M8891 First in Human in Solid Tumors | NCT03138538

M8891 First in Human in Solid Tumors | NCT03138538 | Trialant

Sponsor/Collaborators Module

Name	Class
Merck KGaA, Darmstadt, Germany	INDUSTRY

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
M8891 7 mg	Experimental	Participant received M8891 at dose of 7 milligrams (mg) orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.	Drug: Part 1: M8891
M8891 12 mg	Experimental	Participant received M8891 at dose of 12 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.	Drug: Part 1: M8891
M8891 20 mg	Experimental	Participant received M8891 at dose of 20 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.	Drug: Part 1: M8891
M8891 35 mg	Experimental	Participant received M8891 at dose of 35 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Part 1: M8891	Drug	Participants receives M8891 orally once daily at escalated dose levels under fasting condition for consecutive 21-day cycles of continuous treatment until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Participants Who Experienced Dose Limiting Toxicities (DLTs) Assessed Using National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) Version 4.03	A DLT was defined as the occurrence of any of following events that were judged by the study investigator, to be related to the study medication: Grade 4 liver enzyme elevation; Grade 4 neutropenia lasting >5 days or Grade >= 3 neutropenia with fever; Grade 4 thrombocytopenia lasting >5 days or Grade >=3 thrombocytopenia with clinically significant bleeding; Any treatment interruption >7 days or >30% of total dose in Cycle 1 due to AEs not related to the underlying disease or concomitant medication; Grade >=3 non-hematologic toxicity excluding Grade 3 nausea or vomiting lasting <48 hours, and resolves to <= Grade 1 either spontaneously or with medication, Grade 3 fatigue <= 3 days, Grade 3 hypertension in the absence of maximal medical therapy, Grade 3 rash <= 3 days, Grade 3 electrolyte abnormality that lasts <72 hours, is not clinically complicated, and resolves spontaneously or responds to conventional medication and Grade >=3 single lab value increase without clinical correlate.	At the end of Cycle 1 (each Cycle is of 21 days)

Secondary Outcomes

Measure	Description	Time Frame
Number of Participants With Treatment-Emergent Adverse Events (TEAE) and TEAEs Leading to Death	An Adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease associated with the use of study drug, whether or not considered related to the study drug or worsening of pre-existing medical condition, whether or not related to study drug. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. The term TEAE is defined as AEs starting or worsening after the first intake of the study drug. TEAEs include both Serious TEAEs and non-serious TEAEs.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Participants must be refractory to or intolerant of existing cancer therapy(ies) known to provide clinical benefit.
Histologically confirmed advanced solid tumors with no clear curative treatment options available after at least 1 prior systemic anticancer therapy.
Tumor accessible for biopsies and agreement to conduct pre-dose and post-dose fresh tumor biopsies.
Male or female subjects at least 18 years of age
Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 1 at Screening
Histologic or cytologic evidence/proven of metastatic renal cell carcinoma (mRCC) with clear cell component
Part 2A: Participants should have progressed to 1 or more previous lines of systemic anticancer therapy, excluding treatment with cabozantinib
Part 2B: Participants should have progressed to 1 or 2 previous lines of systemic anticancer therapy, excluding treatment with cabozantinib. Participants should have failed to only 1 previous TKI for metastatic disease. Adjuvant therapy with sunitinib will be considered as 1 line of therapy for metastatic disease in the case that disease progression occurs during or within 3 months of the completion of the treatment.
Other protocol defined inclusion criteria could apply

Exclusion Criteria:

ECOG PS >= 2
Extensive prior radiotherapy on more than 30% of bone marrow reserves, or prior bone marrow/stem cell transplantation within 5 years of study start.
Severe bone marrow, renal or liver impairment.
Tumor in contact with, invading or encasing major blood vessels or radiographic evidence of significant cavitary pulmonary lesions
Uncontrolled hypertension defined as sustained Blood Pressure (BP) > 150 millimeters of mercury (mm Hg) systolic or > 100 mm Hg diastolic despite optimal antihypertensive treatment
Participant is pregnant or breastfeeding
Part 2A and 2B: Previous use of cabozantinib or a MetAP2 inhibitor, tumor in contact with invading or encasing major blood vessels or radiographic evidence of significant cavitary pulmonary lesions
Other protocol defined exclusion criteria could apply

Contacts/Locations Module

Name	Affiliation	Role
Medical Responsible	EMD Serono Research & Development Institute, Inc., a business of Merck KGaA, Darmstadt, Germany	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Smilow Cancer Hospital - Yale		New Haven	Connecticut	06510	United States
Indiana University Health Hospital

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
37798538	Derived	Lignet F, Friese-Hamim M, Jaehrling F, El Bawab S, Rohdich F. Preclinical Pharmacokinetics and Translational Pharmacokinetic/Pharmacodynamic Modeling of M8891, a Potent and Reversible Inhibitor of Methionine Aminopeptidase 2. Pharm Res. 2023 Dec;40(12):3011-3023. doi: 10.1007/s11095-023-03611-z. Epub 2023 Oct 5.
37637935	Derived

Label	URL
Trial Awareness and Transparency website	View source

Arm/Group Information

ID	Title	Description
FG000	M8891 7 mg	Participant received M8891 at dose of 7 milligrams (mg) orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
FG001	M8891 12 mg	Participant received M8891 at dose of 12 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
FG002	M8891 20 mg	Participant received M8891 at dose of 20 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
FG003	M8891 35 mg	Participant received M8891 at dose of 35 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
FG004	M8891 60 mg	Participant received M8891 at dose of 60 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
FG005	M8891 80 mg	Participant received M8891 at dose of 80 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.

Periods

Title

Milestones

Reasons Not Completed

Overall Study

Type	Comment	Milestone Data
STARTED		FG0003 subjects FG0013 subjects FG0023 subjects FG0038 subjects FG0047 subjects FG0053 subjects
COMPLETED		FG0003 subjects FG0013 subjects FG0023 subjects FG0038 subjects FG004
NOT COMPLETED		FG0000 subjects FG0010 subjects FG0020 subjects FG0030 subjects FG004

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	M8891 7 mg	Participant received M8891 at dose of 7 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
BG001

Units	Counts
Participants	BG000

Baseline Measures

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Categorical			Count of Participants

Outcome Measures Module

Outcome Measures

Type	Title	Description	Population Description	Reporting Status	Anticipated Posting Date	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Time Frame	Units Analyzed	Denominator Units Selected	Arm/Group Information	Denominators	Classes	Analyses
Primary	Number of Participants Who Experienced Dose Limiting Toxicities (DLTs) Assessed Using National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) Version 4.03	A DLT was defined as the occurrence of any of following events that were judged by the study investigator, to be related to the study medication: Grade 4 liver enzyme elevation; Grade 4 neutropenia lasting >5 days or Grade >= 3 neutropenia with fever; Grade 4 thrombocytopenia lasting >5 days or Grade >=3 thrombocytopenia with clinically significant bleeding; Any treatment interruption >7 days or >30% of total dose in Cycle 1 due to AEs not related to the underlying disease or concomitant medication; Grade >=3 non-hematologic toxicity excluding Grade 3 nausea or vomiting lasting <48 hours, and resolves to <= Grade 1 either spontaneously or with medication, Grade 3 fatigue <= 3 days, Grade 3 hypertension in the absence of maximal medical therapy, Grade 3 rash <= 3 days, Grade 3 electrolyte abnormality that lasts <72 hours, is not clinically complicated, and resolves spontaneously or responds to conventional medication and Grade >=3 single lab value increase without clinical correlate.	Dose escalation set included all participants treated in dose-escalation cohorts who did not miss > 4 cumulative days planned doses of M8891 in the first cycle of the dose-escalation part for other than safety reasons.	Posted		Count of Participants		Participants		At the end of Cycle 1 (each Cycle is of 21 days)

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	M8891 7 mg	Participant received M8891 at dose of 7 milligrams (mg) orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Disease progression	General disorders	MedDRA version 23.0.	Non-systematic Assessment

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Abdominal distension	Gastrointestinal disorders	MedDRA version 23.0.	Non-systematic Assessment

More Info Module

Certain Agreements

Title	Organization	Phone	Extension	Email
Communication Center	Merck KGaA, Darmstadt, Germany	+49-6151-72-5200		service@emdgroup.com

Uploaded Document Information

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Mar 11, 2020	Dec 21, 2021	Prot_000.pdf
SAP	No	Yes	No	Statistical Analysis Plan	Apr 20, 2018	Dec 15, 2021	SAP_001.pdf

Condition Browse Module

ID	Term
D002292	Carcinoma, Renal Cell

ID	Term
D000230	Adenocarcinoma
D002277	Carcinoma
D009375	Neoplasms, Glandular and Epithelial
D009370	Neoplasms by Histologic Type

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 BG0020 BG0030 BG0040 BG0050 BG0060
Asian	BG0001 BG0010 BG0020 BG0032 BG004
Native Hawaiian or Other Pacific Islander	BG0000 BG0010 BG0020 BG0030 BG004
Black or African American	BG0000 BG0010 BG0020 BG0032 BG004
White	BG0002 BG0013 BG0023 BG0034 BG004
More than one race	BG0000 BG0010 BG0020 BG0030 BG004
Unknown or Not Reported	BG0000 BG0010 BG0020 BG0030 BG004

ID	Title	Description
OG000	M8891 7 mg	Participant received M8891 at dose of 7 milligrams (mg) orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG001	M8891 12 mg	Participant received M8891 at dose of 12 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG002	M8891 20 mg	Participant received M8891 at dose of 20 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG003	M8891 35 mg	Participant received M8891 at dose of 35 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG004	M8891 60 mg	Participant received M8891 at dose of 60 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG005	M8891 80 mg	Participant received M8891 at dose of 80 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.

Secondary

Number of Participants With Treatment-Emergent Adverse Events (TEAE) and TEAEs Leading to Death

An Adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease associated with the use of study drug, whether or not considered related to the study drug or worsening of pre-existing medical condition, whether or not related to study drug. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. The term TEAE is defined as AEs starting or worsening after the first intake of the study drug. TEAEs include both Serious TEAEs and non-serious TEAEs.

Safety analysis set included all participants who received at least 1 dose of study drug.

Posted

Count of Participants

Participants

Up to 1136 Days

ID	Title	Description
OG000	M8891 7 mg	Participant received M8891 at dose of 7 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG001	M8891 12 mg	Participant received M8891 at dose of 12 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG002	M8891 20 mg	Participant received M8891 at dose of 20 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG003	M8891 35 mg	Participant received M8891 at dose of 35 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG004	M8891 60 mg	Participant received M8891 at dose of 60 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG005	M8891 80 mg	Participant received M8891 at dose of 12 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.

Units	Counts
Participants	OG0003 OG0013 OG0023 OG003

Title

Denominators

Categories

TEAEs

Title	Measurements
	OG0003 OG0012 OG0023 OG003

Secondary

Number of Participants With Treatment-Emergent Adverse Events (TEAE) by Severity

Severity of adverse events (AE) were assessed by the investigator according to National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) version 4.03 as Grade 1 to Grade 5. Grade 1= Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4= Life-threatening and Grade 5= Death. The number of participants that experienced at least one solicited local TEAE were summarized by grade. The term TEAE is defined as AEs starting or worsening after the first intake of the study drug. TEAEs include both Serious TEAEs and non-serious TEAEs. Number of participants with Grade >=3, >=4 and 5 were reported.

Safety analysis set included all participants who received at least 1 dose of study drug.

Posted

Count of Participants

Participants

Up to 1136 Days

ID	Title	Description
OG000	M8891 7 mg	Participant received M8891 at dose of 7 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG001	M8891 12 mg	Participant received M8891 at dose of 12 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG002	M8891 20 mg	Participant received M8891 at dose of 20 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG003	M8891 35 mg	Participant received M8891 at dose of 35 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG004	M8891 60 mg	Participant received M8891 at dose of 60 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG005	M8891 80 mg	Participant received M8891 at dose of 80 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.

Units	Counts
Participants	OG0003 OG0013 OG0023 OG003

Title

Denominators

Categories

Grade >=3

Title	Measurements
	OG0000 OG0011 OG0023 OG003

Secondary

Maximum Observed Plasma Concentration (Cmax) of M8891

Maximum observed plasma concentration (Cmax) was taken directly from the observed concentration-time curve.

Pharmacokinetic (PK) analysis set included all participants from the safety analysis set without major protocol deviations/violations or events that would affect PK. Here "Number Analyzed"=number of participants evaluable at specified time points.

Posted

Geometric Mean

Geometric Coefficient of Variation

Nanogram per milliliter (ng/mL)

Cycle 1 Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose on Day 1 and 15 (Each cycle is of 21 days)

ID	Title	Description
OG000	M8891 7 mg	Participant received M8891 at dose of 7 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG001	M8891 12 mg	Participant received M8891 at dose of 12 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG002	M8891 20 mg	Participant received M8891 at dose of 20 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG003	M8891 35 mg	Participant received M8891 at dose of 35 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG004	M8891 60 mg	Participant received M8891 at dose of 60 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG005	M8891 80 mg	Participant received M8891 at dose of 80 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.

Units	Counts
Participants	OG0003 OG0013 OG0023 OG003

Title	Denominators	Categories
Day 1	ParticipantsOG0003 ParticipantsOG0013 ParticipantsOG0023 ParticipantsOG003

Secondary

Time to Reach Maximum Observed Plasma Concentration (Tmax) of M8891

The time to reach the maximum observed plasma concentration (tmax) was obtained directly from the concentration versus time curve.

PK analysis set included all participants from the safety analysis set without major protocol deviations/violations or events that would affect PK. Here "Number Analyzed"=number of participants evaluable at specified time points.

Posted

Median

Full Range

Hour

Cycle 1 Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose on Day 1 and 15 (Each cycle is of 21 days)

ID	Title	Description
OG000	M8891 7 mg	Participant received M8891 at dose of 7 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG001	M8891 12 mg	Participant received M8891 at dose of 12 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG002	M8891 20 mg	Participant received M8891 at dose of 20 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG003	M8891 35 mg	Participant received M8891 at dose of 35 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG004	M8891 60 mg	Participant received M8891 at dose of 60 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG005	M8891 80 mg	Participant received M8891 at dose of 80 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.

Units	Counts
Participants	OG0003 OG0013 OG0023 OG003

Title	Denominators	Categories
Day 1	ParticipantsOG0003 ParticipantsOG0013 ParticipantsOG0023 ParticipantsOG003

Secondary

Area Under the Plasma Concentration Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of M8891

The AUC from time zero (= dosing time) to the last sampling time (tlast) at which the concentration is at or above the lower limit of quantification (LLOQ), calculated using the mixed log-linear trapezoidal rule (linear up, log down).

Posted

Geometric Mean

Geometric Coefficient of Variation

Nanogram*hour per milliliter (ng*h/mL)

Cycle 1 Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose on Day 1 and 15 (Each cycle is of 21 days)

ID	Title	Description
OG000	M8891 7 mg	Participant received M8891 at dose of 7 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG001	M8891 12 mg	Participant received M8891 at dose of 12 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG002	M8891 20 mg	Participant received M8891 at dose of 20 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG003	M8891 35 mg	Participant received M8891 at dose of 35 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG004	M8891 60 mg	Participant received M8891 at dose of 60 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG005	M8891 80 mg	Participant received M8891 at dose of 80 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.

Units	Counts
Participants	OG0003 OG0013 OG0023 OG003

Title	Denominators	Categories
Day 1	ParticipantsOG0003 ParticipantsOG0013 ParticipantsOG0023 ParticipantsOG003

Secondary

Area Under the Concentration-time Curve From Zero Extrapolated to Infinity (AUC0-inf) of M8891

The AUC from time zero (dosing time) extrapolated to infinity, based on the predicted value for the concentration at tlast, as estimated using the linear regression from the determination of the terminal first order (elimination) rate constant (lambda z). AUC0-inf = AUC0-t plus Clast pred/lambda z. Lambda Z was terminal elimination rate constant determined from the terminal slope of the log-transformed plasma concentration curve using linear regression on terminal data points of the curve. Clastpred was the last predicted quantifiable concentration.

PK analysis set included all participants from the safety analysis set without major protocol deviations/violations or events that would affect PK. As R2 was <0.80, %AUCextra was >20% and elimination phase was not characterized, AUC0-inf derived from lambda z was regarded as implausible and not calculated.

Posted

Cycle 1 Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose on Day 1 and 15 (Each cycle is of 21 days)

ID	Title	Description
OG000	M8891 7 mg	Participant received M8891 at dose of 7 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG001	M8891 12 mg	Participant received M8891 at dose of 12 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG002	M8891 20 mg	Participant received M8891 at dose of 20 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG003	M8891 35 mg	Participant received M8891 at dose of 35 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG004	M8891 60 mg	Participant received M8891 at dose of 60 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG005	M8891 80 mg	Participant received M8891 at dose of 80 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.

Units	Counts
Participants	OG0000 OG0010 OG0020 OG003

Secondary

Area Under the Plasma Concentration Versus Time Curve Within One Dosing Interval (AUC0-tau) of M8891

AUC (0-tau) is the area under the plasma concentration time curve within 1 dosing interval. Calculated using the mixed log linear trapezoidal rule (linear up, log down).

Posted

Geometric Mean

Geometric Coefficient of Variation

ng*h/mL

Cycle 1 Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose on Day 1 and 15 (Each cycle is of 21 days)

ID	Title	Description
OG000	M8891 7 mg	Participant received M8891 at dose of 7 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG001	M8891 12 mg	Participant received M8891 at dose of 12 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG002	M8891 20 mg	Participant received M8891 at dose of 20 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG003	M8891 35 mg	Participant received M8891 at dose of 35 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG004	M8891 60 mg	Participant received M8891 at dose of 60 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG005	M8891 80 mg	Participant received M8891 at dose of 80 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.

Units	Counts
Participants	OG0003 OG0013 OG0023 OG003

Title	Denominators	Categories
Day 1	ParticipantsOG0003 ParticipantsOG0013 ParticipantsOG0023 ParticipantsOG003

Secondary

Apparent Terminal Half Life (t1/2) of M8891

Terminal half-life of M8891 in Plasma was calculated as log2/ lambda z. Lambda z was determined from the terminal slope of the log-transformed concentration curve using linear regression on terminal data points of the curve.

PK analysis set included all participants from the safety analysis set without major protocol deviations/violations or events that would affect PK. As coefficient of correlation (R2) was <0.80, %AUCextra was >20% and elimination phase was not characterized, t1/2 derived from lambda z was regarded as implausible and not calculated.

Posted

Cycle 1 Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose on Day 1 and 15 (Each cycle is of 21 days)

ID	Title	Description
OG000	M8891 7 mg	Participant received M8891 at dose of 7 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG001	M8891 12 mg	Participant received M8891 at dose of 12 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG002	M8891 20 mg	Participant received M8891 at dose of 20 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG003	M8891 35 mg	Participant received M8891 at dose of 35 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG004	M8891 60 mg	Participant received M8891 at dose of 60 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG005	M8891 80 mg	Participant received M8891 at dose of 80 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.

Units	Counts
Participants	OG0000 OG0010 OG0020 OG003

Secondary

Terminal Elimination Rate Constant (Lambda z) of M8891

Lambda z was determined from the terminal slope of the log-transformed concentration curve using linear regression on terminal data points of the curve.

PK analysis set included all participants from the safety analysis set without major protocol deviations/violations or events that would affect PK. As R2 was <0.80, %AUCextra was >20% and elimination phase was not characterized, lambda z was regarded as implausible and not calculated.

Posted

Cycle 1 Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose on Day 1 and 15 (Each cycle is of 21 days)

ID	Title	Description
OG000	M8891 7 mg	Participant received M8891 at dose of 7 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG001	M8891 12 mg	Participant received M8891 at dose of 12 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG002	M8891 20 mg	Participant received M8891 at dose of 20 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG003	M8891 35 mg	Participant received M8891 at dose of 35 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG004	M8891 60 mg	Participant received M8891 at dose of 60 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG005	M8891 80 mg	Participant received M8891 at dose of 80 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.

Units	Counts
Participants	OG0000 OG0010 OG0020 OG003

Secondary

Apparent Total Body Clearance (CL/f) of M8891

Apparent total body clearance of drug from plasma following extravascular administration, calculated as dose/AUC0-infinity for M8891. Area under the plasma concentration-time curve from time zero (dosing time) extrapolated to infinity of unchanged drug calculated as AUC0-t + AUCextra. AUCextra represents the extrapolated part of AUC0-infinity calculated by Clastpred/lambda z, where Clastpred is the predicted plasma concentration at the last sampling time point, calculated from the log linear regression line for lambda z determination at which the measured plasma concentration is at or above lower limit of quantification.

PK analysis set included all participants from the safety analysis set without major protocol deviations/violations or events that would affect PK. As R2 was <0.80, %AUCextra was >20% and elimination phase was not characterized, CL/f derived from lambda z was regarded as implausible and not calculated.

Posted

Cycle 1 Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose on Day 1 and 15 (Each cycle is of 21 days)

ID	Title	Description
OG000	M8891 7 mg	Participant received M8891 at dose of 7 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG001	M8891 12 mg	Participant received M8891 at dose of 12 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG002	M8891 20 mg	Participant received M8891 at dose of 20 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG003	M8891 35 mg	Participant received M8891 at dose of 35 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG004	M8891 60 mg	Participant received M8891 at dose of 60 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG005	M8891 80 mg	Participant received M8891 at dose of 80 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.

Units	Counts
Participants	OG0000 OG0010 OG0020 OG003

Secondary

Apparent Body Clearance of Drug Following Extravascular Administration At Steady State (CLss/f) of M8891

The apparent total body clearance of drug at steady state following extravascular administration, taking into account the fraction of dose absorbed. It is calculated as dose/AUCtau for M8891.

PK analysis set included all participants from the safety analysis set without major protocol deviations/violations or events that would affect PK. As R2 was <0.80, %AUCextra was >20% and elimination phase was not characterized, CLss/f derived from lambda z was regarded as implausible and not calculated.

Posted

Cycle 1 Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose on Day 1 and 15 (Each cycle is of 21 days)

ID	Title	Description
OG000	M8891 7 mg	Participant received M8891 at dose of 7 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG001	M8891 12 mg	Participant received M8891 at dose of 12 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG002	M8891 20 mg	Participant received M8891 at dose of 20 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG003	M8891 35 mg	Participant received M8891 at dose of 35 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG004	M8891 60 mg	Participant received M8891 at dose of 60 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG005	M8891 80 mg	Participant received M8891 at dose of 80 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.

Units	Counts
Participants	OG0000 OG0010 OG0020 OG003

Secondary

Apparent Volume of Distribution During Terminal Phase (VZ/f) of M8891

Apparent volume of distribution during the terminal phase following extravascular administration for M8891 was calculated. Vz/f = Dose/(AUC0-infinity multiply by Lambda z) following single dose. The AUC from time zero (dosing time) extrapolated to infinity, based on the predicted value for the concentration at tlast, as estimated using the linear regression from lambda z determination. AUC(0- inf)=AUC0-t plus Clastpred/lambda z where Clastpred was last predicted concentration. Lambda Z was terminal elimination rate constant determined from the terminal slope of the log-transformed plasma concentration curve using linear regression on terminal data points of the curve.

PK analysis set included all participants from the safety analysis set without major protocol deviations/violations or events that would affect PK. As R2 was <0.80, %AUCextra was >20% and elimination phase was not characterized, VZ/f derived from lambda z was regarded as implausible and not calculated.

Posted

Cycle 1 Pre-dose, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose on Day 1 and 15 (Each cycle is of 21 days)

ID	Title	Description
OG000	M8891 7 mg	Participant received M8891 at dose of 7 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG001	M8891 12 mg	Participant received M8891 at dose of 12 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG002	M8891 20 mg	Participant received M8891 at dose of 20 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG003	M8891 35 mg	Participant received M8891 at dose of 35 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG004	M8891 60 mg	Participant received M8891 at dose of 60 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG005	M8891 80 mg	Participant received M8891 at dose of 80 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.

Units	Counts
Participants	OG0000 OG0010 OG0020 OG003

Secondary

Accumulation Ratios of AUC (Racc AUC) of M8891

Racc (AUC) is defined as the accumulation factor to assess the increase in exposure until steady state is reached. Accumulation ratio for AUC was calculated as AUC, after dosing on Day 15 divided by AUC, after dosing on Day 1 of Cycle 1.

Posted

Geometric Mean

Geometric Coefficient of Variation

Ratio

Pre-dose and at 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose on Day 1 and 15 of Cycle 1 (each cycle is 21 days)

ID	Title	Description
OG000	M8891 7 mg	Participant received M8891 at dose of 7 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG001	M8891 12 mg	Participant received M8891 at dose of 12 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG002	M8891 20 mg	Participant received M8891 at dose of 20 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG003	M8891 35 mg	Participant received M8891 at dose of 35 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG004	M8891 60 mg	Participant received M8891 at dose of 60 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG005	M8891 80 mg	Participant received M8891 at dose of 80 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.

Units	Counts
Participants	OG0003 OG0013 OG0022 OG003

Title

Denominators

Categories

Title	Measurements
	OG0002.82± 29.3 OG0012.36± 27.4 OG002NA± NABased on pre-specified criteria Geometric Mean and Geometric Coefficient of Variation were not calculated if fewer than 3 participants have reportable parameter values.

Secondary

Accumulation Ratio of Cmax (Racc Cmax) of M8891

Accumulation ratio of Cmax was calculated as Cmax, after dosing on Day 15 divided by Cmax, after dosing on Day 1 of Cycle 1.

Posted

Geometric Mean

Geometric Coefficient of Variation

Ratio

Pre-dose and at 1, 2, 3, 4, 5, 6, 8, 12, 24 hours post-dose on Day 1 and 15 of Cycle 1 (each cycle is 21 days)

ID	Title	Description
OG000	M8891 7 mg	Participant received M8891 at dose of 7 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG001	M8891 12 mg	Participant received M8891 at dose of 12 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG002	M8891 20 mg	Participant received M8891 at dose of 20 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG003	M8891 35 mg	Participant received M8891 at dose of 35 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG004	M8891 60 mg	Participant received M8891 at dose of 60 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG005	M8891 80 mg	Participant received M8891 at dose of 80 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.

Units	Counts
Participants	OG0003 OG0013 OG0022 OG003

Title

Denominators

Categories

Title	Measurements
	OG0002.46± 27.5 OG0012.36± 33.5 OG002NA± NABased on pre-specified criteria Geometric Mean and Geometric Coefficient of Variation were not calculated if fewer than 3 participants have reportable parameter values.

Secondary

Number of Participants With Best Overall Response Assessment According to Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1) Criteria

BOR was determined according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) as assessed by investigators. BOR is defined as the best response of any of the complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) recorded from the date of randomization until disease progression. CR: Disappearance of all evidence of target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimeter (mm). PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. Stable disease (SD) defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SLD while on study. PD is defined as at least a 20 percent (%) increase in the SLD of target lesion, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.

Safety analysis set included all participants who received at least 1 dose of study drug.

Posted

Count of Participants

Participants

Up to 1136 Days

ID	Title	Description
OG000	M8891 7 mg	Participant received M8891 at dose of 7 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG001	M8891 12 mg	Participant received M8891 at dose of 12 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG002	M8891 20 mg	Participant received M8891 at dose of 20 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG003	M8891 35 mg	Participant received M8891 at dose of 35 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG004	M8891 60 mg	Participant received M8891 at dose of 60 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG005	M8891 80 mg	Participant received M8891 at dose of 80 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.

Units	Counts
Participants	OG0003 OG0013 OG0023 OG003

Title

Denominators

Categories

Complete Response

Title	Measurements
	OG0000 OG0010 OG0020 OG003

Secondary

Number of Participants With Clinical Benefit

Clinical benefit defined as Complete Response (CR), Partial Response (PR) or Stable Disease (SD) for >= 12 weeks. Clinical benefit was assessed according to RECIST Version 1.1. CR: defined as disappearance of all target and all non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimeter (mm). PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. SD: defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest SLD while on study. PD is defined as at least a 20 percent (%) increase in the SLD of target lesion, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.

Safety analysis set included all participants who received at least 1 dose of study drug.

Posted

Count of Participants

Participants

Up to 1136 Days

ID	Title	Description
OG000	M8891 7 mg	Participant received M8891 at dose of 7 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG001	M8891 12 mg	Participant received M8891 at dose of 12 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG002	M8891 20 mg	Participant received M8891 at dose of 20 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG003	M8891 35 mg	Participant received M8891 at dose of 35 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG004	M8891 60 mg	Participant received M8891 at dose of 60 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG005	M8891 80 mg	Participant received M8891 at dose of 80 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.

Units	Counts
Participants	OG0003 OG0013 OG0023 OG003

Title

Denominators

Categories

Complete Response

Title	Measurements
	OG0000 OG0010 OG0020 OG003

Secondary

Progression-Free Survival (PFS)

Progression-free survival (PFS) defined as the time from first study drug administration to either first observation of progressive disease (PD) (as assessed by Investigators according to RECIST v1.1) or occurrence of death due to any cause, whichever occurs first. Progressive disease (PD) defined as at least a 20% increase in sum of longest diameter (SLD) of target lesions, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. PFS was measured using Kaplan-Meier (KM) estimates. Here the 20 mg dose level was selected for stratification as the highest dose level equal to or smaller than the median of all dose levels administered to at least 1 participant.

Safety analysis set included all participants who received at least 1 dose of study drug.

Posted

Median

95% Confidence Interval

Months

Up to 1136 Days

ID	Title	Description
OG000	Less Than or Equal to (<=) 20 mg M8891	All participants who received oral capsule of M8891 at dose <= 20 mg first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG001	Greater Than (>) 20 mg M8891	All participants who received oral capsule of M8891 at dose of > 20mg first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.

Units	Counts
Participants	OG0009 OG00118

Title

Denominators

Categories

Title	Measurements
	OG0002.7598(1.05 to 4.40) OG0011.3799(0.82 to 1.54)

Secondary

Number of Participants With Change From Baseline in Laboratory Test Abnormalities to Grade 3 or Higher Severity Based on NCI-CTCAE Version 4.03

The laboratory measurements included hematology, biochemistry, and urinalysis values were graded with National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 toxicity grades (where Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life threatening and Grade 5 = death). Number of participants with change from baseline to grade 3 or higher values for the hematology, biochemistry and urinalysis parameters were reported.

Safety analysis set included all participants who received at least 1 dose of study drug.

Posted

Count of Participants

Participants

Up to 1136 Days

ID	Title	Description
OG000	M8891 7 mg	Participant received M8891 at dose of 7 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG001	M8891 12 mg qd	Participant received M8891 at dose of 12 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG002	M8891 20 mg	Participant received M8891 at dose of 20 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG003	M8891 35 mg	Participant received M8891 at dose of 35 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG004	M8891 60 mg	Participant received M8891 at dose of 60 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG005	M8891 80 mg	Participant received M8891 at dose of 80 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.

Units	Counts
Participants	OG0003 OG0013 OG0023 OG003

Title

Denominators

Categories

Grade >= 3 biochemistry

Title	Measurements
	OG0000 OG0010 OG0022 OG003

Secondary

Number of Participants With Clinically Meaningful Changes From Baseline in Vital Signs

Vital sign assessments included assessments of heart rate, diastolic blood pressure, systolic blood pressure, weight, respiratory rate and temperature. Clinical relevance was assessed by the investigator. Number of participants who had any clinically meaningful change from baseline in vital signs were reported.

Safety analysis set included all participants who received at least 1 dose of study drug.

Posted

Count of Participants

Participants

Up to 1136 Days

ID	Title	Description
OG000	M8891 7 mg	Participant received M8891 at dose of 7 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG001	M8891 12 mg	Participant received M8891 at dose of 12 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG002	M8891 20 mg	Participant received M8891 at dose of 20 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG003	M8891 35 mg	Participant received M8891 at dose of 35 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG004	M8891 60 mg	Participant received M8891 at dose of 60 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG005	M8891 80 mg	Participant received M8891 at dose of 80 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.

Units	Counts
Participants	OG0003 OG0013 OG0023 OG003

Title

Denominators

Categories

Title	Measurements
	OG0000 OG0010 OG0020 OG003

Secondary

Number of Participants With Clinically Meaningful Changes From Baseline in Electrocardiogram (ECG) Values

ECG parameters included rhythm, heart rate (as measured by RR interval), PR interval, QRS duration, QT intervals, and corrected QT(QTc) intervals. Clinical significance was determined by the investigator. Number of participants with clinically meaningful change from baseline in 12-lead ECG were reported.

Safety analysis set included all participants who received at least 1 dose of study drug.

Posted

Count of Participants

Participants

Up to 1136 Days

ID	Title	Description
OG000	M8891 7 mg	Participant received M8891 at dose of 7 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG001	M8891 12 mg	Participant received M8891 at dose of 12 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG002	M8891 20 mg	Participant received M8891 at dose of 20 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG003	M8891 35 mg	Participant received M8891 at dose of 35 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG004	M8891 60 mg	Participant received M8891 at dose of 60 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG005	M8891 80 mg	Participant received M8891 at dose of 80 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.

Units	Counts
Participants	OG0003 OG0013 OG0023 OG003

Title

Denominators

Categories

Title	Measurements
	OG0000 OG0010 OG0020 OG003

Secondary

Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status (PF) Score of 2 or Higher Than 2

ECOG PS score is widely used by doctors and researchers to assess how a participants' disease is progressing, and is used to assess how the disease affects the daily living abilities of the participant, and determine appropriate treatment and prognosis. The score ranges from Grade 0 to Grade 5, where Grade 0 = Fully active, able to carry on all pre-disease performance without restriction, Grade 1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature (like light house work, office work), Grade 2 = Ambulatory and capable of all self-care but unable to carry out any work activities, Grade 3 = Capable of only limited self-care, confined to bed or chair more than 50% of waking hours and Grade 4 = Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair, Grade 5 = Death. Number of participants with ECOG performance status score of 2 or higher than 2 were reported.

Safety analysis set included all participants who received at least 1 dose of study drug.

Posted

Count of Participants

Participants

Up to 1136 Days

ID	Title	Description
OG000	M8891 7 mg	Participant received M8891 at dose of 7 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG001	M8891 12 mg	Participant received M8891 at dose of 12 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG002	M8891 20 mg	Participant received M8891 at dose of 20 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG003	M8891 35 mg	Participant received M8891 at dose of 35 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG004	M8891 60 mg	Participant received M8891 at dose of 60 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG005	M8891 80 mg	Participant received M8891 at dose of 80 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.

Units	Counts
Participants	OG0003 OG0013 OG0023 OG003

Title

Denominators

Categories

Title	Measurements
	OG0000 OG0011 OG0021 OG003

Secondary

Percentage of Participants With Objective Response

Objective response is defined as the percentage of participants with complete response (CR) and partial response (PR). CR is defined as disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions.

Safety analysis set included all participants who received at least 1 dose of study drug.

Posted

Number

95% Confidence Interval

Percentage of participants

Up to 1136 Days

ID	Title	Description
OG000	M8891 7 mg	Participant received M8891 at dose of 7 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG001	M8891 12 mg	Participant received M8891 at dose of 12 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG002	M8891 20 mg	Participant received M8891 at dose of 20 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG003	M8891 35 mg	Participant received M8891 at dose of 35 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG004	M8891 60 mg	Participant received M8891 at dose of 60 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
OG005	M8891 80 mg	Participant received M8891 at dose of 80 mg orally with first dose in Cycle 1 Day 1 and consist of consecutive 21-day cycles of continuous once daily M8891 monotherapy under fasting conditions until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.

Units	Counts
Participants	OG0003 OG0013 OG0023 OG003

Title

Denominators

Categories

Title	Measurements
	OG0000(0.0 to 70.8) OG0010(0.0 to 84.2) OG0020(0.0 to 84.2) OG003

Day 15

- ParticipantsOG0003
- ParticipantsOG0013
- ParticipantsOG0022
- ParticipantsOG0035
- ParticipantsOG0044
- ParticipantsOG0052

Title	Measurements
	OG0001260± 39.2 OG0012210± 21.1 OG002NA± NABased on pre-specified criteria Geometric Mean and Geometric Coefficient of Variation were not calculated if fewer than 3 participants have reportable parameter values. OG003

Day 15

- ParticipantsOG0003
- ParticipantsOG0013
- ParticipantsOG0022
- ParticipantsOG0035
- ParticipantsOG0044
- ParticipantsOG0053

Title	Measurements
	OG0004.00(3.10 to 4.98) OG0012.00(1.10 to 3.00) OG002NA(2.83 to 3.97)Based on pre-specified criteria Median was not calculated if fewer than 3 participants have reportable parameter values. OG003

Day 15

- ParticipantsOG0003
- ParticipantsOG0013
- ParticipantsOG0022
- ParticipantsOG0035
- ParticipantsOG0044
- ParticipantsOG0052

Title	Measurements
	OG00025400± 50.3 OG00138600± 17.6 OG002NA± NABased on pre-specified criteria Geometric Mean and Geometric Coefficient of Variation were not calculated if fewer than 3 participants have reportable parameter values. OG003

Day 15

- ParticipantsOG0003
- ParticipantsOG0013
- ParticipantsOG0022
- ParticipantsOG0035
- ParticipantsOG0044
- ParticipantsOG0052

Title	Measurements
	OG00025700± 48.4 OG00138500± 18.7 OG002NA± NABased on pre-specified criteria Geometric Mean and Geometric Coefficient of Variation were not calculated if fewer than 3 participants have reportable parameter values. OG003