) for step-up dosing
Population: Safety population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 180 mg 5/14 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Nausea | 0 Participants |
| Cohort 180 mg 5/14 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Mental status changes | 0 Participants |
| Cohort 180 mg 5/14 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Subarachnoid haemorrhage | 0 Participants |
| Cohort 180 mg 5/14 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Upper respiratory tract infection | 0 Participants |
| Cohort 180 mg 5/14 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Alanine aminotransferase increased | 0 Participants |
| Cohort 180 mg 5/14 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Vomiting | 0 Participants |
| Cohort 180 mg 5/14 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Hypertension | 0 Participants |
| Cohort 180 mg 5/14 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Anemia | 0 Participants |
| Cohort 180 mg 5/14 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Thrombocytopenia | 0 Participants |
| Cohort 180 mg 5/14 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Pain in jaw | 0 Participants |
| Cohort 180 mg 5/14 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Aspartate aminotransferase increased | 0 Participants |
| Cohort 180 mg 5/14 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Participants reporting >=1 DLT | 0 Participants |
| Cohort 210 mg 5/14 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Thrombocytopenia | 1 Participants |
| Cohort 210 mg 5/14 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Subarachnoid haemorrhage | 1 Participants |
| Cohort 210 mg 5/14 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Participants reporting >=1 DLT | 3 Participants |
| Cohort 210 mg 5/14 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Upper respiratory tract infection | 0 Participants |
| Cohort 210 mg 5/14 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Pain in jaw | 0 Participants |
| Cohort 210 mg 5/14 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Mental status changes | 0 Participants |
| Cohort 210 mg 5/14 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Vomiting | 0 Participants |
| Cohort 210 mg 5/14 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Alanine aminotransferase increased | 1 Participants |
| Cohort 210 mg 5/14 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Nausea | 0 Participants |
| Cohort 210 mg 5/14 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Aspartate aminotransferase increased | 1 Participants |
| Cohort 210 mg 5/14 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Anemia | 0 Participants |
| Cohort 210 mg 5/14 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Hypertension | 1 Participants |
| Cohort 150/180 mg 5/14 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Mental status changes | 1 Participants |
| Cohort 150/180 mg 5/14 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Anemia | 0 Participants |
| Cohort 150/180 mg 5/14 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Thrombocytopenia | 0 Participants |
| Cohort 150/180 mg 5/14 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Aspartate aminotransferase increased | 0 Participants |
| Cohort 150/180 mg 5/14 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Participants reporting >=1 DLT | 1 Participants |
| Cohort 150/180 mg 5/14 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Subarachnoid haemorrhage | 0 Participants |
| Cohort 150/180 mg 5/14 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Hypertension | 0 Participants |
| Cohort 150/180 mg 5/14 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Vomiting | 0 Participants |
| Cohort 150/180 mg 5/14 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Nausea | 0 Participants |
| Cohort 150/180 mg 5/14 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Upper respiratory tract infection | 0 Participants |
| Cohort 150/180 mg 5/14 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Pain in jaw | 0 Participants |
| Cohort 150/180 mg 5/14 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Alanine aminotransferase increased | 0 Participants |
| Cohort 210 mg 2/7 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Hypertension | 0 Participants |
| Cohort 210 mg 2/7 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Alanine aminotransferase increased | 0 Participants |
| Cohort 210 mg 2/7 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Nausea | 0 Participants |
| Cohort 210 mg 2/7 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Subarachnoid haemorrhage | 0 Participants |
| Cohort 210 mg 2/7 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Vomiting | 0 Participants |
| Cohort 210 mg 2/7 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Thrombocytopenia | 0 Participants |
| Cohort 210 mg 2/7 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Aspartate aminotransferase increased | 0 Participants |
| Cohort 210 mg 2/7 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Pain in jaw | 0 Participants |
| Cohort 210 mg 2/7 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Anemia | 0 Participants |
| Cohort 210 mg 2/7 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Participants reporting >=1 DLT | 0 Participants |
| Cohort 210 mg 2/7 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Upper respiratory tract infection | 0 Participants |
| Cohort 210 mg 2/7 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Mental status changes | 0 Participants |
| Cohort 240 mg 2/7 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Alanine aminotransferase increased | 0 Participants |
| Cohort 240 mg 2/7 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Participants reporting >=1 DLT | 0 Participants |
| Cohort 240 mg 2/7 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Mental status changes | 0 Participants |
| Cohort 240 mg 2/7 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Aspartate aminotransferase increased | 0 Participants |
| Cohort 240 mg 2/7 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Hypertension | 0 Participants |
| Cohort 240 mg 2/7 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Subarachnoid haemorrhage | 0 Participants |
| Cohort 240 mg 2/7 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Thrombocytopenia | 0 Participants |
| Cohort 240 mg 2/7 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Anemia | 0 Participants |
| Cohort 240 mg 2/7 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Nausea | 0 Participants |
| Cohort 240 mg 2/7 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Upper respiratory tract infection | 0 Participants |
| Cohort 240 mg 2/7 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Vomiting | 0 Participants |
| Cohort 240 mg 2/7 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Pain in jaw | 0 Participants |
| Cohort 270 mg 2/7 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Anemia | 0 Participants |
| Cohort 270 mg 2/7 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Thrombocytopenia | 1 Participants |
| Cohort 270 mg 2/7 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Pain in jaw | 1 Participants |
| Cohort 270 mg 2/7 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Alanine aminotransferase increased | 0 Participants |
| Cohort 270 mg 2/7 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Hypertension | 0 Participants |
| Cohort 270 mg 2/7 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Subarachnoid haemorrhage | 0 Participants |
| Cohort 270 mg 2/7 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Vomiting | 0 Participants |
| Cohort 270 mg 2/7 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Mental status changes | 0 Participants |
| Cohort 270 mg 2/7 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Upper respiratory tract infection | 0 Participants |
| Cohort 270 mg 2/7 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Participants reporting >=1 DLT | 2 Participants |
| Cohort 270 mg 2/7 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Aspartate aminotransferase increased | 0 Participants |
| Cohort 270 mg 2/7 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Nausea | 0 Participants |
| Cohort 300 mg 2/7 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Hypertension | 0 Participants |
| Cohort 300 mg 2/7 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Thrombocytopenia | 0 Participants |
| Cohort 300 mg 2/7 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Aspartate aminotransferase increased | 0 Participants |
| Cohort 300 mg 2/7 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Anemia | 0 Participants |
| Cohort 300 mg 2/7 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Alanine aminotransferase increased | 0 Participants |
| Cohort 300 mg 2/7 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Nausea | 0 Participants |
| Cohort 300 mg 2/7 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Pain in jaw | 0 Participants |
| Cohort 300 mg 2/7 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Upper respiratory tract infection | 0 Participants |
| Cohort 300 mg 2/7 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Mental status changes | 0 Participants |
| Cohort 300 mg 2/7 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Vomiting | 0 Participants |
| Cohort 300 mg 2/7 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Participants reporting >=1 DLT | 0 Participants |
| Cohort 300 mg 2/7 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Subarachnoid haemorrhage | 0 Participants |
| Cohort 330 mg 2/7 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Hypertension | 0 Participants |
| Cohort 330 mg 2/7 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Upper respiratory tract infection | 1 Participants |
| Cohort 330 mg 2/7 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Vomiting | 1 Participants |
| Cohort 330 mg 2/7 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Mental status changes | 0 Participants |
| Cohort 330 mg 2/7 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Subarachnoid haemorrhage | 0 Participants |
| Cohort 330 mg 2/7 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Alanine aminotransferase increased | 0 Participants |
| Cohort 330 mg 2/7 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Participants reporting >=1 DLT | 2 Participants |
| Cohort 330 mg 2/7 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Thrombocytopenia | 0 Participants |
| Cohort 330 mg 2/7 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Anemia | 0 Participants |
| Cohort 330 mg 2/7 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Aspartate aminotransferase increased | 0 Participants |
| Cohort 330 mg 2/7 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Nausea | 1 Participants |
| Cohort 330 mg 2/7 Schedule (Phase 1b) | Participants With Dose-Limiting Toxicities (DLT) | Pain in jaw | 0 Participants |
| Phase 2 300 mg 2/7 Schedule | Participants With Dose-Limiting Toxicities (DLT) | Nausea | 0 Participants |
| Phase 2 300 mg 2/7 Schedule | Participants With Dose-Limiting Toxicities (DLT) | Mental status changes | 0 Participants |
| Phase 2 300 mg 2/7 Schedule | Participants With Dose-Limiting Toxicities (DLT) | Upper respiratory tract infection | 0 Participants |
| Phase 2 300 mg 2/7 Schedule | Participants With Dose-Limiting Toxicities (DLT) | Aspartate aminotransferase increased | 0 Participants |
| Phase 2 300 mg 2/7 Schedule | Participants With Dose-Limiting Toxicities (DLT) | Participants reporting >=1 DLT | 1 Participants |
| Phase 2 300 mg 2/7 Schedule | Participants With Dose-Limiting Toxicities (DLT) | Thrombocytopenia | 0 Participants |
| Phase 2 300 mg 2/7 Schedule | Participants With Dose-Limiting Toxicities (DLT) | Subarachnoid haemorrhage | 0 Participants |
| Phase 2 300 mg 2/7 Schedule | Participants With Dose-Limiting Toxicities (DLT) | Vomiting | 0 Participants |
| Phase 2 300 mg 2/7 Schedule | Participants With Dose-Limiting Toxicities (DLT) | Alanine aminotransferase increased | 0 Participants |
| Phase 2 300 mg 2/7 Schedule | Participants With Dose-Limiting Toxicities (DLT) | Anemia | 1 Participants |
| Phase 2 300 mg 2/7 Schedule | Participants With Dose-Limiting Toxicities (DLT) | Hypertension | 0 Participants |
| Phase 2 300 mg 2/7 Schedule | Participants With Dose-Limiting Toxicities (DLT) | Pain in jaw | 0 Participants |
Primary
Participants With Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2
AE defined as any untoward medical occurrence in a clinical trial participant. Treatment-emergent adverse events were defined as adverse events that start on or after the first day of study treatment and within 30 days of the last day of study treatment. An adverse event that was present before the first administration of study treatment and subsequently worsens in severity during treatment was also considered to be treatment-emergent. Serious AE defined as AE that is fatal, life threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or other significant medical hazard. Severity of AEs assessed according to Common Terminology Criteria for Adverse Events (CTCAE, v4.03) based on the general guideline: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening or disabling; Grade 5: Death related to AE. IP=investigational product
Time frame: Day 1 up to Week 282
Population: Safety population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 180 mg 5/14 Schedule (Phase 1b) | Participants With Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | Leading to discontinuation of IP | 4 Participants |
| Cohort 180 mg 5/14 Schedule (Phase 1b) | Participants With Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | Fatal AE | 0 Participants |
| Cohort 180 mg 5/14 Schedule (Phase 1b) | Participants With Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | Serious AE | 4 Participants |
| Cohort 180 mg 5/14 Schedule (Phase 1b) | Participants With Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | >=1 TEAE | 9 Participants |
| Cohort 180 mg 5/14 Schedule (Phase 1b) | Participants With Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | Grade >=3 (severe) | 8 Participants |
| Cohort 210 mg 5/14 Schedule (Phase 1b) | Participants With Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | >=1 TEAE | 7 Participants |
| Cohort 210 mg 5/14 Schedule (Phase 1b) | Participants With Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | Leading to discontinuation of IP | 6 Participants |
| Cohort 210 mg 5/14 Schedule (Phase 1b) | Participants With Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | Fatal AE | 1 Participants |
| Cohort 210 mg 5/14 Schedule (Phase 1b) | Participants With Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | Grade >=3 (severe) | 5 Participants |
| Cohort 210 mg 5/14 Schedule (Phase 1b) | Participants With Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | Serious AE | 2 Participants |
| Cohort 150/180 mg 5/14 Schedule (Phase 1b) | Participants With Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | Fatal AE | 0 Participants |
| Cohort 150/180 mg 5/14 Schedule (Phase 1b) | Participants With Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | Leading to discontinuation of IP | 1 Participants |
| Cohort 150/180 mg 5/14 Schedule (Phase 1b) | Participants With Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | Serious AE | 2 Participants |
| Cohort 150/180 mg 5/14 Schedule (Phase 1b) | Participants With Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | >=1 TEAE | 3 Participants |
| Cohort 150/180 mg 5/14 Schedule (Phase 1b) | Participants With Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | Grade >=3 (severe) | 2 Participants |
| Cohort 210 mg 2/7 Schedule (Phase 1b) | Participants With Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | Leading to discontinuation of IP | 0 Participants |
| Cohort 210 mg 2/7 Schedule (Phase 1b) | Participants With Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | >=1 TEAE | 4 Participants |
| Cohort 210 mg 2/7 Schedule (Phase 1b) | Participants With Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | Fatal AE | 0 Participants |
| Cohort 210 mg 2/7 Schedule (Phase 1b) | Participants With Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | Grade >=3 (severe) | 3 Participants |
| Cohort 210 mg 2/7 Schedule (Phase 1b) | Participants With Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | Serious AE | 2 Participants |
| Cohort 240 mg 2/7 Schedule (Phase 1b) | Participants With Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | Fatal AE | 1 Participants |
| Cohort 240 mg 2/7 Schedule (Phase 1b) | Participants With Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | Leading to discontinuation of IP | 1 Participants |
| Cohort 240 mg 2/7 Schedule (Phase 1b) | Participants With Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | >=1 TEAE | 4 Participants |
| Cohort 240 mg 2/7 Schedule (Phase 1b) | Participants With Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | Serious AE | 1 Participants |
| Cohort 240 mg 2/7 Schedule (Phase 1b) | Participants With Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | Grade >=3 (severe) | 3 Participants |
| Cohort 270 mg 2/7 Schedule (Phase 1b) | Participants With Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | Fatal AE | 0 Participants |
| Cohort 270 mg 2/7 Schedule (Phase 1b) | Participants With Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | Serious AE | 1 Participants |
| Cohort 270 mg 2/7 Schedule (Phase 1b) | Participants With Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | >=1 TEAE | 6 Participants |
| Cohort 270 mg 2/7 Schedule (Phase 1b) | Participants With Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | Leading to discontinuation of IP | 1 Participants |
| Cohort 270 mg 2/7 Schedule (Phase 1b) | Participants With Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | Grade >=3 (severe) | 5 Participants |
| Cohort 300 mg 2/7 Schedule (Phase 1b) | Participants With Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | Leading to discontinuation of IP | 2 Participants |
| Cohort 300 mg 2/7 Schedule (Phase 1b) | Participants With Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | >=1 TEAE | 8 Participants |
| Cohort 300 mg 2/7 Schedule (Phase 1b) | Participants With Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | Grade >=3 (severe) | 6 Participants |
| Cohort 300 mg 2/7 Schedule (Phase 1b) | Participants With Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | Serious AE | 3 Participants |
| Cohort 300 mg 2/7 Schedule (Phase 1b) | Participants With Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | Fatal AE | 0 Participants |
| Cohort 330 mg 2/7 Schedule (Phase 1b) | Participants With Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | Leading to discontinuation of IP | 1 Participants |
| Cohort 330 mg 2/7 Schedule (Phase 1b) | Participants With Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | Serious AE | 0 Participants |
| Cohort 330 mg 2/7 Schedule (Phase 1b) | Participants With Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | >=1 TEAE | 6 Participants |
| Cohort 330 mg 2/7 Schedule (Phase 1b) | Participants With Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | Fatal AE | 0 Participants |
| Cohort 330 mg 2/7 Schedule (Phase 1b) | Participants With Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | Grade >=3 (severe) | 5 Participants |
| Phase 2 300 mg 2/7 Schedule | Participants With Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | >=1 TEAE | 18 Participants |
| Phase 2 300 mg 2/7 Schedule | Participants With Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | Leading to discontinuation of IP | 11 Participants |
| Phase 2 300 mg 2/7 Schedule | Participants With Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | Serious AE | 9 Participants |
| Phase 2 300 mg 2/7 Schedule | Participants With Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | Fatal AE | 0 Participants |
| Phase 2 300 mg 2/7 Schedule | Participants With Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | Grade >=3 (severe) | 16 Participants |
Primary
Participants With Treatment-Related, Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2
AE defined as any untoward medical occurrence in a clinical trial participant. TEAEs were defined as AEs that start on or after the first day of study treatment and within 30 days of the last day of study treatment. An AE that was present before the first administration of study treatment and subsequently worsens in severity during treatment was also considered a TEAE. Investigator assessed AEs for relatedness to study drug. Serious AE defined as AE that is fatal, life threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or other significant medical hazard. Severity of AEs assessed according to Common Terminology Criteria for Adverse Events (CTCAE, v4.03) based on the general guideline: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening or disabling; Grade 5: Death related to AE. IP=investigational product
Time frame: Day 1 up to Week 282
Population: Safety population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 180 mg 5/14 Schedule (Phase 1b) | Participants With Treatment-Related, Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | Grade >=3 (severe) | 8 Participants |
| Cohort 180 mg 5/14 Schedule (Phase 1b) | Participants With Treatment-Related, Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | Leading to discontinuation of IP | 3 Participants |
| Cohort 180 mg 5/14 Schedule (Phase 1b) | Participants With Treatment-Related, Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | >=1 related TEAE | 9 Participants |
| Cohort 180 mg 5/14 Schedule (Phase 1b) | Participants With Treatment-Related, Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | Fatal AE | 0 Participants |
| Cohort 180 mg 5/14 Schedule (Phase 1b) | Participants With Treatment-Related, Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | Serious AE | 3 Participants |
| Cohort 210 mg 5/14 Schedule (Phase 1b) | Participants With Treatment-Related, Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | Grade >=3 (severe) | 5 Participants |
| Cohort 210 mg 5/14 Schedule (Phase 1b) | Participants With Treatment-Related, Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | Fatal AE | 1 Participants |
| Cohort 210 mg 5/14 Schedule (Phase 1b) | Participants With Treatment-Related, Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | Leading to discontinuation of IP | 6 Participants |
| Cohort 210 mg 5/14 Schedule (Phase 1b) | Participants With Treatment-Related, Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | >=1 related TEAE | 7 Participants |
| Cohort 210 mg 5/14 Schedule (Phase 1b) | Participants With Treatment-Related, Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | Serious AE | 2 Participants |
| Cohort 150/180 mg 5/14 Schedule (Phase 1b) | Participants With Treatment-Related, Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | Fatal AE | 0 Participants |
| Cohort 150/180 mg 5/14 Schedule (Phase 1b) | Participants With Treatment-Related, Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | Serious AE | 0 Participants |
| Cohort 150/180 mg 5/14 Schedule (Phase 1b) | Participants With Treatment-Related, Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | Grade >=3 (severe) | 2 Participants |
| Cohort 150/180 mg 5/14 Schedule (Phase 1b) | Participants With Treatment-Related, Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | Leading to discontinuation of IP | 0 Participants |
| Cohort 150/180 mg 5/14 Schedule (Phase 1b) | Participants With Treatment-Related, Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | >=1 related TEAE | 3 Participants |
| Cohort 210 mg 2/7 Schedule (Phase 1b) | Participants With Treatment-Related, Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | Fatal AE | 0 Participants |
| Cohort 210 mg 2/7 Schedule (Phase 1b) | Participants With Treatment-Related, Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | >=1 related TEAE | 4 Participants |
| Cohort 210 mg 2/7 Schedule (Phase 1b) | Participants With Treatment-Related, Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | Grade >=3 (severe) | 2 Participants |
| Cohort 210 mg 2/7 Schedule (Phase 1b) | Participants With Treatment-Related, Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | Serious AE | 1 Participants |
| Cohort 210 mg 2/7 Schedule (Phase 1b) | Participants With Treatment-Related, Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | Leading to discontinuation of IP | 0 Participants |
| Cohort 240 mg 2/7 Schedule (Phase 1b) | Participants With Treatment-Related, Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | Serious AE | 0 Participants |
| Cohort 240 mg 2/7 Schedule (Phase 1b) | Participants With Treatment-Related, Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | Leading to discontinuation of IP | 1 Participants |
| Cohort 240 mg 2/7 Schedule (Phase 1b) | Participants With Treatment-Related, Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | Grade >=3 (severe) | 2 Participants |
| Cohort 240 mg 2/7 Schedule (Phase 1b) | Participants With Treatment-Related, Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | >=1 related TEAE | 4 Participants |
| Cohort 240 mg 2/7 Schedule (Phase 1b) | Participants With Treatment-Related, Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | Fatal AE | 0 Participants |
| Cohort 270 mg 2/7 Schedule (Phase 1b) | Participants With Treatment-Related, Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | >=1 related TEAE | 6 Participants |
| Cohort 270 mg 2/7 Schedule (Phase 1b) | Participants With Treatment-Related, Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | Fatal AE | 0 Participants |
| Cohort 270 mg 2/7 Schedule (Phase 1b) | Participants With Treatment-Related, Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | Leading to discontinuation of IP | 1 Participants |
| Cohort 270 mg 2/7 Schedule (Phase 1b) | Participants With Treatment-Related, Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | Grade >=3 (severe) | 2 Participants |
| Cohort 270 mg 2/7 Schedule (Phase 1b) | Participants With Treatment-Related, Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | Serious AE | 0 Participants |
| Cohort 300 mg 2/7 Schedule (Phase 1b) | Participants With Treatment-Related, Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | Leading to discontinuation of IP | 1 Participants |
| Cohort 300 mg 2/7 Schedule (Phase 1b) | Participants With Treatment-Related, Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | Fatal AE | 0 Participants |
| Cohort 300 mg 2/7 Schedule (Phase 1b) | Participants With Treatment-Related, Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | Grade >=3 (severe) | 4 Participants |
| Cohort 300 mg 2/7 Schedule (Phase 1b) | Participants With Treatment-Related, Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | Serious AE | 2 Participants |
| Cohort 300 mg 2/7 Schedule (Phase 1b) | Participants With Treatment-Related, Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | >=1 related TEAE | 8 Participants |
| Cohort 330 mg 2/7 Schedule (Phase 1b) | Participants With Treatment-Related, Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | Fatal AE | 0 Participants |
| Cohort 330 mg 2/7 Schedule (Phase 1b) | Participants With Treatment-Related, Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | Grade >=3 (severe) | 3 Participants |
| Cohort 330 mg 2/7 Schedule (Phase 1b) | Participants With Treatment-Related, Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | Serious AE | 0 Participants |
| Cohort 330 mg 2/7 Schedule (Phase 1b) | Participants With Treatment-Related, Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | Leading to discontinuation of IP | 1 Participants |
| Cohort 330 mg 2/7 Schedule (Phase 1b) | Participants With Treatment-Related, Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | >=1 related TEAE | 6 Participants |
| Phase 2 300 mg 2/7 Schedule | Participants With Treatment-Related, Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | Leading to discontinuation of IP | 7 Participants |
| Phase 2 300 mg 2/7 Schedule | Participants With Treatment-Related, Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | Serious AE | 3 Participants |
| Phase 2 300 mg 2/7 Schedule | Participants With Treatment-Related, Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | >=1 related TEAE | 18 Participants |
| Phase 2 300 mg 2/7 Schedule | Participants With Treatment-Related, Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | Fatal AE | 0 Participants |
| Phase 2 300 mg 2/7 Schedule | Participants With Treatment-Related, Treatment-Emergent Adverse Events (TEAEs) During Phase 1b and 2 | Grade >=3 (severe) | 14 Participants |
Primary
Percentage of Participants Who Achieved an Overall Response As Assessed by Investigator During Phase 2
The overall response rate (ORR) was defined as the percentage of participants with the best overall response of stringent complete response (sCR), complete response (CR), near complete response (nCR), very good partial response (VGPR), and partial response (PR) as defined by the International Myeloma Working Group-Uniform Response Criteria (IMWG-URC) and modified European Group for Blood and Marrow Transplantation (EBMT) criteria.
Time frame: Screening: Day 14 to Day -1; During study: Day 1 up to 13.16 months
Population: Safety Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 180 mg 5/14 Schedule (Phase 1b) | Percentage of Participants Who Achieved an Overall Response As Assessed by Investigator During Phase 2 | 66.7 percentage of participants |
Secondary
Kaplan-Meier Estimate for Time to Progression (TTP) as Assessed by Investigator During Phase 2
Time to progression (TTP) was defined as the number of months between the start of treatment to the first documentation of disease progression. Disease progression was determined using IMWG-URC as assessed by the investigator. The same censoring rules, except for death, as in analysis of PFS were applied in the calculation of TTP. Participants who died prior to progressive disease were censored at the date of last evaluable response assessment.
Time frame: Day 1 up to 14.1 months
Population: Safety population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 180 mg 5/14 Schedule (Phase 1b) | Kaplan-Meier Estimate for Time to Progression (TTP) as Assessed by Investigator During Phase 2 | 12.2 months |
Secondary
Kaplan-Meier Estimates for Duration of Response (DOR) as Assessed by Investigator During Phase 2
Duration of response was defined as the time from first evidence of partial response (PR) or better (i.e. best overall response) to confirmation of disease progression or death due to any cause. Durations were calculated for responders only. Medians and percentiles were estimated using the Kaplan-Meier method. 95% confidence intervals for medians and percentiles were estimated using the method by Klein and Moeschberger (1997) with log-log transformation.
Time frame: Day 1 up to 13.16 months
Population: Safety population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 180 mg 5/14 Schedule (Phase 1b) | Kaplan-Meier Estimates for Duration of Response (DOR) as Assessed by Investigator During Phase 2 | NA months |
Secondary
Kaplan-Meier Estimates for Progression-free Survival (PFS) as Assessed by Investigator During Phase 2
Progression-free survival (PFS) was defined as number of months between start of treatment and first evidence of documented disease progression or death (due to any cause), whichever occurs first. Disease progression was determined using IMWG-URC per investigator. The duration of PFS was right-censored for participants who met 1 of the following conditions: * 1\) starting a new anticancer therapy before documentation of disease progression or death; * 2\) death or disease progression immediately after more than 1 consecutively missed disease assessment visit or; * 3\) alive without documentation of disease progression before the data cutoff date. 95% CIs for medians were estimated using the method by Klein and Moeschberger (1997) with log-log transformation.
Time frame: Day 1 up to 14.1 months
Population: Safety population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 180 mg 5/14 Schedule (Phase 1b) | Kaplan-Meier Estimates for Progression-free Survival (PFS) as Assessed by Investigator During Phase 2 | 12.2 months |
Secondary
Percentage of Participants Who Achieved a Clinical Benefit Response As Assessed by Investigator During Phase 2
The clinical benefit rate (CBR) was defined as Overall Response Rate (ORR) plus Minimal Response (MR) as defined by the European Group for Blood and Marrow Transplantation (EBMT) criteria.
Time frame: Screening: Day 14 to Day -1; During study: Day 1 up to 13.16 months
Population: Safety Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 180 mg 5/14 Schedule (Phase 1b) | Percentage of Participants Who Achieved a Clinical Benefit Response As Assessed by Investigator During Phase 2 | 72.2 percentage of participants |
Secondary
Pharmacokinetic (PK) Parameter for Oprozomib, Tablet and ER Formulation: Apparent Drug Clearance After Oral Administration (CL/F) on Cycle 1, Day 1
The apparent drug clearance after oral administration (CL/F) was calculated as the dose divided by AUCinf. PK samples obtained on the following schedule: Phase 1b Continuous Dosing, Cycles 1 and 2: Day 1: pre-dose, post-dose at 15 and 30 minutes, 1, 2, 4, 6, and 8 hours post-dose plus pre-dose on Day 2 Phase 1b Step-up Dosing, Day 1: pre-dose, post-dose at 15 and 30 minutes, 1, 2, 4, 6, and 7 hours post-dose plus pre-dose on Day 2 Phase 2, Day 1: pre-dose, post-dose at 15 and 30 minutes, 1, 2, 4, 6, and 7 hours post-dose plus pre-dose on Day 2
Time frame: Day 1
Population: Safety population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 180 mg 5/14 Schedule (Phase 1b) | Pharmacokinetic (PK) Parameter for Oprozomib, Tablet and ER Formulation: Apparent Drug Clearance After Oral Administration (CL/F) on Cycle 1, Day 1 | 190000 mL/hr | Geometric Coefficient of Variation 229.7 |
| Cohort 210 mg 5/14 Schedule (Phase 1b) | Pharmacokinetic (PK) Parameter for Oprozomib, Tablet and ER Formulation: Apparent Drug Clearance After Oral Administration (CL/F) on Cycle 1, Day 1 | 131000 mL/hr | Geometric Coefficient of Variation 127.2 |
| Cohort 150/180 mg 5/14 Schedule (Phase 1b) | Pharmacokinetic (PK) Parameter for Oprozomib, Tablet and ER Formulation: Apparent Drug Clearance After Oral Administration (CL/F) on Cycle 1, Day 1 | 110000 mL/hr | Geometric Coefficient of Variation 51.6 |
| Cohort 210 mg 2/7 Schedule (Phase 1b) | Pharmacokinetic (PK) Parameter for Oprozomib, Tablet and ER Formulation: Apparent Drug Clearance After Oral Administration (CL/F) on Cycle 1, Day 1 | 137000 mL/hr | Geometric Coefficient of Variation 88.8 |
| Cohort 240 mg 2/7 Schedule (Phase 1b) | Pharmacokinetic (PK) Parameter for Oprozomib, Tablet and ER Formulation: Apparent Drug Clearance After Oral Administration (CL/F) on Cycle 1, Day 1 | 118000 mL/hr | Geometric Coefficient of Variation 63.5 |
| Cohort 270 mg 2/7 Schedule (Phase 1b) | Pharmacokinetic (PK) Parameter for Oprozomib, Tablet and ER Formulation: Apparent Drug Clearance After Oral Administration (CL/F) on Cycle 1, Day 1 | NA mL/hr | — |
| Cohort 300 mg 2/7 Schedule (Phase 1b) | Pharmacokinetic (PK) Parameter for Oprozomib, Tablet and ER Formulation: Apparent Drug Clearance After Oral Administration (CL/F) on Cycle 1, Day 1 | 157000 mL/hr | Geometric Coefficient of Variation 77.7 |
| Cohort 330 mg 2/7 Schedule (Phase 1b) | Pharmacokinetic (PK) Parameter for Oprozomib, Tablet and ER Formulation: Apparent Drug Clearance After Oral Administration (CL/F) on Cycle 1, Day 1 | 153000 mL/hr | Geometric Coefficient of Variation 27.6 |
Secondary
Pharmacokinetic (PK) Parameter for Oprozomib, Tablet and ER Formulation: Apparent Volume of Distribution After Oral Administration (Vz/F) on Cycle 1, Day 1
The apparent volume of distribution after oral administration (Vz/F) calculated as the dose divided by AUCinf times ƒz, where ƒz was the first-order terminal rate constant estimated via linear regression of the terminal log-linear phase. PK samples obtained on the following schedule: Phase 1b Continuous Dosing, Cycles 1 and 2: Day 1: pre-dose, post-dose at 15 and 30 minutes, 1, 2, 4, 6, and 8 hours post-dose plus pre-dose on Day 2 Phase 1b Step-up Dosing, Day 1: pre-dose, post-dose at 15 and 30 minutes, 1, 2, 4, 6, and 7 hours post-dose plus pre-dose on Day 2 Phase 2, Day 1: pre-dose, post-dose at 15 and 30 minutes, 1, 2, 4, 6, and 7 hours post-dose plus pre-dose on Day 2
Time frame: Day 1
Population: Safety population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 180 mg 5/14 Schedule (Phase 1b) | Pharmacokinetic (PK) Parameter for Oprozomib, Tablet and ER Formulation: Apparent Volume of Distribution After Oral Administration (Vz/F) on Cycle 1, Day 1 | 264000 mL | Geometric Coefficient of Variation 235.6 |
| Cohort 210 mg 5/14 Schedule (Phase 1b) | Pharmacokinetic (PK) Parameter for Oprozomib, Tablet and ER Formulation: Apparent Volume of Distribution After Oral Administration (Vz/F) on Cycle 1, Day 1 | 108000 mL | Geometric Coefficient of Variation 106.7 |
| Cohort 150/180 mg 5/14 Schedule (Phase 1b) | Pharmacokinetic (PK) Parameter for Oprozomib, Tablet and ER Formulation: Apparent Volume of Distribution After Oral Administration (Vz/F) on Cycle 1, Day 1 | 154000 mL | Geometric Coefficient of Variation 79.5 |
| Cohort 210 mg 2/7 Schedule (Phase 1b) | Pharmacokinetic (PK) Parameter for Oprozomib, Tablet and ER Formulation: Apparent Volume of Distribution After Oral Administration (Vz/F) on Cycle 1, Day 1 | 168000 mL | Geometric Coefficient of Variation 138.9 |
| Cohort 240 mg 2/7 Schedule (Phase 1b) | Pharmacokinetic (PK) Parameter for Oprozomib, Tablet and ER Formulation: Apparent Volume of Distribution After Oral Administration (Vz/F) on Cycle 1, Day 1 | 231000 mL | Geometric Coefficient of Variation 54.7 |
| Cohort 270 mg 2/7 Schedule (Phase 1b) | Pharmacokinetic (PK) Parameter for Oprozomib, Tablet and ER Formulation: Apparent Volume of Distribution After Oral Administration (Vz/F) on Cycle 1, Day 1 | NA mL | — |
| Cohort 300 mg 2/7 Schedule (Phase 1b) | Pharmacokinetic (PK) Parameter for Oprozomib, Tablet and ER Formulation: Apparent Volume of Distribution After Oral Administration (Vz/F) on Cycle 1, Day 1 | 161000 mL | Geometric Coefficient of Variation 69 |
| Cohort 330 mg 2/7 Schedule (Phase 1b) | Pharmacokinetic (PK) Parameter for Oprozomib, Tablet and ER Formulation: Apparent Volume of Distribution After Oral Administration (Vz/F) on Cycle 1, Day 1 | 178000 mL | Geometric Coefficient of Variation 44.3 |
Secondary
Pharmacokinetic (PK) Parameter for Oprozomib, Tablet and ER Formulation: Area Under the Curve at the Last Measurable Time Point (AUClast) on Cycle 1, Day 1
The area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration (AUClast) was estimated using the linear trapezoidal method. PK samples obtained on the following schedule: Phase 1b Continuous Dosing, Cycles 1 and 2: Day 1: pre-dose, post-dose at 15 and 30 minutes, 1, 2, 4, 6, and 8 hours post-dose plus pre-dose on Day 2 Phase 1b Step-up Dosing, Day 1: pre-dose, post-dose at 15 and 30 minutes, 1, 2, 4, 6, and 7 hours post-dose plus pre-dose on Day 2 Phase 2, Day 1: pre-dose, post-dose at 15 and 30 minutes, 1, 2, 4, 6, and 7 hours post-dose plus pre-dose on Day 2
Time frame: Day 1
Population: Safety population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 180 mg 5/14 Schedule (Phase 1b) | Pharmacokinetic (PK) Parameter for Oprozomib, Tablet and ER Formulation: Area Under the Curve at the Last Measurable Time Point (AUClast) on Cycle 1, Day 1 | 1140 hr*ng/mL | Geometric Coefficient of Variation 197.4 |
| Cohort 210 mg 5/14 Schedule (Phase 1b) | Pharmacokinetic (PK) Parameter for Oprozomib, Tablet and ER Formulation: Area Under the Curve at the Last Measurable Time Point (AUClast) on Cycle 1, Day 1 | 1770 hr*ng/mL | Geometric Coefficient of Variation 104.7 |
| Cohort 150/180 mg 5/14 Schedule (Phase 1b) | Pharmacokinetic (PK) Parameter for Oprozomib, Tablet and ER Formulation: Area Under the Curve at the Last Measurable Time Point (AUClast) on Cycle 1, Day 1 | 2170 hr*ng/mL | Geometric Coefficient of Variation 51.8 |
| Cohort 210 mg 2/7 Schedule (Phase 1b) | Pharmacokinetic (PK) Parameter for Oprozomib, Tablet and ER Formulation: Area Under the Curve at the Last Measurable Time Point (AUClast) on Cycle 1, Day 1 | 1900 hr*ng/mL | Geometric Coefficient of Variation 68.9 |
| Cohort 240 mg 2/7 Schedule (Phase 1b) | Pharmacokinetic (PK) Parameter for Oprozomib, Tablet and ER Formulation: Area Under the Curve at the Last Measurable Time Point (AUClast) on Cycle 1, Day 1 | 2530 hr*ng/mL | Geometric Coefficient of Variation 63.4 |
| Cohort 270 mg 2/7 Schedule (Phase 1b) | Pharmacokinetic (PK) Parameter for Oprozomib, Tablet and ER Formulation: Area Under the Curve at the Last Measurable Time Point (AUClast) on Cycle 1, Day 1 | 1690 hr*ng/mL | Geometric Coefficient of Variation 16.1 |
| Cohort 300 mg 2/7 Schedule (Phase 1b) | Pharmacokinetic (PK) Parameter for Oprozomib, Tablet and ER Formulation: Area Under the Curve at the Last Measurable Time Point (AUClast) on Cycle 1, Day 1 | 1740 hr*ng/mL | Geometric Coefficient of Variation 70.3 |
| Cohort 330 mg 2/7 Schedule (Phase 1b) | Pharmacokinetic (PK) Parameter for Oprozomib, Tablet and ER Formulation: Area Under the Curve at the Last Measurable Time Point (AUClast) on Cycle 1, Day 1 | 1690 hr*ng/mL | Geometric Coefficient of Variation 70.8 |
Secondary
Pharmacokinetic (PK) Parameter for Oprozomib, Tablet and ER Formulation: Area Under the Curve From Time 0 to Time Infinity (AUCinf) on Cycle 1, Day 1
The area under the plasma concentration-curve from time 0 to time infinity (AUCinf) was estimated using the linear trapezoidal method PK samples obtained on the following schedule: Phase 1b Continuous Dosing, Cycles 1 and 2: Day 1: pre-dose, post-dose at 15 and 30 minutes, 1, 2, 4, 6, and 8 hours post-dose plus pre-dose on Day 2 Phase 1b Step-up Dosing, Day 1: pre-dose, post-dose at 15 and 30 minutes, 1, 2, 4, 6, and 7 hours post-dose plus pre-dose on Day 2 Phase 2, Day 1: pre-dose, post-dose at 15 and 30 minutes, 1, 2, 4, 6, and 7 hours post-dose plus pre-dose on Day 2
Time frame: Day 1
Population: Safety population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 180 mg 5/14 Schedule (Phase 1b) | Pharmacokinetic (PK) Parameter for Oprozomib, Tablet and ER Formulation: Area Under the Curve From Time 0 to Time Infinity (AUCinf) on Cycle 1, Day 1 | 947 hr*ng/mL | Geometric Coefficient of Variation 229.7 |
| Cohort 210 mg 5/14 Schedule (Phase 1b) | Pharmacokinetic (PK) Parameter for Oprozomib, Tablet and ER Formulation: Area Under the Curve From Time 0 to Time Infinity (AUCinf) on Cycle 1, Day 1 | 1600 hr*ng/mL | Geometric Coefficient of Variation 127.2 |
| Cohort 150/180 mg 5/14 Schedule (Phase 1b) | Pharmacokinetic (PK) Parameter for Oprozomib, Tablet and ER Formulation: Area Under the Curve From Time 0 to Time Infinity (AUCinf) on Cycle 1, Day 1 | 2180 hr*ng/mL | Geometric Coefficient of Variation 51.6 |
| Cohort 210 mg 2/7 Schedule (Phase 1b) | Pharmacokinetic (PK) Parameter for Oprozomib, Tablet and ER Formulation: Area Under the Curve From Time 0 to Time Infinity (AUCinf) on Cycle 1, Day 1 | 1970 hr*ng/mL | Geometric Coefficient of Variation 88.8 |
| Cohort 240 mg 2/7 Schedule (Phase 1b) | Pharmacokinetic (PK) Parameter for Oprozomib, Tablet and ER Formulation: Area Under the Curve From Time 0 to Time Infinity (AUCinf) on Cycle 1, Day 1 | 2550 hr*ng/mL | Geometric Coefficient of Variation 63.5 |
| Cohort 270 mg 2/7 Schedule (Phase 1b) | Pharmacokinetic (PK) Parameter for Oprozomib, Tablet and ER Formulation: Area Under the Curve From Time 0 to Time Infinity (AUCinf) on Cycle 1, Day 1 | NA hr*ng/mL | — |
| Cohort 300 mg 2/7 Schedule (Phase 1b) | Pharmacokinetic (PK) Parameter for Oprozomib, Tablet and ER Formulation: Area Under the Curve From Time 0 to Time Infinity (AUCinf) on Cycle 1, Day 1 | 1900 hr*ng/mL | Geometric Coefficient of Variation 77.7 |
| Cohort 330 mg 2/7 Schedule (Phase 1b) | Pharmacokinetic (PK) Parameter for Oprozomib, Tablet and ER Formulation: Area Under the Curve From Time 0 to Time Infinity (AUCinf) on Cycle 1, Day 1 | 2150 hr*ng/mL | Geometric Coefficient of Variation 27.6 |
Secondary
Pharmacokinetic (PK) Parameter for Oprozomib, Tablet and ER Formulation: Maximum Serum Concentration (Cmax) on Cycle 1, Day 1
PK samples obtained on the following schedule: Phase 1b Continuous Dosing, Cycles 1 and 2: Day 1: pre-dose, post-dose at 15 and 30 minutes, 1, 2, 4, 6, and 8 hours post-dose plus pre-dose on Day 2 Phase 1b Step-up Dosing, Day 1: pre-dose, post-dose at 15 and 30 minutes, 1, 2, 4, 6, and 7 hours post-dose plus pre-dose on Day 2 Phase 2, Day 1: pre-dose, post-dose at 15 and 30 minutes, 1, 2, 4, 6, and 7 hours post-dose plus pre-dose on Day 2
Time frame: Day 1
Population: Safety population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 180 mg 5/14 Schedule (Phase 1b) | Pharmacokinetic (PK) Parameter for Oprozomib, Tablet and ER Formulation: Maximum Serum Concentration (Cmax) on Cycle 1, Day 1 | 633 ng/mL | Geometric Coefficient of Variation 192.1 |
| Cohort 210 mg 5/14 Schedule (Phase 1b) | Pharmacokinetic (PK) Parameter for Oprozomib, Tablet and ER Formulation: Maximum Serum Concentration (Cmax) on Cycle 1, Day 1 | 754 ng/mL | Geometric Coefficient of Variation 91.7 |
| Cohort 150/180 mg 5/14 Schedule (Phase 1b) | Pharmacokinetic (PK) Parameter for Oprozomib, Tablet and ER Formulation: Maximum Serum Concentration (Cmax) on Cycle 1, Day 1 | 841 ng/mL | Geometric Coefficient of Variation 73.8 |
| Cohort 210 mg 2/7 Schedule (Phase 1b) | Pharmacokinetic (PK) Parameter for Oprozomib, Tablet and ER Formulation: Maximum Serum Concentration (Cmax) on Cycle 1, Day 1 | 906 ng/mL | Geometric Coefficient of Variation 69.3 |
| Cohort 240 mg 2/7 Schedule (Phase 1b) | Pharmacokinetic (PK) Parameter for Oprozomib, Tablet and ER Formulation: Maximum Serum Concentration (Cmax) on Cycle 1, Day 1 | 881 ng/mL | Geometric Coefficient of Variation 37.8 |
| Cohort 270 mg 2/7 Schedule (Phase 1b) | Pharmacokinetic (PK) Parameter for Oprozomib, Tablet and ER Formulation: Maximum Serum Concentration (Cmax) on Cycle 1, Day 1 | 672 ng/mL | Geometric Coefficient of Variation 54.5 |
| Cohort 300 mg 2/7 Schedule (Phase 1b) | Pharmacokinetic (PK) Parameter for Oprozomib, Tablet and ER Formulation: Maximum Serum Concentration (Cmax) on Cycle 1, Day 1 | 785 ng/mL | Geometric Coefficient of Variation 63.7 |
| Cohort 330 mg 2/7 Schedule (Phase 1b) | Pharmacokinetic (PK) Parameter for Oprozomib, Tablet and ER Formulation: Maximum Serum Concentration (Cmax) on Cycle 1, Day 1 | 578 ng/mL | Geometric Coefficient of Variation 80.1 |
Secondary
Pharmacokinetic (PK) Parameter for Oprozomib, Tablet and ER Formulation: Terminal Half-Life (t1/2,z) on Cycle 1, Day 1
PK samples obtained on the following schedule: Phase 1b Continuous Dosing, Cycles 1 and 2: Day 1: pre-dose, post-dose at 15 and 30 minutes, 1, 2, 4, 6, and 8 hours post-dose plus pre-dose on Day 2 Phase 1b Step-up Dosing, Day 1: pre-dose, post-dose at 15 and 30 minutes, 1, 2, 4, 6, and 7 hours post-dose plus pre-dose on Day 2 Phase 2, Day 1: pre-dose, post-dose at 15 and 30 minutes, 1, 2, 4, 6, and 7 hours post-dose plus pre-dose on Day 2
Time frame: Day 1
Population: Safety population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 180 mg 5/14 Schedule (Phase 1b) | Pharmacokinetic (PK) Parameter for Oprozomib, Tablet and ER Formulation: Terminal Half-Life (t1/2,z) on Cycle 1, Day 1 | 0.962 hr | Geometric Coefficient of Variation 40.6 |
| Cohort 210 mg 5/14 Schedule (Phase 1b) | Pharmacokinetic (PK) Parameter for Oprozomib, Tablet and ER Formulation: Terminal Half-Life (t1/2,z) on Cycle 1, Day 1 | 0.573 hr | Geometric Coefficient of Variation 29.4 |
| Cohort 150/180 mg 5/14 Schedule (Phase 1b) | Pharmacokinetic (PK) Parameter for Oprozomib, Tablet and ER Formulation: Terminal Half-Life (t1/2,z) on Cycle 1, Day 1 | 0.970 hr | Geometric Coefficient of Variation 79.2 |
| Cohort 210 mg 2/7 Schedule (Phase 1b) | Pharmacokinetic (PK) Parameter for Oprozomib, Tablet and ER Formulation: Terminal Half-Life (t1/2,z) on Cycle 1, Day 1 | 0.850 hr | Geometric Coefficient of Variation 29.5 |
| Cohort 240 mg 2/7 Schedule (Phase 1b) | Pharmacokinetic (PK) Parameter for Oprozomib, Tablet and ER Formulation: Terminal Half-Life (t1/2,z) on Cycle 1, Day 1 | 1.36 hr | Geometric Coefficient of Variation 80.1 |
| Cohort 270 mg 2/7 Schedule (Phase 1b) | Pharmacokinetic (PK) Parameter for Oprozomib, Tablet and ER Formulation: Terminal Half-Life (t1/2,z) on Cycle 1, Day 1 | NA hr | — |
| Cohort 300 mg 2/7 Schedule (Phase 1b) | Pharmacokinetic (PK) Parameter for Oprozomib, Tablet and ER Formulation: Terminal Half-Life (t1/2,z) on Cycle 1, Day 1 | 0.710 hr | Geometric Coefficient of Variation 40.7 |
| Cohort 330 mg 2/7 Schedule (Phase 1b) | Pharmacokinetic (PK) Parameter for Oprozomib, Tablet and ER Formulation: Terminal Half-Life (t1/2,z) on Cycle 1, Day 1 | 0.805 hr | Geometric Coefficient of Variation 40.1 |
Secondary
Pharmacokinetic (PK) Parameter for Oprozomib, Tablet and ER Formulation: Time to Maximum Serum Concentration (Tmax) on Cycle 1, Day 1
PK samples obtained on the following schedule: Phase 1b Continuous Dosing, Cycles 1 and 2: Day 1: pre-dose, post-dose at 15 and 30 minutes, 1, 2, 4, 6, and 8 hours post-dose plus pre-dose on Day 2 Phase 1b Step-up Dosing, Day 1: pre-dose, post-dose at 15 and 30 minutes, 1, 2, 4, 6, and 7 hours post-dose plus pre-dose on Day 2 Phase 2, Day 1: pre-dose, post-dose at 15 and 30 minutes, 1, 2, 4, 6, and 7 hours post-dose plus pre-dose on Day 2
Time frame: Day 1
Population: Safety population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 180 mg 5/14 Schedule (Phase 1b) | Pharmacokinetic (PK) Parameter for Oprozomib, Tablet and ER Formulation: Time to Maximum Serum Concentration (Tmax) on Cycle 1, Day 1 | 1.0 hours |
| Cohort 210 mg 5/14 Schedule (Phase 1b) | Pharmacokinetic (PK) Parameter for Oprozomib, Tablet and ER Formulation: Time to Maximum Serum Concentration (Tmax) on Cycle 1, Day 1 | 1.1 hours |
| Cohort 150/180 mg 5/14 Schedule (Phase 1b) | Pharmacokinetic (PK) Parameter for Oprozomib, Tablet and ER Formulation: Time to Maximum Serum Concentration (Tmax) on Cycle 1, Day 1 | 1.0 hours |
| Cohort 210 mg 2/7 Schedule (Phase 1b) | Pharmacokinetic (PK) Parameter for Oprozomib, Tablet and ER Formulation: Time to Maximum Serum Concentration (Tmax) on Cycle 1, Day 1 | 1.0 hours |
| Cohort 240 mg 2/7 Schedule (Phase 1b) | Pharmacokinetic (PK) Parameter for Oprozomib, Tablet and ER Formulation: Time to Maximum Serum Concentration (Tmax) on Cycle 1, Day 1 | 2.0 hours |
| Cohort 270 mg 2/7 Schedule (Phase 1b) | Pharmacokinetic (PK) Parameter for Oprozomib, Tablet and ER Formulation: Time to Maximum Serum Concentration (Tmax) on Cycle 1, Day 1 | 2.0 hours |
| Cohort 300 mg 2/7 Schedule (Phase 1b) | Pharmacokinetic (PK) Parameter for Oprozomib, Tablet and ER Formulation: Time to Maximum Serum Concentration (Tmax) on Cycle 1, Day 1 | 1.0 hours |
| Cohort 330 mg 2/7 Schedule (Phase 1b) | Pharmacokinetic (PK) Parameter for Oprozomib, Tablet and ER Formulation: Time to Maximum Serum Concentration (Tmax) on Cycle 1, Day 1 | 1.5 hours |