Acute Myeloid Leukemia
Conditions
Keywords
Sabatolimab, MBG453, TIM-3, Azacitidine, Acute Myeloid Leukemia, AML, Allogeneic Hematopoietic Stem Cell Transplantation, aHSCT, Measurable Residual Disease, MRD, Phase Ib/II, Acute myeloid leukemia Hematopoietic stem cell transplantation
Brief summary
The primary purpose of this study was to test the hypothesis that preemptive treatment with sabatolimab, alone or in combination with azacitidine, when administered to participants with Acute myeloid leukemia (AML)/secondary AML who were in complete remission with positive measurable residual disease post-allogeneic hematopoietic stem cell transplantation (Minimal residual disease (MRD)+ post- Allogeneic hematopoietic stem cell transplantation (aHSCT)), could enhance the graft versus leukemia (GvL) response and prevent or delay hematologic relapse without an unacceptable level of treatment-emergent toxicities, including clinically significant acute and/or chronic graft-versus-host disease (GvHD) and immune-related adverse events
Detailed description
This is a phase Ib/II, open label, multi-center study of sabatolimab as monotherapy and in combination with azacitidine, in participants with AML/secondary AML who had received one aHSCT and achieved complete remission but MRD+, by local assessment, anytime at \>= Day 60 after aHSCT and at least 2 weeks after immunosuppressive medications had been tapered off. The study was planned to enroll approximately 59 participants and be conducted in two parts: Part 1 was a Safety Run-in of approximately 20 participants, to assess whether sabatolimab as monotherapy at the two tested dose levels (400 mg and 800 mg intravenously Q4W) was safe when administered in the post-aHSCT setting. For each dose level, once the required number of evaluable participants had been confirmed, enrollment would be halted until participants had completed the dose limiting toxicities (DLT) observation period (≥ 8 weeks following the first dose). Following the observation period for DLTs, a Safety Review Meeting was to be conducted after each dose level to assess safety and determine the recommended dose for expansion to proceed with enrollment of additional cohorts in Part 2 of the study. Part 2 consisted of sabatolimab monotherapy expansion cohort of approximately 13 participants, sabatolimab in combination with azacitidine cohort of approximately 20 participants, and an adolescent cohort of approximately 6 participants (≥ 12 years but \< 18 years of age) with sabatolimab as monotherapy. Sabatolimab was to be administered at the recommended dose for expansion determined in Part 1. After initiating Part 2, Novartis took the decision to put enrollment in permanent halt and terminate the sabatolimab program. This decision was not driven by any safety concerns.
Interventions
BIOLOGICALSabatolimab
Sabatolimab is a solution in vial for IV infusion
DRUGAzacitidine
Azacitidine comes in Vial for IV infusion or subcutaneous administration
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Signed informed consent must be obtained prior to participation in the study. * At the date of signing the informed consent form (ICF), eligible participants must be ≥ 18 years for the adult cohorts; and ≥ 12 years old but \< 18 years old for the adolescent cohort (cohort 5), which will open after completion of Safety Run-in. * Participants in complete remission (\< 5% bone marrow blasts, absence of circulating blasts, and absence of extramedullary disease) with MRD positivity by local assessment or by central assessment where required (e.g., USA sites), any time at ≥ Day 60 after aHSCT * Diagnosis of AML/secondary AML and received one prior aHSCT performed to control AML * Ability to provide a fresh bone marrow aspirate sample collected within 28 days from enrollment/randomization, and immediately shipped to a Novartis designated central laboratory for MRD testing. * Systemic GvHD (graft versus host disease) prophylaxis or treatment \[immunosuppressive treatment (IST)\] completely tapered for at least two weeks prior to study entry. Prednisone dose ≤ 5 mg/day or equivalent corticosteroid dose is allowed. * Participants who are found with MRD positivity while still on or tapering systemic GvHD prophylaxis or treatment, MRD positivity must be re-confirmed at least 2 week after the last dose of IST * For the adult cohorts, participants must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2. For the adolescent cohort, participants must have a Karnofsky (age ≥ 16 years) or Lansky (age \< 16 years) performance status score ≥ 50%.
Exclusion criteria
* Prior exposure to TIM-3 directed therapy at anytime. * History of severe hypersensitivity reactions to any ingredient of study drug(s) (azacitidine, sabatolimab) or monoclonal antibodies (mAbs) and/or their excipients * Active Hepatitis B (HBV) or Hepatitis C (HCV) infection. Participants whose disease is controlled under antiviral therapy should not be excluded. * Active acute GvHD grade III-IV according to standard criteria (Harris 2016). * Active moderate chronic GvHD of the lungs according to NIH consensus criteria. Active severe chronic GvHD according to NIH consensus criteria. * History of another primary malignancy that is currently clinically significant or currently requires active intervention. Participants who are receiving adjuvant therapy, such as hormone therapy, are eligible * Any concurrent severe and/or active uncontrolled infection requiring parenteral antibacterial, antiviral or antifungal therapy (such as severe pneumonia, meningitis, or septicemia) * Active autoimmune disease requiring systemic therapy (e.g. corticosteroids). Topical, inhaled, nasal and ophthalmic steroids are not prohibited. Replacement corticosteroids therapy is allowed and not considered a form of systemic treatment * Live vaccine administered within 30 days prior to the first day of study treatment (Cycle 1 Day 1) * Other concurrent severe and/or uncontrolled medical conditions (e.g. uncontrolled diabetes mellitus, chronic obstructive or chronic restrictive pulmonary disease including dyspnoea at rest from any cause) or history of serious organ dysfunction or disease involving the heart, kidney, or liver
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Dose Limiting Toxicities (Safety Run-in in Adult Sabatolimab 400mg & 800mg Only) | From Cycle 1 Day 1 to end of Cycle 2; Cycle =28 Days | Assessment of tolerability of sabatolimab in adults and adolescents in the post allogenic stem cell transplantation setting. This was determined by the number of participants with at least one event - All grades. A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value considered by the Investigator to be at least possibly related to sabatolimab as a single contributor that occurs during the DLT observation period and meets the severity criteria as per protocol. |
| Percentage of Adult Subjects With Absence of Hematologic Relapse Per Investigator Assessment (Safety Run-in and Expansion) | From Cycle 1 Day 1 to end of Cycle 6; Cycle = 28 Days | The percentage of adult participants for whom no evidence of hematologic relapse (no evidence of bone marrow blasts ≥5%, no evidence of reappearance of blasts in the blood; no evidence of development of extramedullary disease) has been documented after 6 cycles of study treatment or earlier discontinuation at the recommended dose of sabatolimab 800 mg. |
| Rate of Dose Limiting Toxicities (Safety Confirmation in Adolescent Cohort Only) | From Cycle 1 Day 1 to end of Cycle 2; Cycle =28 Days | Assessment of tolerability of sabatolimab in adolescent participants in the post allogeneic stem cell transplantation setting. This was determined by the number of participants with at least one event - All grades. A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value considered by the Investigator to be at least possibly related to sabatolimab as a single contributor that occurs during the DLT observation period and meets the severity criteria as per protocol. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Trough Serum Concentration of (Cmin) Sabatolimab | Adult cohorts: Pre-dose on Day 1 (safety run-in) or Day 5 (expansion) of Cycle 1, 3, 6 and 24 (safety run-in only); Adolescent cohort: Pre-dose on Day 1 of Cycle 1, 2, 3 and 6; Cycle = 28 Days | Cmin is the concentration of sabatolimab prior to next dosing or after end of treatment. |
| Graft Versus Host Disease (GvHD)-Free/Relapse-free Survival (GRFS) | From start of treatment to up to 36 months from last patient first treatment | Time from start of treatment to the date of first documented occurrence or worsening of treatment emergent grade III or IV aGvHD or moderate to severe cGvHD requiring initiation of systemic treatment, morphologic/hematologic relapse, or death due to any cause, whichever occurs first |
| Incidence of Grade III or IV Acute Graft Versus Host Disease (aGvHD) | From start of treatment to up to 36 months from last patient first treatment. | Assessment of the treatment emergent grade III or IV aGvHD. Acute GvHD: Grade IV acute GvHD, Stage ≥3 lower GI acute GvHD (consistent with Grade III acute GvHD) or Stage ≥3 liver acute GvHD (consistent with Grade III GvHD). |
| Percentage of Participants With Measurable Residual Disease (MRD) Positive at Baseline Who Become MRD Negative | From start of treatment until end of Cycle 6 (Cycle = 28 Days) | Percentage of participants with centrally confirmed MRD+ status at baseline converting to MRD- within the first 6 cycles of study treatment. |
| Relapse-free Survival (RFS) | From start of treatment to up to 36 months from last patient first treatment | Time from start of treatment to the date of first documented hematologic relapse or death due to any cause, whichever occurs first. |
| Incidence of Moderate to Severe Chronic GVHD (cGvHD) | From start of treatment to up to 36 months from last patient first treatment. | Assessment of the treatment emergent moderate or severe cGvHD. Chronic GvHD: Moderate chronic GvHD of the lungs, Severe chronic GvHD. |
| Peak of Serum Concentration (Cmax) Sabatolimab | Cycle 1 Day 5 (end of infusion) and Cycle 3 Day 1 or Day 5 (end of infusion) and Cycle 24 Day 1 (end of infusion); Cycle =28 Days | Cmax is the maximal serum concentration of sabatolimab. |
Countries
France, Germany, Italy, Spain
Participant flow
Recruitment details
A total of 24 participants were enrolled in this study: 21 in Safety run-in sabatolimab monotherapy and 3 in Expansion part.
Pre-assignment details
Due to the recruitment halt by Novartis, recruitment in the expansion phase was not completed.
Participants by arm
| Arm | Count |
|---|---|
| Sabatolimab 400mg Mono Adults Safety run-in cohort: Adult participants in this arm received sabatolimab 400mg only. | 10 |
| Sabatolimab 800mg Mono Adults Safety run-in cohort: Adult participants in this arm received sabatolimab 800mg only. | 11 |
| Sabatolimab 800mg + Azacitidine Adults Expansion cohort: Adult participants in this arm received sabatolimab 800 mg + azacitidine combination | 2 |
| Sabatolimab 800mg Mono Adolescent Adolescent safety cohort: ≥12 to \< 18-year-old adolescent participants in this arm received sabatolimab 800mg only. | 1 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Death | 5 | 2 | 0 | 0 |
| Overall Study | Physician Decision | 1 | 0 | 0 | 0 |
| Overall Study | Terminated by Sponsor | 3 | 2 | 2 | 0 |
Baseline characteristics
| Characteristic | Sabatolimab 400mg Mono Adults | Sabatolimab 800mg Mono Adults | Sabatolimab 800mg + Azacitidine Adults | Sabatolimab 800mg Mono Adolescent | Total |
|---|---|---|---|---|---|
| Age, Customized Category 1 : 12 - <18 years | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Age, Customized Category 1 : 18 - <65 years | 8 Participants | 7 Participants | 1 Participants | 0 Participants | 16 Participants |
| Age, Customized Category 1 : 65 - <85 years | 2 Participants | 4 Participants | 1 Participants | 0 Participants | 7 Participants |
| Race/Ethnicity, Customized Unknown | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized White | 9 Participants | 9 Participants | 2 Participants | 1 Participants | 21 Participants |
| Sex: Female, Male Female | 5 Participants | 6 Participants | 2 Participants | 1 Participants | 14 Participants |
| Sex: Female, Male Male | 5 Participants | 5 Participants | 0 Participants | 0 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 5 / 10 | 2 / 11 | 0 / 2 | 0 / 1 |
| other Total, other adverse events | 9 / 10 | 9 / 11 | 2 / 2 | 1 / 1 |
| serious Total, serious adverse events | 2 / 10 | 3 / 11 | 0 / 2 | 0 / 1 |
Outcome results
Primary
Percentage of Adult Subjects With Absence of Hematologic Relapse Per Investigator Assessment (Safety Run-in and Expansion)
The percentage of adult participants for whom no evidence of hematologic relapse (no evidence of bone marrow blasts ≥5%, no evidence of reappearance of blasts in the blood; no evidence of development of extramedullary disease) has been documented after 6 cycles of study treatment or earlier discontinuation at the recommended dose of sabatolimab 800 mg.
Time frame: From Cycle 1 Day 1 to end of Cycle 6; Cycle = 28 Days
Population: All adult participants treated with sabatolimab 800 mg monotherapy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sabatolimab 800mg Mono Adults | Percentage of Adult Subjects With Absence of Hematologic Relapse Per Investigator Assessment (Safety Run-in and Expansion) | 36.4 Percentage of participants |
Primary
Rate of Dose Limiting Toxicities (Safety Confirmation in Adolescent Cohort Only)
Assessment of tolerability of sabatolimab in adolescent participants in the post allogeneic stem cell transplantation setting. This was determined by the number of participants with at least one event - All grades. A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value considered by the Investigator to be at least possibly related to sabatolimab as a single contributor that occurs during the DLT observation period and meets the severity criteria as per protocol.
Time frame: From Cycle 1 Day 1 to end of Cycle 2; Cycle =28 Days
Population: Dose Determining Set included all participants from the FAS enrolled in the adolescent cohort who met the minimum exposure criterion described and had sufficient safety evaluations or experienced a dose limiting toxicity (DLT) between Cycle 1 Day 1 (first dose of sabatolimab) and the end of Cycle 2 (both inclusive).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sabatolimab 400mg Mono Adults | Rate of Dose Limiting Toxicities (Safety Confirmation in Adolescent Cohort Only) | 0 Participants |
Primary
Rate of Dose Limiting Toxicities (Safety Run-in in Adult Sabatolimab 400mg & 800mg Only)
Assessment of tolerability of sabatolimab in adults and adolescents in the post allogenic stem cell transplantation setting. This was determined by the number of participants with at least one event - All grades. A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value considered by the Investigator to be at least possibly related to sabatolimab as a single contributor that occurs during the DLT observation period and meets the severity criteria as per protocol.
Time frame: From Cycle 1 Day 1 to end of Cycle 2; Cycle =28 Days
Population: Dose Determining Set included all participants from the FAS enrolled in the safety run-in part who met the minimum exposure criterion described and had sufficient safety evaluations or experienced a dose limiting toxicity (DLT) between Cycle 1 Day 1 (first dose of sabatolimab) and the end of Cycle 2 (both inclusive).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sabatolimab 400mg Mono Adults | Rate of Dose Limiting Toxicities (Safety Run-in in Adult Sabatolimab 400mg & 800mg Only) | 0 Participants |
| Sabatolimab 800mg Mono Adults | Rate of Dose Limiting Toxicities (Safety Run-in in Adult Sabatolimab 400mg & 800mg Only) | 1 Participants |
Secondary
Graft Versus Host Disease (GvHD)-Free/Relapse-free Survival (GRFS)
Time from start of treatment to the date of first documented occurrence or worsening of treatment emergent grade III or IV aGvHD or moderate to severe cGvHD requiring initiation of systemic treatment, morphologic/hematologic relapse, or death due to any cause, whichever occurs first
Time frame: From start of treatment to up to 36 months from last patient first treatment
Population: Full Analysis Set (FAS) included all participants who received at least one dose of any component of the study treatment (i.e. at least one dose of sabatolimab or at least one dose of azacitidine).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sabatolimab 400mg Mono Adults | Graft Versus Host Disease (GvHD)-Free/Relapse-free Survival (GRFS) | NA Months |
| Sabatolimab 800mg Mono Adults | Graft Versus Host Disease (GvHD)-Free/Relapse-free Survival (GRFS) | NA Months |
| Sabatolimab 800mg + Azacitidine Adults | Graft Versus Host Disease (GvHD)-Free/Relapse-free Survival (GRFS) | NA Months |
| Sabatolimab 800mg Mono Adolescent | Graft Versus Host Disease (GvHD)-Free/Relapse-free Survival (GRFS) | NA Months |
Secondary
Incidence of Grade III or IV Acute Graft Versus Host Disease (aGvHD)
Assessment of the treatment emergent grade III or IV aGvHD. Acute GvHD: Grade IV acute GvHD, Stage ≥3 lower GI acute GvHD (consistent with Grade III acute GvHD) or Stage ≥3 liver acute GvHD (consistent with Grade III GvHD).
Time frame: From start of treatment to up to 36 months from last patient first treatment.
Population: Safety Set includes all participants from the FAS.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sabatolimab 400mg Mono Adults | Incidence of Grade III or IV Acute Graft Versus Host Disease (aGvHD) | 0 Participants |
| Sabatolimab 800mg Mono Adults | Incidence of Grade III or IV Acute Graft Versus Host Disease (aGvHD) | 0 Participants |
| Sabatolimab 800mg + Azacitidine Adults | Incidence of Grade III or IV Acute Graft Versus Host Disease (aGvHD) | 0 Participants |
| Sabatolimab 800mg Mono Adolescent | Incidence of Grade III or IV Acute Graft Versus Host Disease (aGvHD) | 0 Participants |
Secondary
Incidence of Moderate to Severe Chronic GVHD (cGvHD)
Assessment of the treatment emergent moderate or severe cGvHD. Chronic GvHD: Moderate chronic GvHD of the lungs, Severe chronic GvHD.
Time frame: From start of treatment to up to 36 months from last patient first treatment.
Population: Safety Set includes all participants from the FAS.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sabatolimab 400mg Mono Adults | Incidence of Moderate to Severe Chronic GVHD (cGvHD) | 0 Participants |
| Sabatolimab 800mg Mono Adults | Incidence of Moderate to Severe Chronic GVHD (cGvHD) | 1 Participants |
| Sabatolimab 800mg + Azacitidine Adults | Incidence of Moderate to Severe Chronic GVHD (cGvHD) | 0 Participants |
| Sabatolimab 800mg Mono Adolescent | Incidence of Moderate to Severe Chronic GVHD (cGvHD) | 0 Participants |
Secondary
Peak of Serum Concentration (Cmax) Sabatolimab
Cmax is the maximal serum concentration of sabatolimab.
Time frame: Cycle 1 Day 5 (end of infusion) and Cycle 3 Day 1 or Day 5 (end of infusion) and Cycle 24 Day 1 (end of infusion); Cycle =28 Days
Population: Pharmacokinetics (PK) analysis set included all participants from the Safety Set who provided at least one evaluable sabatolimab PK concentration at the considered timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Sabatolimab 400mg Mono Adults | Peak of Serum Concentration (Cmax) Sabatolimab | Cycle 3 Day 1 at 2 hr (end of infusion) | 137 ug/ml | Geometric Coefficient of Variation 52.7 |
| Sabatolimab 400mg Mono Adults | Peak of Serum Concentration (Cmax) Sabatolimab | Cycle 24 Day 1 at 2 hr (end of infusion) | 163 ug/ml | Geometric Coefficient of Variation 23.7 |
| Sabatolimab 800mg Mono Adults | Peak of Serum Concentration (Cmax) Sabatolimab | Cycle 3 Day 1 at 2 hr (end of infusion) | 304 ug/ml | Geometric Coefficient of Variation 31.4 |
| Sabatolimab 800mg + Azacitidine Adults | Peak of Serum Concentration (Cmax) Sabatolimab | Cycle 1 Day 5 at 2 hours (hr) (end of infusion) | 256 ug/ml | Geometric Coefficient of Variation 0 |
| Sabatolimab 800mg + Azacitidine Adults | Peak of Serum Concentration (Cmax) Sabatolimab | Cycle 3 Day 5 at 2 hr (end of infusion) | 315 ug/ml | Geometric Coefficient of Variation 0 |
Secondary
Percentage of Participants With Measurable Residual Disease (MRD) Positive at Baseline Who Become MRD Negative
Percentage of participants with centrally confirmed MRD+ status at baseline converting to MRD- within the first 6 cycles of study treatment.
Time frame: From start of treatment until end of Cycle 6 (Cycle = 28 Days)
Population: FAS included all participants who received at least one dose of any component of the study treatment (i.e. at least one dose of sabatolimab or at least one dose of azacitidine).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sabatolimab 400mg Mono Adults | Percentage of Participants With Measurable Residual Disease (MRD) Positive at Baseline Who Become MRD Negative | 0 Percentage of participants |
| Sabatolimab 800mg Mono Adults | Percentage of Participants With Measurable Residual Disease (MRD) Positive at Baseline Who Become MRD Negative | 0 Percentage of participants |
| Sabatolimab 800mg + Azacitidine Adults | Percentage of Participants With Measurable Residual Disease (MRD) Positive at Baseline Who Become MRD Negative | 0 Percentage of participants |
| Sabatolimab 800mg Mono Adolescent | Percentage of Participants With Measurable Residual Disease (MRD) Positive at Baseline Who Become MRD Negative | 0 Percentage of participants |
Secondary
Relapse-free Survival (RFS)
Time from start of treatment to the date of first documented hematologic relapse or death due to any cause, whichever occurs first.
Time frame: From start of treatment to up to 36 months from last patient first treatment
Population: FAS included all participants who received at least one dose of any component of the study treatment (i.e. at least one dose of sabatolimab or at least one dose of azacitidine).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sabatolimab 400mg Mono Adults | Relapse-free Survival (RFS) | 2.56 Months |
| Sabatolimab 800mg Mono Adults | Relapse-free Survival (RFS) | 6.74 Months |
| Sabatolimab 800mg + Azacitidine Adults | Relapse-free Survival (RFS) | NA Months |
| Sabatolimab 800mg Mono Adolescent | Relapse-free Survival (RFS) | 7.16 Months |
Secondary
Trough Serum Concentration of (Cmin) Sabatolimab
Cmin is the concentration of sabatolimab prior to next dosing or after end of treatment.
Time frame: Adult cohorts: Pre-dose on Day 1 (safety run-in) or Day 5 (expansion) of Cycle 1, 3, 6 and 24 (safety run-in only); Adolescent cohort: Pre-dose on Day 1 of Cycle 1, 2, 3 and 6; Cycle = 28 Days
Population: Pharmacokinetics (PK) analysis set included all participants from the Safety Set who provided at least one evaluable sabatolimab PK concentration at the considered timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Sabatolimab 400mg Mono Adults | Trough Serum Concentration of (Cmin) Sabatolimab | 0 hr (pre-dose) at Cycle 24 Day 1 | 49.7 µg/ml | Geometric Coefficient of Variation 44.1 |
| Sabatolimab 400mg Mono Adults | Trough Serum Concentration of (Cmin) Sabatolimab | 0 hr (pre-dose) at Cycle 3 Day 1 | 40.4 µg/ml | Geometric Coefficient of Variation 20.2 |
| Sabatolimab 400mg Mono Adults | Trough Serum Concentration of (Cmin) Sabatolimab | 0-hour (hr) Pre-dose at Cycle 1 Day 1 | 0.00 µg/ml | Geometric Coefficient of Variation 0 |
| Sabatolimab 400mg Mono Adults | Trough Serum Concentration of (Cmin) Sabatolimab | 0 hr (pre-dose) at Cycle 6 Day 1 | 46.4 µg/ml | Geometric Coefficient of Variation 66.4 |
| Sabatolimab 800mg Mono Adults | Trough Serum Concentration of (Cmin) Sabatolimab | 0 hr (pre-dose) at Cycle 3 Day 1 | 70.7 µg/ml | Geometric Coefficient of Variation 47.5 |
| Sabatolimab 800mg Mono Adults | Trough Serum Concentration of (Cmin) Sabatolimab | 0-hour (hr) Pre-dose at Cycle 1 Day 1 | 0.00 µg/ml | Geometric Coefficient of Variation 0 |
| Sabatolimab 800mg Mono Adults | Trough Serum Concentration of (Cmin) Sabatolimab | 0 hr (pre-dose) at Cycle 6 Day 1 | 99.8 µg/ml | Geometric Coefficient of Variation 52.1 |
| Sabatolimab 800mg + Azacitidine Adults | Trough Serum Concentration of (Cmin) Sabatolimab | 0 hr (pre-dose) at Cycle 6 Day 5 | 71.9 µg/ml | Geometric Coefficient of Variation 0 |
| Sabatolimab 800mg + Azacitidine Adults | Trough Serum Concentration of (Cmin) Sabatolimab | 0 hr (pre-dose) at Cycle 3 Day 5 | 42.9 µg/ml | Geometric Coefficient of Variation 0 |
| Sabatolimab 800mg + Azacitidine Adults | Trough Serum Concentration of (Cmin) Sabatolimab | 0 hr (pre-dose) at Cycle 1 Day 5 | 0.00 µg/ml | Geometric Coefficient of Variation 0 |
| Sabatolimab 800mg Mono Adolescent | Trough Serum Concentration of (Cmin) Sabatolimab | 0 hr (pre-dose) at Cycle 2 Day 1 | 70.7 µg/ml | Geometric Coefficient of Variation 0 |
| Sabatolimab 800mg Mono Adolescent | Trough Serum Concentration of (Cmin) Sabatolimab | 0-hour (hr) Pre-dose at Cycle 1 Day 1 | 0.00 µg/ml | Geometric Coefficient of Variation 0 |
| Sabatolimab 800mg Mono Adolescent | Trough Serum Concentration of (Cmin) Sabatolimab | 0 hr (pre-dose) at Cycle 3 Day 1 | 129 µg/ml | Geometric Coefficient of Variation 0 |
| Sabatolimab 800mg Mono Adolescent | Trough Serum Concentration of (Cmin) Sabatolimab | 0 hr (pre-dose) at Cycle 6 Day 1 | 219 µg/ml | Geometric Coefficient of Variation 0 |