Multiple Myeloma
Conditions
Keywords
Leukemia, Immunoproliferative Disorder, Neoplasma by Histologic Type, Immune System Diseases, Hematologic Diseases, Blood Protein Disorders, Paraproteinemias, Multiple Myeloma, Hematologic Disorders, Leukemia, Chronic, B-cell, Leukemia, B-cell, Leukemia, Chronic, Neoplasms, Plasma Cell, Monoclonal Gammopathy of unknown significance (MGUS)
Brief summary
The purpose of this study is to assess the safety and benefits of the investigational study drug, KW-2478, when given with bortezomib (Velcade®), a drug approved for the treatment of Multiple Myeloma (MM). The primary objectives: * To establish the safety, tolerability, and recommended Phase II dose (RP2D) of KW-2478 in combination with bortezomib (Phase I); * To assess the overall response rate (ORR) when subjects with advanced MM are treated (Phase II). The secondary objectives: * To characterize the Pharmacokinetic (PK) and Pharmacodynamic (PD) of KW-2478 with bortezomib (Phase I only); * To evaluate for preliminary evidence of efficacy (Phase I); * To determine progression free survival (PFS) and duration of response of KW-2478 with bortezomib (Phase II).
Detailed description
This is a multicenter, open label, dose escalation, Phase I / II study in subjects with relapsed and/or refractory MM. Up to 24 subjects to be enrolled in the Phase I to determine the RP2D. Up to 77 additional evaluable subjects to be enrolled in Phase II for a maximum up to 101 subjects treated in the study. Study centers in the USA and the UK will participate in Phase I and II. Centers in the Philippines will be participating in Phase II only. The planned enrollment period is 22 months and the planned study duration is 28 months.
Interventions
DRUGKW-2478
Administered Days 1, 4, 8 and 11 of a 21 day cycle
DRUGBortezomib
Administered on Days 1, 4, 8 and 11 of a 21 day cycle
Sponsors
Kyowa Hakko Kirin Pharma, Inc.
Kyowa Kirin Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Accepts Healthy Volunteers: No Inclusion Criteria: 1. Subjects with a confirmed diagnosis of Multiple Myeloma who have had one and no more than three prior regimens for MM to which they did not respond (failed) or from which they have relapsed. 2. Signed either an IRB or IEC approved informed consent 3. ECOG performance status of ≤ 2 4. Life expectancy of at least 3 months 5. M protein in either serum or urine, or free light chains if not measurable M protein in serum or urine, and clonal bone marrow plasma cells \> 10%, and evidence of end organ damage 6. Adequate hematologic status, liver and renal function 7. Subjects of reproductive potential must agree to follow accepted pregnancy prevention methods during the study.
Exclusion criteria
1. No anti-cancer treatment for ≥ 4 weeks and no bortezomib treatment ≥ 60 days prior to receiving study drug 2. Any other severe, acute or chronic illness 3. No other prior or concurrent malignancy 4. No immunosuppressant therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To Establish the Safety, Tolerability, and RP2D (Phase 1); To Assess the Overall Response Rate in Subjects With Advanced Multiple Myeloma (Phase 2). | 21 day cycle, up to 52 weeks | The safety of KW-2478 was determined by reported TEAEs, observed DLTs, changes in PEs, vital sign measurements, ECGs, and laboratory analyses. The ORR, was defined as the best response over a specified number of cycles (calculated and summarized). Disease control rate (DCR) was defined as the best response over a specified number of cycles (calculated and summarized). Progression-free survival was defined as the time from the first day of treatment until the date of disease progression or death is first reported (calculated and summarized). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1: PK Absorption Tmax hr Day 11 | PK collected Day 11 of 21-day cycle | Descriptive summary statistics (number, arithmetic mean, standard deviation \[SDev\], coefficient of variation \[CV%\]) for concentration and PK data for KW-2478 and Bortezomib in Phase 1 were presented by cohort, dose level and day. |
| Phase 1: PK Exposure Cmax ng/mL Day 11 | PK collected Day 11 of 21-day cycle | Descriptive summary statistics (number, arithmetic mean, standard deviation \[SDev\], coefficient of variation \[CV%\]) for concentration and PK data for KW-2478 and Bortezomib in Phase 1 were presented by cohort, dose level and day. |
| Phase 1: PK Exposure AUC0-t hr*ng/mL Day 11 | PK collected Day 11 of 21-day cycle | Descriptive summary statistics (number, arithmetic mean, standard deviation \[SDev\], coefficient of variation \[CV%\]) for concentration and PK data for KW-2478 and Bortezomib in Phase 1 were presented by cohort, dose level and day. |
| Phase 1: PK Elimination t½ hr Day 11 | PK collected Day 11 of 21-day cycle | Descriptive summary statistics (number, arithmetic mean, standard deviation \[SDev\], coefficient of variation \[CV%\]) for concentration and PK data for KW-2478 and Bortezomib in Phase 1 were presented by cohort, dose level and day. |
Countries
Philippines, United Kingdom, United States
Participant flow
Recruitment details
Study centers in the USA and the UK participated in the Phase 1 portion, and study centers in the USA, UK, and Philippines participated in the Phase 2 portion.
Participants by arm
| Arm | Count |
|---|---|
| KW-2478 and Bortezomib The target population in both Phase 1 and 2 were adults (≥18 years) of either gender with a confirmed history of MM by IMWG criteria had relapsed or failed to respond to 1-3 prior MM regimens with an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 and a life expectancy ≥ 3 months. Subjects had to have disease that could be evaluated by serum or urinary levels of M protein or serum free light chains in the absence of measurable M protein in serum or urine.
For Phase 1, the design was a standard 3+3 study of KW-2478 (130 or 175 mg/m\^2) and Bortezomib(1.0 or 1.3 mg/m\^2) on Days 1, 4, 8, and 11 of a 21-day cycle utilizing four dose-escalation cohorts (overall N=15). The Phase 2 portion of the study enrolled 80 subjects to determine the preliminary efficacy of KW 2478 and Bortezomib at the RP2D (KW-2478 175 mg/m\^2 / Bortezomib 1.3 mg/m\^2). | 95 |
| Total | 95 |
Baseline characteristics
| Characteristic | KW-2478 and Bortezomib |
|---|---|
| Age, Continuous | 64.3 years STANDARD_DEVIATION 9.3 |
| Body Surface Area (BSA) | 1.87 m^2 STANDARD_DEVIATION 0.27 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 22 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Race (NIH/OMB) White | 61 Participants |
| Region of Enrollment Philippines | 20 participants |
| Region of Enrollment United Kingdom | 57 participants |
| Region of Enrollment United States | 18 participants |
| Sex: Female, Male Female | 41 Participants |
| Sex: Female, Male Male | 54 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 |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 95 / 95 | 3 / 3 | 3 / 3 | 3 / 3 | 6 / 6 | 80 / 80 |
| serious Total, serious adverse events | 48 / 95 | 2 / 3 | 3 / 3 | 3 / 3 | 4 / 6 | 36 / 80 |
Outcome results
Primary
To Establish the Safety, Tolerability, and RP2D (Phase 1); To Assess the Overall Response Rate in Subjects With Advanced Multiple Myeloma (Phase 2).
The safety of KW-2478 was determined by reported TEAEs, observed DLTs, changes in PEs, vital sign measurements, ECGs, and laboratory analyses. The ORR, was defined as the best response over a specified number of cycles (calculated and summarized). Disease control rate (DCR) was defined as the best response over a specified number of cycles (calculated and summarized). Progression-free survival was defined as the time from the first day of treatment until the date of disease progression or death is first reported (calculated and summarized).
Time frame: 21 day cycle, up to 52 weeks
Population: All subjects who received at least 1 dose, including a partial dose, of KW-2478 were evaluated for safety.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase 1 & 2: KW-2478 175 mg/m^2 and Bortezomib 1.3mg/m^2 | To Establish the Safety, Tolerability, and RP2D (Phase 1); To Assess the Overall Response Rate in Subjects With Advanced Multiple Myeloma (Phase 2). | Severe (CTCAE 3) TEAE | 54 participants |
| Phase 1 & 2: KW-2478 175 mg/m^2 and Bortezomib 1.3mg/m^2 | To Establish the Safety, Tolerability, and RP2D (Phase 1); To Assess the Overall Response Rate in Subjects With Advanced Multiple Myeloma (Phase 2). | Subjects with Any DLT | 1 participants |
| Phase 1 & 2: KW-2478 175 mg/m^2 and Bortezomib 1.3mg/m^2 | To Establish the Safety, Tolerability, and RP2D (Phase 1); To Assess the Overall Response Rate in Subjects With Advanced Multiple Myeloma (Phase 2). | Life Threatening TEAE | 13 participants |
| Phase 1 & 2: KW-2478 175 mg/m^2 and Bortezomib 1.3mg/m^2 | To Establish the Safety, Tolerability, and RP2D (Phase 1); To Assess the Overall Response Rate in Subjects With Advanced Multiple Myeloma (Phase 2). | Serious Treatment-Emergent AE | 48 participants |
| Phase 1 & 2: KW-2478 175 mg/m^2 and Bortezomib 1.3mg/m^2 | To Establish the Safety, Tolerability, and RP2D (Phase 1); To Assess the Overall Response Rate in Subjects With Advanced Multiple Myeloma (Phase 2). | Subjects with Any TEAE | 95 participants |
| Phase 1 & 2: KW-2478 175 mg/m^2 and Bortezomib 1.3mg/m^2 | To Establish the Safety, Tolerability, and RP2D (Phase 1); To Assess the Overall Response Rate in Subjects With Advanced Multiple Myeloma (Phase 2). | Moderate (CTCAE 2) TEAE | 22 participants |
| Phase 1 & 2: KW-2478 175 mg/m^2 and Bortezomib 1.3mg/m^2 | To Establish the Safety, Tolerability, and RP2D (Phase 1); To Assess the Overall Response Rate in Subjects With Advanced Multiple Myeloma (Phase 2). | Related TEAE | 88 participants |
| Phase 1 Cohort 1: KW-2478 130 mg/m^2 and Bortezomib 1.0mg/m^2 | To Establish the Safety, Tolerability, and RP2D (Phase 1); To Assess the Overall Response Rate in Subjects With Advanced Multiple Myeloma (Phase 2). | Subjects with Any DLT | 0 participants |
| Phase 1 Cohort 1: KW-2478 130 mg/m^2 and Bortezomib 1.0mg/m^2 | To Establish the Safety, Tolerability, and RP2D (Phase 1); To Assess the Overall Response Rate in Subjects With Advanced Multiple Myeloma (Phase 2). | Life Threatening TEAE | 0 participants |
| Phase 1 Cohort 1: KW-2478 130 mg/m^2 and Bortezomib 1.0mg/m^2 | To Establish the Safety, Tolerability, and RP2D (Phase 1); To Assess the Overall Response Rate in Subjects With Advanced Multiple Myeloma (Phase 2). | Related TEAE | 3 participants |
| Phase 1 Cohort 1: KW-2478 130 mg/m^2 and Bortezomib 1.0mg/m^2 | To Establish the Safety, Tolerability, and RP2D (Phase 1); To Assess the Overall Response Rate in Subjects With Advanced Multiple Myeloma (Phase 2). | Subjects with Any TEAE | 3 participants |
| Phase 1 Cohort 1: KW-2478 130 mg/m^2 and Bortezomib 1.0mg/m^2 | To Establish the Safety, Tolerability, and RP2D (Phase 1); To Assess the Overall Response Rate in Subjects With Advanced Multiple Myeloma (Phase 2). | Moderate (CTCAE 2) TEAE | 0 participants |
| Phase 1 Cohort 1: KW-2478 130 mg/m^2 and Bortezomib 1.0mg/m^2 | To Establish the Safety, Tolerability, and RP2D (Phase 1); To Assess the Overall Response Rate in Subjects With Advanced Multiple Myeloma (Phase 2). | Serious Treatment-Emergent AE | 2 participants |
| Phase 1 Cohort 1: KW-2478 130 mg/m^2 and Bortezomib 1.0mg/m^2 | To Establish the Safety, Tolerability, and RP2D (Phase 1); To Assess the Overall Response Rate in Subjects With Advanced Multiple Myeloma (Phase 2). | Severe (CTCAE 3) TEAE | 3 participants |
| Phase 1 Cohort 2: KW-2478 130 mg/m^2 and Bortezomib 1.3mg/m^2 | To Establish the Safety, Tolerability, and RP2D (Phase 1); To Assess the Overall Response Rate in Subjects With Advanced Multiple Myeloma (Phase 2). | Moderate (CTCAE 2) TEAE | 0 participants |
| Phase 1 Cohort 2: KW-2478 130 mg/m^2 and Bortezomib 1.3mg/m^2 | To Establish the Safety, Tolerability, and RP2D (Phase 1); To Assess the Overall Response Rate in Subjects With Advanced Multiple Myeloma (Phase 2). | Subjects with Any TEAE | 3 participants |
| Phase 1 Cohort 2: KW-2478 130 mg/m^2 and Bortezomib 1.3mg/m^2 | To Establish the Safety, Tolerability, and RP2D (Phase 1); To Assess the Overall Response Rate in Subjects With Advanced Multiple Myeloma (Phase 2). | Serious Treatment-Emergent AE | 3 participants |
| Phase 1 Cohort 2: KW-2478 130 mg/m^2 and Bortezomib 1.3mg/m^2 | To Establish the Safety, Tolerability, and RP2D (Phase 1); To Assess the Overall Response Rate in Subjects With Advanced Multiple Myeloma (Phase 2). | Severe (CTCAE 3) TEAE | 2 participants |
| Phase 1 Cohort 2: KW-2478 130 mg/m^2 and Bortezomib 1.3mg/m^2 | To Establish the Safety, Tolerability, and RP2D (Phase 1); To Assess the Overall Response Rate in Subjects With Advanced Multiple Myeloma (Phase 2). | Related TEAE | 3 participants |
| Phase 1 Cohort 2: KW-2478 130 mg/m^2 and Bortezomib 1.3mg/m^2 | To Establish the Safety, Tolerability, and RP2D (Phase 1); To Assess the Overall Response Rate in Subjects With Advanced Multiple Myeloma (Phase 2). | Subjects with Any DLT | 0 participants |
| Phase 1 Cohort 2: KW-2478 130 mg/m^2 and Bortezomib 1.3mg/m^2 | To Establish the Safety, Tolerability, and RP2D (Phase 1); To Assess the Overall Response Rate in Subjects With Advanced Multiple Myeloma (Phase 2). | Life Threatening TEAE | 1 participants |
| Phase 1 Cohort 3: KW-2478 175 mg/m^2 and Bortezomib 1.0mg/m^2 | To Establish the Safety, Tolerability, and RP2D (Phase 1); To Assess the Overall Response Rate in Subjects With Advanced Multiple Myeloma (Phase 2). | Severe (CTCAE 3) TEAE | 2 participants |
| Phase 1 Cohort 3: KW-2478 175 mg/m^2 and Bortezomib 1.0mg/m^2 | To Establish the Safety, Tolerability, and RP2D (Phase 1); To Assess the Overall Response Rate in Subjects With Advanced Multiple Myeloma (Phase 2). | Subjects with Any TEAE | 3 participants |
| Phase 1 Cohort 3: KW-2478 175 mg/m^2 and Bortezomib 1.0mg/m^2 | To Establish the Safety, Tolerability, and RP2D (Phase 1); To Assess the Overall Response Rate in Subjects With Advanced Multiple Myeloma (Phase 2). | Related TEAE | 2 participants |
| Phase 1 Cohort 3: KW-2478 175 mg/m^2 and Bortezomib 1.0mg/m^2 | To Establish the Safety, Tolerability, and RP2D (Phase 1); To Assess the Overall Response Rate in Subjects With Advanced Multiple Myeloma (Phase 2). | Moderate (CTCAE 2) TEAE | 0 participants |
| Phase 1 Cohort 3: KW-2478 175 mg/m^2 and Bortezomib 1.0mg/m^2 | To Establish the Safety, Tolerability, and RP2D (Phase 1); To Assess the Overall Response Rate in Subjects With Advanced Multiple Myeloma (Phase 2). | Life Threatening TEAE | 0 participants |
| Phase 1 Cohort 3: KW-2478 175 mg/m^2 and Bortezomib 1.0mg/m^2 | To Establish the Safety, Tolerability, and RP2D (Phase 1); To Assess the Overall Response Rate in Subjects With Advanced Multiple Myeloma (Phase 2). | Serious Treatment-Emergent AE | 3 participants |
| Phase 1 Cohort 3: KW-2478 175 mg/m^2 and Bortezomib 1.0mg/m^2 | To Establish the Safety, Tolerability, and RP2D (Phase 1); To Assess the Overall Response Rate in Subjects With Advanced Multiple Myeloma (Phase 2). | Subjects with Any DLT | 1 participants |
| Phase 1 Cohort 4: KW-2478 175 mg/m^2 and Bortezomib 1.3mg/m^2 | To Establish the Safety, Tolerability, and RP2D (Phase 1); To Assess the Overall Response Rate in Subjects With Advanced Multiple Myeloma (Phase 2). | Subjects with Any TEAE | 6 participants |
| Phase 1 Cohort 4: KW-2478 175 mg/m^2 and Bortezomib 1.3mg/m^2 | To Establish the Safety, Tolerability, and RP2D (Phase 1); To Assess the Overall Response Rate in Subjects With Advanced Multiple Myeloma (Phase 2). | Moderate (CTCAE 2) TEAE | 0 participants |
| Phase 1 Cohort 4: KW-2478 175 mg/m^2 and Bortezomib 1.3mg/m^2 | To Establish the Safety, Tolerability, and RP2D (Phase 1); To Assess the Overall Response Rate in Subjects With Advanced Multiple Myeloma (Phase 2). | Related TEAE | 6 participants |
| Phase 1 Cohort 4: KW-2478 175 mg/m^2 and Bortezomib 1.3mg/m^2 | To Establish the Safety, Tolerability, and RP2D (Phase 1); To Assess the Overall Response Rate in Subjects With Advanced Multiple Myeloma (Phase 2). | Subjects with Any DLT | 0 participants |
| Phase 1 Cohort 4: KW-2478 175 mg/m^2 and Bortezomib 1.3mg/m^2 | To Establish the Safety, Tolerability, and RP2D (Phase 1); To Assess the Overall Response Rate in Subjects With Advanced Multiple Myeloma (Phase 2). | Serious Treatment-Emergent AE | 4 participants |
| Phase 1 Cohort 4: KW-2478 175 mg/m^2 and Bortezomib 1.3mg/m^2 | To Establish the Safety, Tolerability, and RP2D (Phase 1); To Assess the Overall Response Rate in Subjects With Advanced Multiple Myeloma (Phase 2). | Severe (CTCAE 3) TEAE | 5 participants |
| Phase 1 Cohort 4: KW-2478 175 mg/m^2 and Bortezomib 1.3mg/m^2 | To Establish the Safety, Tolerability, and RP2D (Phase 1); To Assess the Overall Response Rate in Subjects With Advanced Multiple Myeloma (Phase 2). | Life Threatening TEAE | 0 participants |
| Phase 2: KW-2478 175 mg/m^2 and Bortezomib 1.3mg/m^2 | To Establish the Safety, Tolerability, and RP2D (Phase 1); To Assess the Overall Response Rate in Subjects With Advanced Multiple Myeloma (Phase 2). | Subjects with Any DLT | 0 participants |
| Phase 2: KW-2478 175 mg/m^2 and Bortezomib 1.3mg/m^2 | To Establish the Safety, Tolerability, and RP2D (Phase 1); To Assess the Overall Response Rate in Subjects With Advanced Multiple Myeloma (Phase 2). | Life Threatening TEAE | 12 participants |
| Phase 2: KW-2478 175 mg/m^2 and Bortezomib 1.3mg/m^2 | To Establish the Safety, Tolerability, and RP2D (Phase 1); To Assess the Overall Response Rate in Subjects With Advanced Multiple Myeloma (Phase 2). | Moderate (CTCAE 2) TEAE | 22 participants |
| Phase 2: KW-2478 175 mg/m^2 and Bortezomib 1.3mg/m^2 | To Establish the Safety, Tolerability, and RP2D (Phase 1); To Assess the Overall Response Rate in Subjects With Advanced Multiple Myeloma (Phase 2). | Serious Treatment-Emergent AE | 36 participants |
| Phase 2: KW-2478 175 mg/m^2 and Bortezomib 1.3mg/m^2 | To Establish the Safety, Tolerability, and RP2D (Phase 1); To Assess the Overall Response Rate in Subjects With Advanced Multiple Myeloma (Phase 2). | Related TEAE | 74 participants |
| Phase 2: KW-2478 175 mg/m^2 and Bortezomib 1.3mg/m^2 | To Establish the Safety, Tolerability, and RP2D (Phase 1); To Assess the Overall Response Rate in Subjects With Advanced Multiple Myeloma (Phase 2). | Subjects with Any TEAE | 80 participants |
| Phase 2: KW-2478 175 mg/m^2 and Bortezomib 1.3mg/m^2 | To Establish the Safety, Tolerability, and RP2D (Phase 1); To Assess the Overall Response Rate in Subjects With Advanced Multiple Myeloma (Phase 2). | Severe (CTCAE 3) TEAE | 42 participants |
Secondary
Phase 1: PK Absorption Tmax hr Day 11
Descriptive summary statistics (number, arithmetic mean, standard deviation \[SDev\], coefficient of variation \[CV%\]) for concentration and PK data for KW-2478 and Bortezomib in Phase 1 were presented by cohort, dose level and day.
Time frame: PK collected Day 11 of 21-day cycle
Population: The PK of KW-2478 was characterized after single administrations through @25 hours post start of infusion dose on Day 1 and through @7 hours post start of infusion dose on Day 11in Phase 1 only.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase 1 & 2: KW-2478 175 mg/m^2 and Bortezomib 1.3mg/m^2 | Phase 1: PK Absorption Tmax hr Day 11 | 1.03 hr | Standard Deviation 0.0441 |
| Phase 1 Cohort 1: KW-2478 130 mg/m^2 and Bortezomib 1.0mg/m^2 | Phase 1: PK Absorption Tmax hr Day 11 | 1.03 hr | Standard Deviation 0.0481 |
| Phase 1 Cohort 2: KW-2478 130 mg/m^2 and Bortezomib 1.3mg/m^2 | Phase 1: PK Absorption Tmax hr Day 11 | 1.11 hr | Standard Deviation 0.129 |
| Phase 1 Cohort 3: KW-2478 175 mg/m^2 and Bortezomib 1.0mg/m^2 | Phase 1: PK Absorption Tmax hr Day 11 | 1.07 hr | Standard Deviation 0.0638 |
Secondary
Phase 1: PK Elimination t½ hr Day 11
Descriptive summary statistics (number, arithmetic mean, standard deviation \[SDev\], coefficient of variation \[CV%\]) for concentration and PK data for KW-2478 and Bortezomib in Phase 1 were presented by cohort, dose level and day.
Time frame: PK collected Day 11 of 21-day cycle
Population: The PK of KW-2478 was characterized after single administrations through @25 hours post start of infusion dose on Day 1 and through @7 hours post start of infusion dose on Day 11in Phase 1 only.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase 1 & 2: KW-2478 175 mg/m^2 and Bortezomib 1.3mg/m^2 | Phase 1: PK Elimination t½ hr Day 11 | 1.88 hr | Standard Deviation 0.076 |
| Phase 1 Cohort 1: KW-2478 130 mg/m^2 and Bortezomib 1.0mg/m^2 | Phase 1: PK Elimination t½ hr Day 11 | 2.02 hr | Standard Deviation 0 |
| Phase 1 Cohort 2: KW-2478 130 mg/m^2 and Bortezomib 1.3mg/m^2 | Phase 1: PK Elimination t½ hr Day 11 | 1.84 hr | Standard Deviation 0.206 |
| Phase 1 Cohort 3: KW-2478 175 mg/m^2 and Bortezomib 1.0mg/m^2 | Phase 1: PK Elimination t½ hr Day 11 | 1.77 hr | Standard Deviation 0.262 |
Secondary
Phase 1: PK Exposure AUC0-t hr*ng/mL Day 11
Descriptive summary statistics (number, arithmetic mean, standard deviation \[SDev\], coefficient of variation \[CV%\]) for concentration and PK data for KW-2478 and Bortezomib in Phase 1 were presented by cohort, dose level and day.
Time frame: PK collected Day 11 of 21-day cycle
Population: The PK of KW-2478 was characterized after single administrations through @25 hours post start of infusion dose on Day 1 and through @7 hours post start of infusion dose on Day 11 in Phase 1 only.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase 1 & 2: KW-2478 175 mg/m^2 and Bortezomib 1.3mg/m^2 | Phase 1: PK Exposure AUC0-t hr*ng/mL Day 11 | 7940 hr*ng/mL | Standard Deviation 2580 |
| Phase 1 Cohort 1: KW-2478 130 mg/m^2 and Bortezomib 1.0mg/m^2 | Phase 1: PK Exposure AUC0-t hr*ng/mL Day 11 | 26200 hr*ng/mL | Standard Deviation 36700 |
| Phase 1 Cohort 2: KW-2478 130 mg/m^2 and Bortezomib 1.3mg/m^2 | Phase 1: PK Exposure AUC0-t hr*ng/mL Day 11 | 7190 hr*ng/mL | Standard Deviation 2150 |
| Phase 1 Cohort 3: KW-2478 175 mg/m^2 and Bortezomib 1.0mg/m^2 | Phase 1: PK Exposure AUC0-t hr*ng/mL Day 11 | 6040 hr*ng/mL | Standard Deviation 2280 |
Secondary
Phase 1: PK Exposure Cmax ng/mL Day 11
Descriptive summary statistics (number, arithmetic mean, standard deviation \[SDev\], coefficient of variation \[CV%\]) for concentration and PK data for KW-2478 and Bortezomib in Phase 1 were presented by cohort, dose level and day.
Time frame: PK collected Day 11 of 21-day cycle
Population: The PK of KW-2478 was characterized after single administrations through @25 hours post start of infusion dose on Day 1 and through @7 hours post start of infusion dose on Day 11 in Phase 1 only.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase 1 & 2: KW-2478 175 mg/m^2 and Bortezomib 1.3mg/m^2 | Phase 1: PK Exposure Cmax ng/mL Day 11 | 7910 ng/mL | Standard Deviation 5360 |
| Phase 1 Cohort 1: KW-2478 130 mg/m^2 and Bortezomib 1.0mg/m^2 | Phase 1: PK Exposure Cmax ng/mL Day 11 | 41000 ng/mL | Standard Deviation 64100 |
| Phase 1 Cohort 2: KW-2478 130 mg/m^2 and Bortezomib 1.3mg/m^2 | Phase 1: PK Exposure Cmax ng/mL Day 11 | 5990 ng/mL | Standard Deviation 2720 |
| Phase 1 Cohort 3: KW-2478 175 mg/m^2 and Bortezomib 1.0mg/m^2 | Phase 1: PK Exposure Cmax ng/mL Day 11 | 5280 ng/mL | Standard Deviation 2290 |