Unresectable Hepatocellular Carcinoma (HCC)
Conditions
Keywords
Unresectable Hepatocellular Carcinoma (HCC)
Brief summary
This is a Phase I/II, open-label, non-randomized, multicenter study to explore safety, tolerability and antitumor activity of NMS-01940153E as single agent in adult patients with unresectable hepatocellular carcinoma (HCC) previously treated with systemic therapy. The Phase I portion is designed as a dose-escalation study in sequential cohorts of patients aimed to obtain the maximum tolerated dose (MTD) that is defined based on the dose limiting toxicities (DLTs) observed in the first cycle of treatment. The Phase II portion is designed as a two-stage study with an interim analysis for futility and stopping criteria for unacceptable toxicity to assess the antitumor activity of NMS-01940153E in adult patients with unresectable HCC previously treated with systemic therapy measured as objective response rate.
Interventions
DRUGNMS-01940153E
Route of administration: intravenous (IV) solution
Sponsors
Nerviano Medical Sciences
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study: 1. Histological, cytological or radiological diagnosis of HCC, according to the American Association for the Study of Liver Diseases (AASLD) / European Association for the Study of the Liver (EASL) criteria, in subjects that are refractory or not able to tolerate the standard therapy, or subjects for whom the standard therapy is not considered appropriate by the physician. 2. The subject has disease that is not amenable to a curative treatment approach (e.g., transplant, surgery, radiofrequency ablation) and unsuitable for or refractory to locoregional treatments (e.g., TACE). 3. At least one uni-dimensional measurable lesion by CT or MRI according to RECIST 1.1 which is either not previously treated by local therapy or, if treated, it has clearly progressed before the subject is recruited. 4. Phase I only: subjects must have disease relapsed or refractory to the standard of care treatment not exceeding 3 lines of prior systemic treatment. Subjects intolerant to previous treatment with tyrosine kinase inhibitors (TKIs) are eligible. Phase II: subjects must have disease relapsed or refractory to the standard of care treatment including an immunocheckpoint inhibitor as first line and at least a tyrosine kinase inhibitor, not exceeding 3 lines of prior systemic treatment. A minimum of 14 days of treatment with prior TKI would be required to qualify as line of therapy; 5. Child-Pugh score ≤ 6 (class A). 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 7. Age ≥18 years old on day of consent. 8. No history of liver transplantation or not listed for high urgent transplantation. 9. Meets required laboratory data 10. In case of active hepatitis B (HBV) or chronic HIV infection the patient should receive antiviral therapy per local standard of care. 11. Patients must use effective contraception or abstinence. Female subjects must be surgically sterile or, if subjects of childbearing potential, must agree to use effective contraception or abstinence during the period of therapy and in the following 180 days after discontinuation of study treatment. Male subjects must be surgically sterile or must agree to use effective contraception or abstinence during the period of therapy and in the following 90 days after discontinuation of study treatment. 12. With the exception of alopecia, resolution of all acute toxic effects of any prior systemic therapy, surgery or radiotherapy to National Cancer Institute (NCI) common terminology criteria (CTC) (Version 5.0) Grade ≤1 or to the baseline laboratory values as defined in Inclusion Criterion Number 9. 13. Able and willing to comply with scheduled visits, therapy plans, and laboratory tests required in this protocol. 14. Signed and dated independent ethics committee (IEC)-approved Informed Consent Form indicating that the subject is aware of the neoplastic nature of his/her disease and has been informed of the procedures to be followed, the investigational nature of the therapy, potential benefits, side effects, discomforts, risks and alternative treatments.
Exclusion criteria
The presence of any of the following will exclude a subject from study enrollment: 1. Known fibrolamellar HCC or mixed hepato-cholangiocarcinoma. 2. Subjects with untreated or incompletely treated varices with bleeding or high risk for bleeding are excluded with the following clarification: subjects with history of prior variceal bleeding must have been treated with adequate endoscopic therapy without any evidence of recurrent bleeding for at least 6 months prior to study entry and must be stable on optimal medical management (e.g. non-selective beta blocker, proton pump inhibitor) at study entry. 3. Subjects with QT interval using Fridericia standard (QTcF) ≥480 milliseconds or with risk factors for torsade de pointes (e.g., heart failure, uncontrolled hypokalemia, family history of long QT syndrome) or receiving treatment with concomitant medications known to prolong the QT/QTc interval that cannot be replaced with another treatment. 4. Ascites defined as CTCAE Grade ≥2. Subjects who have been on a stable medication regimen for at least 2 months to manage ascites are eligible if they show ascites Grade \<2. Subjects with clinically undetectable ascites who are Child A with detectable ascites at CT/MRI are eligible. 5. Uncontrolled high blood pressure (systolic blood pressure, SBP \>150 mmHg and/or diastolic blood pressure, DBP \>95 mmHg, despite optimal treatment, on at least 2 out of 3 determinations repeated at 30 minutes interval and done in case that the first one meets the criterion for exclusion). 6. Direct-Acting Antivirals (DAA) at the time of treatment start; previous hepatitis C virus (HCV) treatment with DAAs is allowed. 7. Clinical evidence of hepatic encephalopathy. 8. Known brain metastases or evidence of leptomeningeal disease. 9. Known history of allergic reactions to polysorbate 80. 10. Any of the following in the past 6 months: myocardial infarction, uncontrolled cardiac arrhythmia, unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep vein thrombosis (except chronic/stable portal vein thrombosis). 11. Major surgery, other than diagnostic surgery, within 4 weeks before treatment start. 12. Any anticancer agent within 4 weeks or, in absence of toxicity, 5 half-lives (within 6 weeks for nitrosureas, mitomycin C and liposomal doxorubicin) before treatment start. 13. Radiation therapy within 4 weeks or radionuclide treatment (e.g., I-131 or Y-90) within 6 weeks before treatment start. 14. Untreated uncontrolled bacterial, viral, or fungal infections including acute HIV infection or acquired immunodeficiency syndrome (AIDS), untreated uncontrolled HBV, untreated uncontrolled HCV, untreated uncontrolled concomitant HBV and HCV; patients who are seropositive following HBV vaccine are eligible. 15. Subjects under treatment with therapeutic dose of anticoagulants (e.g., warfarin or warfarin-related agents, low-molecular weight heparin, or similar agent such as anti Xa and anti-thrombin agents) or antiplatelet agents (e.g. clopidogrel) or with coagulation disorders. Aspirin at dose up to 100 mg is permitted. Prophylaxis with anticoagulants is allowed to meet the international normalized ratio (INR) value range as cited in inclusion criterion 9. 16. Uncontrolled diabetes mellitus. 17. Pregnant or breast-feeding women. 18. Known second malignancy that is progressing or requiring active treatment. Exceptions include adequately treated basal cell or squamous cell skin cancer or in situ carcinoma of the cervix uteri. 19. Current enrollment or participation in another interventional clinical trial. 20. Clinically significant respiratory or metabolic diseases uncontrolled by medication. 21. Subjects with active alcohol and/or substances abuse. 22. Any known organ dysfunction, serious illness, acute or chronic medical or psychiatric condition, or laboratory abnormality which, in the Investigator's opinion, may increase the risk associated/interfere with study participation, or with the interpretation of the results. 23. Subjects who, within 7 days prior to the first NMS-01940153E intake, are receiving or received strong inducers of flavin-containing monooxygenase FMO1 and FMO3. 24. Subjects who are receiving sensitive CYP3A4 substrates, CYP3A4 and breast cancer resistance protein (BCRP) substrates with narrow therapeutic index (NTI).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase I Drug Related Dose Limiting Toxicities (DLTs) | Phase I: From screening to end of first 28-day cycle (17 months) | All 12 Phase I treated patients were evaluable for DLT (Dose-Limiting Toxicity Evaluable Set) and included 6 patients treated at each of the two dose levels explored (i.e., 100 mg/m2/week and 135 mg/m2/week) who received at least 66% of the study drug in the first 28-day cycle of treatment and underwent a DLT assessment within the DLT window. Participants who experienced DLTs are presented. |
| Phase II Objective Response Rate | Phase II: From Phase II start to Study Completion (23 months) | The objective response rate (ORR) was calculated as the proportion of evaluable patients who achieved, as best overall response (BOR), confirmed complete response (CR) or partial response (PR) measured by investigator-assessed RECIST 1.1 (Phase II). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hematology: Overall Treatment-emergent Abnormalities by Dose Level and Maximum CTC Grade | From screening to 28 days follow-up, an average 6 months | Number of treatment emergent abnormalities (at any grade) at all dose levels are presented. CTC = Common Terminology Criteria WBC = white blood cells |
| Neutrophils Count Decrease: Time to First Occurrence of >=Grade 3 and Time to Recovery to Grade 1 | From screening to 28 days follow-up, an average 6 months | The mean days to first occurrence of neutrophil count decrease are presented for all dose levels. Grade 0: ≥2,000/mm3 Grade 1: ≥1,500-\< 2,000/mm3 Grade 2: ≥1,000- \< 1,500/mm3 Grade 3: ≥500- \< 1,000/mm3 Grade 4: \<500/mm3 * G3 = Time (days) to Treatment Start to First Occurrence of Neutrophil Count Decrease \>=Grade 3 * G3 to Recovery to G1 = Time (days) to First Occurrence of Neutrophil Count Decrease \>= Grade 3 to Recovery to Grade 1 |
| Blood Chemistry: Treatment-emergent Abnormalities by Dose Level | From screening to 28 days follow-up, an average 6 months | Treatment-emergent abnormalities in blood chemistry at any grade are presented by dose level. ALP = Alkaline phosphatase ALT = Alanine aminotransferase AST = Aspartate aminotransferase GGT = Gamma-glutamyl transferase LDH = Lactate dehydrogenase |
| Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | From screening to 28 days follow-up, an average 6 months | Treatment Emergent abnormalities by dose Level are presented for blood chemistry and coagulation parameters. INR = international normalized ratio LNL = lower normal limit NL = normal limit ULN = upper limit of normal |
| Electrocardiogram Abnormalities | From screening to 28 days follow-up, an average 6 months | The number of participants who experienced electrocardiogram abnormalities are presented. |
| Tmax and Tlast of NMS-01940153E | Day 1 to Day 15 | Plasma pharmacokinetic (PK) profiles of NMS-01940153E were characterized on Day 1 and 15 of the first Cycle after infusion. Tmax = Time to maximum observed plasma concentration Tlast = Time of last detectable concentration |
| Cmax and Clast of NMS-01940153E | Day 1 to Day 15 | Plasma pharmacokinetic (PK) profiles of NMS-01940153E were characterized on Day 1 and 15 of the first Cycle after infusion. Cmax = Maximum observed plasma concentration Clast = Last detectable concentration |
| AUClast, AUCweekly, and AUCinf of NMS-01940153E | From Days 1 to 21 (168 hours after the Day 15 infusion) | Plasma pharmacokinetic (PK) profiles of NMS-01940153E were characterized on Day 1 and 15 of the first Cycle after infusion. Infusions occurred on Days 1, 8, and 15. AUClast = Area under the interpolated observed plasma time-concentration curve from infusion start to the last observed plasma concentration AUCweekly = Area under the interpolated observed plasma time-concentration curve from infusion start to 168 hours AUCinf = Area under the interpolated observed plasma time-concentration curve from infusion start extrapolated to infinity based on the last observed plasma concentration |
| t½,z of NMS-01940153E | Day 1 to Day 15 | Plasma pharmacokinetic (PK) profiles of NMS-01940153E were characterized on Day 1 and 15 of the first Cycle after infusion. t½,z = Half-life of the terminal phase of observed plasma concentration |
| Treatment-emergent Adverse Events by Maximum CTC Grade | Phase I: From the Study Start Date to Phase I Completion (32 months) - Phase II: From Phase II start to Study Completion (23 months) | The maximum Common Terminology Criteria (CTC) grade (graded using National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events \[CTCAE\] Version 5.0) experienced by each participant is presented. If an AE was reported for a participant more than once during treatment, the worst CTC Grade is presented here. Phase 2 started before Phase 1 completed. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living. Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4 Life-threatening consequences; urgent intervention indicated. |
| Vss and Vss,SS of NMS-01940153E | Day 1 to Day 15 | Plasma pharmacokinetic (PK) PK profiles of NMS-01940153E were characterized on Day 1 and 15 of the first Cycle after infusion. Vss = Volume of distribution at steady state based last observed concentration extrapolated to infinity and Clearance calculated for a dosing period of 168 h either after a single dose or in steady-state Vss,SS = Volume of distribution at steady state based last observed concentration extrapolated to infinity and clearance based on last observed concentration and extrapolation to infinity |
| RA AUCweekly and RA Cmax of NMS-01940153E | Day 21 (168 hours after the Day 15 infusion) | Plasma pharmacokinetic (PK) PK profiles of NMS-01940153E were characterized on Day 1 and 15 of the first Cycle after infusion. Infusions occurred on Days 1, 8, and 15. RA AUCweekly = Accumulation ratio Day 1 to 15 calculated using area under the interpolated observed plasma time-concentration curve from infusion start to 168 hours RA Cmax = Accumulation ratio Day 1 to 15 calculated using maximum observed plasma concentration |
| FE of NMS-01940153E | Day 1 to Day 15 | Urine pharmacokinetic profiles of NMS-01940153E were characterized on Day 1 and 15 of the first Cycle after infusion. FE = Molar fraction of excreted compound relative to the administered molar dose calculated using urine concentration and volume data |
| Phase I Objective Tumor Response (Partial and Complete Response) | Phase I: From the Study Start Date to Phase I Completion (32 months) | Phase I any dose level, objective response and best overall tumor response are presented, as measured by investigator assessed RECIST 1.1 (Phase I). The objective response rate was calculated as the proportion of evaluable patients who achieved best overall response (BOR), confirmed complete response (CR) or partial response (PR). |
| Phase II Objective Response Rate as Measured by Investigator-assessed mRECIST | Phase II: From Phase II start to Study Completion (23 months) | Objective response rate as measured by investigator-assessed mRECIST in Phase II. |
| Phase I: Duration of Response (DoR) as Measured by Investigator-assessed RECIST 1.1 | Phase I: From the Study Start Date to Phase I Completion (32 months) | Duration of response (DoR) as measured by investigator-assessed Response evaluation criteria in solid tumours (RECIST) 1.1. Duration of Response (months): was time in months from response start date to either date of disease progression/death due to progression of disease. It was calculated only for participants with complete response or partial response as best overall response. |
| Phase II: Duration of Response (DoR) as Measured by Investigator-assessed RECIST 1.1. and Investigator-assessed mRECIST | Phase II: From Phase II start to Study Completion (23 months) | Duration of response (DoR) as measured by investigator-assessed Response evaluation criteria in solid tumours (RECIST) 1.1 and investigator-assessed modified RECIST (mRECIST). Duration of Response (months): was time in months from response start date to either date of disease progression/death due to progression of disease. It was calculated only for participants with complete response or partial response as best overall response. |
| Progression Free Survival, as Measured by Investigator-assessed RECIST 1.1, in Phases I and II | Phase I: From the Study Start Date to Phase I Completion (32 months) - Phase II: From Phase II start to Study Completion (23 months) | Progression Free Survival as measured by investigator assessed RECIST 1.1, for all treated participants in Phase I and Phase II. Phase 2 started before Phase 1 completed. |
| Overall Survival in Phases I and II | Phase I: From the Study Start Date to Phase I Completion (32 months) - Phase II: From Phase II start to Study Completion (23 months) | Overall Survival for all treated participants in Phases I and II. The estimates are based on the Kaplan-Meier (KM) method. Phase 2 started before Phase 1 completed. |
| CL and CLss of NMS-01940153E | Day 1 to Day 15 | Plasma pharmacokinetic (PK) profiles of NMS-01940153E were characterized on Day 1 and 15 of the first Cycle after infusion. CL = Clearance based on last observed concentration and extrapolation to infinity CLss = Clearance calculated for a dosing period of 168 h either after a single dose or in steady-state |
| Treatment-emergent Adverse Events Related to NMS-01940153E | Phase I: From the Study Start Date to Phase I Completion (32 months) - Phase II: From Phase II start to Study Completion (23 months) | The number of treatment-emergent adverse events related to NMS-01940153E by maximum CTC grade experienced (graded using NCI CTCAE Version 5.0). Whether the the AE was related or not was assessed by the investigator. If an AE was reported for a participant more than once during treatment, the worst CTC Grade is presented. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living. Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4 Life-threatening. Phase 2 started before Phase 1 completed. |
Countries
Italy, Spain, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Phase I Participants: 100 mg/m2/Week All participants in Phase I who received 100 mg/m2/week intravenous NMS-01940153E | 6 |
| Phase I Treated Participants: 135 mg/m2/Week All participants in Phase I who received 135 mg/m2/week intravenous NMS-01940153E | 6 |
| Phase II Participants: 100 mg/m2/Week All participants in Phase II who received 100 mg/m2/week intravenous NMS-01940153E | 18 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Enrolled but not treated | 0 | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 | 0 |
| Overall Study | Study terminated by sponsor | 1 | 1 | 8 | 0 |
Baseline characteristics
| Characteristic | Phase I Participants: 100 mg/m2/Week | Phase I Treated Participants: 135 mg/m2/Week | Phase II Participants: 100 mg/m2/Week | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 3 Participants | 8 Participants | 14 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 3 Participants | 10 Participants | 16 Participants |
| Eastern cooperative oncology group performance status ECOG Performance Status 0 | 3 participants | 3 participants | 10 participants | 16 participants |
| Eastern cooperative oncology group performance status ECOG Performance Status 1 | 3 participants | 3 participants | 8 participants | 14 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 6 Participants | 18 Participants | 29 Participants |
| Sex: Female, Male Female | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 5 Participants | 6 Participants | 17 Participants | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 5 / 6 | 5 / 6 | 9 / 18 |
| other Total, other adverse events | 5 / 6 | 6 / 6 | 18 / 18 |
| serious Total, serious adverse events | 1 / 6 | 2 / 6 | 5 / 18 |
Outcome results
Primary
Phase I Drug Related Dose Limiting Toxicities (DLTs)
All 12 Phase I treated patients were evaluable for DLT (Dose-Limiting Toxicity Evaluable Set) and included 6 patients treated at each of the two dose levels explored (i.e., 100 mg/m2/week and 135 mg/m2/week) who received at least 66% of the study drug in the first 28-day cycle of treatment and underwent a DLT assessment within the DLT window. Participants who experienced DLTs are presented.
Time frame: Phase I: From screening to end of first 28-day cycle (17 months)
Population: Phase I treated participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 100 mg/m2/Week Dose (Phase I) | Phase I Drug Related Dose Limiting Toxicities (DLTs) | 0 Participants |
| 135 mg/m2/Week Dose (Phase I) | Phase I Drug Related Dose Limiting Toxicities (DLTs) | 2 Participants |
Primary
Phase II Objective Response Rate
The objective response rate (ORR) was calculated as the proportion of evaluable patients who achieved, as best overall response (BOR), confirmed complete response (CR) or partial response (PR) measured by investigator-assessed RECIST 1.1 (Phase II).
Time frame: Phase II: From Phase II start to Study Completion (23 months)
Population: Evaluable population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 100 mg/m2/Week Dose (Phase I) | Phase II Objective Response Rate | Complete Response | 0 Participants |
| 100 mg/m2/Week Dose (Phase I) | Phase II Objective Response Rate | Partial Response | 0 Participants |
| 100 mg/m2/Week Dose (Phase I) | Phase II Objective Response Rate | Stable Disease | 3 Participants |
| 100 mg/m2/Week Dose (Phase I) | Phase II Objective Response Rate | Progressive Disease | 11 Participants |
Secondary
AUClast, AUCweekly, and AUCinf of NMS-01940153E
Plasma pharmacokinetic (PK) profiles of NMS-01940153E were characterized on Day 1 and 15 of the first Cycle after infusion. Infusions occurred on Days 1, 8, and 15. AUClast = Area under the interpolated observed plasma time-concentration curve from infusion start to the last observed plasma concentration AUCweekly = Area under the interpolated observed plasma time-concentration curve from infusion start to 168 hours AUCinf = Area under the interpolated observed plasma time-concentration curve from infusion start extrapolated to infinity based on the last observed plasma concentration
Time frame: From Days 1 to 21 (168 hours after the Day 15 infusion)
Population: All Phase I participants
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 100 mg/m2/Week Dose (Phase I) | AUClast, AUCweekly, and AUCinf of NMS-01940153E | AUClast: Day 15 | 30.0 h·μM | Standard Deviation 9.16 |
| 100 mg/m2/Week Dose (Phase I) | AUClast, AUCweekly, and AUCinf of NMS-01940153E | AUClast: Day 1 | 20.8 h·μM | Standard Deviation 4.31 |
| 100 mg/m2/Week Dose (Phase I) | AUClast, AUCweekly, and AUCinf of NMS-01940153E | AUCweekly: Day 1 | 20.8 h·μM | Standard Deviation 4.35 |
| 100 mg/m2/Week Dose (Phase I) | AUClast, AUCweekly, and AUCinf of NMS-01940153E | AUCweekly: Day 15 | 32.4 h·μM | Standard Deviation 6.49 |
| 100 mg/m2/Week Dose (Phase I) | AUClast, AUCweekly, and AUCinf of NMS-01940153E | AUCinf: Day 1 | 28.7 h·μM | Standard Deviation 6.88 |
| 100 mg/m2/Week Dose (Phase I) | AUClast, AUCweekly, and AUCinf of NMS-01940153E | AUCinf: Day 15 | 48.1 h·μM | Standard Deviation 19.6 |
| 135 mg/m2/Week Dose (Phase I) | AUClast, AUCweekly, and AUCinf of NMS-01940153E | AUCinf: Day 1 | 37.1 h·μM | Standard Deviation 14.9 |
| 135 mg/m2/Week Dose (Phase I) | AUClast, AUCweekly, and AUCinf of NMS-01940153E | AUCweekly: Day 15 | 39.0 h·μM | Standard Deviation 14.8 |
| 135 mg/m2/Week Dose (Phase I) | AUClast, AUCweekly, and AUCinf of NMS-01940153E | AUClast: Day 1 | 24.8 h·μM | Standard Deviation 8.55 |
| 135 mg/m2/Week Dose (Phase I) | AUClast, AUCweekly, and AUCinf of NMS-01940153E | AUClast: Day 15 | 39.1 h·μM | Standard Deviation 14.9 |
| 135 mg/m2/Week Dose (Phase I) | AUClast, AUCweekly, and AUCinf of NMS-01940153E | AUCinf: Day 15 | 62.9 h·μM | Standard Deviation 34.1 |
| 135 mg/m2/Week Dose (Phase I) | AUClast, AUCweekly, and AUCinf of NMS-01940153E | AUCweekly: Day 1 | 25.7 h·μM | Standard Deviation 7.11 |
Secondary
Blood Chemistry and Coagulation: Treatment-emergent Abnormalities
Treatment Emergent abnormalities by dose Level are presented for blood chemistry and coagulation parameters. INR = international normalized ratio LNL = lower normal limit NL = normal limit ULN = upper limit of normal
Time frame: From screening to 28 days follow-up, an average 6 months
Population: All treated participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 100 mg/m2/Week Dose (Phase I) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | Unconjugated Bilirubin: Total | 3 events |
| 100 mg/m2/Week Dose (Phase I) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | Urea: Above ULN | 5 events |
| 100 mg/m2/Week Dose (Phase I) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | Hyperglycemia: Total | 9 events |
| 100 mg/m2/Week Dose (Phase I) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | INR: Below LNL | 1 events |
| 100 mg/m2/Week Dose (Phase I) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | Urea: Below LNL | 1 events |
| 100 mg/m2/Week Dose (Phase I) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | Hyperglycemia: Above ULN | 9 events |
| 100 mg/m2/Week Dose (Phase I) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | Total Protein: Above/Below NL | 1 events |
| 100 mg/m2/Week Dose (Phase I) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | Urea: Total | 6 events |
| 100 mg/m2/Week Dose (Phase I) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | Hyperglycemia: Above/Below NL | 0 events |
| 100 mg/m2/Week Dose (Phase I) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | Hypokalemia: Below LNL | 0 events |
| 100 mg/m2/Week Dose (Phase I) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | Blood Urea Nitrogen: Above ULN | 2 events |
| 100 mg/m2/Week Dose (Phase I) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | Blood Urea Nitrogen: Total | 2 events |
| 100 mg/m2/Week Dose (Phase I) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | Hyponatremia: Below LNL | 4 events |
| 100 mg/m2/Week Dose (Phase I) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | INR: Above/Below NL | 2 events |
| 100 mg/m2/Week Dose (Phase I) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | Phosphatemia: Total | 11 events |
| 100 mg/m2/Week Dose (Phase I) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | Hyponatremia: Total | 4 events |
| 100 mg/m2/Week Dose (Phase I) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | Total Protein: Below LNL | 4 events |
| 100 mg/m2/Week Dose (Phase I) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | Phosphatemia: Above ULN | 3 events |
| 100 mg/m2/Week Dose (Phase I) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | INR: Above ULN | 8 events |
| 100 mg/m2/Week Dose (Phase I) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | Total Protein: Above ULN | 2 events |
| 100 mg/m2/Week Dose (Phase I) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | Phosphatemia: Below LNL | 7 events |
| 100 mg/m2/Week Dose (Phase I) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | INR: Total | 11 events |
| 100 mg/m2/Week Dose (Phase I) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | Total Protein: Total | 7 events |
| 100 mg/m2/Week Dose (Phase I) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | Phosphatemia: Above/Below NL | 1 events |
| 100 mg/m2/Week Dose (Phase I) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | Hypokalemia: Total | 0 events |
| 100 mg/m2/Week Dose (Phase I) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | Unconjugated Bilirubin: Above ULN | 3 events |
| 135 mg/m2/Week Dose (Phase I) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | Phosphatemia: Above ULN | 0 events |
| 135 mg/m2/Week Dose (Phase I) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | INR: Above ULN | 1 events |
| 135 mg/m2/Week Dose (Phase I) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | Hyponatremia: Total | 2 events |
| 135 mg/m2/Week Dose (Phase I) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | Hyponatremia: Below LNL | 2 events |
| 135 mg/m2/Week Dose (Phase I) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | Hypokalemia: Total | 1 events |
| 135 mg/m2/Week Dose (Phase I) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | Hypokalemia: Below LNL | 1 events |
| 135 mg/m2/Week Dose (Phase I) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | Phosphatemia: Total | 2 events |
| 135 mg/m2/Week Dose (Phase I) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | Phosphatemia: Below LNL | 2 events |
| 135 mg/m2/Week Dose (Phase I) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | Phosphatemia: Above/Below NL | 0 events |
| 135 mg/m2/Week Dose (Phase I) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | Hyperglycemia: Total | 2 events |
| 135 mg/m2/Week Dose (Phase I) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | Hyperglycemia: Above ULN | 1 events |
| 135 mg/m2/Week Dose (Phase I) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | Hyperglycemia: Above/Below NL | 1 events |
| 135 mg/m2/Week Dose (Phase I) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | Blood Urea Nitrogen: Total | 0 events |
| 135 mg/m2/Week Dose (Phase I) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | Blood Urea Nitrogen: Above ULN | 0 events |
| 135 mg/m2/Week Dose (Phase I) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | Urea: Total | 0 events |
| 135 mg/m2/Week Dose (Phase I) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | Urea: Above ULN | 0 events |
| 135 mg/m2/Week Dose (Phase I) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | Urea: Below LNL | 0 events |
| 135 mg/m2/Week Dose (Phase I) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | Unconjugated Bilirubin: Total | 0 events |
| 135 mg/m2/Week Dose (Phase I) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | Unconjugated Bilirubin: Above ULN | 0 events |
| 135 mg/m2/Week Dose (Phase I) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | Total Protein: Total | 2 events |
| 135 mg/m2/Week Dose (Phase I) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | Total Protein: Above ULN | 0 events |
| 135 mg/m2/Week Dose (Phase I) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | INR: Above/Below NL | 0 events |
| 135 mg/m2/Week Dose (Phase I) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | Total Protein: Below LNL | 2 events |
| 135 mg/m2/Week Dose (Phase I) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | Total Protein: Above/Below NL | 0 events |
| 135 mg/m2/Week Dose (Phase I) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | INR: Total | 1 events |
| 135 mg/m2/Week Dose (Phase I) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | INR: Below LNL | 0 events |
| Phase II (Evaluable Population) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | Unconjugated Bilirubin: Total | 3 events |
| Phase II (Evaluable Population) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | Phosphatemia: Above/Below NL | 1 events |
| Phase II (Evaluable Population) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | Hyponatremia: Below LNL | 6 events |
| Phase II (Evaluable Population) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | Unconjugated Bilirubin: Above ULN | 3 events |
| Phase II (Evaluable Population) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | Phosphatemia: Below LNL | 9 events |
| Phase II (Evaluable Population) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | INR: Below LNL | 1 events |
| Phase II (Evaluable Population) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | Total Protein: Total | 9 events |
| Phase II (Evaluable Population) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | Phosphatemia: Above ULN | 3 events |
| Phase II (Evaluable Population) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | INR: Total | 12 events |
| Phase II (Evaluable Population) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | Total Protein: Above ULN | 2 events |
| Phase II (Evaluable Population) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | Phosphatemia: Total | 13 events |
| Phase II (Evaluable Population) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | Hypokalemia: Below LNL | 1 events |
| Phase II (Evaluable Population) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | INR: Above ULN | 9 events |
| Phase II (Evaluable Population) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | Blood Urea Nitrogen: Total | 2 events |
| Phase II (Evaluable Population) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | Hyperglycemia: Above/Below NL | 1 events |
| Phase II (Evaluable Population) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | Hyponatremia: Total | 6 events |
| Phase II (Evaluable Population) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | Blood Urea Nitrogen: Above ULN | 2 events |
| Phase II (Evaluable Population) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | Hyperglycemia: Above ULN | 10 events |
| Phase II (Evaluable Population) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | Total Protein: Below LNL | 6 events |
| Phase II (Evaluable Population) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | Hypokalemia: Total | 1 events |
| Phase II (Evaluable Population) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | Urea: Above ULN | 5 events |
| Phase II (Evaluable Population) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | Hyperglycemia: Total | 11 events |
| Phase II (Evaluable Population) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | INR: Above/Below NL | 2 events |
| Phase II (Evaluable Population) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | Urea: Below LNL | 1 events |
| Phase II (Evaluable Population) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | Urea: Total | 6 events |
| Phase II (Evaluable Population) | Blood Chemistry and Coagulation: Treatment-emergent Abnormalities | Total Protein: Above/Below NL | 1 events |
Secondary
Blood Chemistry: Treatment-emergent Abnormalities by Dose Level
Treatment-emergent abnormalities in blood chemistry at any grade are presented by dose level. ALP = Alkaline phosphatase ALT = Alanine aminotransferase AST = Aspartate aminotransferase GGT = Gamma-glutamyl transferase LDH = Lactate dehydrogenase
Time frame: From screening to 28 days follow-up, an average 6 months
Population: All treated participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 100 mg/m2/Week Dose (Phase I) | Blood Chemistry: Treatment-emergent Abnormalities by Dose Level | Hyperkalemia | 7 events |
| 100 mg/m2/Week Dose (Phase I) | Blood Chemistry: Treatment-emergent Abnormalities by Dose Level | Blood LDH Increased | 14 events |
| 100 mg/m2/Week Dose (Phase I) | Blood Chemistry: Treatment-emergent Abnormalities by Dose Level | Creatinine Increased | 6 events |
| 100 mg/m2/Week Dose (Phase I) | Blood Chemistry: Treatment-emergent Abnormalities by Dose Level | AST Increased | 12 events |
| 100 mg/m2/Week Dose (Phase I) | Blood Chemistry: Treatment-emergent Abnormalities by Dose Level | ALP Increased | 10 events |
| 100 mg/m2/Week Dose (Phase I) | Blood Chemistry: Treatment-emergent Abnormalities by Dose Level | Blood Bilirubin Increased | 7 events |
| 100 mg/m2/Week Dose (Phase I) | Blood Chemistry: Treatment-emergent Abnormalities by Dose Level | Hypoalbuminemia | 8 events |
| 100 mg/m2/Week Dose (Phase I) | Blood Chemistry: Treatment-emergent Abnormalities by Dose Level | Hypoglycemia | 0 events |
| 100 mg/m2/Week Dose (Phase I) | Blood Chemistry: Treatment-emergent Abnormalities by Dose Level | Hypernatremia | 0 events |
| 100 mg/m2/Week Dose (Phase I) | Blood Chemistry: Treatment-emergent Abnormalities by Dose Level | ALT Increased | 8 events |
| 100 mg/m2/Week Dose (Phase I) | Blood Chemistry: Treatment-emergent Abnormalities by Dose Level | Hypomagnesemia | 5 events |
| 100 mg/m2/Week Dose (Phase I) | Blood Chemistry: Treatment-emergent Abnormalities by Dose Level | Hypocalcemia | 1 events |
| 100 mg/m2/Week Dose (Phase I) | Blood Chemistry: Treatment-emergent Abnormalities by Dose Level | GGT Increased | 9 events |
| 135 mg/m2/Week Dose (Phase I) | Blood Chemistry: Treatment-emergent Abnormalities by Dose Level | Blood Bilirubin Increased | 1 events |
| 135 mg/m2/Week Dose (Phase I) | Blood Chemistry: Treatment-emergent Abnormalities by Dose Level | Hypoalbuminemia | 4 events |
| 135 mg/m2/Week Dose (Phase I) | Blood Chemistry: Treatment-emergent Abnormalities by Dose Level | Hypoglycemia | 1 events |
| 135 mg/m2/Week Dose (Phase I) | Blood Chemistry: Treatment-emergent Abnormalities by Dose Level | AST Increased | 3 events |
| 135 mg/m2/Week Dose (Phase I) | Blood Chemistry: Treatment-emergent Abnormalities by Dose Level | ALT Increased | 2 events |
| 135 mg/m2/Week Dose (Phase I) | Blood Chemistry: Treatment-emergent Abnormalities by Dose Level | GGT Increased | 1 events |
| 135 mg/m2/Week Dose (Phase I) | Blood Chemistry: Treatment-emergent Abnormalities by Dose Level | Creatinine Increased | 3 events |
| 135 mg/m2/Week Dose (Phase I) | Blood Chemistry: Treatment-emergent Abnormalities by Dose Level | ALP Increased | 1 events |
| 135 mg/m2/Week Dose (Phase I) | Blood Chemistry: Treatment-emergent Abnormalities by Dose Level | Blood LDH Increased | 4 events |
| 135 mg/m2/Week Dose (Phase I) | Blood Chemistry: Treatment-emergent Abnormalities by Dose Level | Hypocalcemia | 1 events |
| 135 mg/m2/Week Dose (Phase I) | Blood Chemistry: Treatment-emergent Abnormalities by Dose Level | Hypernatremia | 1 events |
| 135 mg/m2/Week Dose (Phase I) | Blood Chemistry: Treatment-emergent Abnormalities by Dose Level | Hyperkalemia | 0 events |
| 135 mg/m2/Week Dose (Phase I) | Blood Chemistry: Treatment-emergent Abnormalities by Dose Level | Hypomagnesemia | 3 events |
| Phase II (Evaluable Population) | Blood Chemistry: Treatment-emergent Abnormalities by Dose Level | Blood LDH Increased | 18 events |
| Phase II (Evaluable Population) | Blood Chemistry: Treatment-emergent Abnormalities by Dose Level | ALT Increased | 10 events |
| Phase II (Evaluable Population) | Blood Chemistry: Treatment-emergent Abnormalities by Dose Level | Hyperkalemia | 7 events |
| Phase II (Evaluable Population) | Blood Chemistry: Treatment-emergent Abnormalities by Dose Level | Hypocalcemia | 2 events |
| Phase II (Evaluable Population) | Blood Chemistry: Treatment-emergent Abnormalities by Dose Level | AST Increased | 15 events |
| Phase II (Evaluable Population) | Blood Chemistry: Treatment-emergent Abnormalities by Dose Level | Hypoalbuminemia | 12 events |
| Phase II (Evaluable Population) | Blood Chemistry: Treatment-emergent Abnormalities by Dose Level | Hypernatremia | 1 events |
| Phase II (Evaluable Population) | Blood Chemistry: Treatment-emergent Abnormalities by Dose Level | Blood Bilirubin Increased | 8 events |
| Phase II (Evaluable Population) | Blood Chemistry: Treatment-emergent Abnormalities by Dose Level | Creatinine Increased | 9 events |
| Phase II (Evaluable Population) | Blood Chemistry: Treatment-emergent Abnormalities by Dose Level | Hypoglycemia | 1 events |
| Phase II (Evaluable Population) | Blood Chemistry: Treatment-emergent Abnormalities by Dose Level | ALP Increased | 11 events |
| Phase II (Evaluable Population) | Blood Chemistry: Treatment-emergent Abnormalities by Dose Level | GGT Increased | 10 events |
| Phase II (Evaluable Population) | Blood Chemistry: Treatment-emergent Abnormalities by Dose Level | Hypomagnesemia | 8 events |
Secondary
CL and CLss of NMS-01940153E
Plasma pharmacokinetic (PK) profiles of NMS-01940153E were characterized on Day 1 and 15 of the first Cycle after infusion. CL = Clearance based on last observed concentration and extrapolation to infinity CLss = Clearance calculated for a dosing period of 168 h either after a single dose or in steady-state
Time frame: Day 1 to Day 15
Population: All Phase I participants
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 100 mg/m2/Week Dose (Phase I) | CL and CLss of NMS-01940153E | CLss: Day 1 | 13.8 L/h | Standard Deviation 4.14 |
| 100 mg/m2/Week Dose (Phase I) | CL and CLss of NMS-01940153E | CL: Day 1 | 10.1 L/h | Standard Deviation 3.16 |
| 100 mg/m2/Week Dose (Phase I) | CL and CLss of NMS-01940153E | CLss: Day 15 | 8.53 L/h | Standard Deviation 2.5 |
| 100 mg/m2/Week Dose (Phase I) | CL and CLss of NMS-01940153E | CL: Day 15 | 6.12 L/h | Standard Deviation 2.24 |
| 135 mg/m2/Week Dose (Phase I) | CL and CLss of NMS-01940153E | CLss: Day 15 | 9.31 L/h | Standard Deviation 2.52 |
| 135 mg/m2/Week Dose (Phase I) | CL and CLss of NMS-01940153E | CL: Day 1 | 10.2 L/h | Standard Deviation 4.01 |
| 135 mg/m2/Week Dose (Phase I) | CL and CLss of NMS-01940153E | CLss: Day 1 | 13.8 L/h | Standard Deviation 3.73 |
| 135 mg/m2/Week Dose (Phase I) | CL and CLss of NMS-01940153E | CL: Day 15 | 6.19 L/h | Standard Deviation 2.08 |
Secondary
Cmax and Clast of NMS-01940153E
Plasma pharmacokinetic (PK) profiles of NMS-01940153E were characterized on Day 1 and 15 of the first Cycle after infusion. Cmax = Maximum observed plasma concentration Clast = Last detectable concentration
Time frame: Day 1 to Day 15
Population: All Phase I participants
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 100 mg/m2/Week Dose (Phase I) | Cmax and Clast of NMS-01940153E | Cmax: Day 15 | 1.35 μM | Standard Deviation 1.1 |
| 100 mg/m2/Week Dose (Phase I) | Cmax and Clast of NMS-01940153E | Clast: Day 1 | 0.0590 μM | Standard Deviation 0.0191 |
| 100 mg/m2/Week Dose (Phase I) | Cmax and Clast of NMS-01940153E | Clast: Day 15 | 0.113 μM | Standard Deviation 0.0454 |
| 100 mg/m2/Week Dose (Phase I) | Cmax and Clast of NMS-01940153E | Cmax: Day 1 | 0.754 μM | Standard Deviation 0.174 |
| 135 mg/m2/Week Dose (Phase I) | Cmax and Clast of NMS-01940153E | Clast: Day 15 | 0.133 μM | Standard Deviation 0.0779 |
| 135 mg/m2/Week Dose (Phase I) | Cmax and Clast of NMS-01940153E | Cmax: Day 1 | 1.91 μM | Standard Deviation 0.64 |
| 135 mg/m2/Week Dose (Phase I) | Cmax and Clast of NMS-01940153E | Clast: Day 1 | 0.0840 μM | Standard Deviation 0.0335 |
| 135 mg/m2/Week Dose (Phase I) | Cmax and Clast of NMS-01940153E | Cmax: Day 15 | 1.59 μM | Standard Deviation 1.31 |
Secondary
Electrocardiogram Abnormalities
The number of participants who experienced electrocardiogram abnormalities are presented.
Time frame: From screening to 28 days follow-up, an average 6 months
Population: All treated participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 100 mg/m2/Week Dose (Phase I) | Electrocardiogram Abnormalities | 0 Participants |
| 135 mg/m2/Week Dose (Phase I) | Electrocardiogram Abnormalities | 0 Participants |
| Phase II (Evaluable Population) | Electrocardiogram Abnormalities | 0 Participants |
Secondary
FE of NMS-01940153E
Urine pharmacokinetic profiles of NMS-01940153E were characterized on Day 1 and 15 of the first Cycle after infusion. FE = Molar fraction of excreted compound relative to the administered molar dose calculated using urine concentration and volume data
Time frame: Day 1 to Day 15
Population: All treated participants
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 100 mg/m2/Week Dose (Phase I) | FE of NMS-01940153E | FE Day 1 | 0.458 percentage | Standard Deviation 0.374 |
| 100 mg/m2/Week Dose (Phase I) | FE of NMS-01940153E | FE Day 15 | 0.563 percentage | Standard Deviation 0.424 |
| 135 mg/m2/Week Dose (Phase I) | FE of NMS-01940153E | FE Day 1 | 0.357 percentage | Standard Deviation 0.26 |
| 135 mg/m2/Week Dose (Phase I) | FE of NMS-01940153E | FE Day 15 | 0.826 percentage | Standard Deviation 0.713 |
Secondary
Hematology: Overall Treatment-emergent Abnormalities by Dose Level and Maximum CTC Grade
Number of treatment emergent abnormalities (at any grade) at all dose levels are presented. CTC = Common Terminology Criteria WBC = white blood cells
Time frame: From screening to 28 days follow-up, an average 6 months
Population: All treated participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 100 mg/m2/Week Dose (Phase I) | Hematology: Overall Treatment-emergent Abnormalities by Dose Level and Maximum CTC Grade | Hemoglobin Decreased | 13 events |
| 100 mg/m2/Week Dose (Phase I) | Hematology: Overall Treatment-emergent Abnormalities by Dose Level and Maximum CTC Grade | Neutrophil Count Decreased | 6 events |
| 100 mg/m2/Week Dose (Phase I) | Hematology: Overall Treatment-emergent Abnormalities by Dose Level and Maximum CTC Grade | WBC Decreased | 8 events |
| 100 mg/m2/Week Dose (Phase I) | Hematology: Overall Treatment-emergent Abnormalities by Dose Level and Maximum CTC Grade | Platelet Count Decreased | 6 events |
| 135 mg/m2/Week Dose (Phase I) | Hematology: Overall Treatment-emergent Abnormalities by Dose Level and Maximum CTC Grade | Platelet Count Decreased | 4 events |
| 135 mg/m2/Week Dose (Phase I) | Hematology: Overall Treatment-emergent Abnormalities by Dose Level and Maximum CTC Grade | Hemoglobin Decreased | 5 events |
| 135 mg/m2/Week Dose (Phase I) | Hematology: Overall Treatment-emergent Abnormalities by Dose Level and Maximum CTC Grade | WBC Decreased | 6 events |
| 135 mg/m2/Week Dose (Phase I) | Hematology: Overall Treatment-emergent Abnormalities by Dose Level and Maximum CTC Grade | Neutrophil Count Decreased | 4 events |
| Phase II (Evaluable Population) | Hematology: Overall Treatment-emergent Abnormalities by Dose Level and Maximum CTC Grade | Platelet Count Decreased | 10 events |
| Phase II (Evaluable Population) | Hematology: Overall Treatment-emergent Abnormalities by Dose Level and Maximum CTC Grade | Neutrophil Count Decreased | 10 events |
| Phase II (Evaluable Population) | Hematology: Overall Treatment-emergent Abnormalities by Dose Level and Maximum CTC Grade | WBC Decreased | 14 events |
| Phase II (Evaluable Population) | Hematology: Overall Treatment-emergent Abnormalities by Dose Level and Maximum CTC Grade | Hemoglobin Decreased | 18 events |
Secondary
Neutrophils Count Decrease: Time to First Occurrence of >=Grade 3 and Time to Recovery to Grade 1
The mean days to first occurrence of neutrophil count decrease are presented for all dose levels. Grade 0: ≥2,000/mm3 Grade 1: ≥1,500-\< 2,000/mm3 Grade 2: ≥1,000- \< 1,500/mm3 Grade 3: ≥500- \< 1,000/mm3 Grade 4: \<500/mm3 * G3 = Time (days) to Treatment Start to First Occurrence of Neutrophil Count Decrease \>=Grade 3 * G3 to Recovery to G1 = Time (days) to First Occurrence of Neutrophil Count Decrease \>= Grade 3 to Recovery to Grade 1
Time frame: From screening to 28 days follow-up, an average 6 months
Population: Only participants who experienced G3 or G4 were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 100 mg/m2/Week Dose (Phase I) | Neutrophils Count Decrease: Time to First Occurrence of >=Grade 3 and Time to Recovery to Grade 1 | >=G3 | 63.00 days | Standard Deviation 19.8 |
| 100 mg/m2/Week Dose (Phase I) | Neutrophils Count Decrease: Time to First Occurrence of >=Grade 3 and Time to Recovery to Grade 1 | >= G3 to Recovery to G1 | 7.00 days | Standard Deviation 1.41 |
| 135 mg/m2/Week Dose (Phase I) | Neutrophils Count Decrease: Time to First Occurrence of >=Grade 3 and Time to Recovery to Grade 1 | >=G3 | 28.00 days | Standard Deviation 15.36 |
| 135 mg/m2/Week Dose (Phase I) | Neutrophils Count Decrease: Time to First Occurrence of >=Grade 3 and Time to Recovery to Grade 1 | >= G3 to Recovery to G1 | 7.33 days | Standard Deviation 3.51 |
| Phase II (Evaluable Population) | Neutrophils Count Decrease: Time to First Occurrence of >=Grade 3 and Time to Recovery to Grade 1 | >=G3 | 39.67 days | Standard Deviation 23.38 |
| Phase II (Evaluable Population) | Neutrophils Count Decrease: Time to First Occurrence of >=Grade 3 and Time to Recovery to Grade 1 | >= G3 to Recovery to G1 | 7.20 days | Standard Deviation 2.59 |
Secondary
Overall Survival in Phases I and II
Overall Survival for all treated participants in Phases I and II. The estimates are based on the Kaplan-Meier (KM) method. Phase 2 started before Phase 1 completed.
Time frame: Phase I: From the Study Start Date to Phase I Completion (32 months) - Phase II: From Phase II start to Study Completion (23 months)
Population: Evaluable population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 100 mg/m2/Week Dose (Phase I) | Overall Survival in Phases I and II | 9.7 months |
| 135 mg/m2/Week Dose (Phase I) | Overall Survival in Phases I and II | 15.7 months |
| Phase II (Evaluable Population) | Overall Survival in Phases I and II | 7.3 months |
Secondary
Phase I: Duration of Response (DoR) as Measured by Investigator-assessed RECIST 1.1
Duration of response (DoR) as measured by investigator-assessed Response evaluation criteria in solid tumours (RECIST) 1.1. Duration of Response (months): was time in months from response start date to either date of disease progression/death due to progression of disease. It was calculated only for participants with complete response or partial response as best overall response.
Time frame: Phase I: From the Study Start Date to Phase I Completion (32 months)
Population: Phase I participants who experienced partial response
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 100 mg/m2/Week Dose (Phase I) | Phase I: Duration of Response (DoR) as Measured by Investigator-assessed RECIST 1.1 | 2.6 months |
| 135 mg/m2/Week Dose (Phase I) | Phase I: Duration of Response (DoR) as Measured by Investigator-assessed RECIST 1.1 | 9.3 months |
Secondary
Phase II: Duration of Response (DoR) as Measured by Investigator-assessed RECIST 1.1. and Investigator-assessed mRECIST
Duration of response (DoR) as measured by investigator-assessed Response evaluation criteria in solid tumours (RECIST) 1.1 and investigator-assessed modified RECIST (mRECIST). Duration of Response (months): was time in months from response start date to either date of disease progression/death due to progression of disease. It was calculated only for participants with complete response or partial response as best overall response.
Time frame: Phase II: From Phase II start to Study Completion (23 months)
Population: Phase II Evaluable Population. No participants had a RECIST or mRECIST complete or partial response observed.
Secondary
Phase II Objective Response Rate as Measured by Investigator-assessed mRECIST
Objective response rate as measured by investigator-assessed mRECIST in Phase II.
Time frame: Phase II: From Phase II start to Study Completion (23 months)
Population: Evaluable participants with at least one mRECIST Assessment on Treatment were analyzed
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 100 mg/m2/Week Dose (Phase I) | Phase II Objective Response Rate as Measured by Investigator-assessed mRECIST | Stable Disease | 3 Participants |
| 100 mg/m2/Week Dose (Phase I) | Phase II Objective Response Rate as Measured by Investigator-assessed mRECIST | Progressive Disease | 11 Participants |
| 100 mg/m2/Week Dose (Phase I) | Phase II Objective Response Rate as Measured by Investigator-assessed mRECIST | Objective Response (Partial Response) | 0 Participants |
| 100 mg/m2/Week Dose (Phase I) | Phase II Objective Response Rate as Measured by Investigator-assessed mRECIST | Objective Response (Complete Response) | 0 Participants |
Secondary
Phase I Objective Tumor Response (Partial and Complete Response)
Phase I any dose level, objective response and best overall tumor response are presented, as measured by investigator assessed RECIST 1.1 (Phase I). The objective response rate was calculated as the proportion of evaluable patients who achieved best overall response (BOR), confirmed complete response (CR) or partial response (PR).
Time frame: Phase I: From the Study Start Date to Phase I Completion (32 months)
Population: Treated Patients with at Least One RECIST 1.1 On-Treatment Assessment
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 100 mg/m2/Week Dose (Phase I) | Phase I Objective Tumor Response (Partial and Complete Response) | Objective Response (Partial Response) | 1 Participants |
| 100 mg/m2/Week Dose (Phase I) | Phase I Objective Tumor Response (Partial and Complete Response) | Stable Disease | 1 Participants |
| 100 mg/m2/Week Dose (Phase I) | Phase I Objective Tumor Response (Partial and Complete Response) | Progressive Disease | 4 Participants |
| 100 mg/m2/Week Dose (Phase I) | Phase I Objective Tumor Response (Partial and Complete Response) | Objective Response (Complete Response) | 0 Participants |
| 135 mg/m2/Week Dose (Phase I) | Phase I Objective Tumor Response (Partial and Complete Response) | Progressive Disease | 2 Participants |
| 135 mg/m2/Week Dose (Phase I) | Phase I Objective Tumor Response (Partial and Complete Response) | Objective Response (Partial Response) | 1 Participants |
| 135 mg/m2/Week Dose (Phase I) | Phase I Objective Tumor Response (Partial and Complete Response) | Objective Response (Complete Response) | 0 Participants |
| 135 mg/m2/Week Dose (Phase I) | Phase I Objective Tumor Response (Partial and Complete Response) | Stable Disease | 2 Participants |
Secondary
Progression Free Survival, as Measured by Investigator-assessed RECIST 1.1, in Phases I and II
Progression Free Survival as measured by investigator assessed RECIST 1.1, for all treated participants in Phase I and Phase II. Phase 2 started before Phase 1 completed.
Time frame: Phase I: From the Study Start Date to Phase I Completion (32 months) - Phase II: From Phase II start to Study Completion (23 months)
Population: All evaluable participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 100 mg/m2/Week Dose (Phase I) | Progression Free Survival, as Measured by Investigator-assessed RECIST 1.1, in Phases I and II | 1.9 months |
| 135 mg/m2/Week Dose (Phase I) | Progression Free Survival, as Measured by Investigator-assessed RECIST 1.1, in Phases I and II | 7.8 months |
| Phase II (Evaluable Population) | Progression Free Survival, as Measured by Investigator-assessed RECIST 1.1, in Phases I and II | 1.9 months |
Secondary
RA AUCweekly and RA Cmax of NMS-01940153E
Plasma pharmacokinetic (PK) PK profiles of NMS-01940153E were characterized on Day 1 and 15 of the first Cycle after infusion. Infusions occurred on Days 1, 8, and 15. RA AUCweekly = Accumulation ratio Day 1 to 15 calculated using area under the interpolated observed plasma time-concentration curve from infusion start to 168 hours RA Cmax = Accumulation ratio Day 1 to 15 calculated using maximum observed plasma concentration
Time frame: Day 21 (168 hours after the Day 15 infusion)
Population: All Phase I participants
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 100 mg/m2/Week Dose (Phase I) | RA AUCweekly and RA Cmax of NMS-01940153E | RA AUCweekly: Day 15 | 1.66 ratio | Standard Deviation 0.188 |
| 100 mg/m2/Week Dose (Phase I) | RA AUCweekly and RA Cmax of NMS-01940153E | RA Cmax: Day 15 | 1.78 ratio | Standard Deviation 1.36 |
| 135 mg/m2/Week Dose (Phase I) | RA AUCweekly and RA Cmax of NMS-01940153E | RA AUCweekly: Day 15 | 1.51 ratio | Standard Deviation 0.293 |
| 135 mg/m2/Week Dose (Phase I) | RA AUCweekly and RA Cmax of NMS-01940153E | RA Cmax: Day 15 | 0.858 ratio | Standard Deviation 0.547 |
Secondary
t½,z of NMS-01940153E
Plasma pharmacokinetic (PK) profiles of NMS-01940153E were characterized on Day 1 and 15 of the first Cycle after infusion. t½,z = Half-life of the terminal phase of observed plasma concentration
Time frame: Day 1 to Day 15
Population: All Phase I participants
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 100 mg/m2/Week Dose (Phase I) | t½,z of NMS-01940153E | t½,z Day 15 | 4.38 days | Standard Deviation 2.64 |
| 100 mg/m2/Week Dose (Phase I) | t½,z of NMS-01940153E | t½,z Day 1 | 3.74 days | Standard Deviation 0.8 |
| 135 mg/m2/Week Dose (Phase I) | t½,z of NMS-01940153E | t½,z Day 1 | 4.17 days | Standard Deviation 1.4 |
| 135 mg/m2/Week Dose (Phase I) | t½,z of NMS-01940153E | t½,z Day 15 | 4.79 days | Standard Deviation 1.15 |
Secondary
Tmax and Tlast of NMS-01940153E
Plasma pharmacokinetic (PK) profiles of NMS-01940153E were characterized on Day 1 and 15 of the first Cycle after infusion. Tmax = Time to maximum observed plasma concentration Tlast = Time of last detectable concentration
Time frame: Day 1 to Day 15
Population: All Phase I participants
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 100 mg/m2/Week Dose (Phase I) | Tmax and Tlast of NMS-01940153E | Tmax: Day 1 | 0.933 hours | Standard Deviation 0.0327 |
| 100 mg/m2/Week Dose (Phase I) | Tmax and Tlast of NMS-01940153E | Tlast: Day 15 | 144 hours | Standard Deviation 48.5 |
| 100 mg/m2/Week Dose (Phase I) | Tmax and Tlast of NMS-01940153E | Tmax: Day 15 | 1.10 hours | Standard Deviation 0.216 |
| 100 mg/m2/Week Dose (Phase I) | Tmax and Tlast of NMS-01940153E | Tlast: Day 1 | 169 hours | Standard Deviation 3.01 |
| 135 mg/m2/Week Dose (Phase I) | Tmax and Tlast of NMS-01940153E | Tlast: Day 15 | 169 hours | Standard Deviation 0.418 |
| 135 mg/m2/Week Dose (Phase I) | Tmax and Tlast of NMS-01940153E | Tmax: Day 1 | 1.19 hours | Standard Deviation 0.513 |
| 135 mg/m2/Week Dose (Phase I) | Tmax and Tlast of NMS-01940153E | Tlast: Day 1 | 154 hours | Standard Deviation 39.2 |
| 135 mg/m2/Week Dose (Phase I) | Tmax and Tlast of NMS-01940153E | Tmax: Day 15 | 1.87 hours | Standard Deviation 1.9 |
Secondary
Treatment-emergent Adverse Events by Maximum CTC Grade
The maximum Common Terminology Criteria (CTC) grade (graded using National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events \[CTCAE\] Version 5.0) experienced by each participant is presented. If an AE was reported for a participant more than once during treatment, the worst CTC Grade is presented here. Phase 2 started before Phase 1 completed. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living. Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4 Life-threatening consequences; urgent intervention indicated.
Time frame: Phase I: From the Study Start Date to Phase I Completion (32 months) - Phase II: From Phase II start to Study Completion (23 months)
Population: All treated participants
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 100 mg/m2/Week Dose (Phase I) | Treatment-emergent Adverse Events by Maximum CTC Grade | Grade 3 | 3 Participants |
| 100 mg/m2/Week Dose (Phase I) | Treatment-emergent Adverse Events by Maximum CTC Grade | Grade 2 | 1 Participants |
| 100 mg/m2/Week Dose (Phase I) | Treatment-emergent Adverse Events by Maximum CTC Grade | Grade 1 | 0 Participants |
| 100 mg/m2/Week Dose (Phase I) | Treatment-emergent Adverse Events by Maximum CTC Grade | Grade 4 | 1 Participants |
| 135 mg/m2/Week Dose (Phase I) | Treatment-emergent Adverse Events by Maximum CTC Grade | Grade 4 | 2 Participants |
| 135 mg/m2/Week Dose (Phase I) | Treatment-emergent Adverse Events by Maximum CTC Grade | Grade 1 | 0 Participants |
| 135 mg/m2/Week Dose (Phase I) | Treatment-emergent Adverse Events by Maximum CTC Grade | Grade 2 | 1 Participants |
| 135 mg/m2/Week Dose (Phase I) | Treatment-emergent Adverse Events by Maximum CTC Grade | Grade 3 | 3 Participants |
| Phase II (Evaluable Population) | Treatment-emergent Adverse Events by Maximum CTC Grade | Grade 1 | 3 Participants |
| Phase II (Evaluable Population) | Treatment-emergent Adverse Events by Maximum CTC Grade | Grade 3 | 7 Participants |
| Phase II (Evaluable Population) | Treatment-emergent Adverse Events by Maximum CTC Grade | Grade 4 | 0 Participants |
| Phase II (Evaluable Population) | Treatment-emergent Adverse Events by Maximum CTC Grade | Grade 2 | 8 Participants |
Secondary
Treatment-emergent Adverse Events Related to NMS-01940153E
The number of treatment-emergent adverse events related to NMS-01940153E by maximum CTC grade experienced (graded using NCI CTCAE Version 5.0). Whether the the AE was related or not was assessed by the investigator. If an AE was reported for a participant more than once during treatment, the worst CTC Grade is presented. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living. Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4 Life-threatening. Phase 2 started before Phase 1 completed.
Time frame: Phase I: From the Study Start Date to Phase I Completion (32 months) - Phase II: From Phase II start to Study Completion (23 months)
Population: All treated participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 100 mg/m2/Week Dose (Phase I) | Treatment-emergent Adverse Events Related to NMS-01940153E | Grade 1 | 0 events |
| 100 mg/m2/Week Dose (Phase I) | Treatment-emergent Adverse Events Related to NMS-01940153E | Grade 2 | 1 events |
| 100 mg/m2/Week Dose (Phase I) | Treatment-emergent Adverse Events Related to NMS-01940153E | Grade 3 | 2 events |
| 100 mg/m2/Week Dose (Phase I) | Treatment-emergent Adverse Events Related to NMS-01940153E | Grade 4 | 1 events |
| 135 mg/m2/Week Dose (Phase I) | Treatment-emergent Adverse Events Related to NMS-01940153E | Grade 4 | 2 events |
| 135 mg/m2/Week Dose (Phase I) | Treatment-emergent Adverse Events Related to NMS-01940153E | Grade 1 | 0 events |
| 135 mg/m2/Week Dose (Phase I) | Treatment-emergent Adverse Events Related to NMS-01940153E | Grade 3 | 2 events |
| 135 mg/m2/Week Dose (Phase I) | Treatment-emergent Adverse Events Related to NMS-01940153E | Grade 2 | 1 events |
| Phase II (Evaluable Population) | Treatment-emergent Adverse Events Related to NMS-01940153E | Grade 4 | 0 events |
| Phase II (Evaluable Population) | Treatment-emergent Adverse Events Related to NMS-01940153E | Grade 2 | 3 events |
| Phase II (Evaluable Population) | Treatment-emergent Adverse Events Related to NMS-01940153E | Grade 3 | 2 events |
| Phase II (Evaluable Population) | Treatment-emergent Adverse Events Related to NMS-01940153E | Grade 1 | 7 events |
Secondary
Vss and Vss,SS of NMS-01940153E
Plasma pharmacokinetic (PK) PK profiles of NMS-01940153E were characterized on Day 1 and 15 of the first Cycle after infusion. Vss = Volume of distribution at steady state based last observed concentration extrapolated to infinity and Clearance calculated for a dosing period of 168 h either after a single dose or in steady-state Vss,SS = Volume of distribution at steady state based last observed concentration extrapolated to infinity and clearance based on last observed concentration and extrapolation to infinity
Time frame: Day 1 to Day 15
Population: All Phase I participants
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 100 mg/m2/Week Dose (Phase I) | Vss and Vss,SS of NMS-01940153E | Vss: Day 1 | 1230 L | Standard Deviation 395 |
| 100 mg/m2/Week Dose (Phase I) | Vss and Vss,SS of NMS-01940153E | Vss: Day 15 | 787 L | Standard Deviation 304 |
| 100 mg/m2/Week Dose (Phase I) | Vss and Vss,SS of NMS-01940153E | Vss,SS: Day 1 | 1700 L | Standard Deviation 620 |
| 100 mg/m2/Week Dose (Phase I) | Vss and Vss,SS of NMS-01940153E | Vss,SS: Day 15 | 1180 L | Standard Deviation 649 |
| 135 mg/m2/Week Dose (Phase I) | Vss and Vss,SS of NMS-01940153E | Vss,SS: Day 15 | 1380 L | Standard Deviation 354 |
| 135 mg/m2/Week Dose (Phase I) | Vss and Vss,SS of NMS-01940153E | Vss: Day 1 | 1210 L | Standard Deviation 199 |
| 135 mg/m2/Week Dose (Phase I) | Vss and Vss,SS of NMS-01940153E | Vss,SS: Day 1 | 1630 L | Standard Deviation 285 |
| 135 mg/m2/Week Dose (Phase I) | Vss and Vss,SS of NMS-01940153E | Vss: Day 15 | 919 L | Standard Deviation 245 |