Refractory Multiple Myeloma, Relapsed Multiple Myeloma
Conditions
Brief summary
This is a first-in-human Phase I, open-label, multicenter, global, dose-escalation study designed to evaluate the safety, tolerability, and pharmacokinetics of RO7297089 and make a preliminary assessment of anti-tumor activity in patients with R/R MM for whom no established therapy for MM is appropriate and available or who are intolerant to those established therapies.
Interventions
DRUGRO7297089
RO7297089 will be given via intravenous (IV) infusion
Sponsors
Genentech, Inc.
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
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 * Life expectancy of at least 12 weeks * R/R MM for which no established therapy for MM is appropriate and available or be intolerant to those established therapies * Measurable disease
Exclusion criteria
* Prior use of any monoclonal antibody, radioimmunoconjugate, or antibody-drug conjugate for the treatment of cancer within 4 weeks before first RO7297089 infusion * Prior treatment with systemic immunotherapeutic agents within 12 weeks or 5 half-lives of the drug, whichever is shorter, before first RO7297089 infusion * Prior treatment with CAR-T therapy within 90 days before first study drug administration * Treatment with any chemotherapeutic agent, or treatment with any other anti-cancer agent (investigational or otherwise) within 4 weeks or 5 half-lives of the drug, whichever is shorter, prior to first RO7297089 infusion * Autologous stem cell transplantation within 100 days prior to first RO7297089 infusion * Allogeneic stem cell transplantation within 180 days prior to first RO7297089 infusion or requiring immunosuppression for treatment or prophylaxis of graft versus host disease * Primary or secondary plasma cell leukemia * Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection requiring treatment with IV anti-microbial therapy within 14 days prior to first RO7297089 infusion * Significant cardiovascular disease * Current CNS involvement by MM
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Adverse Events (AEs), Including Dose Limiting Toxicities (DLTs) | Baseline up to 1 year 7 months | Adverse event severity graded according to NCI CTCAE v5.0 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve (AUC) of RO7297089 | Cycle 1 Day 1 | — |
| Maximum Concentration Observed (Cmax) of RO7297089 | Cycle 1 Day 1, Cycle 2 Day 8 | — |
| Time to Maximum Concentration Observed (Tmax) of RO7297089 | Cycle 1 Day 1 | — |
| Half-life (t1/2) of RO7297089 | Cycle 1 Day 1 | — |
| Objective Response Rate (ORR) | Baseline up to approximately 19 months | ORR is defined as a Stringent Complete Response (Scr), Complete Response (CR), Very Good Partial Response (VGPR) or Partial Response (PR) as determined by the Investigator according to International Myeloma Working Group (IMWG) Uniform Response Criteria |
| Minimum Concentration Observed (Cmin) of RO7297089 | Cycle 1 Day 1, Cycle 2 Day 8 | — |
Countries
Australia, Belgium, Denmark, Norway
Participant flow
Recruitment details
The study consisted of a screening period of up to 28 days and a minimum follow-up period of 90 days after treatment. Following confirmation of eligibility, patients received RO7297089 by intravenous (IV) infusion. Patients were enrolled in two stages: a dose escalation stage and an expansion stage.
Participants by arm
| Arm | Count |
|---|---|
| Dose Escalation Cohort 1: RO7297089 Participants in Arm A received 60 mg dose of RO7297089 as a flat dose at each scheduled study drug administration visit | 3 |
| Dose Escalation Cohort 2: RO7297089 Participants in Arm A received 180 mg dose of RO7297089 as a flat dose at each scheduled study drug administration visit | 5 |
| Dose Escalation Cohort 3: RO7297089 Participants in Arm A received 360 mg dose of RO7297089 as a flat dose at each scheduled study drug administration visit | 4 |
| Dose Escalation Cohort 4: RO7297089 Participants in Arm A received 1080 mg dose of RO7297089 as a flat dose at each scheduled study drug administration visit | 6 |
| Dose Escalation Backfill Cohort 4: RO7297089 Participants in Arm B received the 1080 mg dose of RO7297089 as a split dose divided over two days (Days 1 and 2). The full target dose wasadministered at subsequent study drug administration visits. | 6 |
| Dose Escalation Cohort 5: RO7297089 Participants in Arm B received the 1850 mg dose of RO7297089 as a split dose divided over two days (Days 1 and 2). The full target dose was administered at subsequent study drug administration visits. | 3 |
| Total | 27 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Death | 2 | 3 | 2 | 2 | 2 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 1 | 1 | 0 |
| Overall Study | Study terminated by sponsor | 1 | 1 | 1 | 2 | 3 | 3 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Dose Escalation Cohort 2: RO7297089 | Dose Escalation Cohort 3: RO7297089 | Dose Escalation Cohort 4: RO7297089 | Dose Escalation Backfill Cohort 4: RO7297089 | Dose Escalation Cohort 5: RO7297089 | Dose Escalation Cohort 1: RO7297089 | Total |
|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 0 Participants | 3 Participants | 1 Participants | 1 Participants | 3 Participants | 10 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 4 Participants | 3 Participants | 5 Participants | 2 Participants | 0 Participants | 17 Participants |
| Age, Continuous | 62.6 Years STANDARD_DEVIATION 9.2 | 54.3 Years STANDARD_DEVIATION 9.4 | 63.0 Years STANDARD_DEVIATION 4.1 | 60.2 Years STANDARD_DEVIATION 6.3 | 65.7 Years STANDARD_DEVIATION 7.4 | 66.3 Years STANDARD_DEVIATION 1.2 | 61.7 Years STANDARD_DEVIATION 7.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 3 Participants | 5 Participants | 3 Participants | 3 Participants | 3 Participants | 22 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants | 3 Participants | 0 Participants | 0 Participants | 5 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 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 |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 4 Participants | 3 Participants | 5 Participants | 6 Participants | 3 Participants | 3 Participants | 24 Participants |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 3 Participants | 2 Participants | 0 Participants | 0 Participants | 8 Participants |
| Sex: Female, Male Male | 4 Participants | 2 Participants | 3 Participants | 4 Participants | 3 Participants | 3 Participants | 19 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 | 2 / 3 | 3 / 5 | 2 / 4 | 2 / 6 | 2 / 6 | 0 / 3 |
| other Total, other adverse events | 2 / 3 | 5 / 5 | 3 / 4 | 6 / 6 | 5 / 6 | 3 / 3 |
| serious Total, serious adverse events | 1 / 3 | 5 / 5 | 3 / 4 | 5 / 6 | 4 / 6 | 1 / 3 |
Outcome results
Primary
Percentage of Participants With Adverse Events (AEs), Including Dose Limiting Toxicities (DLTs)
Adverse event severity graded according to NCI CTCAE v5.0
Time frame: Baseline up to 1 year 7 months
Population: Safety-Evaluable Patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose Escalation Cohort 1: RO7297089 | Percentage of Participants With Adverse Events (AEs), Including Dose Limiting Toxicities (DLTs) | 100 Percentage of Participants |
| Dose Escalation Cohort 2: RO7297089 | Percentage of Participants With Adverse Events (AEs), Including Dose Limiting Toxicities (DLTs) | 100 Percentage of Participants |
| Dose Escalation Cohort 3: RO7297089 | Percentage of Participants With Adverse Events (AEs), Including Dose Limiting Toxicities (DLTs) | 75 Percentage of Participants |
| Dose Escalation Cohort 4: RO7297089 | Percentage of Participants With Adverse Events (AEs), Including Dose Limiting Toxicities (DLTs) | 100 Percentage of Participants |
| Dose Escalation Backfill Cohort 4: RO7297089 | Percentage of Participants With Adverse Events (AEs), Including Dose Limiting Toxicities (DLTs) | 83.3 Percentage of Participants |
| Dose Escalation Cohort 5: RO7297089 | Percentage of Participants With Adverse Events (AEs), Including Dose Limiting Toxicities (DLTs) | 100 Percentage of Participants |
Secondary
Area Under the Curve (AUC) of RO7297089
Time frame: Cycle 1 Day 1
Population: Only those participants who received full dose were included in the results summary
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Dose Escalation Cohort 1: RO7297089 | Area Under the Curve (AUC) of RO7297089 | 12.7 ug/mL*day | Standard Deviation 26.3 |
| Dose Escalation Cohort 2: RO7297089 | Area Under the Curve (AUC) of RO7297089 | 78.7 ug/mL*day | Standard Deviation 31.3 |
| Dose Escalation Cohort 3: RO7297089 | Area Under the Curve (AUC) of RO7297089 | 280 ug/mL*day | Standard Deviation 73.6 |
| Dose Escalation Cohort 4: RO7297089 | Area Under the Curve (AUC) of RO7297089 | 1347 ug/mL*day | — |
| Dose Escalation Backfill Cohort 4: RO7297089 | Area Under the Curve (AUC) of RO7297089 | 1046 ug/mL*day | Standard Deviation 28 |
| Dose Escalation Cohort 5: RO7297089 | Area Under the Curve (AUC) of RO7297089 | 1920 ug/mL*day | Standard Deviation 25.4 |
Secondary
Half-life (t1/2) of RO7297089
Time frame: Cycle 1 Day 1
Population: Only those participants who received full dose were included in the results summary
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Dose Escalation Cohort 1: RO7297089 | Half-life (t1/2) of RO7297089 | 1.39 day | Standard Deviation 8.33 |
| Dose Escalation Cohort 2: RO7297089 | Half-life (t1/2) of RO7297089 | 1.25 day | Standard Deviation 14.9 |
| Dose Escalation Cohort 3: RO7297089 | Half-life (t1/2) of RO7297089 | 2.39 day | Standard Deviation 89.5 |
| Dose Escalation Cohort 4: RO7297089 | Half-life (t1/2) of RO7297089 | 6.73 day | — |
| Dose Escalation Backfill Cohort 4: RO7297089 | Half-life (t1/2) of RO7297089 | 4.22 day | Standard Deviation 83.7 |
| Dose Escalation Cohort 5: RO7297089 | Half-life (t1/2) of RO7297089 | 6.52 day | Standard Deviation 24.5 |
Secondary
Maximum Concentration Observed (Cmax) of RO7297089
Time frame: Cycle 1 Day 1, Cycle 2 Day 8
Population: Only those participants who received full dose were included in the results summary
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Escalation Cohort 1: RO7297089 | Maximum Concentration Observed (Cmax) of RO7297089 | C1D1 | 7.79 ug/mL | Standard Deviation 21.6 |
| Dose Escalation Cohort 1: RO7297089 | Maximum Concentration Observed (Cmax) of RO7297089 | C2D8 | 9.50 ug/mL | Standard Deviation 24.1 |
| Dose Escalation Cohort 2: RO7297089 | Maximum Concentration Observed (Cmax) of RO7297089 | C1D1 | 40.9 ug/mL | Standard Deviation 46.3 |
| Dose Escalation Cohort 2: RO7297089 | Maximum Concentration Observed (Cmax) of RO7297089 | C2D8 | 48.6 ug/mL | Standard Deviation 23.6 |
| Dose Escalation Cohort 3: RO7297089 | Maximum Concentration Observed (Cmax) of RO7297089 | C1D1 | 95.9 ug/mL | Standard Deviation 35.8 |
| Dose Escalation Cohort 3: RO7297089 | Maximum Concentration Observed (Cmax) of RO7297089 | C2D8 | 153 ug/mL | Standard Deviation 47.5 |
| Dose Escalation Cohort 4: RO7297089 | Maximum Concentration Observed (Cmax) of RO7297089 | C2D8 | 394 ug/mL | — |
| Dose Escalation Cohort 4: RO7297089 | Maximum Concentration Observed (Cmax) of RO7297089 | C1D1 | 314 ug/mL | — |
| Dose Escalation Backfill Cohort 4: RO7297089 | Maximum Concentration Observed (Cmax) of RO7297089 | C1D1 | 305 ug/mL | Standard Deviation 15.5 |
| Dose Escalation Backfill Cohort 4: RO7297089 | Maximum Concentration Observed (Cmax) of RO7297089 | C2D8 | 541 ug/mL | Standard Deviation 38.9 |
| Dose Escalation Cohort 5: RO7297089 | Maximum Concentration Observed (Cmax) of RO7297089 | C1D1 | 404 ug/mL | Standard Deviation 12.4 |
| Dose Escalation Cohort 5: RO7297089 | Maximum Concentration Observed (Cmax) of RO7297089 | C2D8 | 966 ug/mL | Standard Deviation 24.7 |
Secondary
Minimum Concentration Observed (Cmin) of RO7297089
Time frame: Cycle 1 Day 1, Cycle 2 Day 8
Population: Only those participants who received full dose were included in the results summary
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Escalation Cohort 1: RO7297089 | Minimum Concentration Observed (Cmin) of RO7297089 | C1D1 | 0.19 ug/mL | Standard Deviation 22.3 |
| Dose Escalation Cohort 1: RO7297089 | Minimum Concentration Observed (Cmin) of RO7297089 | C2D8 | 0.25 ug/mL | Standard Deviation 39.9 |
| Dose Escalation Cohort 2: RO7297089 | Minimum Concentration Observed (Cmin) of RO7297089 | C1D1 | 0.96 ug/mL | Standard Deviation 42.5 |
| Dose Escalation Cohort 2: RO7297089 | Minimum Concentration Observed (Cmin) of RO7297089 | C2D8 | 2.99 ug/mL | — |
| Dose Escalation Cohort 3: RO7297089 | Minimum Concentration Observed (Cmin) of RO7297089 | C1D1 | 9.19 ug/mL | Standard Deviation 500 |
| Dose Escalation Cohort 3: RO7297089 | Minimum Concentration Observed (Cmin) of RO7297089 | C2D8 | 19.7 ug/mL | Standard Deviation 372 |
| Dose Escalation Cohort 4: RO7297089 | Minimum Concentration Observed (Cmin) of RO7297089 | C1D1 | 140 ug/mL | — |
| Dose Escalation Cohort 4: RO7297089 | Minimum Concentration Observed (Cmin) of RO7297089 | C2D8 | 163 ug/mL | — |
| Dose Escalation Backfill Cohort 4: RO7297089 | Minimum Concentration Observed (Cmin) of RO7297089 | C1D1 | 81.3 ug/mL | Standard Deviation 85.1 |
| Dose Escalation Backfill Cohort 4: RO7297089 | Minimum Concentration Observed (Cmin) of RO7297089 | C2D8 | 207 ug/mL | Standard Deviation 90 |
| Dose Escalation Cohort 5: RO7297089 | Minimum Concentration Observed (Cmin) of RO7297089 | C1D1 | 197 ug/mL | Standard Deviation 32.6 |
| Dose Escalation Cohort 5: RO7297089 | Minimum Concentration Observed (Cmin) of RO7297089 | C2D8 | 450 ug/mL | Standard Deviation 40.2 |
Secondary
Objective Response Rate (ORR)
ORR is defined as a Stringent Complete Response (Scr), Complete Response (CR), Very Good Partial Response (VGPR) or Partial Response (PR) as determined by the Investigator according to International Myeloma Working Group (IMWG) Uniform Response Criteria
Time frame: Baseline up to approximately 19 months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose Escalation Cohort 1: RO7297089 | Objective Response Rate (ORR) | Minimal Response | 0 Participants |
| Dose Escalation Cohort 1: RO7297089 | Objective Response Rate (ORR) | Partial Response | 0 Participants |
| Dose Escalation Cohort 1: RO7297089 | Objective Response Rate (ORR) | Progressive disease | 2 Participants |
| Dose Escalation Cohort 1: RO7297089 | Objective Response Rate (ORR) | Stable disease | 1 Participants |
| Dose Escalation Cohort 2: RO7297089 | Objective Response Rate (ORR) | Partial Response | 0 Participants |
| Dose Escalation Cohort 2: RO7297089 | Objective Response Rate (ORR) | Stable disease | 2 Participants |
| Dose Escalation Cohort 2: RO7297089 | Objective Response Rate (ORR) | Progressive disease | 2 Participants |
| Dose Escalation Cohort 2: RO7297089 | Objective Response Rate (ORR) | Minimal Response | 0 Participants |
| Dose Escalation Cohort 3: RO7297089 | Objective Response Rate (ORR) | Minimal Response | 1 Participants |
| Dose Escalation Cohort 3: RO7297089 | Objective Response Rate (ORR) | Stable disease | 3 Participants |
| Dose Escalation Cohort 3: RO7297089 | Objective Response Rate (ORR) | Partial Response | 0 Participants |
| Dose Escalation Cohort 3: RO7297089 | Objective Response Rate (ORR) | Progressive disease | 0 Participants |
| Dose Escalation Cohort 4: RO7297089 | Objective Response Rate (ORR) | Stable disease | 4 Participants |
| Dose Escalation Cohort 4: RO7297089 | Objective Response Rate (ORR) | Minimal Response | 0 Participants |
| Dose Escalation Cohort 4: RO7297089 | Objective Response Rate (ORR) | Partial Response | 1 Participants |
| Dose Escalation Cohort 4: RO7297089 | Objective Response Rate (ORR) | Progressive disease | 1 Participants |
| Dose Escalation Backfill Cohort 4: RO7297089 | Objective Response Rate (ORR) | Stable disease | 4 Participants |
| Dose Escalation Backfill Cohort 4: RO7297089 | Objective Response Rate (ORR) | Partial Response | 0 Participants |
| Dose Escalation Backfill Cohort 4: RO7297089 | Objective Response Rate (ORR) | Minimal Response | 1 Participants |
| Dose Escalation Backfill Cohort 4: RO7297089 | Objective Response Rate (ORR) | Progressive disease | 0 Participants |
| Dose Escalation Cohort 5: RO7297089 | Objective Response Rate (ORR) | Progressive disease | 0 Participants |
| Dose Escalation Cohort 5: RO7297089 | Objective Response Rate (ORR) | Partial Response | 1 Participants |
| Dose Escalation Cohort 5: RO7297089 | Objective Response Rate (ORR) | Stable disease | 2 Participants |
| Dose Escalation Cohort 5: RO7297089 | Objective Response Rate (ORR) | Minimal Response | 0 Participants |
Secondary
Time to Maximum Concentration Observed (Tmax) of RO7297089
Time frame: Cycle 1 Day 1
Population: Cohorts reported with participants excluded from descriptive statistics due to not receiving the full dose:~Cohort 2: 1 participant Cohort 3: 1 participant Cohort 4A: 2 participants Cohort 4B reported with 1 participant excluded from descriptive statistics due to apparent outlier and 1 participant due to or missing sample.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dose Escalation Cohort 1: RO7297089 | Time to Maximum Concentration Observed (Tmax) of RO7297089 | 0.25 EOI, day |
| Dose Escalation Cohort 2: RO7297089 | Time to Maximum Concentration Observed (Tmax) of RO7297089 | 0.17 EOI, day |
| Dose Escalation Cohort 3: RO7297089 | Time to Maximum Concentration Observed (Tmax) of RO7297089 | 0.08 EOI, day |
| Dose Escalation Cohort 4: RO7297089 | Time to Maximum Concentration Observed (Tmax) of RO7297089 | 0.25 EOI, day |
| Dose Escalation Backfill Cohort 4: RO7297089 | Time to Maximum Concentration Observed (Tmax) of RO7297089 | 1.08 EOI, day |
| Dose Escalation Cohort 5: RO7297089 | Time to Maximum Concentration Observed (Tmax) of RO7297089 | 1.08 EOI, day |