Acute Myeloid Leukemia
Conditions
Brief summary
The primary objectives of this study are to evaluate the safety and tolerability of emerfetamab in adults with relapsed/refractory acute myeloid leukemia (AML) and to estimate the maximum tolerated dose (MTD) and/or a biologically active dose (eg, recommended phase 2 dose \[RP2D\]).
Detailed description
This is a first-in-human, open-label, phase 1, sequential dose escalation study. Emerfetamab will be evaluated as a short term intravenous (IV) infusion in adults with relapsed/refractory AML The study will consist of a dose escalation phase and a dose expansion phase. The study was terminated prior to the start of the expansion phase.
Interventions
DRUGEmerfetamab
Administered by intravenous (IV) infusion.
Sponsors
Amgen
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Bayesian Model
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subject has provided informed consent prior to initiation of any study-specific activities/procedures. * Subjects ≥ 18 years of age at the time of signing consent. * AML as defined by the World Health Organisation (WHO) Classification persisting or recurring following 1 or more treatment courses except promyelocytic leukemia (APML). * More than 5% myeloblasts in bone marrow. * Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2.
Exclusion criteria
* Known hypersensitivity to immunoglobulins. * Autologous hematopoietic stem cell transplantation (HSCT) within 6 weeks prior to start of AMG 673 treatment. * Allogeneic HSCT within 3 months prior to start of AMG 673 treatment. * Non-manageable graft versus host disease. * Known positive test for human immunodeficiency virus (HIV). * Males and females of reproductive potential who are unwilling to practice a highly effective method(s) of birth control while on study through 15 weeks after receiving the last dose of study drug. Acceptable methods of highly effective birth control include sexual abstinence (males, females); vasectomy; bilateral tubal ligation/occlusion; or a condom with spermicide (men) in combination with hormonal birth control or intrauterine device (IUD) (women). Males who are unwilling to abstain from sperm donation while on study through 5 half-lives after receiving the (last \[multiple-dose studies\]) dose of study drug. * Females who are lactating/breastfeeding or who plan to breastfeed while on study through 15 weeks after receiving the last dose of study drug. * Females with a positive pregnancy test * Females planning to become pregnant while on study through 15 weeks after receiving the last dose of study drug.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events | From first dose of study drug until the end of study; median (minimum, maximum) duration was 1.22 (0.10, 5.98) months. | The severity of each adverse event (AE) was graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 criteria, where Grade 1 = mild AE, Grade 2 = moderate AE, Grade 3 = severe AE, Grade 4 = life-threatening and Grade 5 = death due to AE. A serious adverse event is defined as an adverse event that meets at least 1 of the following serious criteria: * fatal * life threatening * required in patient hospitalization or prolongation of existing hospitalization * resulted in persistent or significant disability/incapacity * congenital anomaly/birth defect * other medically important serious event. |
| Number of Participants With Dose-limiting Toxicities (DLT) | Schedule A: From the start of the first infusion on day 1 until day 14. Schedule B: From the start of the first infusion on day 1 to day 28. | A DLT was defined as any of the events described below occurring in a participant during the DLT window, unless clearly attributable to causes other than emerfetamab: * Any treatment-related death; * Grade 4 neutropenia persisting at 42 days after the last infusion in treatment cycle 1; * Grade 3-5 non-hematologic toxicity not clearly resulting from the underlying leukemia with a few protocol-specified exceptions; * Grade 2 or 3 cytokine release syndrome (CRS) meeting any of the criteria listed below: * Grade 2 CRS that does not resolve, with or without intervention to Grade 1 within 7 days; * Grade 3 CRS that does not resolve, with or without intervention to Grade 2 within 5 days, or grade 1 within 7 days; * Grade 3 CRS reported at the initial dose; * Two separate grade 3 CRS events; * Grade 4 CRS occurring during treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Schedule A: Area Under the Concentration-time Curve From Time Zero to 96 Hours Post-dose (AUC0-96) on Day 1 for Emerfetamab | Cycle 1 day 1 at predose and at 1, 6, 24, 48, and 96 hours after the start of infusion. | Serum concentrations of emerfetamab were determined using a validated assay. Noncompartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (0.0015 ng/mL) were set to zero before data analysis. The area under the curve (AUC) from time zero to 96 hours postdose was calculated using the linear trapezoidal method. |
| Schedule A: Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) for Emerfetamab | Cycle 1 day 5 at predose and 1, 6, 12, 24, 48, 72, and 312 hours after the start of infusion. | Serum concentrations of emerfetamab were determined using a validated assay. Non-compartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (0.0015 ng/mL) were set to zero before data analysis. The area under the concentration-time curve from time 0 relative to the start of the IV infusion to the last quantifiable concentration was estimated using the linear trapezoidal method. |
| Schedule A: Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) for Emerfetamab | Cycle 1 day 5 at predose and 1, 6, 12, 24, 48, 72, and 312 hours after the start of infusion. | Serum concentrations of emerfetamab were determined using a validated assay. Non-compartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (0.0015 ng/mL) were set to zero before data analysis. The area under the concentration-time curve from time 0 relative to the start of the IV infusion to infinity was estimated using the linear trapezoidal method. |
| Schedule A: AUC Total for Emerfetamab | Cycle 1 day 1 at predose and at 1, 6, 24, and 48 hours after the start of infusion, and day 5 at predose and 1, 6, 12, 24, 48, 72, and 312 hours after the start of infusion. | Serum concentrations of emerfetamab were determined using a validated assay. Non-compartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (0.0015 ng/mL) were set to zero before data analysis. The AUC total was calculated as the sum of AUC0-96hr following the Day 1 dose and AUCinf following the Day 5 dose. |
| Schedule A: Terminal Half-life (T1/2,z) of Emerfetamab | Cycle 1 day 5 at predose and 1, 6, 12, 24, 48, 72, and 312 hours after the start of infusion. | Serum concentrations of emerfetamab were determined using a validated assay. Non-compartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (0.0015 ng/mL) were set to zero before data analysis. Terminal half-life (t1/2,z) was calculated as t1/2,z = ln(2)/λz, where λz is the first-order terminal rate constant estimated via linear regression of the terminal log-linear phase. |
| Schedule A: Clearance (CL) of Emerfetamab | Cycle 1 day 5 at predose and 1, 6, 12, 24, 48, 72, and 312 hours after the start of infusion. | Serum concentrations of emerfetamab were determined using a validated assay. Non-compartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (0.0015 ng/mL) were set to zero before data analysis. Clearance was calculated as Dose/λz\*AUCinf. |
| Schedule B: Maximum Observed Concentration (Cmax) of Emerfetamab | Cycle 1 day 14 at predose and 1, 6, 12, 24, 48, 72, 96, and 120 hours after the start of infusion. | Serum concentrations of emerfetamab were determined using a validated assay. Noncompartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (0.0015 ng/mL) were set to zero before data analysis. |
| Schedule B: Time to Maximum Observed Concentration (Tmax) of Emerfetamab | Cycle 1 day 14 at predose and 1, 6, 12, 24, 48, 72, 96, and 120 hours after the start of infusion. | Serum concentrations of emerfetamab were determined using a validated assay. Noncompartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (0.0015 ng/mL) were set to zero before data analysis. |
| Schedule A: Maximum Observed Concentration (Cmax) of Emerfetamab | Cycle 1 day 1 at predose and at 1, 6, 24, and 48 hours after the start of infusion, and day 5 at predose and 1, 6, 12, 24, 48, 72, and 312 hours after the start of infusion. | Serum concentrations of emerfetamab were determined using a validated assay. Noncompartmental analysis was performed for estimation of pharmacokinetic (PK) parameters. Concentrations below the lower limit of quantitation (LLOQ; 0.0015 ng/mL) were set to zero before data analysis. |
| Schedule B: Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) for Emerfetamab | Cycle 1 day 14 at predose and 1, 6, 12, 24, 48, 72, 96, and 120 hours after the start of infusion. | Serum concentrations of emerfetamab were determined using a validated assay. Noncompartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (0.0015 ng/mL) were set to zero before data analysis. The area under the concentration-time curve from time 0 relative to the start of the IV infusion to infinity was estimated using the linear trapezoidal method. |
| Schedule B: Terminal Half-life (T1/2,z) of Emerfetamab | Cycle 1 day 14 at predose and 1, 6, 12, 24, 48, 72, 96, and 120 hours after the start of infusion. | Serum concentrations of emerfetamab were determined using a validated assay. Noncompartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (0.0015 ng/mL) were set to zero before data analysis. |
| Schedule B: Clearance of Emerfetamab | Cycle 1 day 14 at predose and 1, 6, 12, 24, 48, 72, 96, and 120 hours after the start of infusion. | Serum concentrations of emerfetamab were determined using a validated assay. Noncompartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (0.0015 ng/mL) were set to zero before data analysis. |
| Response Rate | Disease response was assessed on day 14 of every treatment cycle and at the end of study; median (min, max) duration was 1.22 (0.10, 5.98) months. | Disease response was based upon review of cytogenetics, bone marrow (BM) aspirates/biopsies, and peripheral blood count. Response rate is defined as the percentage of participants with a best overall response of complete remission (CR), CR with incomplete recovery (CRi) or morphologic leukemia-free state (MLFS) according to Revised International Working Group (IWG) response criteria, or CR with partial hematologic recovery (CRh\*). CR: BM blasts \< 5%; absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count (ANC) \> 1.0 x 10\^9/L; platelet count \> 100 x 10\^9/L; independence of red cell transfusions. CRi: All CR criteria except residual neutropenia or thrombocytopenia. MLFS: BM blasts \< 5%; absence of blasts with Auer rods; absence of extramedullary disease; no hematologic recovery required. CRh\*: \< 5% blasts in BM; no evidence of disease; partial recovery of peripheral blood counts: platelets \> 50,000/μl, and ANC \> 500/μl; no extramedullary disease. |
| Duration of Response | Disease response was assessed on day 14 of every treatment cycle and at the end of study; median (min, max) duration was 1.22 (0.10, 5.98) months. | Duration of response is defined as the interval from the date of the first disease assessment indicating an overall response to the first documented relapse or death due to any cause, whichever occurred first. |
| Time to Response | Disease response was assessed on day 14 of every treatment cycle and at the end of study; median (min, max) duration was 1.22 (0.10, 5.98) months. | Time to response is defined as the interval from the first administration of study drug to the first documentation of response. Time to response was evaluated only for participants who achieved a response. |
| Time to Progression | Disease response was assessed on day 14 of every treatment cycle and at the end of study; median (min, max) duration was 1.22 (0.10, 5.98) months. | Time to progression (event-free survival) is defined as the interval from first administration of study drug to the earliest of date of treatment failure, relapse for responders, or death due to any cause. For non-responders, the event date for treatment failure was assigned as the date of first administration of study drug. |
| Schedule B: Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) for Emerfetamab | Cycle 1 day 14 at predose and 1, 6, 12, 24, 48, 72, 96, and 120 hours after the start of infusion. | Serum concentrations of emerfetamab were determined using a validated assay. Noncompartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (0.0015 ng/mL) were set to zero before data analysis. The area under the concentration-time curve from time 0 relative to the start of the IV infusion to the last quantifiable concentration was estimated using the linear trapezoidal method. |
| Schedule A: Time to Maximum Observed Concentration (Tmax) of Emerfetamab | Cycle 1 day 1 at predose and at 1, 6, 24, and 48 hours after the start of infusion, and day 5 at predose and 1, 6, 12, 24, 48, 72, and 312 hours after the start of infusion. | Serum concentrations of emerfetamab were determined using a validated assay. Noncompartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (0.0015 ng/mL) were set to zero before data analysis. |
Countries
Australia, Germany, United States
Participant flow
Recruitment details
This study was conducted at 7 centers in United States, Australia, and Germany.
Participants by arm
| Arm | Count |
|---|---|
| Schedule A Cohort 1: 0.05 µg Emerfetamab Participants received 0.05 µg emerfetamab intravenously on day 1 and day 5 of each 14-day cycle for up to 12 total treatment cycles. | 1 |
| Schedule A Cohort 2: 0.15 µg Emerfetamab Participants received 0.15 µg emerfetamab intravenously on day 1 and day 5 of each 14-day cycle for up to 12 total treatment cycles. | 1 |
| Schedule A Cohort 3: 0.45 µg Emerfetamab Participants received 0.45 µg emerfetamab intravenously on day 1 and day 5 of each 14-day cycle for up to 12 total treatment cycles. | 3 |
| Schedule A Cohort 4: 1.5 µg Emerfetamab Participants received 1.5 µg emerfetamab intravenously on day 1 and day 5 of each 14-day cycle for up to 12 total treatment cycles. | 3 |
| Schedule A Cohort 5: 4.5 µg Emerfetamab Participants received 4.5 µg emerfetamab intravenously on day 1 and day 5 of each 14-day cycle for up to 12 total treatment cycles. | 3 |
| Schedule A Cohort 6: 7 µg Emerfetamab Participants received 7 µg emerfetamab intravenously on day 1 and day 5 of each 14-day cycle for up to 12 total treatment cycles. | 3 |
| Schedule A Cohort 7: 9 µg Emerfetamab Participants received 9 µg emerfetamab intravenously on day 1 and day 5 of each 14-day cycle for up to 12 total treatment cycles. | 3 |
| Schedule A Cohort 8: 18 µg Emerfetamab Participants received 18 µg emerfetamab intravenously on day 1 and day 5 of each 14-day cycle for up to 12 total treatment cycles. | 3 |
| Schedule A Cohort 9: 36 µg Emerfetamab Participants received 36 µg emerfetamab intravenously on day 1 and day 5 of each 14-day cycle for up to 12 total treatment cycles. | 4 |
| Schedule A Cohort 10: 72 µg Emerfetamab Participants received 72 µg emerfetamab intravenously on day 1 and day 5 of each 14-day cycle for up to 12 total treatment cycles. | 6 |
| Schedule A Cohort 11: 110 µg Emerfetamab Participants received 110 µg emerfetamab intravenously on day 1 and day 5 of each 14-day cycle for up to 12 total treatment cycles. | 4 |
| Schedule A Cohort 12: 36/72 µg Emerfetamab Participants received 36 µg emerfetamab intravenously on day 1 and 72 µg emerfetamab on day 5 and thereafter of each 14-day cycle for up to 12 total treatment cycles. | 4 |
| Schedule B Cohort 1: 72 µg Emerfetamab Participants received 72 µg emerfetamab intravenously once a day (QD) from days 1 to 14 for the first treatment cycle then on day 1, day 4, day 8, and day 11 of each subsequent 14-day cycle for up to a total of 12 cycles. | 5 |
| Schedule B Cohort 2: 110 µg Emerfetamab Participants received 72 µg emerfetamab intravenously on day 1 and day 2 then 110 µg emerfetamab once a day from days 3 to 14 in the first treatment cycle, then 110 µg emerfetamab on day 1, day 4, day 8, and day 11 of each subsequent 14-day cycle for up to a total of 12 cycles. | 3 |
| Total | 46 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Death | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Sponsor Decision | 0 | 0 | 0 | 1 | 1 | 2 | 1 | 1 | 1 | 2 | 1 | 1 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Schedule A Cohort 1: 0.05 µg Emerfetamab | Schedule A Cohort 2: 0.15 µg Emerfetamab | Schedule A Cohort 3: 0.45 µg Emerfetamab | Schedule A Cohort 4: 1.5 µg Emerfetamab | Schedule A Cohort 5: 4.5 µg Emerfetamab | Schedule A Cohort 6: 7 µg Emerfetamab | Schedule A Cohort 7: 9 µg Emerfetamab | Schedule A Cohort 8: 18 µg Emerfetamab | Schedule A Cohort 9: 36 µg Emerfetamab | Schedule A Cohort 10: 72 µg Emerfetamab | Schedule A Cohort 11: 110 µg Emerfetamab | Schedule A Cohort 12: 36/72 µg Emerfetamab | Schedule B Cohort 1: 72 µg Emerfetamab | Schedule B Cohort 2: 110 µg Emerfetamab | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 25.0 years | 61.0 years | 49.3 years STANDARD_DEVIATION 16.3 | 69.3 years STANDARD_DEVIATION 8.1 | 60.3 years STANDARD_DEVIATION 23.9 | 60.7 years STANDARD_DEVIATION 18.9 | 73.7 years STANDARD_DEVIATION 2.1 | 45.7 years STANDARD_DEVIATION 14.6 | 68.8 years STANDARD_DEVIATION 11.8 | 71.8 years STANDARD_DEVIATION 7 | 57.5 years STANDARD_DEVIATION 11.6 | 72.0 years STANDARD_DEVIATION 5.1 | 61.4 years STANDARD_DEVIATION 18.2 | 54.0 years STANDARD_DEVIATION 7.5 | 62.1 years STANDARD_DEVIATION 15.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 0 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 4 Participants | 6 Participants | 4 Participants | 3 Participants | 4 Participants | 2 Participants | 41 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized 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 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Black (or African American) | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized 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 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 1 Participants | 1 Participants | 3 Participants | 3 Participants | 1 Participants | 3 Participants | 3 Participants | 2 Participants | 4 Participants | 6 Participants | 4 Participants | 3 Participants | 4 Participants | 3 Participants | 41 Participants |
| Sex: Female, Male Female | 1 Participants | 0 Participants | 2 Participants | 1 Participants | 1 Participants | 2 Participants | 0 Participants | 1 Participants | 2 Participants | 3 Participants | 3 Participants | 2 Participants | 3 Participants | 2 Participants | 23 Participants |
| Sex: Female, Male Male | 0 Participants | 1 Participants | 1 Participants | 2 Participants | 2 Participants | 1 Participants | 3 Participants | 2 Participants | 2 Participants | 3 Participants | 1 Participants | 2 Participants | 2 Participants | 1 Participants | 23 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 | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 1 / 1 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 | 1 / 3 | 0 / 4 | 0 / 6 | 0 / 4 | 1 / 4 | 0 / 5 | 0 / 3 |
| other Total, other adverse events | 1 / 1 | 1 / 1 | 2 / 3 | 3 / 3 | 3 / 3 | 3 / 3 | 3 / 3 | 3 / 3 | 4 / 4 | 6 / 6 | 4 / 4 | 4 / 4 | 5 / 5 | 3 / 3 |
| serious Total, serious adverse events | 1 / 1 | 1 / 1 | 2 / 3 | 1 / 3 | 2 / 3 | 1 / 3 | 2 / 3 | 3 / 3 | 2 / 4 | 5 / 6 | 3 / 4 | 4 / 4 | 1 / 5 | 2 / 3 |
Outcome results
Primary
Number of Participants With Dose-limiting Toxicities (DLT)
A DLT was defined as any of the events described below occurring in a participant during the DLT window, unless clearly attributable to causes other than emerfetamab: * Any treatment-related death; * Grade 4 neutropenia persisting at 42 days after the last infusion in treatment cycle 1; * Grade 3-5 non-hematologic toxicity not clearly resulting from the underlying leukemia with a few protocol-specified exceptions; * Grade 2 or 3 cytokine release syndrome (CRS) meeting any of the criteria listed below: * Grade 2 CRS that does not resolve, with or without intervention to Grade 1 within 7 days; * Grade 3 CRS that does not resolve, with or without intervention to Grade 2 within 5 days, or grade 1 within 7 days; * Grade 3 CRS reported at the initial dose; * Two separate grade 3 CRS events; * Grade 4 CRS occurring during treatment.
Time frame: Schedule A: From the start of the first infusion on day 1 until day 14. Schedule B: From the start of the first infusion on day 1 to day 28.
Population: Enrolled participants who received at least 1 dose of study drug who received the minimum cycle 1 doses planned for the respective cohort:~Schedule A: 2 doses within 14-day window; Schedule B: completed ≥ 70% of the planned target doses within 28-day window.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Schedule A Cohort 1: 0.05 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Cytokine release syndrome | 0 Participants |
| Schedule A Cohort 1: 0.05 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Any dose-limiting toxicity | 0 Participants |
| Schedule A Cohort 1: 0.05 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Lipase increased | 0 Participants |
| Schedule A Cohort 1: 0.05 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Gamma-glutamyltransferase increased | 0 Participants |
| Schedule A Cohort 1: 0.05 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Aspartate aminotransferase increased | 0 Participants |
| Schedule A Cohort 1: 0.05 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Acute kidney injury | 0 Participants |
| Schedule A Cohort 1: 0.05 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Alanine aminotransferase increased | 0 Participants |
| Schedule A Cohort 1: 0.05 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Bone pain | 0 Participants |
| Schedule A Cohort 2: 0.15 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Acute kidney injury | 0 Participants |
| Schedule A Cohort 2: 0.15 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Bone pain | 0 Participants |
| Schedule A Cohort 2: 0.15 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Gamma-glutamyltransferase increased | 0 Participants |
| Schedule A Cohort 2: 0.15 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Lipase increased | 0 Participants |
| Schedule A Cohort 2: 0.15 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Alanine aminotransferase increased | 0 Participants |
| Schedule A Cohort 2: 0.15 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Cytokine release syndrome | 0 Participants |
| Schedule A Cohort 2: 0.15 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Aspartate aminotransferase increased | 0 Participants |
| Schedule A Cohort 2: 0.15 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Any dose-limiting toxicity | 0 Participants |
| Schedule A Cohort 3: 0.45 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Acute kidney injury | 0 Participants |
| Schedule A Cohort 3: 0.45 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Alanine aminotransferase increased | 0 Participants |
| Schedule A Cohort 3: 0.45 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Bone pain | 0 Participants |
| Schedule A Cohort 3: 0.45 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Lipase increased | 0 Participants |
| Schedule A Cohort 3: 0.45 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Aspartate aminotransferase increased | 0 Participants |
| Schedule A Cohort 3: 0.45 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Gamma-glutamyltransferase increased | 0 Participants |
| Schedule A Cohort 3: 0.45 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Any dose-limiting toxicity | 0 Participants |
| Schedule A Cohort 3: 0.45 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Cytokine release syndrome | 0 Participants |
| Schedule A Cohort 4: 1.5 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Alanine aminotransferase increased | 0 Participants |
| Schedule A Cohort 4: 1.5 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Lipase increased | 0 Participants |
| Schedule A Cohort 4: 1.5 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Cytokine release syndrome | 0 Participants |
| Schedule A Cohort 4: 1.5 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Acute kidney injury | 0 Participants |
| Schedule A Cohort 4: 1.5 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Aspartate aminotransferase increased | 0 Participants |
| Schedule A Cohort 4: 1.5 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Gamma-glutamyltransferase increased | 0 Participants |
| Schedule A Cohort 4: 1.5 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Bone pain | 0 Participants |
| Schedule A Cohort 4: 1.5 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Any dose-limiting toxicity | 0 Participants |
| Schedule A Cohort 5: 4.5 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Acute kidney injury | 0 Participants |
| Schedule A Cohort 5: 4.5 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Gamma-glutamyltransferase increased | 0 Participants |
| Schedule A Cohort 5: 4.5 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Alanine aminotransferase increased | 1 Participants |
| Schedule A Cohort 5: 4.5 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Lipase increased | 0 Participants |
| Schedule A Cohort 5: 4.5 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Bone pain | 0 Participants |
| Schedule A Cohort 5: 4.5 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Cytokine release syndrome | 0 Participants |
| Schedule A Cohort 5: 4.5 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Any dose-limiting toxicity | 1 Participants |
| Schedule A Cohort 5: 4.5 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Aspartate aminotransferase increased | 0 Participants |
| Schedule A Cohort 6: 7 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Cytokine release syndrome | 0 Participants |
| Schedule A Cohort 6: 7 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Acute kidney injury | 0 Participants |
| Schedule A Cohort 6: 7 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Gamma-glutamyltransferase increased | 0 Participants |
| Schedule A Cohort 6: 7 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Alanine aminotransferase increased | 0 Participants |
| Schedule A Cohort 6: 7 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Any dose-limiting toxicity | 0 Participants |
| Schedule A Cohort 6: 7 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Aspartate aminotransferase increased | 0 Participants |
| Schedule A Cohort 6: 7 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Lipase increased | 0 Participants |
| Schedule A Cohort 6: 7 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Bone pain | 0 Participants |
| Schedule A Cohort 7: 9 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Any dose-limiting toxicity | 0 Participants |
| Schedule A Cohort 7: 9 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Aspartate aminotransferase increased | 0 Participants |
| Schedule A Cohort 7: 9 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Lipase increased | 0 Participants |
| Schedule A Cohort 7: 9 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Cytokine release syndrome | 0 Participants |
| Schedule A Cohort 7: 9 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Bone pain | 0 Participants |
| Schedule A Cohort 7: 9 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Acute kidney injury | 0 Participants |
| Schedule A Cohort 7: 9 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Alanine aminotransferase increased | 0 Participants |
| Schedule A Cohort 7: 9 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Gamma-glutamyltransferase increased | 0 Participants |
| Schedule A Cohort 8: 18 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Any dose-limiting toxicity | 0 Participants |
| Schedule A Cohort 8: 18 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Alanine aminotransferase increased | 0 Participants |
| Schedule A Cohort 8: 18 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Cytokine release syndrome | 0 Participants |
| Schedule A Cohort 8: 18 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Acute kidney injury | 0 Participants |
| Schedule A Cohort 8: 18 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Gamma-glutamyltransferase increased | 0 Participants |
| Schedule A Cohort 8: 18 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Bone pain | 0 Participants |
| Schedule A Cohort 8: 18 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Aspartate aminotransferase increased | 0 Participants |
| Schedule A Cohort 8: 18 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Lipase increased | 0 Participants |
| Schedule A Cohort 9: 36 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Cytokine release syndrome | 0 Participants |
| Schedule A Cohort 9: 36 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Bone pain | 0 Participants |
| Schedule A Cohort 9: 36 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Any dose-limiting toxicity | 1 Participants |
| Schedule A Cohort 9: 36 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Gamma-glutamyltransferase increased | 0 Participants |
| Schedule A Cohort 9: 36 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Acute kidney injury | 0 Participants |
| Schedule A Cohort 9: 36 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Aspartate aminotransferase increased | 0 Participants |
| Schedule A Cohort 9: 36 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Alanine aminotransferase increased | 0 Participants |
| Schedule A Cohort 9: 36 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Lipase increased | 1 Participants |
| Schedule A Cohort 10: 72 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Aspartate aminotransferase increased | 0 Participants |
| Schedule A Cohort 10: 72 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Lipase increased | 0 Participants |
| Schedule A Cohort 10: 72 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Any dose-limiting toxicity | 3 Participants |
| Schedule A Cohort 10: 72 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Alanine aminotransferase increased | 1 Participants |
| Schedule A Cohort 10: 72 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Acute kidney injury | 1 Participants |
| Schedule A Cohort 10: 72 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Bone pain | 0 Participants |
| Schedule A Cohort 10: 72 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Cytokine release syndrome | 0 Participants |
| Schedule A Cohort 10: 72 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Gamma-glutamyltransferase increased | 1 Participants |
| Schedule A Cohort 11: 110 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Aspartate aminotransferase increased | 1 Participants |
| Schedule A Cohort 11: 110 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Gamma-glutamyltransferase increased | 0 Participants |
| Schedule A Cohort 11: 110 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Bone pain | 1 Participants |
| Schedule A Cohort 11: 110 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Acute kidney injury | 0 Participants |
| Schedule A Cohort 11: 110 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Lipase increased | 0 Participants |
| Schedule A Cohort 11: 110 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Any dose-limiting toxicity | 2 Participants |
| Schedule A Cohort 11: 110 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Cytokine release syndrome | 1 Participants |
| Schedule A Cohort 11: 110 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Alanine aminotransferase increased | 1 Participants |
| Schedule A Cohort 12: 36/72 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Lipase increased | 0 Participants |
| Schedule A Cohort 12: 36/72 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Cytokine release syndrome | 0 Participants |
| Schedule A Cohort 12: 36/72 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Bone pain | 0 Participants |
| Schedule A Cohort 12: 36/72 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Aspartate aminotransferase increased | 0 Participants |
| Schedule A Cohort 12: 36/72 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Acute kidney injury | 0 Participants |
| Schedule A Cohort 12: 36/72 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Alanine aminotransferase increased | 0 Participants |
| Schedule A Cohort 12: 36/72 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Gamma-glutamyltransferase increased | 0 Participants |
| Schedule A Cohort 12: 36/72 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Any dose-limiting toxicity | 0 Participants |
| Schedule B Cohort 1: 72 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Bone pain | 0 Participants |
| Schedule B Cohort 1: 72 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Gamma-glutamyltransferase increased | 0 Participants |
| Schedule B Cohort 1: 72 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Lipase increased | 0 Participants |
| Schedule B Cohort 1: 72 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Any dose-limiting toxicity | 0 Participants |
| Schedule B Cohort 1: 72 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Cytokine release syndrome | 0 Participants |
| Schedule B Cohort 1: 72 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Aspartate aminotransferase increased | 0 Participants |
| Schedule B Cohort 1: 72 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Alanine aminotransferase increased | 0 Participants |
| Schedule B Cohort 1: 72 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Acute kidney injury | 0 Participants |
| Schedule B Cohort 2: 110 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Lipase increased | 0 Participants |
| Schedule B Cohort 2: 110 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Any dose-limiting toxicity | 0 Participants |
| Schedule B Cohort 2: 110 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Alanine aminotransferase increased | 0 Participants |
| Schedule B Cohort 2: 110 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Acute kidney injury | 0 Participants |
| Schedule B Cohort 2: 110 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Aspartate aminotransferase increased | 0 Participants |
| Schedule B Cohort 2: 110 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Bone pain | 0 Participants |
| Schedule B Cohort 2: 110 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Cytokine release syndrome | 0 Participants |
| Schedule B Cohort 2: 110 µg Emerfetamab | Number of Participants With Dose-limiting Toxicities (DLT) | Gamma-glutamyltransferase increased | 0 Participants |
Primary
Number of Participants With Treatment-emergent Adverse Events
The severity of each adverse event (AE) was graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 criteria, where Grade 1 = mild AE, Grade 2 = moderate AE, Grade 3 = severe AE, Grade 4 = life-threatening and Grade 5 = death due to AE. A serious adverse event is defined as an adverse event that meets at least 1 of the following serious criteria: * fatal * life threatening * required in patient hospitalization or prolongation of existing hospitalization * resulted in persistent or significant disability/incapacity * congenital anomaly/birth defect * other medically important serious event.
Time frame: From first dose of study drug until the end of study; median (minimum, maximum) duration was 1.22 (0.10, 5.98) months.
Population: All enrolled participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Schedule A Cohort 1: 0.05 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | SAE leading to discontinuation of study drug | 0 Participants |
| Schedule A Cohort 1: 0.05 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | Treatment related TEAEs | 1 Participants |
| Schedule A Cohort 1: 0.05 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | TEAE Grade ≥ 2 | 1 Participants |
| Schedule A Cohort 1: 0.05 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | TEAE leading to discontinuation of study drug | 0 Participants |
| Schedule A Cohort 1: 0.05 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | SAE leading to interruption of study drug | 0 Participants |
| Schedule A Cohort 1: 0.05 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | Serious adverse events (SAE) | 1 Participants |
| Schedule A Cohort 1: 0.05 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | TEAE Grade ≥ 4 | 1 Participants |
| Schedule A Cohort 1: 0.05 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | TEAE leading to interruption of study drug | 0 Participants |
| Schedule A Cohort 1: 0.05 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | Fatal adverse events | 0 Participants |
| Schedule A Cohort 1: 0.05 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | TEAE Grade ≥ 3 | 1 Participants |
| Schedule A Cohort 1: 0.05 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | Any treatment emergent adverse event (TEAE) | 1 Participants |
| Schedule A Cohort 2: 0.15 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | SAE leading to discontinuation of study drug | 0 Participants |
| Schedule A Cohort 2: 0.15 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | SAE leading to interruption of study drug | 0 Participants |
| Schedule A Cohort 2: 0.15 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | Serious adverse events (SAE) | 1 Participants |
| Schedule A Cohort 2: 0.15 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | Treatment related TEAEs | 1 Participants |
| Schedule A Cohort 2: 0.15 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | TEAE Grade ≥ 2 | 1 Participants |
| Schedule A Cohort 2: 0.15 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | Any treatment emergent adverse event (TEAE) | 1 Participants |
| Schedule A Cohort 2: 0.15 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | TEAE Grade ≥ 3 | 1 Participants |
| Schedule A Cohort 2: 0.15 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | TEAE leading to discontinuation of study drug | 0 Participants |
| Schedule A Cohort 2: 0.15 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | Fatal adverse events | 1 Participants |
| Schedule A Cohort 2: 0.15 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | TEAE Grade ≥ 4 | 1 Participants |
| Schedule A Cohort 2: 0.15 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | TEAE leading to interruption of study drug | 0 Participants |
| Schedule A Cohort 3: 0.45 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | SAE leading to discontinuation of study drug | 0 Participants |
| Schedule A Cohort 3: 0.45 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | TEAE Grade ≥ 3 | 2 Participants |
| Schedule A Cohort 3: 0.45 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | TEAE leading to interruption of study drug | 0 Participants |
| Schedule A Cohort 3: 0.45 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | TEAE leading to discontinuation of study drug | 0 Participants |
| Schedule A Cohort 3: 0.45 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | Serious adverse events (SAE) | 2 Participants |
| Schedule A Cohort 3: 0.45 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | Fatal adverse events | 0 Participants |
| Schedule A Cohort 3: 0.45 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | Any treatment emergent adverse event (TEAE) | 3 Participants |
| Schedule A Cohort 3: 0.45 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | SAE leading to interruption of study drug | 0 Participants |
| Schedule A Cohort 3: 0.45 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | Treatment related TEAEs | 1 Participants |
| Schedule A Cohort 3: 0.45 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | TEAE Grade ≥ 4 | 0 Participants |
| Schedule A Cohort 3: 0.45 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | TEAE Grade ≥ 2 | 3 Participants |
| Schedule A Cohort 4: 1.5 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | TEAE Grade ≥ 3 | 2 Participants |
| Schedule A Cohort 4: 1.5 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | SAE leading to discontinuation of study drug | 0 Participants |
| Schedule A Cohort 4: 1.5 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | TEAE leading to interruption of study drug | 0 Participants |
| Schedule A Cohort 4: 1.5 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | Treatment related TEAEs | 3 Participants |
| Schedule A Cohort 4: 1.5 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | Fatal adverse events | 0 Participants |
| Schedule A Cohort 4: 1.5 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | Serious adverse events (SAE) | 1 Participants |
| Schedule A Cohort 4: 1.5 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | TEAE leading to discontinuation of study drug | 0 Participants |
| Schedule A Cohort 4: 1.5 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | TEAE Grade ≥ 4 | 0 Participants |
| Schedule A Cohort 4: 1.5 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | TEAE Grade ≥ 2 | 3 Participants |
| Schedule A Cohort 4: 1.5 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | Any treatment emergent adverse event (TEAE) | 3 Participants |
| Schedule A Cohort 4: 1.5 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | SAE leading to interruption of study drug | 0 Participants |
| Schedule A Cohort 5: 4.5 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | TEAE Grade ≥ 4 | 1 Participants |
| Schedule A Cohort 5: 4.5 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | TEAE Grade ≥ 3 | 2 Participants |
| Schedule A Cohort 5: 4.5 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | Treatment related TEAEs | 3 Participants |
| Schedule A Cohort 5: 4.5 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | TEAE Grade ≥ 2 | 2 Participants |
| Schedule A Cohort 5: 4.5 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | Serious adverse events (SAE) | 2 Participants |
| Schedule A Cohort 5: 4.5 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | SAE leading to discontinuation of study drug | 0 Participants |
| Schedule A Cohort 5: 4.5 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | SAE leading to interruption of study drug | 0 Participants |
| Schedule A Cohort 5: 4.5 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | TEAE leading to interruption of study drug | 1 Participants |
| Schedule A Cohort 5: 4.5 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | Any treatment emergent adverse event (TEAE) | 3 Participants |
| Schedule A Cohort 5: 4.5 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | TEAE leading to discontinuation of study drug | 1 Participants |
| Schedule A Cohort 5: 4.5 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | Fatal adverse events | 0 Participants |
| Schedule A Cohort 6: 7 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | SAE leading to interruption of study drug | 0 Participants |
| Schedule A Cohort 6: 7 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | SAE leading to discontinuation of study drug | 0 Participants |
| Schedule A Cohort 6: 7 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | Any treatment emergent adverse event (TEAE) | 3 Participants |
| Schedule A Cohort 6: 7 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | TEAE Grade ≥ 2 | 3 Participants |
| Schedule A Cohort 6: 7 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | Fatal adverse events | 0 Participants |
| Schedule A Cohort 6: 7 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | TEAE Grade ≥ 3 | 1 Participants |
| Schedule A Cohort 6: 7 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | TEAE Grade ≥ 4 | 0 Participants |
| Schedule A Cohort 6: 7 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | Serious adverse events (SAE) | 1 Participants |
| Schedule A Cohort 6: 7 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | Treatment related TEAEs | 1 Participants |
| Schedule A Cohort 6: 7 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | TEAE leading to interruption of study drug | 0 Participants |
| Schedule A Cohort 6: 7 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | TEAE leading to discontinuation of study drug | 0 Participants |
| Schedule A Cohort 7: 9 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | TEAE Grade ≥ 2 | 2 Participants |
| Schedule A Cohort 7: 9 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | SAE leading to interruption of study drug | 0 Participants |
| Schedule A Cohort 7: 9 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | TEAE leading to interruption of study drug | 0 Participants |
| Schedule A Cohort 7: 9 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | TEAE Grade ≥ 3 | 2 Participants |
| Schedule A Cohort 7: 9 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | Fatal adverse events | 0 Participants |
| Schedule A Cohort 7: 9 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | SAE leading to discontinuation of study drug | 0 Participants |
| Schedule A Cohort 7: 9 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | TEAE leading to discontinuation of study drug | 0 Participants |
| Schedule A Cohort 7: 9 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | Any treatment emergent adverse event (TEAE) | 3 Participants |
| Schedule A Cohort 7: 9 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | Treatment related TEAEs | 3 Participants |
| Schedule A Cohort 7: 9 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | TEAE Grade ≥ 4 | 0 Participants |
| Schedule A Cohort 7: 9 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | Serious adverse events (SAE) | 2 Participants |
| Schedule A Cohort 8: 18 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | Fatal adverse events | 1 Participants |
| Schedule A Cohort 8: 18 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | Serious adverse events (SAE) | 3 Participants |
| Schedule A Cohort 8: 18 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | Any treatment emergent adverse event (TEAE) | 3 Participants |
| Schedule A Cohort 8: 18 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | TEAE Grade ≥ 4 | 2 Participants |
| Schedule A Cohort 8: 18 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | TEAE leading to interruption of study drug | 0 Participants |
| Schedule A Cohort 8: 18 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | TEAE Grade ≥ 2 | 3 Participants |
| Schedule A Cohort 8: 18 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | SAE leading to discontinuation of study drug | 0 Participants |
| Schedule A Cohort 8: 18 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | SAE leading to interruption of study drug | 0 Participants |
| Schedule A Cohort 8: 18 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | Treatment related TEAEs | 3 Participants |
| Schedule A Cohort 8: 18 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | TEAE Grade ≥ 3 | 3 Participants |
| Schedule A Cohort 8: 18 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | TEAE leading to discontinuation of study drug | 0 Participants |
| Schedule A Cohort 9: 36 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | Fatal adverse events | 0 Participants |
| Schedule A Cohort 9: 36 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | Any treatment emergent adverse event (TEAE) | 4 Participants |
| Schedule A Cohort 9: 36 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | TEAE Grade ≥ 2 | 4 Participants |
| Schedule A Cohort 9: 36 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | TEAE Grade ≥ 3 | 3 Participants |
| Schedule A Cohort 9: 36 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | TEAE Grade ≥ 4 | 2 Participants |
| Schedule A Cohort 9: 36 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | Serious adverse events (SAE) | 2 Participants |
| Schedule A Cohort 9: 36 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | TEAE leading to discontinuation of study drug | 0 Participants |
| Schedule A Cohort 9: 36 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | SAE leading to discontinuation of study drug | 0 Participants |
| Schedule A Cohort 9: 36 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | TEAE leading to interruption of study drug | 1 Participants |
| Schedule A Cohort 9: 36 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | SAE leading to interruption of study drug | 1 Participants |
| Schedule A Cohort 9: 36 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | Treatment related TEAEs | 4 Participants |
| Schedule A Cohort 10: 72 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | SAE leading to interruption of study drug | 1 Participants |
| Schedule A Cohort 10: 72 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | Treatment related TEAEs | 6 Participants |
| Schedule A Cohort 10: 72 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | TEAE Grade ≥ 3 | 5 Participants |
| Schedule A Cohort 10: 72 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | SAE leading to discontinuation of study drug | 1 Participants |
| Schedule A Cohort 10: 72 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | TEAE leading to interruption of study drug | 2 Participants |
| Schedule A Cohort 10: 72 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | Any treatment emergent adverse event (TEAE) | 6 Participants |
| Schedule A Cohort 10: 72 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | Serious adverse events (SAE) | 5 Participants |
| Schedule A Cohort 10: 72 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | Fatal adverse events | 0 Participants |
| Schedule A Cohort 10: 72 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | TEAE Grade ≥ 4 | 3 Participants |
| Schedule A Cohort 10: 72 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | TEAE leading to discontinuation of study drug | 1 Participants |
| Schedule A Cohort 10: 72 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | TEAE Grade ≥ 2 | 6 Participants |
| Schedule A Cohort 11: 110 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | Treatment related TEAEs | 4 Participants |
| Schedule A Cohort 11: 110 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | SAE leading to interruption of study drug | 0 Participants |
| Schedule A Cohort 11: 110 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | Any treatment emergent adverse event (TEAE) | 4 Participants |
| Schedule A Cohort 11: 110 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | TEAE Grade ≥ 4 | 4 Participants |
| Schedule A Cohort 11: 110 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | TEAE Grade ≥ 3 | 4 Participants |
| Schedule A Cohort 11: 110 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | TEAE leading to discontinuation of study drug | 1 Participants |
| Schedule A Cohort 11: 110 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | Serious adverse events (SAE) | 3 Participants |
| Schedule A Cohort 11: 110 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | Fatal adverse events | 0 Participants |
| Schedule A Cohort 11: 110 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | TEAE Grade ≥ 2 | 4 Participants |
| Schedule A Cohort 11: 110 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | TEAE leading to interruption of study drug | 0 Participants |
| Schedule A Cohort 11: 110 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | SAE leading to discontinuation of study drug | 1 Participants |
| Schedule A Cohort 12: 36/72 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | SAE leading to discontinuation of study drug | 1 Participants |
| Schedule A Cohort 12: 36/72 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | Treatment related TEAEs | 4 Participants |
| Schedule A Cohort 12: 36/72 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | TEAE leading to interruption of study drug | 2 Participants |
| Schedule A Cohort 12: 36/72 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | TEAE Grade ≥ 4 | 2 Participants |
| Schedule A Cohort 12: 36/72 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | SAE leading to interruption of study drug | 1 Participants |
| Schedule A Cohort 12: 36/72 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | TEAE Grade ≥ 3 | 4 Participants |
| Schedule A Cohort 12: 36/72 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | TEAE Grade ≥ 2 | 4 Participants |
| Schedule A Cohort 12: 36/72 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | Fatal adverse events | 1 Participants |
| Schedule A Cohort 12: 36/72 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | Any treatment emergent adverse event (TEAE) | 4 Participants |
| Schedule A Cohort 12: 36/72 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | TEAE leading to discontinuation of study drug | 1 Participants |
| Schedule A Cohort 12: 36/72 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | Serious adverse events (SAE) | 4 Participants |
| Schedule B Cohort 1: 72 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | TEAE leading to discontinuation of study drug | 1 Participants |
| Schedule B Cohort 1: 72 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | TEAE leading to interruption of study drug | 0 Participants |
| Schedule B Cohort 1: 72 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | Fatal adverse events | 0 Participants |
| Schedule B Cohort 1: 72 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | Serious adverse events (SAE) | 1 Participants |
| Schedule B Cohort 1: 72 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | TEAE Grade ≥ 4 | 4 Participants |
| Schedule B Cohort 1: 72 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | TEAE Grade ≥ 3 | 5 Participants |
| Schedule B Cohort 1: 72 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | Treatment related TEAEs | 5 Participants |
| Schedule B Cohort 1: 72 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | Any treatment emergent adverse event (TEAE) | 5 Participants |
| Schedule B Cohort 1: 72 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | SAE leading to interruption of study drug | 0 Participants |
| Schedule B Cohort 1: 72 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | SAE leading to discontinuation of study drug | 1 Participants |
| Schedule B Cohort 1: 72 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | TEAE Grade ≥ 2 | 5 Participants |
| Schedule B Cohort 2: 110 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | TEAE leading to interruption of study drug | 2 Participants |
| Schedule B Cohort 2: 110 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | TEAE Grade ≥ 3 | 3 Participants |
| Schedule B Cohort 2: 110 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | TEAE Grade ≥ 4 | 2 Participants |
| Schedule B Cohort 2: 110 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | Fatal adverse events | 0 Participants |
| Schedule B Cohort 2: 110 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | Any treatment emergent adverse event (TEAE) | 3 Participants |
| Schedule B Cohort 2: 110 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | Serious adverse events (SAE) | 2 Participants |
| Schedule B Cohort 2: 110 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | SAE leading to discontinuation of study drug | 0 Participants |
| Schedule B Cohort 2: 110 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | TEAE leading to discontinuation of study drug | 0 Participants |
| Schedule B Cohort 2: 110 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | Treatment related TEAEs | 3 Participants |
| Schedule B Cohort 2: 110 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | SAE leading to interruption of study drug | 1 Participants |
| Schedule B Cohort 2: 110 µg Emerfetamab | Number of Participants With Treatment-emergent Adverse Events | TEAE Grade ≥ 2 | 3 Participants |
Secondary
Duration of Response
Duration of response is defined as the interval from the date of the first disease assessment indicating an overall response to the first documented relapse or death due to any cause, whichever occurred first.
Time frame: Disease response was assessed on day 14 of every treatment cycle and at the end of study; median (min, max) duration was 1.22 (0.10, 5.98) months.
Population: All participants who received at least one dose of study drug with a best response of CR, CRi, MLFS, or CRh\*
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Schedule A Cohort 9: 36 µg Emerfetamab | Duration of Response | 22 days |
| Schedule B Cohort 1: 72 µg Emerfetamab | Duration of Response | 21 days |
Secondary
Response Rate
Disease response was based upon review of cytogenetics, bone marrow (BM) aspirates/biopsies, and peripheral blood count. Response rate is defined as the percentage of participants with a best overall response of complete remission (CR), CR with incomplete recovery (CRi) or morphologic leukemia-free state (MLFS) according to Revised International Working Group (IWG) response criteria, or CR with partial hematologic recovery (CRh\*). CR: BM blasts \< 5%; absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count (ANC) \> 1.0 x 10\^9/L; platelet count \> 100 x 10\^9/L; independence of red cell transfusions. CRi: All CR criteria except residual neutropenia or thrombocytopenia. MLFS: BM blasts \< 5%; absence of blasts with Auer rods; absence of extramedullary disease; no hematologic recovery required. CRh\*: \< 5% blasts in BM; no evidence of disease; partial recovery of peripheral blood counts: platelets \> 50,000/μl, and ANC \> 500/μl; no extramedullary disease.
Time frame: Disease response was assessed on day 14 of every treatment cycle and at the end of study; median (min, max) duration was 1.22 (0.10, 5.98) months.
Population: All participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Schedule A Cohort 1: 0.05 µg Emerfetamab | Response Rate | 0.0 percentage of participants |
| Schedule A Cohort 2: 0.15 µg Emerfetamab | Response Rate | 0.0 percentage of participants |
| Schedule A Cohort 3: 0.45 µg Emerfetamab | Response Rate | 0.0 percentage of participants |
| Schedule A Cohort 4: 1.5 µg Emerfetamab | Response Rate | 0.0 percentage of participants |
| Schedule A Cohort 5: 4.5 µg Emerfetamab | Response Rate | 0.0 percentage of participants |
| Schedule A Cohort 6: 7 µg Emerfetamab | Response Rate | 0.0 percentage of participants |
| Schedule A Cohort 7: 9 µg Emerfetamab | Response Rate | 0.0 percentage of participants |
| Schedule A Cohort 8: 18 µg Emerfetamab | Response Rate | 0.0 percentage of participants |
| Schedule A Cohort 9: 36 µg Emerfetamab | Response Rate | 25.0 percentage of participants |
| Schedule A Cohort 10: 72 µg Emerfetamab | Response Rate | 0.0 percentage of participants |
| Schedule A Cohort 11: 110 µg Emerfetamab | Response Rate | 0.0 percentage of participants |
| Schedule A Cohort 12: 36/72 µg Emerfetamab | Response Rate | 0.0 percentage of participants |
| Schedule B Cohort 1: 72 µg Emerfetamab | Response Rate | 40.0 percentage of participants |
| Schedule B Cohort 2: 110 µg Emerfetamab | Response Rate | 0.0 percentage of participants |
Secondary
Schedule A: Area Under the Concentration-time Curve From Time Zero to 96 Hours Post-dose (AUC0-96) on Day 1 for Emerfetamab
Serum concentrations of emerfetamab were determined using a validated assay. Noncompartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (0.0015 ng/mL) were set to zero before data analysis. The area under the curve (AUC) from time zero to 96 hours postdose was calculated using the linear trapezoidal method.
Time frame: Cycle 1 day 1 at predose and at 1, 6, 24, 48, and 96 hours after the start of infusion.
Population: Participants who received at least 1 dose of study drug, had at least 1 PK sample collected, with enough data for calculation of the PK parameter.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Schedule A Cohort 1: 0.05 µg Emerfetamab | Schedule A: Area Under the Concentration-time Curve From Time Zero to 96 Hours Post-dose (AUC0-96) on Day 1 for Emerfetamab | 0.222 hr*ng/mL | — |
| Schedule A Cohort 2: 0.15 µg Emerfetamab | Schedule A: Area Under the Concentration-time Curve From Time Zero to 96 Hours Post-dose (AUC0-96) on Day 1 for Emerfetamab | 0.84 hr*ng/mL | — |
| Schedule A Cohort 3: 0.45 µg Emerfetamab | Schedule A: Area Under the Concentration-time Curve From Time Zero to 96 Hours Post-dose (AUC0-96) on Day 1 for Emerfetamab | 0.659 hr*ng/mL | Standard Deviation 0.664 |
| Schedule A Cohort 4: 1.5 µg Emerfetamab | Schedule A: Area Under the Concentration-time Curve From Time Zero to 96 Hours Post-dose (AUC0-96) on Day 1 for Emerfetamab | 1.03 hr*ng/mL | — |
| Schedule A Cohort 5: 4.5 µg Emerfetamab | Schedule A: Area Under the Concentration-time Curve From Time Zero to 96 Hours Post-dose (AUC0-96) on Day 1 for Emerfetamab | 5.37 hr*ng/mL | Standard Deviation 1.23 |
| Schedule A Cohort 6: 7 µg Emerfetamab | Schedule A: Area Under the Concentration-time Curve From Time Zero to 96 Hours Post-dose (AUC0-96) on Day 1 for Emerfetamab | 12.0 hr*ng/mL | Standard Deviation 8.79 |
| Schedule A Cohort 7: 9 µg Emerfetamab | Schedule A: Area Under the Concentration-time Curve From Time Zero to 96 Hours Post-dose (AUC0-96) on Day 1 for Emerfetamab | 13.5 hr*ng/mL | Standard Deviation 10.4 |
| Schedule A Cohort 8: 18 µg Emerfetamab | Schedule A: Area Under the Concentration-time Curve From Time Zero to 96 Hours Post-dose (AUC0-96) on Day 1 for Emerfetamab | 16.5 hr*ng/mL | Standard Deviation 13 |
| Schedule A Cohort 9: 36 µg Emerfetamab | Schedule A: Area Under the Concentration-time Curve From Time Zero to 96 Hours Post-dose (AUC0-96) on Day 1 for Emerfetamab | 22.4 hr*ng/mL | Standard Deviation 9.66 |
| Schedule A Cohort 10: 72 µg Emerfetamab | Schedule A: Area Under the Concentration-time Curve From Time Zero to 96 Hours Post-dose (AUC0-96) on Day 1 for Emerfetamab | 34.4 hr*ng/mL | Standard Deviation 11.7 |
| Schedule A Cohort 11: 110 µg Emerfetamab | Schedule A: Area Under the Concentration-time Curve From Time Zero to 96 Hours Post-dose (AUC0-96) on Day 1 for Emerfetamab | 62.4 hr*ng/mL | Standard Deviation 10.4 |
| Schedule A Cohort 12: 36/72 µg Emerfetamab | Schedule A: Area Under the Concentration-time Curve From Time Zero to 96 Hours Post-dose (AUC0-96) on Day 1 for Emerfetamab | 18.3 hr*ng/mL | Standard Deviation 5.02 |
Secondary
Schedule A: Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) for Emerfetamab
Serum concentrations of emerfetamab were determined using a validated assay. Non-compartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (0.0015 ng/mL) were set to zero before data analysis. The area under the concentration-time curve from time 0 relative to the start of the IV infusion to infinity was estimated using the linear trapezoidal method.
Time frame: Cycle 1 day 5 at predose and 1, 6, 12, 24, 48, 72, and 312 hours after the start of infusion.
Population: Participants who received at least 1 dose of study drug, had at least 1 PK sample collected, with enough data for calculation of the PK parameter.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Schedule A Cohort 2: 0.15 µg Emerfetamab | Schedule A: Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) for Emerfetamab | 0.784 hr*ng/mL | — |
| Schedule A Cohort 3: 0.45 µg Emerfetamab | Schedule A: Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) for Emerfetamab | 1.56 hr*ng/mL | Standard Deviation 0.394 |
| Schedule A Cohort 4: 1.5 µg Emerfetamab | Schedule A: Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) for Emerfetamab | 1.56 hr*ng/mL | — |
| Schedule A Cohort 5: 4.5 µg Emerfetamab | Schedule A: Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) for Emerfetamab | 6.16 hr*ng/mL | — |
| Schedule A Cohort 6: 7 µg Emerfetamab | Schedule A: Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) for Emerfetamab | 23.6 hr*ng/mL | Standard Deviation 25.1 |
| Schedule A Cohort 7: 9 µg Emerfetamab | Schedule A: Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) for Emerfetamab | 15.3 hr*ng/mL | Standard Deviation 10.8 |
| Schedule A Cohort 8: 18 µg Emerfetamab | Schedule A: Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) for Emerfetamab | 16.3 hr*ng/mL | — |
| Schedule A Cohort 9: 36 µg Emerfetamab | Schedule A: Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) for Emerfetamab | 28.6 hr*ng/mL | Standard Deviation 13.1 |
| Schedule A Cohort 10: 72 µg Emerfetamab | Schedule A: Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) for Emerfetamab | 36.8 hr*ng/mL | Standard Deviation 9.04 |
| Schedule A Cohort 11: 110 µg Emerfetamab | Schedule A: Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) for Emerfetamab | 61.0 hr*ng/mL | Standard Deviation 36.5 |
| Schedule A Cohort 12: 36/72 µg Emerfetamab | Schedule A: Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) for Emerfetamab | 38.3 hr*ng/mL | Standard Deviation 10.9 |
Secondary
Schedule A: Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) for Emerfetamab
Serum concentrations of emerfetamab were determined using a validated assay. Non-compartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (0.0015 ng/mL) were set to zero before data analysis. The area under the concentration-time curve from time 0 relative to the start of the IV infusion to the last quantifiable concentration was estimated using the linear trapezoidal method.
Time frame: Cycle 1 day 5 at predose and 1, 6, 12, 24, 48, 72, and 312 hours after the start of infusion.
Population: Participants who received at least 1 dose of study drug, had at least 1 PK sample collected, with enough data for calculation of the PK parameter.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Schedule A Cohort 1: 0.05 µg Emerfetamab | Schedule A: Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) for Emerfetamab | 0.302 hr*ng/mL | — |
| Schedule A Cohort 2: 0.15 µg Emerfetamab | Schedule A: Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) for Emerfetamab | 0.745 hr*ng/mL | — |
| Schedule A Cohort 3: 0.45 µg Emerfetamab | Schedule A: Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) for Emerfetamab | 1.38 hr*ng/mL | Standard Deviation 0.406 |
| Schedule A Cohort 4: 1.5 µg Emerfetamab | Schedule A: Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) for Emerfetamab | 1.01 hr*ng/mL | Standard Deviation 0.855 |
| Schedule A Cohort 5: 4.5 µg Emerfetamab | Schedule A: Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) for Emerfetamab | 5.93 hr*ng/mL | — |
| Schedule A Cohort 6: 7 µg Emerfetamab | Schedule A: Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) for Emerfetamab | 22.7 hr*ng/mL | Standard Deviation 24.2 |
| Schedule A Cohort 7: 9 µg Emerfetamab | Schedule A: Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) for Emerfetamab | 14.4 hr*ng/mL | Standard Deviation 9.69 |
| Schedule A Cohort 8: 18 µg Emerfetamab | Schedule A: Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) for Emerfetamab | 19.3 hr*ng/mL | Standard Deviation 8.95 |
| Schedule A Cohort 9: 36 µg Emerfetamab | Schedule A: Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) for Emerfetamab | 27.1 hr*ng/mL | Standard Deviation 12.9 |
| Schedule A Cohort 10: 72 µg Emerfetamab | Schedule A: Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) for Emerfetamab | 35.3 hr*ng/mL | Standard Deviation 9.13 |
| Schedule A Cohort 11: 110 µg Emerfetamab | Schedule A: Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) for Emerfetamab | 56.8 hr*ng/mL | Standard Deviation 31.3 |
| Schedule A Cohort 12: 36/72 µg Emerfetamab | Schedule A: Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) for Emerfetamab | 35.7 hr*ng/mL | Standard Deviation 7.85 |
Secondary
Schedule A: AUC Total for Emerfetamab
Serum concentrations of emerfetamab were determined using a validated assay. Non-compartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (0.0015 ng/mL) were set to zero before data analysis. The AUC total was calculated as the sum of AUC0-96hr following the Day 1 dose and AUCinf following the Day 5 dose.
Time frame: Cycle 1 day 1 at predose and at 1, 6, 24, and 48 hours after the start of infusion, and day 5 at predose and 1, 6, 12, 24, 48, 72, and 312 hours after the start of infusion.
Population: Participants who received at least 1 dose of study drug, had at least 1 PK sample collected, with enough data for calculation of the PK parameter.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Schedule A Cohort 2: 0.15 µg Emerfetamab | Schedule A: AUC Total for Emerfetamab | 1.62 hr*ng/mL | — |
| Schedule A Cohort 3: 0.45 µg Emerfetamab | Schedule A: AUC Total for Emerfetamab | 2.22 hr*ng/mL | Standard Deviation 1.05 |
| Schedule A Cohort 4: 1.5 µg Emerfetamab | Schedule A: AUC Total for Emerfetamab | 2.59 hr*ng/mL | — |
| Schedule A Cohort 5: 4.5 µg Emerfetamab | Schedule A: AUC Total for Emerfetamab | 10.8 hr*ng/mL | — |
| Schedule A Cohort 6: 7 µg Emerfetamab | Schedule A: AUC Total for Emerfetamab | 35.6 hr*ng/mL | Standard Deviation 26.4 |
| Schedule A Cohort 7: 9 µg Emerfetamab | Schedule A: AUC Total for Emerfetamab | 28.8 hr*ng/mL | Standard Deviation 16.4 |
| Schedule A Cohort 8: 18 µg Emerfetamab | Schedule A: AUC Total for Emerfetamab | 25.5 hr*ng/mL | — |
| Schedule A Cohort 9: 36 µg Emerfetamab | Schedule A: AUC Total for Emerfetamab | 51.1 hr*ng/mL | Standard Deviation 16.6 |
| Schedule A Cohort 10: 72 µg Emerfetamab | Schedule A: AUC Total for Emerfetamab | 71.2 hr*ng/mL | Standard Deviation 18.9 |
| Schedule A Cohort 11: 110 µg Emerfetamab | Schedule A: AUC Total for Emerfetamab | 126 hr*ng/mL | Standard Deviation 42.7 |
| Schedule A Cohort 12: 36/72 µg Emerfetamab | Schedule A: AUC Total for Emerfetamab | 51.2 hr*ng/mL | Standard Deviation 6.39 |
Secondary
Schedule A: Clearance (CL) of Emerfetamab
Serum concentrations of emerfetamab were determined using a validated assay. Non-compartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (0.0015 ng/mL) were set to zero before data analysis. Clearance was calculated as Dose/λz\*AUCinf.
Time frame: Cycle 1 day 5 at predose and 1, 6, 12, 24, 48, 72, and 312 hours after the start of infusion.
Population: Participants who received at least 1 dose of study drug, had at least 1 PK sample collected, with enough data for calculation of the PK parameter.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Schedule A Cohort 2: 0.15 µg Emerfetamab | Schedule A: Clearance (CL) of Emerfetamab | 191 mL/hr | — |
| Schedule A Cohort 3: 0.45 µg Emerfetamab | Schedule A: Clearance (CL) of Emerfetamab | 300 mL/hr | Standard Deviation 66.2 |
| Schedule A Cohort 4: 1.5 µg Emerfetamab | Schedule A: Clearance (CL) of Emerfetamab | 963 mL/hr | — |
| Schedule A Cohort 5: 4.5 µg Emerfetamab | Schedule A: Clearance (CL) of Emerfetamab | 742 mL/hr | — |
| Schedule A Cohort 6: 7 µg Emerfetamab | Schedule A: Clearance (CL) of Emerfetamab | 584 mL/hr | Standard Deviation 434 |
| Schedule A Cohort 7: 9 µg Emerfetamab | Schedule A: Clearance (CL) of Emerfetamab | 897 mL/hr | Standard Deviation 718 |
| Schedule A Cohort 8: 18 µg Emerfetamab | Schedule A: Clearance (CL) of Emerfetamab | 1330 mL/hr | — |
| Schedule A Cohort 9: 36 µg Emerfetamab | Schedule A: Clearance (CL) of Emerfetamab | 1420 mL/hr | Standard Deviation 474 |
| Schedule A Cohort 10: 72 µg Emerfetamab | Schedule A: Clearance (CL) of Emerfetamab | 2070 mL/hr | Standard Deviation 611 |
| Schedule A Cohort 11: 110 µg Emerfetamab | Schedule A: Clearance (CL) of Emerfetamab | 2210 mL/hr | Standard Deviation 1030 |
| Schedule A Cohort 12: 36/72 µg Emerfetamab | Schedule A: Clearance (CL) of Emerfetamab | 1980 mL/hr | Standard Deviation 459 |
Secondary
Schedule A: Maximum Observed Concentration (Cmax) of Emerfetamab
Serum concentrations of emerfetamab were determined using a validated assay. Noncompartmental analysis was performed for estimation of pharmacokinetic (PK) parameters. Concentrations below the lower limit of quantitation (LLOQ; 0.0015 ng/mL) were set to zero before data analysis.
Time frame: Cycle 1 day 1 at predose and at 1, 6, 24, and 48 hours after the start of infusion, and day 5 at predose and 1, 6, 12, 24, 48, 72, and 312 hours after the start of infusion.
Population: Participants who received at least 1 dose of study drug, had at least 1 PK sample collected, with enough data for calculation of the PK parameter.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Schedule A Cohort 1: 0.05 µg Emerfetamab | Schedule A: Maximum Observed Concentration (Cmax) of Emerfetamab | Day 1 | 0.00979 ng/mL | — |
| Schedule A Cohort 1: 0.05 µg Emerfetamab | Schedule A: Maximum Observed Concentration (Cmax) of Emerfetamab | Day 5 | 0.011 ng/mL | — |
| Schedule A Cohort 2: 0.15 µg Emerfetamab | Schedule A: Maximum Observed Concentration (Cmax) of Emerfetamab | Day 1 | 0.038 ng/mL | — |
| Schedule A Cohort 2: 0.15 µg Emerfetamab | Schedule A: Maximum Observed Concentration (Cmax) of Emerfetamab | Day 5 | 0.027 ng/mL | — |
| Schedule A Cohort 3: 0.45 µg Emerfetamab | Schedule A: Maximum Observed Concentration (Cmax) of Emerfetamab | Day 1 | 0.0255 ng/mL | Standard Deviation 0.0335 |
| Schedule A Cohort 3: 0.45 µg Emerfetamab | Schedule A: Maximum Observed Concentration (Cmax) of Emerfetamab | Day 5 | 0.0448 ng/mL | Standard Deviation 0.00672 |
| Schedule A Cohort 4: 1.5 µg Emerfetamab | Schedule A: Maximum Observed Concentration (Cmax) of Emerfetamab | Day 1 | 0.0463 ng/mL | Standard Deviation 0.0436 |
| Schedule A Cohort 4: 1.5 µg Emerfetamab | Schedule A: Maximum Observed Concentration (Cmax) of Emerfetamab | Day 5 | 0.0587 ng/mL | Standard Deviation 0.0517 |
| Schedule A Cohort 5: 4.5 µg Emerfetamab | Schedule A: Maximum Observed Concentration (Cmax) of Emerfetamab | Day 5 | 0.264 ng/mL | — |
| Schedule A Cohort 5: 4.5 µg Emerfetamab | Schedule A: Maximum Observed Concentration (Cmax) of Emerfetamab | Day 1 | 0.347 ng/mL | Standard Deviation 0.133 |
| Schedule A Cohort 6: 7 µg Emerfetamab | Schedule A: Maximum Observed Concentration (Cmax) of Emerfetamab | Day 1 | 1.04 ng/mL | Standard Deviation 1.43 |
| Schedule A Cohort 6: 7 µg Emerfetamab | Schedule A: Maximum Observed Concentration (Cmax) of Emerfetamab | Day 5 | 0.731 ng/mL | Standard Deviation 0.529 |
| Schedule A Cohort 7: 9 µg Emerfetamab | Schedule A: Maximum Observed Concentration (Cmax) of Emerfetamab | Day 5 | 0.961 ng/mL | Standard Deviation 1.3 |
| Schedule A Cohort 7: 9 µg Emerfetamab | Schedule A: Maximum Observed Concentration (Cmax) of Emerfetamab | Day 1 | 0.960 ng/mL | Standard Deviation 1.1 |
| Schedule A Cohort 8: 18 µg Emerfetamab | Schedule A: Maximum Observed Concentration (Cmax) of Emerfetamab | Day 1 | 1.12 ng/mL | Standard Deviation 1.12 |
| Schedule A Cohort 8: 18 µg Emerfetamab | Schedule A: Maximum Observed Concentration (Cmax) of Emerfetamab | Day 5 | 1.23 ng/mL | Standard Deviation 0.586 |
| Schedule A Cohort 9: 36 µg Emerfetamab | Schedule A: Maximum Observed Concentration (Cmax) of Emerfetamab | Day 1 | 2.16 ng/mL | Standard Deviation 1.78 |
| Schedule A Cohort 9: 36 µg Emerfetamab | Schedule A: Maximum Observed Concentration (Cmax) of Emerfetamab | Day 5 | 2.01 ng/mL | Standard Deviation 0.926 |
| Schedule A Cohort 10: 72 µg Emerfetamab | Schedule A: Maximum Observed Concentration (Cmax) of Emerfetamab | Day 1 | 3.15 ng/mL | Standard Deviation 1.9 |
| Schedule A Cohort 10: 72 µg Emerfetamab | Schedule A: Maximum Observed Concentration (Cmax) of Emerfetamab | Day 5 | 3.14 ng/mL | Standard Deviation 1.8 |
| Schedule A Cohort 11: 110 µg Emerfetamab | Schedule A: Maximum Observed Concentration (Cmax) of Emerfetamab | Day 5 | 5.07 ng/mL | Standard Deviation 2.53 |
| Schedule A Cohort 11: 110 µg Emerfetamab | Schedule A: Maximum Observed Concentration (Cmax) of Emerfetamab | Day 1 | 4.65 ng/mL | Standard Deviation 1.64 |
| Schedule A Cohort 12: 36/72 µg Emerfetamab | Schedule A: Maximum Observed Concentration (Cmax) of Emerfetamab | Day 5 | 3.29 ng/mL | Standard Deviation 0.484 |
| Schedule A Cohort 12: 36/72 µg Emerfetamab | Schedule A: Maximum Observed Concentration (Cmax) of Emerfetamab | Day 1 | 1.84 ng/mL | Standard Deviation 1.08 |
Secondary
Schedule A: Terminal Half-life (T1/2,z) of Emerfetamab
Serum concentrations of emerfetamab were determined using a validated assay. Non-compartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (0.0015 ng/mL) were set to zero before data analysis. Terminal half-life (t1/2,z) was calculated as t1/2,z = ln(2)/λz, where λz is the first-order terminal rate constant estimated via linear regression of the terminal log-linear phase.
Time frame: Cycle 1 day 5 at predose and 1, 6, 12, 24, 48, 72, and 312 hours after the start of infusion.
Population: Participants who received at least 1 dose of study drug, had at least 1 PK sample collected, with enough data for calculation of the PK parameter.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Schedule A Cohort 2: 0.15 µg Emerfetamab | Schedule A: Terminal Half-life (T1/2,z) of Emerfetamab | 16.3 hours | — |
| Schedule A Cohort 3: 0.45 µg Emerfetamab | Schedule A: Terminal Half-life (T1/2,z) of Emerfetamab | 35.1 hours | Standard Deviation 21.7 |
| Schedule A Cohort 4: 1.5 µg Emerfetamab | Schedule A: Terminal Half-life (T1/2,z) of Emerfetamab | 14.3 hours | — |
| Schedule A Cohort 5: 4.5 µg Emerfetamab | Schedule A: Terminal Half-life (T1/2,z) of Emerfetamab | 35.2 hours | — |
| Schedule A Cohort 6: 7 µg Emerfetamab | Schedule A: Terminal Half-life (T1/2,z) of Emerfetamab | 54.7 hours | Standard Deviation 20.5 |
| Schedule A Cohort 7: 9 µg Emerfetamab | Schedule A: Terminal Half-life (T1/2,z) of Emerfetamab | 55.8 hours | Standard Deviation 38.3 |
| Schedule A Cohort 8: 18 µg Emerfetamab | Schedule A: Terminal Half-life (T1/2,z) of Emerfetamab | 46.5 hours | — |
| Schedule A Cohort 9: 36 µg Emerfetamab | Schedule A: Terminal Half-life (T1/2,z) of Emerfetamab | 36.5 hours | Standard Deviation 13.3 |
| Schedule A Cohort 10: 72 µg Emerfetamab | Schedule A: Terminal Half-life (T1/2,z) of Emerfetamab | 41.7 hours | Standard Deviation 17.8 |
| Schedule A Cohort 11: 110 µg Emerfetamab | Schedule A: Terminal Half-life (T1/2,z) of Emerfetamab | 36.8 hours | Standard Deviation 22.4 |
| Schedule A Cohort 12: 36/72 µg Emerfetamab | Schedule A: Terminal Half-life (T1/2,z) of Emerfetamab | 40.6 hours | Standard Deviation 15.2 |
Secondary
Schedule A: Time to Maximum Observed Concentration (Tmax) of Emerfetamab
Serum concentrations of emerfetamab were determined using a validated assay. Noncompartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (0.0015 ng/mL) were set to zero before data analysis.
Time frame: Cycle 1 day 1 at predose and at 1, 6, 24, and 48 hours after the start of infusion, and day 5 at predose and 1, 6, 12, 24, 48, 72, and 312 hours after the start of infusion.
Population: Participants who received at least 1 dose of study drug, had at least 1 pharmacokinetic (PK) sample collected, with enough data for calculation of the PK parameter.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Schedule A Cohort 1: 0.05 µg Emerfetamab | Schedule A: Time to Maximum Observed Concentration (Tmax) of Emerfetamab | Day 5 | 4.08 hours |
| Schedule A Cohort 1: 0.05 µg Emerfetamab | Schedule A: Time to Maximum Observed Concentration (Tmax) of Emerfetamab | Day 1 | 0.53 hours |
| Schedule A Cohort 2: 0.15 µg Emerfetamab | Schedule A: Time to Maximum Observed Concentration (Tmax) of Emerfetamab | Day 1 | 0.50 hours |
| Schedule A Cohort 2: 0.15 µg Emerfetamab | Schedule A: Time to Maximum Observed Concentration (Tmax) of Emerfetamab | Day 5 | 2 hours |
| Schedule A Cohort 3: 0.45 µg Emerfetamab | Schedule A: Time to Maximum Observed Concentration (Tmax) of Emerfetamab | Day 1 | 0.62 hours |
| Schedule A Cohort 3: 0.45 µg Emerfetamab | Schedule A: Time to Maximum Observed Concentration (Tmax) of Emerfetamab | Day 5 | 2.3 hours |
| Schedule A Cohort 4: 1.5 µg Emerfetamab | Schedule A: Time to Maximum Observed Concentration (Tmax) of Emerfetamab | Day 5 | 2.1 hours |
| Schedule A Cohort 4: 1.5 µg Emerfetamab | Schedule A: Time to Maximum Observed Concentration (Tmax) of Emerfetamab | Day 1 | 0.48 hours |
| Schedule A Cohort 5: 4.5 µg Emerfetamab | Schedule A: Time to Maximum Observed Concentration (Tmax) of Emerfetamab | Day 1 | 0.5 hours |
| Schedule A Cohort 5: 4.5 µg Emerfetamab | Schedule A: Time to Maximum Observed Concentration (Tmax) of Emerfetamab | Day 5 | 1.9 hours |
| Schedule A Cohort 6: 7 µg Emerfetamab | Schedule A: Time to Maximum Observed Concentration (Tmax) of Emerfetamab | Day 1 | 0.50 hours |
| Schedule A Cohort 6: 7 µg Emerfetamab | Schedule A: Time to Maximum Observed Concentration (Tmax) of Emerfetamab | Day 5 | 2.0 hours |
| Schedule A Cohort 7: 9 µg Emerfetamab | Schedule A: Time to Maximum Observed Concentration (Tmax) of Emerfetamab | Day 1 | 2.0 hours |
| Schedule A Cohort 7: 9 µg Emerfetamab | Schedule A: Time to Maximum Observed Concentration (Tmax) of Emerfetamab | Day 5 | 1.1 hours |
| Schedule A Cohort 8: 18 µg Emerfetamab | Schedule A: Time to Maximum Observed Concentration (Tmax) of Emerfetamab | Day 5 | 1.1 hours |
| Schedule A Cohort 8: 18 µg Emerfetamab | Schedule A: Time to Maximum Observed Concentration (Tmax) of Emerfetamab | Day 1 | 1.0 hours |
| Schedule A Cohort 9: 36 µg Emerfetamab | Schedule A: Time to Maximum Observed Concentration (Tmax) of Emerfetamab | Day 5 | 1.0 hours |
| Schedule A Cohort 9: 36 µg Emerfetamab | Schedule A: Time to Maximum Observed Concentration (Tmax) of Emerfetamab | Day 1 | 1.0 hours |
| Schedule A Cohort 10: 72 µg Emerfetamab | Schedule A: Time to Maximum Observed Concentration (Tmax) of Emerfetamab | Day 5 | 1.1 hours |
| Schedule A Cohort 10: 72 µg Emerfetamab | Schedule A: Time to Maximum Observed Concentration (Tmax) of Emerfetamab | Day 1 | 1.1 hours |
| Schedule A Cohort 11: 110 µg Emerfetamab | Schedule A: Time to Maximum Observed Concentration (Tmax) of Emerfetamab | Day 1 | 1.1 hours |
| Schedule A Cohort 11: 110 µg Emerfetamab | Schedule A: Time to Maximum Observed Concentration (Tmax) of Emerfetamab | Day 5 | 1.0 hours |
| Schedule A Cohort 12: 36/72 µg Emerfetamab | Schedule A: Time to Maximum Observed Concentration (Tmax) of Emerfetamab | Day 1 | 0.97 hours |
| Schedule A Cohort 12: 36/72 µg Emerfetamab | Schedule A: Time to Maximum Observed Concentration (Tmax) of Emerfetamab | Day 5 | 1.1 hours |
Secondary
Schedule B: Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) for Emerfetamab
Serum concentrations of emerfetamab were determined using a validated assay. Noncompartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (0.0015 ng/mL) were set to zero before data analysis. The area under the concentration-time curve from time 0 relative to the start of the IV infusion to infinity was estimated using the linear trapezoidal method.
Time frame: Cycle 1 day 14 at predose and 1, 6, 12, 24, 48, 72, 96, and 120 hours after the start of infusion.
Population: Participants who received at least 1 dose of study drug, had at least 1 PK sample collected, with enough data for calculation of the PK parameter. No participants in Schedule B cohort 2 had data available for calculation of AUCinf.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Schedule A Cohort 1: 0.05 µg Emerfetamab | Schedule B: Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) for Emerfetamab | 106 hr*ng/mL |
Secondary
Schedule B: Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) for Emerfetamab
Serum concentrations of emerfetamab were determined using a validated assay. Noncompartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (0.0015 ng/mL) were set to zero before data analysis. The area under the concentration-time curve from time 0 relative to the start of the IV infusion to the last quantifiable concentration was estimated using the linear trapezoidal method.
Time frame: Cycle 1 day 14 at predose and 1, 6, 12, 24, 48, 72, 96, and 120 hours after the start of infusion.
Population: Participants who received at least 1 dose of study drug, had at least 1 PK sample collected, with enough data for calculation of the PK parameter.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Schedule A Cohort 1: 0.05 µg Emerfetamab | Schedule B: Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) for Emerfetamab | 97.2 hr*ng/mL | — |
| Schedule A Cohort 2: 0.15 µg Emerfetamab | Schedule B: Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) for Emerfetamab | 42.9 hr*ng/mL | Standard Deviation 20.4 |
Secondary
Schedule B: Clearance of Emerfetamab
Serum concentrations of emerfetamab were determined using a validated assay. Noncompartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (0.0015 ng/mL) were set to zero before data analysis.
Time frame: Cycle 1 day 14 at predose and 1, 6, 12, 24, 48, 72, 96, and 120 hours after the start of infusion.
Population: Participants who received at least 1 dose of study drug, had at least 1 PK sample collected, with enough data for calculation of the PK parameter. No participants in Schedule B cohort 2 had data available for calculation of clearance.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Schedule A Cohort 1: 0.05 µg Emerfetamab | Schedule B: Clearance of Emerfetamab | 0.677 mL/hr |
Secondary
Schedule B: Maximum Observed Concentration (Cmax) of Emerfetamab
Serum concentrations of emerfetamab were determined using a validated assay. Noncompartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (0.0015 ng/mL) were set to zero before data analysis.
Time frame: Cycle 1 day 14 at predose and 1, 6, 12, 24, 48, 72, 96, and 120 hours after the start of infusion.
Population: Participants who received at least 1 dose of study drug, had at least 1 PK sample collected, with enough data for calculation of the PK parameter.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Schedule A Cohort 1: 0.05 µg Emerfetamab | Schedule B: Maximum Observed Concentration (Cmax) of Emerfetamab | 4.07 ng/mL | — |
| Schedule A Cohort 2: 0.15 µg Emerfetamab | Schedule B: Maximum Observed Concentration (Cmax) of Emerfetamab | 4.71 ng/mL | Standard Deviation 2.01 |
Secondary
Schedule B: Terminal Half-life (T1/2,z) of Emerfetamab
Serum concentrations of emerfetamab were determined using a validated assay. Noncompartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (0.0015 ng/mL) were set to zero before data analysis.
Time frame: Cycle 1 day 14 at predose and 1, 6, 12, 24, 48, 72, 96, and 120 hours after the start of infusion.
Population: Participants who received at least 1 dose of study drug, had at least 1 PK sample collected, with enough data for calculation of the PK parameter. No participants in Schedule B cohort 2 had data available for calculation of T1/2,z.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Schedule A Cohort 1: 0.05 µg Emerfetamab | Schedule B: Terminal Half-life (T1/2,z) of Emerfetamab | 30.5 hours |
Secondary
Schedule B: Time to Maximum Observed Concentration (Tmax) of Emerfetamab
Serum concentrations of emerfetamab were determined using a validated assay. Noncompartmental analysis was performed for estimation of PK parameters. Concentrations below the LLOQ (0.0015 ng/mL) were set to zero before data analysis.
Time frame: Cycle 1 day 14 at predose and 1, 6, 12, 24, 48, 72, 96, and 120 hours after the start of infusion.
Population: Participants who received at least 1 dose of study drug, had at least 1 PK sample collected, with enough data for calculation of the PK parameter.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Schedule A Cohort 1: 0.05 µg Emerfetamab | Schedule B: Time to Maximum Observed Concentration (Tmax) of Emerfetamab | 5.5 hours |
| Schedule A Cohort 2: 0.15 µg Emerfetamab | Schedule B: Time to Maximum Observed Concentration (Tmax) of Emerfetamab | 1.0 hours |
Secondary
Time to Progression
Time to progression (event-free survival) is defined as the interval from first administration of study drug to the earliest of date of treatment failure, relapse for responders, or death due to any cause. For non-responders, the event date for treatment failure was assigned as the date of first administration of study drug.
Time frame: Disease response was assessed on day 14 of every treatment cycle and at the end of study; median (min, max) duration was 1.22 (0.10, 5.98) months.
Population: All participants who received at least one dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Schedule A Cohort 1: 0.05 µg Emerfetamab | Time to Progression | 1 days |
| Schedule A Cohort 2: 0.15 µg Emerfetamab | Time to Progression | 1 days |
| Schedule A Cohort 3: 0.45 µg Emerfetamab | Time to Progression | 1 days |
| Schedule A Cohort 4: 1.5 µg Emerfetamab | Time to Progression | 1 days |
| Schedule A Cohort 5: 4.5 µg Emerfetamab | Time to Progression | 1 days |
| Schedule A Cohort 6: 7 µg Emerfetamab | Time to Progression | 1 days |
| Schedule A Cohort 7: 9 µg Emerfetamab | Time to Progression | 1 days |
| Schedule A Cohort 8: 18 µg Emerfetamab | Time to Progression | 1 days |
| Schedule A Cohort 9: 36 µg Emerfetamab | Time to Progression | 1 days |
| Schedule A Cohort 10: 72 µg Emerfetamab | Time to Progression | 1 days |
| Schedule A Cohort 11: 110 µg Emerfetamab | Time to Progression | 1 days |
| Schedule A Cohort 12: 36/72 µg Emerfetamab | Time to Progression | 1 days |
| Schedule B Cohort 1: 72 µg Emerfetamab | Time to Progression | 1 days |
| Schedule B Cohort 2: 110 µg Emerfetamab | Time to Progression | 1 days |
Secondary
Time to Response
Time to response is defined as the interval from the first administration of study drug to the first documentation of response. Time to response was evaluated only for participants who achieved a response.
Time frame: Disease response was assessed on day 14 of every treatment cycle and at the end of study; median (min, max) duration was 1.22 (0.10, 5.98) months.
Population: All participants who received at least one dose of study drug with a best response of CR, CRi, MLFS, or CRh\*
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Schedule A Cohort 9: 36 µg Emerfetamab | Time to Response | 42 days |
| Schedule B Cohort 1: 72 µg Emerfetamab | Time to Response | 22 days |