First in Human Dose Escalation of M3258 as a Single Agent and Expansion Study of M3258 in Combination With Dexamethasone

A Phase I Open Label First in Human Dose Escalation of the Immunoproteasome Inhibitor M3258 as a Single Agent and Expansion Study of M3258 in Combination With Dexamethasone in Participants With Relapsed Refractory Multiple Myeloma

Status

Terminated

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04075721

Enrollment

Registered

2019-09-03

Start date

2019-09-26

Completion date

2021-04-01

Last updated

2023-03-24

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Multiple Myeloma

Keywords

M3258, Dexamethasone, Pharmacokinetics, Relapsed Refractory Multiple Myeloma

Brief summary

The purpose of this study was to determine the safety, tolerability, pharmacokinetics, pharmacodynamics and early efficacy signs of M3258 as a single agent and co-administered with dexamethasone in participants with Relapsed Refractory Multiple Myeloma (RRMM).

Interventions

DRUGM3258

Participants received M3258 at a dose of 10 milligrams (mg) orally, once daily (QD) or twice per week on Day 1 and Day 4 until disease progression.

DRUGM3258 20 mg

Participants received M3258 at a dose of 20 mg orally, twice per week on Day 1 and Day 4 until disease progression.

Study design

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Participants having Eastern Co-operative Oncology Group (ECOG) Performance Status less than or equals to (\<=) 1 * Adequate hematological, hepatic and renal function as defined in the protocol * Participant must have measurable disease of Multiple Myeloma (MM) and received greater than (\>) 3 prior lines of therapy for MM including a Proteasome Inhibitors (PI), an Immunomodulatory Imide Drug (IMiD) and an anti-CD38 mAb or who are refractory to at least PI agent (carfilzomib or bortezomib) and IMiD according to the International Myeloma Working Group (IMWG) criteria * Participant must have documented evidence progressive disease as defined by the IMWG criteria either on or after their last regimen * Other protocol defined inclusion criteria could apply

Exclusion criteria

* Any condition, including any uncontrolled disease state that in the Investigator's opinion constitutes an inappropriate risk or a contraindication for participation in the study or that could interfere with the study objectives, conduct, or evaluation. * An active second malignancy or evidence of disease of cancer (other than MM) before the date of enrollment (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy that in the opinion of the Investigator, with concurrence with the Sponsor's medical monitor, is considered cured with minimal risk of recurrence within 3 years). * Cerebrovascular accident/stroke (\< 6 months prior enrollment) or neurologic instability per clinical evaluation due to tumor involvement of the Central Nervous System * Diagnosis of fever within 1 week prior to study intervention administration * Part B: Participants planning to undergo a stem cell transplant should not be enrolled to reduce disease burden prior to transplant. * Other protocol defined

Design outcomes

Primary

Measure	Time frame	Description
Part A: Number of Participants With Dose-Limiting Toxicities (DLTs) as Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0	Day 1 up to Day 28	DLT: any of adverse events (AEs), assessed by Investigator and/Sponsor at any dose, regimen, and judged not to be related to underlying disease/any previous/concomitant medication/concurrent condition during first cycle of study treatment. DLT was confirmed by Safety Monitoring Committee. DLTs: Grade (Gr) greater than/equal to (\>=) 3 nonhematologic AE with exception of: Single laboratory values out of abnormal range; Gr3 diarrhea persisting less than or equal to \[\<=\] 72 hour (hr); Nausea and vomiting \<= 72 hr; Transient Gr3 fatigue, local reactions, flu-like symptoms \<= 72 hr; Gr3 nonrecurrent skin toxicity; Asymptomatic Gr \>= 3 lipase/amylase elevation. Any Gr \>= 4 hematologic AE: Gr \>= 3 febrile neutropenia with Absolute Neutrophil Count (ANC) \<1000 per cube millimeter and temperature of \>38.3 Celsius (°C); Gr \>= 3 thrombocytopenia; Gr4 thrombocytopenia lasting \>7 days.
Part A: Number of Participants With Treatment-Emergent Adverse Event (TEAEs) and Treatment-Related Adverse Event (TRAEs)	Time from first treatment up to 30 days after end of study intervention (assessed up to 24.3 weeks)	Adverse Event (AE): any untoward medical occurrence in a participant administered with a study drug, which does not necessarily have a causal relationship with this treatment. TEAEs: events that started from first dose of study intervention to 30 days after end of study intervention, or the cutoff date, whichever occurred first. TEAEs included both serious TEAEs (Serious AE: AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect) and non-serious TEAEs. TRAEs are defined as those AEs which are reasonably related to the study intervention.
Part A: Number of Participants With Treatment-Emergent Adverse Event (TEAEs) Outside of Dose-Limiting Toxicity (DLT) Period That Safety Monitoring Committee Deems Relevant for Determination of the Maximum Tolerated Dose	Day 29 up to 20.1 weeks	Adverse Event (AE): any untoward medical occurrence in a participant administered with a study drug, which does not necessarily have a causal relationship with this treatment. TEAEs: events that started from first dose of study intervention to 30 days after end of study intervention, or the cutoff date, whichever occurred first. TEAEs included both serious TEAEs (Serious AE: AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect) and non-serious TEAEs. TRAEs are defined as those AEs which are reasonably related to the study intervention.
Part A: Change From Baseline in 12-lead Electrocardiogram (ECG) Findings: QT Interval - Fridericia's Correction Formula	Cycle 1 Day 1 pre-dose (Baseline), pre-dose on Cycle 2 Day 1 (each Cycle is of 28 days)	12-lead ECG were recorded after the participants have rested for at least 15 minutes in supine position. Change from baseline in 12-Lead ECG findings that is QT interval - Fridericia's correction formula at pre-dose on Cycle 2 Day 1 were reported.
Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Time from first treatment up to 30 days after end of study intervention (assessed up to 24.3 weeks)	ECOG performance status measured to assess participant's performance status on a scale of 0 to 5, where 0 = Fully active, able to carry on all pre-disease activities without restriction; 1 = Restricted in physically strenuous activity, ambulatory and able to carry out light or sedentary work; 2 = Ambulatory and capable of all selfcare but unable to carry out any work activities; 3 = Capable of only limited self-care, confined to bed/chair for more than 50 percent of waking hours; 4 = Completely disabled, cannot carry on any self-care, totally confined to bed/chair; 5 = dead. ECOG performance status was reported in terms of number of participants with shifts in score from baseline value vs worst post-baseline value (that is \[i.e.\] highest score).
Number of Participants With Shift From Baseline Grade Less Than (<) 3 in Clinical Laboratory Parameters to Grade Greater Than or Equal to (>=) 3 on Treatment	Time from first treatment up to 30 days after end of study intervention (assessed up to 24.3 weeks)	Laboratory parameters included hematology, chemistry, and coagulation. Number of participants with shifts from baseline (Grade \<3) to \>= Grade 3 were reported as per NCI-CTCAE, v5.0 graded from Grade 1 to 5. Grade 1: Mild, Grade 2: Moderate; Grade 3: Severe. Grade 4: Life-threatening and Grade 5: Death.

Secondary

Measure	Time frame	Description
Part A: Single Dose: Area Under Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) of M3258	Cycle 1 Day 1: Pre-dose 1, 2, 3, 4, 5, 6, 8 and 24 hours post-dose (each Cycle is of 28 days)	Area under the plasma concentration versus time curve from time zero to 24 hours post dosing for M3258. Single dose PK data on Day 1 were summarized by dose level, such that all 10 mg arms were combined as descriptive statistics of PK were only calculated for N greater than (\>) 2 in which a measurement of greater than (\>) lower limit of quantification (LLOQ) represents a valid measurement.
Part A: Multiple Dose: Area Under Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) of M3258	Cycle 1 Day 8 or Cycle 1 Day 15: Pre-dose 1, 2, 3, 4, 5, 6, and 8 hours post-dose (each Cycle is of 28 days)	Area under the plasma concentration versus time curve from time zero to 24 hours post dosing for M3258.
Part A: Single Dose: Ratio to Baseline in Large Multifunctional Protease 7 (LMP7) Activity at Cycle 1 Day 1	Baseline (Pre-dose), 2, 6 and 24 hours post-dose on Cycle 1 Day 1 (each Cycle is of 28 days)	Ratio to baseline was calculated dividing post-baseline measurements by the baseline measurement. Single dose Pd data on Day 1 were summarized by dose level, such that all 10 mg arms were combined as descriptive statistics of PK were only calculated for N greater than (\>) 2 in which a measurement of greater than (\>) lower limit of quantification (LLOQ) represents a valid measurement.
Part A: Multiple Dose: Ratio to Baseline in Large Multifunctional Protease 7 (LMP7) Activity at Cycle 1 Day 8 (or Day 15)	Cycle 1 Day 1 pre-dose (Baseline), Pre-dose, 2 and 6 hours post-dose on Cycle 1 Day 8 (or Day 15) (each Cycle is of 28 days)	Ratio to baseline was calculated dividing post-baseline measurements by the baseline measurement.
Part A: Change From Baseline in Serum Monoclonal (M)-Protein Level Measured Using Electrophoresis	Baseline, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, Cycle 6 Day 1 and end of study intervention (Week 20.1) (each Cycle is of 28 days)	Change from baseline in serum monoclonal (M)-protein level was measured by using electrophoresis at Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, Cycle 6 Day 1 and end of study intervention.
Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Body Temperature Increase	Time from first treatment up to 30 days after end of study intervention (assessed up to 24.3 weeks)	The number of participants with treatment-emergent changes from baseline in increased Body Temperature (degree Celsius \[°C\]) were reported by using criteria: Baseline temperature (temp.) less than (\<) 37°C, on treatment change \<1°C, 1 - \<2°C, 2 - \<3°C and greater than or equal to (\>=)3°C; Baseline temp. 37 - \<38°C, on treatment change \<1°C, 1 - \<2°C, 2 - \<3°C and \>=3°C; Baseline temp. 38 - \<39°C, on treatment change \<1°C, 1 - \<2°C, 2 - \<3°C and \>=3°C; Baseline temp. 39-\<40°C, on treatment change \<1°C, 1 - \<2°C, 2 - \<3°C and \>=3°C; Baseline temp. \>=40°C, on treatment change \<1°C, 1 - \<2°C, 2 - \<3°C and \>=3°C.
Part A: Change From Baseline in Free Light Chain Ratio	Baseline, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, Cycle 6 Day 1 and end of study intervention (Week 20.1) (each Cycle is of 28 days)	Change from baseline in free light chain ratio was reported at Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, Cycle 6 Day 1 and end of study intervention.
Part A: Number of Participants With Overall Response (OR) as Assessed by Investigator Using International Myeloma Working Group (IMWG) Criteria	Time from first dose of study treatment up to 18.2 months	OR is defined as a best overall response of stringent complete response (sCR), complete response (CR), very good partial response (VGPR) or partial response (PR) based on the IMWG Criteria: sCR: CR (negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \< 5% plasma cells in bone marrow); normal free light chain (FLC) ratio and no clonal cells in bone marrow; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis/\>= 90% reduction in serum M-protein and urine M-protein level \< 100 mg/24 hours; PR: \>= 50% reduction of serum M-Protein and reduction in urinary M-protein by \>= 90%/to \< 200 mg/24 hours. In addition to the above, if present at baseline a \>= 50% reduction in the size of soft tissue plasmacytomas is also required.
Duration of Response (DoR) as Assessed by Investigator Using International Myeloma Working Group (IMWG) Criteria	Time from first documentation of objective response until date of first documentation of PD or death due to any cause, whichever occurred first, assessed up to 18.2 months	DOR was defined participants with confirmed response, as time from first documentation of objective response (Complete Response \[CR\] or Partial Response \[PR\]) to date of first documentation of progression disease (PD)/death due to any cause, whichever occurred first. CR: Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \< 5% plasma cells in bone marrow. PR: \>= 50% reduction of serum M-Protein and reduction in urinary M-protein by \>= 90%/to \< 200 mg/24 hours. In addition to the above, if present at baseline a \>= 50% reduction in the size of soft tissue plasmacytomas is also required. PD: \>= 25% increase from lowest response value in serum. Development of new or increased size of existing bone lesions or soft tissue plasmacytomas. Hypercalcemia attributed to the plasma cell proliferative disorder.
Time to Response as Assessed by Investigator Using International Myeloma Working Group (IMWG) Criteria	Time from the first dose of study treatment up to documentation of first response, assessed up to 18.2 months	Time to response was defined as the time from the first dose of M3258 to the documentation of first response (Complete Response \[CR\] or Partial Response \[PR\]). CR: Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \< 5% plasma cells in bone marrow. PR: \>= 50% reduction of serum M-Protein and reduction in urinary M-protein by \>= 90% or to \< 200 mg/24 hours. In addition to the above, if present at baseline a \>= 50% reduction in the size of soft tissue plasmacytomas is also required.
Part A: Change From Baseline in Urine M-protein Level Using Electrophoresis	Baseline, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, Cycle 6 Day 1 and end of study intervention (Week 20.1) (each Cycle is of 28 days)	Change from baseline in urine M-protein level was measured by using electrophoresis at Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, Cycle 6 Day 1 and end of study intervention.
Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease	Time from first treatment up to 30 days after end of study intervention (assessed up to 24.3 weeks)	The number of participants with treatment-emergent changes from baseline (BS) in Increase (Ic.)/Decrease (Dc.) Systolic Blood Pressure (SBP) and diastolic blood pressure (DBP) (millimeter of mercury \[mmHg\]) were reported by using criteria: Ic./Dc. BS SBP/DBP \<140/\<90 mmHg, on maximal treatment (TR) change =\<20 mmHg, \>20 - =\<40 mmHg and \>40 mmHg; Ic./Dc. BS SBP/DBP \>=140/\>=90 mmHg, on maximal TR change =\<20 mmHg, \>20 - =\<40 mmHg and \>40 mmHg.
Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Respiration Rate Increase/Decrease	Time from first treatment up to 30 days after end of study intervention (assessed up to 24.3 weeks)	The number of participants with treatment-emergent changes from baseline in Increase (Ic.)/Decrease (Dc.) maximal Respiration Rate (RR) were reported by using criteria: Ic./Dc. BS RR \<20 breaths per minute (breaths/min), on TR change (ch) =\<5 breaths/min, \>5 - =\<10 breaths/min and \>10 breaths/min. Ic./Dc. BS RR \>=20 breaths/min, on TR ch =\<5 breaths/min, \>5 - =\<10 breaths/min and \>10 breaths/min.
Part A: Single Dose: Maximum Observed Plasma Concentration (Cmax) of M3258	Cycle 1 Day 1: Pre-dose 1, 2, 3, 4, 5, 6, 8 and 24 hours post-dose (each Cycle is of 28 days)	Cmax was obtained directly from the concentration versus time curve. Single dose PK data on Day 1 were summarized by dose level, such that all 10 mg arms were combined as descriptive statistics of PK were only calculated for N greater than (\>) 2 in which a measurement of greater than (\>) lower limit of quantification (LLOQ) represents a valid measurement.
Part A: Mutilple Dose: Maximum Observed Plasma Concentration (Cmax) of M3258	Cycle 1 Day 8 or Cycle 1 Day 15: Pre-dose 1, 2, 3, 4, 5, 6, and 8 hours post-dose (each Cycle is of 28 days)	Cmax was obtained directly from the concentration versus time curve.
Part A: Single Dose: Area Under Plasma Concentration-Time Curve (AUC) From Time Zero to Last Sampling Time (AUC0-t) of M3258	Cycle 1 Day 1: Pre-dose 1, 2, 3, 4, 5, 6, 8 and 24 hours post-dose (each Cycle is of 28 days)	Area under the plasma concentration versus time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLOQ). AUC0-t was calculated according to the mixed log-linear trapezoidal rule. Single dose PK data on Day 1 were summarized by dose level, such that all 10 mg arms were combined as descriptive statistics of PK were only calculated for N greater than (\>) 2 in which a measurement of greater than (\>) lower limit of quantification (LLOQ) represents a valid measurement.

Countries

France, United States

Participant flow

Recruitment details

First participant signed informed consent: 26 September 2019, Last participant last visit: 01 April 2021.

Pre-assignment details

This study was planned to be conducted in 2 parts; Part A: Dose escalation part and Part B: Dose expansion part. However, because of early discontinuation, only Part A was conducted; due to lack of participant enrollment before Part A reached its primary objective and before Part B was started.

Participants by arm

Arm	Count
M3258 10 mg QD Participants received M3258 at a dose of 10 milligrams (mg) orally, once daily (QD) until disease progression.	2
M3258 10 mg Twice Per Week Participants received M3258 at a dose of 10 mg orally, twice per week on Day 1 and Day 4 until disease progression.	4
M3258 20 mg Twice Per Week Participants received M3258 at a dose of 20 mg orally, twice per week on Day 1 and Day 4 until disease progression.	4
Total	10

Baseline characteristics

Characteristic	M3258 10 mg QD	M3258 10 mg Twice Per Week	M3258 20 mg Twice Per Week	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	1 Participants	2 Participants	3 Participants	6 Participants
Age, Categorical Between 18 and 65 years	1 Participants	2 Participants	1 Participants	4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants	0 Participants	0 Participants	0 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	2 Participants	4 Participants	3 Participants	9 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	1 Participants	1 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	0 Participants	1 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	3 Participants	4 Participants	7 Participants
Race (NIH/OMB) White	2 Participants	0 Participants	0 Participants	2 Participants
Sex: Female, Male Female	1 Participants	3 Participants	2 Participants	6 Participants
Sex: Female, Male Male	1 Participants	1 Participants	2 Participants	4 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	0 / 2	0 / 4	1 / 4
other Total, other adverse events	2 / 2	4 / 4	4 / 4
serious Total, serious adverse events	0 / 2	3 / 4	3 / 4

Outcome results

Primary

Number of Participants With Shift From Baseline Grade Less Than (<) 3 in Clinical Laboratory Parameters to Grade Greater Than or Equal to (>=) 3 on Treatment

Laboratory parameters included hematology, chemistry, and coagulation. Number of participants with shifts from baseline (Grade \<3) to \>= Grade 3 were reported as per NCI-CTCAE, v5.0 graded from Grade 1 to 5. Grade 1: Mild, Grade 2: Moderate; Grade 3: Severe. Grade 4: Life-threatening and Grade 5: Death.

Time frame: Time from first treatment up to 30 days after end of study intervention (assessed up to 24.3 weeks)

Population: Safety analysis set included all participants who were administered any dose of the study medication.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
M3258 10 mg QD	Number of Participants With Shift From Baseline Grade Less Than (<) 3 in Clinical Laboratory Parameters to Grade Greater Than or Equal to (>=) 3 on Treatment	Chemistry	0 Participants
M3258 10 mg QD	Number of Participants With Shift From Baseline Grade Less Than (<) 3 in Clinical Laboratory Parameters to Grade Greater Than or Equal to (>=) 3 on Treatment	Hematology	2 Participants
M3258 10 mg QD	Number of Participants With Shift From Baseline Grade Less Than (<) 3 in Clinical Laboratory Parameters to Grade Greater Than or Equal to (>=) 3 on Treatment	Coagulation	0 Participants
M3258 10 mg Twice Per Week	Number of Participants With Shift From Baseline Grade Less Than (<) 3 in Clinical Laboratory Parameters to Grade Greater Than or Equal to (>=) 3 on Treatment	Chemistry	0 Participants
M3258 10 mg Twice Per Week	Number of Participants With Shift From Baseline Grade Less Than (<) 3 in Clinical Laboratory Parameters to Grade Greater Than or Equal to (>=) 3 on Treatment	Hematology	3 Participants
M3258 10 mg Twice Per Week	Number of Participants With Shift From Baseline Grade Less Than (<) 3 in Clinical Laboratory Parameters to Grade Greater Than or Equal to (>=) 3 on Treatment	Coagulation	0 Participants
M3258 20 mg Twice Per Week	Number of Participants With Shift From Baseline Grade Less Than (<) 3 in Clinical Laboratory Parameters to Grade Greater Than or Equal to (>=) 3 on Treatment	Hematology	4 Participants
M3258 20 mg Twice Per Week	Number of Participants With Shift From Baseline Grade Less Than (<) 3 in Clinical Laboratory Parameters to Grade Greater Than or Equal to (>=) 3 on Treatment	Coagulation	0 Participants
M3258 20 mg Twice Per Week	Number of Participants With Shift From Baseline Grade Less Than (<) 3 in Clinical Laboratory Parameters to Grade Greater Than or Equal to (>=) 3 on Treatment	Chemistry	3 Participants

Primary

Part A: Change From Baseline in 12-lead Electrocardiogram (ECG) Findings: QT Interval - Fridericia's Correction Formula

12-lead ECG were recorded after the participants have rested for at least 15 minutes in supine position. Change from baseline in 12-Lead ECG findings that is QT interval - Fridericia's correction formula at pre-dose on Cycle 2 Day 1 were reported.

Time frame: Cycle 1 Day 1 pre-dose (Baseline), pre-dose on Cycle 2 Day 1 (each Cycle is of 28 days)

Population: Safety analysis set included all participants who were administered any dose of the study medication. Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.

Arm	Measure	Value (MEAN)	Dispersion
M3258 10 mg QD	Part A: Change From Baseline in 12-lead Electrocardiogram (ECG) Findings: QT Interval - Fridericia's Correction Formula	-10.0 milliseconds (msec)	Full Range -10
M3258 10 mg Twice Per Week	Part A: Change From Baseline in 12-lead Electrocardiogram (ECG) Findings: QT Interval - Fridericia's Correction Formula	6.3 milliseconds (msec)	Full Range -17
M3258 20 mg Twice Per Week	Part A: Change From Baseline in 12-lead Electrocardiogram (ECG) Findings: QT Interval - Fridericia's Correction Formula	6.0 milliseconds (msec)	Full Range 6

Primary

Part A: Number of Participants With Dose-Limiting Toxicities (DLTs) as Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0

DLT: any of adverse events (AEs), assessed by Investigator and/Sponsor at any dose, regimen, and judged not to be related to underlying disease/any previous/concomitant medication/concurrent condition during first cycle of study treatment. DLT was confirmed by Safety Monitoring Committee. DLTs: Grade (Gr) greater than/equal to (\>=) 3 nonhematologic AE with exception of: Single laboratory values out of abnormal range; Gr3 diarrhea persisting less than or equal to \[\<=\] 72 hour (hr); Nausea and vomiting \<= 72 hr; Transient Gr3 fatigue, local reactions, flu-like symptoms \<= 72 hr; Gr3 nonrecurrent skin toxicity; Asymptomatic Gr \>= 3 lipase/amylase elevation. Any Gr \>= 4 hematologic AE: Gr \>= 3 febrile neutropenia with Absolute Neutrophil Count (ANC) \<1000 per cube millimeter and temperature of \>38.3 Celsius (°C); Gr \>= 3 thrombocytopenia; Gr4 thrombocytopenia lasting \>7 days.

Time frame: Day 1 up to Day 28

Population: DLT analysis set: all participants who received at least 1 dose of study intervention and meet at least 1 of criteria specified in statistical analysis plan.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
M3258 10 mg QD	Part A: Number of Participants With Dose-Limiting Toxicities (DLTs) as Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0	1 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Dose-Limiting Toxicities (DLTs) as Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0	0 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Dose-Limiting Toxicities (DLTs) as Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0	1 Participants

Primary

Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score

ECOG performance status measured to assess participant's performance status on a scale of 0 to 5, where 0 = Fully active, able to carry on all pre-disease activities without restriction; 1 = Restricted in physically strenuous activity, ambulatory and able to carry out light or sedentary work; 2 = Ambulatory and capable of all selfcare but unable to carry out any work activities; 3 = Capable of only limited self-care, confined to bed/chair for more than 50 percent of waking hours; 4 = Completely disabled, cannot carry on any self-care, totally confined to bed/chair; 5 = dead. ECOG performance status was reported in terms of number of participants with shifts in score from baseline value vs worst post-baseline value (that is \[i.e.\] highest score).

Time frame: Time from first treatment up to 30 days after end of study intervention (assessed up to 24.3 weeks)

Population: Safety analysis set included all participants who were administered any dose of the study medication.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
M3258 10 mg QD	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 1, worst post-baseline score 1	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 5, worst post-baseline score 3	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 3, worst post-baseline score 4	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 1, worst post-baseline score 2	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 3, worst post-baseline score 2	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 3, worst post-baseline score 3	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 0, worst post-baseline score 4	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 1, worst post-baseline score 4	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 4, worst post-baseline score 5	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 1, worst post-baseline score 5	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 1, worst post-baseline score 0	1 Participants
M3258 10 mg QD	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 0, worst post-baseline score 0	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 4, worst post-baseline score 4	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 3, worst post-baseline score 1	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 2, worst post-baseline score 1	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 5, worst post-baseline score 4	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 3, worst post-baseline score 0	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 2, worst post-baseline score 2	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 1, worst post-baseline score 3	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 2, worst post-baseline score 5	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 2, worst post-baseline score 3	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 2, worst post-baseline score 4	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 5, worst post-baseline score 2	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 0, worst post-baseline score 2	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 5, worst post-baseline score 1	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 4, worst post-baseline score 3	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 0, worst post-baseline score 3	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 2, worst post-baseline score 0	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 4, worst post-baseline score 2	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 5, worst post-baseline score 5	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 4, worst post-baseline score 1	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 0, worst post-baseline score 5	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 5, worst post-baseline score 0	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 4, worst post-baseline score 0	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 0, worst post-baseline score 1	1 Participants
M3258 10 mg QD	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 3, worst post-baseline score 5	0 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 3, worst post-baseline score 2	0 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 0, worst post-baseline score 0	0 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 2, worst post-baseline score 3	0 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 3, worst post-baseline score 0	0 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 3, worst post-baseline score 1	0 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 3, worst post-baseline score 3	0 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 5, worst post-baseline score 1	0 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 5, worst post-baseline score 4	0 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 0, worst post-baseline score 1	2 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 0, worst post-baseline score 2	0 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 0, worst post-baseline score 3	0 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 0, worst post-baseline score 4	0 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 0, worst post-baseline score 5	0 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 1, worst post-baseline score 0	1 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 1, worst post-baseline score 1	1 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 1, worst post-baseline score 2	0 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 1, worst post-baseline score 3	0 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 1, worst post-baseline score 4	0 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 1, worst post-baseline score 5	0 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 2, worst post-baseline score 0	0 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 2, worst post-baseline score 1	0 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 2, worst post-baseline score 2	0 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 2, worst post-baseline score 4	0 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 2, worst post-baseline score 5	0 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 3, worst post-baseline score 4	0 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 3, worst post-baseline score 5	0 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 4, worst post-baseline score 0	0 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 4, worst post-baseline score 1	0 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 4, worst post-baseline score 2	0 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 4, worst post-baseline score 3	0 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 4, worst post-baseline score 4	0 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 4, worst post-baseline score 5	0 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 5, worst post-baseline score 0	0 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 5, worst post-baseline score 2	0 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 5, worst post-baseline score 3	0 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 5, worst post-baseline score 5	0 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 5, worst post-baseline score 0	0 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 1, worst post-baseline score 0	0 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 1, worst post-baseline score 4	0 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 3, worst post-baseline score 5	0 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 0, worst post-baseline score 5	0 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 1, worst post-baseline score 3	1 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 4, worst post-baseline score 0	0 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 0, worst post-baseline score 4	0 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 0, worst post-baseline score 0	0 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 4, worst post-baseline score 1	0 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 0, worst post-baseline score 3	1 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 5, worst post-baseline score 2	0 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 4, worst post-baseline score 2	0 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 0, worst post-baseline score 2	0 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 0, worst post-baseline score 1	1 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 4, worst post-baseline score 3	0 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 5, worst post-baseline score 1	0 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 5, worst post-baseline score 5	0 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 4, worst post-baseline score 4	0 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 3, worst post-baseline score 4	0 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 5, worst post-baseline score 3	0 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 4, worst post-baseline score 5	0 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 2, worst post-baseline score 3	0 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 2, worst post-baseline score 4	0 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 2, worst post-baseline score 2	0 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 5, worst post-baseline score 4	0 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 2, worst post-baseline score 5	0 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 2, worst post-baseline score 1	0 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 3, worst post-baseline score 0	0 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 2, worst post-baseline score 0	0 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 3, worst post-baseline score 1	0 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 1, worst post-baseline score 5	0 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 3, worst post-baseline score 2	0 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 1, worst post-baseline score 2	1 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 3, worst post-baseline score 3	0 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score	Baseline score 1, worst post-baseline score 1	0 Participants

Primary

Part A: Number of Participants With Treatment-Emergent Adverse Event (TEAEs) and Treatment-Related Adverse Event (TRAEs)

Adverse Event (AE): any untoward medical occurrence in a participant administered with a study drug, which does not necessarily have a causal relationship with this treatment. TEAEs: events that started from first dose of study intervention to 30 days after end of study intervention, or the cutoff date, whichever occurred first. TEAEs included both serious TEAEs (Serious AE: AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect) and non-serious TEAEs. TRAEs are defined as those AEs which are reasonably related to the study intervention.

Time frame: Time from first treatment up to 30 days after end of study intervention (assessed up to 24.3 weeks)

Population: Safety analysis set included all participants who were administered any dose of the study medication.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
M3258 10 mg QD	Part A: Number of Participants With Treatment-Emergent Adverse Event (TEAEs) and Treatment-Related Adverse Event (TRAEs)	Participants with TEAEs	2 Participants
M3258 10 mg QD	Part A: Number of Participants With Treatment-Emergent Adverse Event (TEAEs) and Treatment-Related Adverse Event (TRAEs)	Participants with TRAEs	2 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Adverse Event (TEAEs) and Treatment-Related Adverse Event (TRAEs)	Participants with TRAEs	3 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Adverse Event (TEAEs) and Treatment-Related Adverse Event (TRAEs)	Participants with TEAEs	4 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Adverse Event (TEAEs) and Treatment-Related Adverse Event (TRAEs)	Participants with TRAEs	3 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Adverse Event (TEAEs) and Treatment-Related Adverse Event (TRAEs)	Participants with TEAEs	4 Participants

Primary

Part A: Number of Participants With Treatment-Emergent Adverse Event (TEAEs) Outside of Dose-Limiting Toxicity (DLT) Period That Safety Monitoring Committee Deems Relevant for Determination of the Maximum Tolerated Dose

Time frame: Day 29 up to 20.1 weeks

Population: Safety analysis set included all participants who were administered any dose of the study medication.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
M3258 10 mg QD	Part A: Number of Participants With Treatment-Emergent Adverse Event (TEAEs) Outside of Dose-Limiting Toxicity (DLT) Period That Safety Monitoring Committee Deems Relevant for Determination of the Maximum Tolerated Dose	0 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Adverse Event (TEAEs) Outside of Dose-Limiting Toxicity (DLT) Period That Safety Monitoring Committee Deems Relevant for Determination of the Maximum Tolerated Dose	0 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Adverse Event (TEAEs) Outside of Dose-Limiting Toxicity (DLT) Period That Safety Monitoring Committee Deems Relevant for Determination of the Maximum Tolerated Dose	0 Participants

Secondary

Duration of Response (DoR) as Assessed by Investigator Using International Myeloma Working Group (IMWG) Criteria

DOR was defined participants with confirmed response, as time from first documentation of objective response (Complete Response \[CR\] or Partial Response \[PR\]) to date of first documentation of progression disease (PD)/death due to any cause, whichever occurred first. CR: Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \< 5% plasma cells in bone marrow. PR: \>= 50% reduction of serum M-Protein and reduction in urinary M-protein by \>= 90%/to \< 200 mg/24 hours. In addition to the above, if present at baseline a \>= 50% reduction in the size of soft tissue plasmacytomas is also required. PD: \>= 25% increase from lowest response value in serum. Development of new or increased size of existing bone lesions or soft tissue plasmacytomas. Hypercalcemia attributed to the plasma cell proliferative disorder.

Time frame: Time from first documentation of objective response until date of first documentation of PD or death due to any cause, whichever occurred first, assessed up to 18.2 months

Population: Data could not be calculated as none of the participants showed objective response.

Secondary

Part A: Change From Baseline in Free Light Chain Ratio

Change from baseline in free light chain ratio was reported at Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, Cycle 6 Day 1 and end of study intervention.

Time frame: Baseline, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, Cycle 6 Day 1 and end of study intervention (Week 20.1) (each Cycle is of 28 days)

Population: Safety analysis set included all participants who were administered any dose of the trial medication. Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure and Number Analyzed signifies those participants who were evaluable for specified timepoints.

Arm	Measure	Group	Value (MEAN)
M3258 10 mg QD	Part A: Change From Baseline in Free Light Chain Ratio	End of Study Intervention	-0.005 ratio
M3258 10 mg QD	Part A: Change From Baseline in Free Light Chain Ratio	Cycle 2 Day 1	0.000 ratio
M3258 10 mg Twice Per Week	Part A: Change From Baseline in Free Light Chain Ratio	Cycle 3 Day 1	0.000 ratio
M3258 10 mg Twice Per Week	Part A: Change From Baseline in Free Light Chain Ratio	Cycle 4 Day 1	0.000 ratio
M3258 10 mg Twice Per Week	Part A: Change From Baseline in Free Light Chain Ratio	Cycle 2 Day 1	0.000 ratio
M3258 10 mg Twice Per Week	Part A: Change From Baseline in Free Light Chain Ratio	Cycle 5 Day 1	0.000 ratio
M3258 10 mg Twice Per Week	Part A: Change From Baseline in Free Light Chain Ratio	Cycle 6 Day 1	-0.010 ratio
M3258 10 mg Twice Per Week	Part A: Change From Baseline in Free Light Chain Ratio	End of Study Intervention	-0.010 ratio
M3258 20 mg Twice Per Week	Part A: Change From Baseline in Free Light Chain Ratio	Cycle 3 Day 1	0.010 ratio
M3258 20 mg Twice Per Week	Part A: Change From Baseline in Free Light Chain Ratio	Cycle 2 Day 1	0.000 ratio
M3258 20 mg Twice Per Week	Part A: Change From Baseline in Free Light Chain Ratio	End of Study Intervention	0.000 ratio

Secondary

Part A: Change From Baseline in Serum Monoclonal (M)-Protein Level Measured Using Electrophoresis

Change from baseline in serum monoclonal (M)-protein level was measured by using electrophoresis at Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, Cycle 6 Day 1 and end of study intervention.

Time frame: Baseline, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, Cycle 6 Day 1 and end of study intervention (Week 20.1) (each Cycle is of 28 days)

Arm	Measure	Group	Value (MEAN)
M3258 10 mg QD	Part A: Change From Baseline in Serum Monoclonal (M)-Protein Level Measured Using Electrophoresis	End of Study Intervention	0.100 gram per deciliter (g/dL)
M3258 10 mg Twice Per Week	Part A: Change From Baseline in Serum Monoclonal (M)-Protein Level Measured Using Electrophoresis	Cycle 3 Day 1	0.107 gram per deciliter (g/dL)
M3258 10 mg Twice Per Week	Part A: Change From Baseline in Serum Monoclonal (M)-Protein Level Measured Using Electrophoresis	Cycle 2 Day 1	-0.113 gram per deciliter (g/dL)
M3258 10 mg Twice Per Week	Part A: Change From Baseline in Serum Monoclonal (M)-Protein Level Measured Using Electrophoresis	Cycle 4 Day 1	0.050 gram per deciliter (g/dL)
M3258 10 mg Twice Per Week	Part A: Change From Baseline in Serum Monoclonal (M)-Protein Level Measured Using Electrophoresis	Cycle 6 Day 1	0.100 gram per deciliter (g/dL)
M3258 10 mg Twice Per Week	Part A: Change From Baseline in Serum Monoclonal (M)-Protein Level Measured Using Electrophoresis	End of Study Intervention	0.678 gram per deciliter (g/dL)
M3258 20 mg Twice Per Week	Part A: Change From Baseline in Serum Monoclonal (M)-Protein Level Measured Using Electrophoresis	Cycle 3 Day 1	0.100 gram per deciliter (g/dL)
M3258 20 mg Twice Per Week	Part A: Change From Baseline in Serum Monoclonal (M)-Protein Level Measured Using Electrophoresis	Cycle 2 Day 1	0.000 gram per deciliter (g/dL)
M3258 20 mg Twice Per Week	Part A: Change From Baseline in Serum Monoclonal (M)-Protein Level Measured Using Electrophoresis	End of Study Intervention	1.223 gram per deciliter (g/dL)

Secondary

Part A: Change From Baseline in Urine M-protein Level Using Electrophoresis

Change from baseline in urine M-protein level was measured by using electrophoresis at Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, Cycle 6 Day 1 and end of study intervention.

Time frame: Baseline, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, Cycle 6 Day 1 and end of study intervention (Week 20.1) (each Cycle is of 28 days)

Arm	Measure	Group	Value (MEAN)
M3258 10 mg Twice Per Week	Part A: Change From Baseline in Urine M-protein Level Using Electrophoresis	End of Study Intervention	610.50 milligrams per day (mg/day)
M3258 10 mg Twice Per Week	Part A: Change From Baseline in Urine M-protein Level Using Electrophoresis	Cycle 6 Day 1	3320.00 milligrams per day (mg/day)
M3258 10 mg Twice Per Week	Part A: Change From Baseline in Urine M-protein Level Using Electrophoresis	Cycle 2 Day 1	25.25 milligrams per day (mg/day)
M3258 10 mg Twice Per Week	Part A: Change From Baseline in Urine M-protein Level Using Electrophoresis	Cycle 3 Day 1	256.00 milligrams per day (mg/day)
M3258 10 mg Twice Per Week	Part A: Change From Baseline in Urine M-protein Level Using Electrophoresis	Cycle 4 Day 1	-130.00 milligrams per day (mg/day)
M3258 10 mg Twice Per Week	Part A: Change From Baseline in Urine M-protein Level Using Electrophoresis	Cycle 5 Day 1	268.00 milligrams per day (mg/day)
M3258 20 mg Twice Per Week	Part A: Change From Baseline in Urine M-protein Level Using Electrophoresis	Cycle 2 Day 1	26.50 milligrams per day (mg/day)
M3258 20 mg Twice Per Week	Part A: Change From Baseline in Urine M-protein Level Using Electrophoresis	Cycle 3 Day 1	67.00 milligrams per day (mg/day)

Secondary

Part A: Multiple Dose: Area Under Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) of M3258

Area under the plasma concentration versus time curve from time zero to 24 hours post dosing for M3258.

Time frame: Cycle 1 Day 8 or Cycle 1 Day 15: Pre-dose 1, 2, 3, 4, 5, 6, and 8 hours post-dose (each Cycle is of 28 days)

Population: The most participants who had evaluable PK, samples at 24 hour (Day 2) were collected. Therefore, the AUC0-t and AUC0-24 would not differ and AUC0-24 at single dose was not reported. It was also planned to carry the trough value at steady state for QD dosing forward and impute it as trough value at 24 hours. Due to the change from the QD to twice per week dosing this did not apply anymore and AUC0-24 at steady state was not calculated.

Secondary

Part A: Multiple Dose: Ratio to Baseline in Large Multifunctional Protease 7 (LMP7) Activity at Cycle 1 Day 8 (or Day 15)

Ratio to baseline was calculated dividing post-baseline measurements by the baseline measurement.

Time frame: Cycle 1 Day 1 pre-dose (Baseline), Pre-dose, 2 and 6 hours post-dose on Cycle 1 Day 8 (or Day 15) (each Cycle is of 28 days)

Population: The Pd population included all participants who received at least one dose of study intervention, had no clinically important protocol deviations or important events affecting Pd, and provide at least one measurable Pd endpoint post-dose. Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure and Number Analyzed signifies those participants who were evaluable for specified timepoints.

Arm	Measure	Group	Value (MEAN)
M3258 10 mg QD	Part A: Multiple Dose: Ratio to Baseline in Large Multifunctional Protease 7 (LMP7) Activity at Cycle 1 Day 8 (or Day 15)	Cycle 1 Day 8 (or Day 15): Pre-dose	0.26 ratio
M3258 10 mg QD	Part A: Multiple Dose: Ratio to Baseline in Large Multifunctional Protease 7 (LMP7) Activity at Cycle 1 Day 8 (or Day 15)	Cycle 1 Day 8 (or Day 15): 2 hours post-dose	0.25 ratio
M3258 10 mg Twice Per Week	Part A: Multiple Dose: Ratio to Baseline in Large Multifunctional Protease 7 (LMP7) Activity at Cycle 1 Day 8 (or Day 15)	Cycle 1 Day 8 (or Day 15): 2 hours post-dose	0.202 ratio
M3258 10 mg Twice Per Week	Part A: Multiple Dose: Ratio to Baseline in Large Multifunctional Protease 7 (LMP7) Activity at Cycle 1 Day 8 (or Day 15)	Cycle 1 Day 8 (or Day 15): Pre-dose	0.364 ratio
M3258 10 mg Twice Per Week	Part A: Multiple Dose: Ratio to Baseline in Large Multifunctional Protease 7 (LMP7) Activity at Cycle 1 Day 8 (or Day 15)	Cycle 1 Day 8 (or Day 15): 6 hours post-dose	0.178 ratio
M3258 20 mg Twice Per Week	Part A: Multiple Dose: Ratio to Baseline in Large Multifunctional Protease 7 (LMP7) Activity at Cycle 1 Day 8 (or Day 15)	Cycle 1 Day 8 (or Day 15): 2 hours post-dose	0.299 ratio
M3258 20 mg Twice Per Week	Part A: Multiple Dose: Ratio to Baseline in Large Multifunctional Protease 7 (LMP7) Activity at Cycle 1 Day 8 (or Day 15)	Cycle 1 Day 8 (or Day 15): 6 hours post-dose	0.22 ratio
M3258 20 mg Twice Per Week	Part A: Multiple Dose: Ratio to Baseline in Large Multifunctional Protease 7 (LMP7) Activity at Cycle 1 Day 8 (or Day 15)	Cycle 1 Day 8 (or Day 15): Pre-dose	0.31 ratio

Secondary

Part A: Mutilple Dose: Maximum Observed Plasma Concentration (Cmax) of M3258

Cmax was obtained directly from the concentration versus time curve.

Time frame: Cycle 1 Day 8 or Cycle 1 Day 15: Pre-dose 1, 2, 3, 4, 5, 6, and 8 hours post-dose (each Cycle is of 28 days)

Population: Pharmacokinetic (PK) analysis set included all participants, who received at least one dose of study intervention, have no clinically important protocol deviations or important events affecting PK, and provide at least one measurable post-dose concentration. Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.

Arm	Measure	Value (GEOMETRIC_MEAN)
M3258 10 mg QD	Part A: Mutilple Dose: Maximum Observed Plasma Concentration (Cmax) of M3258	NA nanogram per milliliter (ng/mL)
M3258 10 mg Twice Per Week	Part A: Mutilple Dose: Maximum Observed Plasma Concentration (Cmax) of M3258	213 nanogram per milliliter (ng/mL)
M3258 20 mg Twice Per Week	Part A: Mutilple Dose: Maximum Observed Plasma Concentration (Cmax) of M3258	511 nanogram per milliliter (ng/mL)

Secondary

Part A: Number of Participants With Overall Response (OR) as Assessed by Investigator Using International Myeloma Working Group (IMWG) Criteria

OR is defined as a best overall response of stringent complete response (sCR), complete response (CR), very good partial response (VGPR) or partial response (PR) based on the IMWG Criteria: sCR: CR (negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \< 5% plasma cells in bone marrow); normal free light chain (FLC) ratio and no clonal cells in bone marrow; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis/\>= 90% reduction in serum M-protein and urine M-protein level \< 100 mg/24 hours; PR: \>= 50% reduction of serum M-Protein and reduction in urinary M-protein by \>= 90%/to \< 200 mg/24 hours. In addition to the above, if present at baseline a \>= 50% reduction in the size of soft tissue plasmacytomas is also required.

Time frame: Time from first dose of study treatment up to 18.2 months

Population: Safety analysis set included all participants who were administered any dose of the trial medication.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
M3258 10 mg QD	Part A: Number of Participants With Overall Response (OR) as Assessed by Investigator Using International Myeloma Working Group (IMWG) Criteria	Stringent Complete Response	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Overall Response (OR) as Assessed by Investigator Using International Myeloma Working Group (IMWG) Criteria	Complete Response	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Overall Response (OR) as Assessed by Investigator Using International Myeloma Working Group (IMWG) Criteria	Partial Response	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Overall Response (OR) as Assessed by Investigator Using International Myeloma Working Group (IMWG) Criteria	Very good Partial Response	0 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Overall Response (OR) as Assessed by Investigator Using International Myeloma Working Group (IMWG) Criteria	Partial Response	0 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Overall Response (OR) as Assessed by Investigator Using International Myeloma Working Group (IMWG) Criteria	Stringent Complete Response	0 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Overall Response (OR) as Assessed by Investigator Using International Myeloma Working Group (IMWG) Criteria	Very good Partial Response	0 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Overall Response (OR) as Assessed by Investigator Using International Myeloma Working Group (IMWG) Criteria	Complete Response	0 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Overall Response (OR) as Assessed by Investigator Using International Myeloma Working Group (IMWG) Criteria	Complete Response	0 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Overall Response (OR) as Assessed by Investigator Using International Myeloma Working Group (IMWG) Criteria	Very good Partial Response	0 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Overall Response (OR) as Assessed by Investigator Using International Myeloma Working Group (IMWG) Criteria	Partial Response	0 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Overall Response (OR) as Assessed by Investigator Using International Myeloma Working Group (IMWG) Criteria	Stringent Complete Response	0 Participants

Secondary

Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Body Temperature Increase

The number of participants with treatment-emergent changes from baseline in increased Body Temperature (degree Celsius \[°C\]) were reported by using criteria: Baseline temperature (temp.) less than (\<) 37°C, on treatment change \<1°C, 1 - \<2°C, 2 - \<3°C and greater than or equal to (\>=)3°C; Baseline temp. 37 - \<38°C, on treatment change \<1°C, 1 - \<2°C, 2 - \<3°C and \>=3°C; Baseline temp. 38 - \<39°C, on treatment change \<1°C, 1 - \<2°C, 2 - \<3°C and \>=3°C; Baseline temp. 39-\<40°C, on treatment change \<1°C, 1 - \<2°C, 2 - \<3°C and \>=3°C; Baseline temp. \>=40°C, on treatment change \<1°C, 1 - \<2°C, 2 - \<3°C and \>=3°C.

Time frame: Time from first treatment up to 30 days after end of study intervention (assessed up to 24.3 weeks)

Population: Safety analysis set included all participants who were administered any dose of the study medication.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
M3258 10 mg QD	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Body Temperature Increase	Baseline temp. >=40°C, on treatment change <1°C	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Body Temperature Increase	Baseline temp. 38 - <39°C, on treatment change 1 - <2°C	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Body Temperature Increase	Baseline temp. 37 - <38°C, on treatment change <1°C	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Body Temperature Increase	Baseline temp. >=40°C, on treatment change 1 - <2°C	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Body Temperature Increase	Baseline temp. <37°C, on treatment change <1°C	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Body Temperature Increase	Baseline temp. <37°C, on treatment change >=3°C	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Body Temperature Increase	Baseline temp. >=40°C, on treatment change 2 - <3°C	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Body Temperature Increase	Baseline temp. 39 - <40°C, on treatment change <1°C	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Body Temperature Increase	Baseline temp. >=40°C, on treatment change >=3°C	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Body Temperature Increase	Baseline temp. 38 - <39°C, on treatment change 2 - <3°C	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Body Temperature Increase	Baseline temp. <37°C, on treatment change 2 - <3°C	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Body Temperature Increase	Baseline temp. 37 - <38°C, on treatment change >=3°C	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Body Temperature Increase	Baseline temp.<37°C, on treatment change 1 - <2°C	2 Participants
M3258 10 mg QD	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Body Temperature Increase	Baseline temp. 39 - <40°C, on treatment change 1 - <2°C	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Body Temperature Increase	Baseline temp. 38 - <39°C, on treatment change <1°C	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Body Temperature Increase	Baseline temp. 37 - <38°C, on treatment change 2 - <3°C	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Body Temperature Increase	Baseline temp. 39 - <40°C, on treatment change 2 - <3°C	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Body Temperature Increase	Baseline temp. 39 - <40°C, on treatment change >=3°C	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Body Temperature Increase	Baseline temp. 38 - <39°C, on treatment change >=3°C	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Body Temperature Increase	Baseline temp. 37 - <38°C, on treatment change 1 - <2°C	0 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Body Temperature Increase	Baseline temp. 37 - <38°C, on treatment change >=3°C	0 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Body Temperature Increase	Baseline temp. 38 - <39°C, on treatment change <1°C	0 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Body Temperature Increase	Baseline temp. 38 - <39°C, on treatment change 1 - <2°C	0 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Body Temperature Increase	Baseline temp. 38 - <39°C, on treatment change 2 - <3°C	0 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Body Temperature Increase	Baseline temp. 38 - <39°C, on treatment change >=3°C	0 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Body Temperature Increase	Baseline temp. 39 - <40°C, on treatment change <1°C	0 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Body Temperature Increase	Baseline temp. 39 - <40°C, on treatment change 1 - <2°C	0 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Body Temperature Increase	Baseline temp. 39 - <40°C, on treatment change >=3°C	0 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Body Temperature Increase	Baseline temp. >=40°C, on treatment change <1°C	0 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Body Temperature Increase	Baseline temp. >=40°C, on treatment change 1 - <2°C	0 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Body Temperature Increase	Baseline temp. >=40°C, on treatment change 2 - <3°C	0 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Body Temperature Increase	Baseline temp. >=40°C, on treatment change >=3°C	0 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Body Temperature Increase	Baseline temp. <37°C, on treatment change <1°C	1 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Body Temperature Increase	Baseline temp.<37°C, on treatment change 1 - <2°C	0 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Body Temperature Increase	Baseline temp. <37°C, on treatment change 2 - <3°C	0 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Body Temperature Increase	Baseline temp. <37°C, on treatment change >=3°C	1 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Body Temperature Increase	Baseline temp. 37 - <38°C, on treatment change <1°C	2 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Body Temperature Increase	Baseline temp. 37 - <38°C, on treatment change 1 - <2°C	0 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Body Temperature Increase	Baseline temp. 37 - <38°C, on treatment change 2 - <3°C	0 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Body Temperature Increase	Baseline temp. 39 - <40°C, on treatment change 2 - <3°C	0 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Body Temperature Increase	Baseline temp. 38 - <39°C, on treatment change 1 - <2°C	0 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Body Temperature Increase	Baseline temp. <37°C, on treatment change >=3°C	0 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Body Temperature Increase	Baseline temp. >=40°C, on treatment change <1°C	0 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Body Temperature Increase	Baseline temp. 38 - <39°C, on treatment change <1°C	0 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Body Temperature Increase	Baseline temp. 37 - <38°C, on treatment change <1°C	1 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Body Temperature Increase	Baseline temp. 39 - <40°C, on treatment change >=3°C	0 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Body Temperature Increase	Baseline temp. >=40°C, on treatment change 2 - <3°C	0 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Body Temperature Increase	Baseline temp. 37 - <38°C, on treatment change 1 - <2°C	0 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Body Temperature Increase	Baseline temp. 39 - <40°C, on treatment change 1 - <2°C	0 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Body Temperature Increase	Baseline temp. 39 - <40°C, on treatment change 2 - <3°C	0 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Body Temperature Increase	Baseline temp. 37 - <38°C, on treatment change 2 - <3°C	0 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Body Temperature Increase	Baseline temp. 39 - <40°C, on treatment change <1°C	0 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Body Temperature Increase	Baseline temp. 38 - <39°C, on treatment change >=3°C	0 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Body Temperature Increase	Baseline temp. <37°C, on treatment change <1°C	2 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Body Temperature Increase	Baseline temp. 37 - <38°C, on treatment change >=3°C	0 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Body Temperature Increase	Baseline temp.<37°C, on treatment change 1 - <2°C	1 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Body Temperature Increase	Baseline temp. >=40°C, on treatment change >=3°C	0 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Body Temperature Increase	Baseline temp. 38 - <39°C, on treatment change 2 - <3°C	0 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Body Temperature Increase	Baseline temp. <37°C, on treatment change 2 - <3°C	0 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Body Temperature Increase	Baseline temp. >=40°C, on treatment change 1 - <2°C	0 Participants

Secondary

Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Respiration Rate Increase/Decrease

The number of participants with treatment-emergent changes from baseline in Increase (Ic.)/Decrease (Dc.) maximal Respiration Rate (RR) were reported by using criteria: Ic./Dc. BS RR \<20 breaths per minute (breaths/min), on TR change (ch) =\<5 breaths/min, \>5 - =\<10 breaths/min and \>10 breaths/min. Ic./Dc. BS RR \>=20 breaths/min, on TR ch =\<5 breaths/min, \>5 - =\<10 breaths/min and \>10 breaths/min.

Time frame: Time from first treatment up to 30 days after end of study intervention (assessed up to 24.3 weeks)

Population: Safety analysis set included all participants who were administered any dose of the study medication.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
M3258 10 mg QD	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Respiration Rate Increase/Decrease	Ic. BS RR <20 breaths/min, on TR ch =<5 breaths/min	2 Participants
M3258 10 mg QD	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Respiration Rate Increase/Decrease	Ic.BS RR<20 breaths/min, on TR Ch >5 - = <10 breaths/min	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Respiration Rate Increase/Decrease	Ic. BS RR <20 breaths/min, on TR ch >10 breaths/min	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Respiration Rate Increase/Decrease	Ic. BS RR >=20 breaths/min, on TR ch =<5 breaths/min	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Respiration Rate Increase/Decrease	IC.BS RR >=20 breaths/min, on TR ch >5 - =<10 breaths/min	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Respiration Rate Increase/Decrease	Ic. BS RR >=20 breaths/min, on TR ch >10 breaths/min	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Respiration Rate Increase/Decrease	Dc. BS RR <20 breaths/min, on TR ch =<5 breaths/min	2 Participants
M3258 10 mg QD	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Respiration Rate Increase/Decrease	Dc. BS RR <20 breaths/min, on TR Ch >5 - =<10 breaths/min	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Respiration Rate Increase/Decrease	Dc. BS RR <20 breaths/min, on TR ch >10 breaths/min	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Respiration Rate Increase/Decrease	Dc. BS RR >=20 breaths/min, on TR ch =<5 breaths/min	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Respiration Rate Increase/Decrease	Dc.BS RR >=20 breaths/min, on TR ch >5 - =<10 breaths/min	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Respiration Rate Increase/Decrease	Dc. BS RR >=20 breaths/min, on TR ch >10 breaths/min	0 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Respiration Rate Increase/Decrease	Dc. BS RR >=20 breaths/min, on TR ch >10 breaths/min	0 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Respiration Rate Increase/Decrease	Ic. BS RR <20 breaths/min, on TR ch =<5 breaths/min	1 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Respiration Rate Increase/Decrease	Dc. BS RR <20 breaths/min, on TR ch =<5 breaths/min	2 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Respiration Rate Increase/Decrease	Dc. BS RR <20 breaths/min, on TR ch >10 breaths/min	0 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Respiration Rate Increase/Decrease	Ic.BS RR<20 breaths/min, on TR Ch >5 - = <10 breaths/min	1 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Respiration Rate Increase/Decrease	Ic. BS RR >=20 breaths/min, on TR ch >10 breaths/min	0 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Respiration Rate Increase/Decrease	Dc.BS RR >=20 breaths/min, on TR ch >5 - =<10 breaths/min	0 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Respiration Rate Increase/Decrease	Ic. BS RR <20 breaths/min, on TR ch >10 breaths/min	0 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Respiration Rate Increase/Decrease	Dc. BS RR <20 breaths/min, on TR Ch >5 - =<10 breaths/min	0 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Respiration Rate Increase/Decrease	IC.BS RR >=20 breaths/min, on TR ch >5 - =<10 breaths/min	0 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Respiration Rate Increase/Decrease	Ic. BS RR >=20 breaths/min, on TR ch =<5 breaths/min	2 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Respiration Rate Increase/Decrease	Dc. BS RR >=20 breaths/min, on TR ch =<5 breaths/min	2 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Respiration Rate Increase/Decrease	Ic. BS RR >=20 breaths/min, on TR ch =<5 breaths/min	0 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Respiration Rate Increase/Decrease	IC.BS RR >=20 breaths/min, on TR ch >5 - =<10 breaths/min	0 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Respiration Rate Increase/Decrease	Dc. BS RR >=20 breaths/min, on TR ch =<5 breaths/min	0 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Respiration Rate Increase/Decrease	Ic. BS RR >=20 breaths/min, on TR ch >10 breaths/min	0 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Respiration Rate Increase/Decrease	Dc. BS RR <20 breaths/min, on TR ch =<5 breaths/min	4 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Respiration Rate Increase/Decrease	Dc. BS RR <20 breaths/min, on TR Ch >5 - =<10 breaths/min	0 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Respiration Rate Increase/Decrease	Dc.BS RR >=20 breaths/min, on TR ch >5 - =<10 breaths/min	0 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Respiration Rate Increase/Decrease	Ic. BS RR <20 breaths/min, on TR ch =<5 breaths/min	2 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Respiration Rate Increase/Decrease	Ic.BS RR<20 breaths/min, on TR Ch >5 - = <10 breaths/min	2 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Respiration Rate Increase/Decrease	Dc. BS RR <20 breaths/min, on TR ch >10 breaths/min	0 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Respiration Rate Increase/Decrease	Ic. BS RR <20 breaths/min, on TR ch >10 breaths/min	0 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Respiration Rate Increase/Decrease	Dc. BS RR >=20 breaths/min, on TR ch >10 breaths/min	0 Participants

Secondary

Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease

The number of participants with treatment-emergent changes from baseline (BS) in Increase (Ic.)/Decrease (Dc.) Systolic Blood Pressure (SBP) and diastolic blood pressure (DBP) (millimeter of mercury \[mmHg\]) were reported by using criteria: Ic./Dc. BS SBP/DBP \<140/\<90 mmHg, on maximal treatment (TR) change =\<20 mmHg, \>20 - =\<40 mmHg and \>40 mmHg; Ic./Dc. BS SBP/DBP \>=140/\>=90 mmHg, on maximal TR change =\<20 mmHg, \>20 - =\<40 mmHg and \>40 mmHg.

Time frame: Time from first treatment up to 30 days after end of study intervention (assessed up to 24.3 weeks)

Population: Safety analysis set included all participants who were administered any dose of the study medication.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
M3258 10 mg QD	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease	Dc. BS DBP >=90 mmHg, on TR change =<20 mmHg	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease	Dc. BS DBP <90 mmHg, on TR change =<20 mmHg	2 Participants
M3258 10 mg QD	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease	Dc. BS SBP <140 mmHg, on TR change >20 - =<40 mmHg	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease	Dc. BS DBP <90 mmHg, on TR change >20 - =<40 mmHg	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease	Dc. BS DBP <90 mmHg, on TR change >40 mmHg	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease	Ic. BS SBP <140 mmHg, on TR change >20 - =<40 mmHg	1 Participants
M3258 10 mg QD	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease	Ic. BS DBP >=90 mmHg, on TR change >40 mmHg	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease	Ic. BS SBP <140 mmHg, on TR change =<20 mmHg	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease	Dc. BS DBP >=90 mmHg,on TR change >20 - =<40 mmHg	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease	Dc. BS SBP <140 mmHg, on TR change >40 mmHg	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease	Dc. BS DBP >=90 mmHg, on TR change >40 mmHg	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease	Ic. BS SBP >=140 mmHg, on TR change >20 - =<40 mmHg	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease	Ic. BS SBP >=140 mmHg, on TR change >40 mmHg	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease	Ic. BS SBP >=140 mmHg, on TR change =<20 mmHg	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease	Dc. BS SBP >=140 mmHg, on TR change =<20 mmHg	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease	Dc. BS SBP >=140 mmHg, on TR change >20 - =<40 mmHg	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease	Dc. BS SBP >=140 mmHg, on TR change >40 mmHg	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease	Ic. BS DBP <90 mmHg, on TR change =<20 mmHg	1 Participants
M3258 10 mg QD	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease	Ic. BS DBP <90 mmHg, on TR change >20 - =<40 mmHg	1 Participants
M3258 10 mg QD	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease	Ic. BS DBP <90 mmHg, on TR change >40 mmHg	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease	Ic. BS SBP <140 mmHg, on TR change >40 mmHg	1 Participants
M3258 10 mg QD	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease	Ic. BS DBP >=90 mmHg, on TR change =<20 mmHg	0 Participants
M3258 10 mg QD	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease	Dc. BS SBP <140 mmHg, on TR change =<20 mmHg	2 Participants
M3258 10 mg QD	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease	Ic. BS DBP >=90 mmHg, on TR change >20 - =<40 mmHg	0 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease	Dc. BS SBP <140 mmHg, on TR change =<20 mmHg	3 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease	Ic. BS DBP >=90 mmHg, on TR change >40 mmHg	0 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease	Ic. BS SBP <140 mmHg, on TR change >40 mmHg	1 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease	Ic. BS DBP <90 mmHg, on TR change >20 - =<40 mmHg	1 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease	Dc. BS DBP <90 mmHg, on TR change =<20 mmHg	3 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease	Dc. BS SBP >=140 mmHg, on TR change =<20 mmHg	1 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease	Ic. BS SBP >=140 mmHg, on TR change =<20 mmHg	1 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease	Dc. BS DBP <90 mmHg, on TR change >20 - =<40 mmHg	0 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease	Dc. BS SBP <140 mmHg, on TR change >20 - =<40 mmHg	0 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease	Ic. BS SBP >=140 mmHg, on TR change >40 mmHg	0 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease	Dc. BS DBP <90 mmHg, on TR change >40 mmHg	0 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease	Dc. BS SBP >=140 mmHg, on TR change >20 - =<40 mmHg	0 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease	Ic. BS SBP <140 mmHg, on TR change >20 - =<40 mmHg	1 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease	Dc. BS DBP >=90 mmHg, on TR change =<20 mmHg	1 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease	Ic. BS DBP >=90 mmHg, on TR change =<20 mmHg	1 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease	Dc. BS SBP >=140 mmHg, on TR change >40 mmHg	0 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease	Dc. BS DBP >=90 mmHg,on TR change >20 - =<40 mmHg	0 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease	Ic. BS SBP >=140 mmHg, on TR change >20 - =<40 mmHg	0 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease	Ic. BS DBP >=90 mmHg, on TR change >20 - =<40 mmHg	0 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease	Dc. BS DBP >=90 mmHg, on TR change >40 mmHg	0 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease	Dc. BS SBP <140 mmHg, on TR change >40 mmHg	0 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease	Ic. BS DBP <90 mmHg, on TR change >40 mmHg	1 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease	Ic. BS DBP <90 mmHg, on TR change =<20 mmHg	1 Participants
M3258 10 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease	Ic. BS SBP <140 mmHg, on TR change =<20 mmHg	1 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease	Dc. BS DBP >=90 mmHg, on TR change =<20 mmHg	1 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease	Ic. BS SBP <140 mmHg, on TR change =<20 mmHg	1 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease	Ic. BS SBP <140 mmHg, on TR change >20 - =<40 mmHg	1 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease	Ic. BS SBP <140 mmHg, on TR change >40 mmHg	1 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease	Ic. BS SBP >=140 mmHg, on TR change =<20 mmHg	1 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease	Ic. BS SBP >=140 mmHg, on TR change >20 - =<40 mmHg	0 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease	Ic. BS SBP >=140 mmHg, on TR change >40 mmHg	0 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease	Dc. BS SBP <140 mmHg, on TR change =<20 mmHg	3 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease	Dc. BS SBP <140 mmHg, on TR change >20 - =<40 mmHg	0 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease	Dc. BS SBP <140 mmHg, on TR change >40 mmHg	0 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease	Dc. BS SBP >=140 mmHg, on TR change =<20 mmHg	1 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease	Dc. BS SBP >=140 mmHg, on TR change >20 - =<40 mmHg	0 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease	Dc. BS SBP >=140 mmHg, on TR change >40 mmHg	0 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease	Ic. BS DBP <90 mmHg, on TR change =<20 mmHg	3 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease	Ic. BS DBP <90 mmHg, on TR change >20 - =<40 mmHg	0 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease	Ic. BS DBP <90 mmHg, on TR change >40 mmHg	0 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease	Ic. BS DBP >=90 mmHg, on TR change =<20 mmHg	1 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease	Ic. BS DBP >=90 mmHg, on TR change >20 - =<40 mmHg	0 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease	Ic. BS DBP >=90 mmHg, on TR change >40 mmHg	0 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease	Dc. BS DBP <90 mmHg, on TR change =<20 mmHg	3 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease	Dc. BS DBP <90 mmHg, on TR change >20 - =<40 mmHg	0 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease	Dc. BS DBP <90 mmHg, on TR change >40 mmHg	0 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease	Dc. BS DBP >=90 mmHg,on TR change >20 - =<40 mmHg	0 Participants
M3258 20 mg Twice Per Week	Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease	Dc. BS DBP >=90 mmHg, on TR change >40 mmHg	0 Participants

Secondary

Part A: Single Dose: Area Under Plasma Concentration-Time Curve (AUC) From Time Zero to Last Sampling Time (AUC0-t) of M3258

Area under the plasma concentration versus time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLOQ). AUC0-t was calculated according to the mixed log-linear trapezoidal rule. Single dose PK data on Day 1 were summarized by dose level, such that all 10 mg arms were combined as descriptive statistics of PK were only calculated for N greater than (\>) 2 in which a measurement of greater than (\>) lower limit of quantification (LLOQ) represents a valid measurement.

Time frame: Cycle 1 Day 1: Pre-dose 1, 2, 3, 4, 5, 6, 8 and 24 hours post-dose (each Cycle is of 28 days)

Population: PK analysis set included all participants, who received at least one dose of study intervention, have no clinically important protocol deviations or important events affecting PK, and provide at least one measurable post-dose concentration. Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure.

Arm	Measure	Value (GEOMETRIC_MEAN)
M3258 10 mg QD	Part A: Single Dose: Area Under Plasma Concentration-Time Curve (AUC) From Time Zero to Last Sampling Time (AUC0-t) of M3258	2000 hournanogram per milliliter (hng/mL)
M3258 10 mg Twice Per Week	Part A: Single Dose: Area Under Plasma Concentration-Time Curve (AUC) From Time Zero to Last Sampling Time (AUC0-t) of M3258	3300 hournanogram per milliliter (hng/mL)

Secondary

Part A: Single Dose: Area Under Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) of M3258

Area under the plasma concentration versus time curve from time zero to 24 hours post dosing for M3258. Single dose PK data on Day 1 were summarized by dose level, such that all 10 mg arms were combined as descriptive statistics of PK were only calculated for N greater than (\>) 2 in which a measurement of greater than (\>) lower limit of quantification (LLOQ) represents a valid measurement.

Time frame: Cycle 1 Day 1: Pre-dose 1, 2, 3, 4, 5, 6, 8 and 24 hours post-dose (each Cycle is of 28 days)

Secondary

Part A: Single Dose: Maximum Observed Plasma Concentration (Cmax) of M3258

Cmax was obtained directly from the concentration versus time curve. Single dose PK data on Day 1 were summarized by dose level, such that all 10 mg arms were combined as descriptive statistics of PK were only calculated for N greater than (\>) 2 in which a measurement of greater than (\>) lower limit of quantification (LLOQ) represents a valid measurement.

Time frame: Cycle 1 Day 1: Pre-dose 1, 2, 3, 4, 5, 6, 8 and 24 hours post-dose (each Cycle is of 28 days)

Arm	Measure	Value (GEOMETRIC_MEAN)
M3258 10 mg QD	Part A: Single Dose: Maximum Observed Plasma Concentration (Cmax) of M3258	153 nanogram per milliliter (ng/mL)
M3258 10 mg Twice Per Week	Part A: Single Dose: Maximum Observed Plasma Concentration (Cmax) of M3258	215 nanogram per milliliter (ng/mL)

Secondary

Part A: Single Dose: Ratio to Baseline in Large Multifunctional Protease 7 (LMP7) Activity at Cycle 1 Day 1

Ratio to baseline was calculated dividing post-baseline measurements by the baseline measurement. Single dose Pd data on Day 1 were summarized by dose level, such that all 10 mg arms were combined as descriptive statistics of PK were only calculated for N greater than (\>) 2 in which a measurement of greater than (\>) lower limit of quantification (LLOQ) represents a valid measurement.

Time frame: Baseline (Pre-dose), 2, 6 and 24 hours post-dose on Cycle 1 Day 1 (each Cycle is of 28 days)

Population: The Pharmacodynamic (Pd) population included all participants who received at least one dose of study intervention, had no clinically important protocol deviations or important events affecting Pd, and provide at least one measurable Pd endpoint post-dose. Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure and Number Analyzed signifies those participants who were evaluable for specified timepoints.

Arm	Measure	Group	Value (MEAN)
M3258 10 mg QD	Part A: Single Dose: Ratio to Baseline in Large Multifunctional Protease 7 (LMP7) Activity at Cycle 1 Day 1	Cycle 1 Day 1: 2 hours post-dose	0.308 ratio
M3258 10 mg QD	Part A: Single Dose: Ratio to Baseline in Large Multifunctional Protease 7 (LMP7) Activity at Cycle 1 Day 1	Cycle 1 Day 1: 6 hours post-dose	0.337 ratio
M3258 10 mg QD	Part A: Single Dose: Ratio to Baseline in Large Multifunctional Protease 7 (LMP7) Activity at Cycle 1 Day 1	Cycle 1 Day 1: 24 hours post-dose	0.387 ratio
M3258 10 mg Twice Per Week	Part A: Single Dose: Ratio to Baseline in Large Multifunctional Protease 7 (LMP7) Activity at Cycle 1 Day 1	Cycle 1 Day 1: 6 hours post-dose	0.178 ratio
M3258 10 mg Twice Per Week	Part A: Single Dose: Ratio to Baseline in Large Multifunctional Protease 7 (LMP7) Activity at Cycle 1 Day 1	Cycle 1 Day 1: 2 hours post-dose	0.370 ratio
M3258 10 mg Twice Per Week	Part A: Single Dose: Ratio to Baseline in Large Multifunctional Protease 7 (LMP7) Activity at Cycle 1 Day 1	Cycle 1 Day 1: 24 hours post-dose	0.262 ratio

Secondary

Time to Response as Assessed by Investigator Using International Myeloma Working Group (IMWG) Criteria

Time to response was defined as the time from the first dose of M3258 to the documentation of first response (Complete Response \[CR\] or Partial Response \[PR\]). CR: Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \< 5% plasma cells in bone marrow. PR: \>= 50% reduction of serum M-Protein and reduction in urinary M-protein by \>= 90% or to \< 200 mg/24 hours. In addition to the above, if present at baseline a \>= 50% reduction in the size of soft tissue plasmacytomas is also required.

Time frame: Time from the first dose of study treatment up to documentation of first response, assessed up to 18.2 months

Population: Data could not be calculated as none of the participants showed response.

Source: ClinicalTrials.gov · Data processed: Feb 15, 2026

First in Human Dose Escalation of M3258 as a Single Agent and Expansion Study of M3258 in Combination With Dexamethasone

Conditions

Keywords

Brief summary

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Recruitment details

Pre-assignment details

Participants by arm

Baseline characteristics

Adverse events

Outcome results

Number of Participants With Shift From Baseline Grade Less Than (<) 3 in Clinical Laboratory Parameters to Grade Greater Than or Equal to (>=) 3 on Treatment

Part A: Change From Baseline in 12-lead Electrocardiogram (ECG) Findings: QT Interval - Fridericia's Correction Formula

Part A: Number of Participants With Dose-Limiting Toxicities (DLTs) as Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0

Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score

Part A: Number of Participants With Treatment-Emergent Adverse Event (TEAEs) and Treatment-Related Adverse Event (TRAEs)

Part A: Number of Participants With Treatment-Emergent Adverse Event (TEAEs) Outside of Dose-Limiting Toxicity (DLT) Period That Safety Monitoring Committee Deems Relevant for Determination of the Maximum Tolerated Dose

Duration of Response (DoR) as Assessed by Investigator Using International Myeloma Working Group (IMWG) Criteria

Part A: Change From Baseline in Free Light Chain Ratio

Part A: Change From Baseline in Serum Monoclonal (M)-Protein Level Measured Using Electrophoresis

Part A: Change From Baseline in Urine M-protein Level Using Electrophoresis

Part A: Multiple Dose: Area Under Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) of M3258

Part A: Multiple Dose: Ratio to Baseline in Large Multifunctional Protease 7 (LMP7) Activity at Cycle 1 Day 8 (or Day 15)

Part A: Mutilple Dose: Maximum Observed Plasma Concentration (Cmax) of M3258

Part A: Number of Participants With Overall Response (OR) as Assessed by Investigator Using International Myeloma Working Group (IMWG) Criteria

Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Body Temperature Increase

Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Respiration Rate Increase/Decrease

Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease

Part A: Single Dose: Area Under Plasma Concentration-Time Curve (AUC) From Time Zero to Last Sampling Time (AUC0-t) of M3258

Part A: Single Dose: Area Under Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) of M3258

Part A: Single Dose: Maximum Observed Plasma Concentration (Cmax) of M3258

Part A: Single Dose: Ratio to Baseline in Large Multifunctional Protease 7 (LMP7) Activity at Cycle 1 Day 1

Time to Response as Assessed by Investigator Using International Myeloma Working Group (IMWG) Criteria