First-in-Human Study of MS201408-0005A as Single Agent an... | NCT03306420

First-in-Human Study of MS201408-0005A as Single Agent an... | NCT03306420 | Trialant

Sponsor/Collaborators Module

Name	Class
Merck KGaA, Darmstadt, Germany	INDUSTRY

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Part IA Dose Escalation: M4112 100 mg	Experimental	Participants received an oral dose of 100 milligrams (mg) M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).	Drug: M4112
Part IA Dose Escalation: M4112 200 mg	Experimental	Participants received an oral dose of 200 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).	Drug: M4112
Part IA Dose Escalation: M4112 400 mg	Experimental	Participants received an oral dose of 400 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).	Drug: M4112
Part IA Dose Escalation: M4112 600 mg	Experimental	Participants received an oral dose of 600 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).	Drug: M4112
Part IA Dose Escalation: M4112 800 mg	Experimental

Interventions

Name	Type	Description	Arm Group Labels	Other Names
M4112	Drug	All participants who received M4112 100,200,400,600 and 800 mg twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Part 1A Dose Escalation: Number of Participants Who Experienced Dose Limiting Toxicities (DLTs) as Per National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03	DLTs was assessed as per NCI CTCAE v 4.03. DLT defined as any Grade greater than or equal (>=) 3 nonhematological AE or Immune-related adverse event (irAE) assessed by Investigator or Sponsor during first Cycle (first 28 days) of study treatment. Asymptomatic Grade >= 3 lipase or amylase elevation not associated with clinical manifestations of pancreatitis. Any TEAE observed in subsequent cycle. Any Grade 4 neutropenia of >= 5 days duration, Grade >= 3 febrile neutropenia, Grade 3 hemoglobin decrease despite blood transfusion or erythroid growth factor. Grade 4 hemoglobin decrease assessed as related to study drug. Any Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with bleeding. Any Grade >= 3 clinical signs and symptoms related to increased QTc.	Cycle 1 (Each Cycle is of 28 days)
Part 1A Dose Escalation: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Who Experienced a Treatment Related Adverse Events (TRAE) According to National Cancer Institute Common Toxicity Criteria for Adverse Events Version 4.03	An adverse event (AE) was defined as any untoward medical occurrence in participant which does not necessarily have casual relationship with treatment was any unfavorable and unintended sign(including abnormal laboratory finding), symptom/disease temporally associated with use of medicinal product, whether/not considered related to medicinal product. A serious adverse event(SAE) was AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Term TEAE is defined as AEs starting/worsening after first intake of the study drug. TEAEs included both Serious TEAEs and non-serious TEAEs. Treatment related AE was defined as having a "Possible" or "Related" relationship to study treatment, as assessed by the Investigator.	Baseline up to safety follow-up visit, assessed up to 15.4 months
Part 1A Dose Escalation: Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters

Secondary Outcomes

Measure	Description	Time Frame
Part 1A Dose Escalation: Area Under the Plasma Concentration Curve From Time Zero to 8 Hours Post Dose AUC(0-8h) of M4112	Area under the drug concentration-time curve from 0 to 8 h post dosing for M4112. AUC0-8 was calculated according to the mixed log-linear trapezoidal rule.	Pre-dose, 0.5, 1, 2, 3, 4, 6 and 8 h post-dose on Day 1 and 15 of Cycle 1 (Each Cycle is for 28 days)

Eligibility Module

Contacts/Locations Module

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

Facility	Status	City	State	ZIP	Country	Contacts
Yale Cancer Center		New Haven	Connecticut	06510	United States
University of TX M.D. Anderson Cancer Center-Investigational Cancer Therapeutics Partner

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
32843490	Derived	Naing A, Eder JP, Piha-Paul SA, Gimmi C, Hussey E, Zhang S, Hildebrand V, Hosagrahara V, Habermehl C, Moisan J, Papadopoulos KP. Preclinical investigations and a first-in-human phase I trial of M4112, the first dual inhibitor of indoleamine 2,3-dioxygenase 1 and tryptophan 2,3-dioxygenase 2, in patients with advanced solid tumors. J Immunother Cancer. 2020 Aug;8(2):e000870. doi: 10.1136/jitc-2020-000870.

Arm/Group Information

ID	Title	Description
FG000	Part 1A Dose Escalation: M4112 100 mg	Participants received an oral dose of 100 milligrams (mg) M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
FG001	Part 1A Dose Escalation: M4112 200 mg	Participants received an oral dose of 200 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
FG002	Part 1A Dose Escalation: M4112 400 mg	Participants received an oral dose of 400 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
FG003	Part 1A Dose Escalation: M4112 600 mg	Participants received an oral dose of 600 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
FG004	Part 1A Dose Escalation: M4112 800 mg	Participants received an oral dose of 800 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).

Periods

Title

Milestones

Reasons Not Completed

Overall Study

Type	Comment	Milestone Data
STARTED		FG0003 subjects FG0013 subjects FG0023 subjects FG0033 subjects FG0043 subjects
COMPLETED		FG0003 subjects FG0013 subjects FG0023 subjects FG0033 subjects FG004
NOT COMPLETED		FG0000 subjects FG0010 subjects FG0020 subjects FG0030 subjects FG004

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Part 1A Dose Escalation: M4112 100 mg	Participants received an oral dose of 100 milligrams (mg) M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
BG001	Part 1A Dose Escalation: M4112 200 mg

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

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	Part 1A Dose Escalation: Number of Participants Who Experienced Dose Limiting Toxicities (DLTs) as Per National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03	DLTs was assessed as per NCI CTCAE v 4.03. DLT defined as any Grade greater than or equal (>=) 3 nonhematological AE or Immune-related adverse event (irAE) assessed by Investigator or Sponsor during first Cycle (first 28 days) of study treatment. Asymptomatic Grade >= 3 lipase or amylase elevation not associated with clinical manifestations of pancreatitis. Any TEAE observed in subsequent cycle. Any Grade 4 neutropenia of >= 5 days duration, Grade >= 3 febrile neutropenia, Grade 3 hemoglobin decrease despite blood transfusion or erythroid growth factor. Grade 4 hemoglobin decrease assessed as related to study drug. Any Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with bleeding. Any Grade >= 3 clinical signs and symptoms related to increased QTc.	DLT analysis set included all participants treated in dose escalation cohorts who do not miss greater than (>) 5 planned total daily doses of M4112 in the first cycle (first 28 days) of the dose escalation part for other than DLT.	Posted		Count of Participants		Participants		Cycle 1 (Each Cycle is of 28 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	Part 1A Dose Escalation: M4112 100 mg	Participants received an oral dose of 100 milligrams (mg) M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Ascites	Gastrointestinal disorders	MedDRA version 21.1	Non-systematic Assessment

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA version 21.1	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
SAP	No	Yes	No	Statistical Analysis Plan	Feb 7, 2019	Dec 16, 2019	SAP_000.pdf
Prot	Yes	No	No	Study Protocol	Sep 8, 2017	Dec 16, 2019	Prot_001.pdf

Condition Browse Module

ID	Term
D009362	Neoplasm Metastasis

ID	Term
D009385	Neoplastic Processes
D009369	Neoplasms
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG0001 BG0010 BG0021 BG0031 BG0040 BG0053
Not Hispanic or Latino	BG0002 BG0013 BG0022 BG0032 BG004
Unknown or Not Reported	BG0000 BG0010 BG0020 BG0030 BG004

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 BG0020 BG0030 BG0040 BG0050
Asian	BG0000 BG0010 BG0020 BG0030 BG004
Native Hawaiian or Other Pacific Islander	BG0000 BG0010 BG0020 BG0030 BG004
Black or African American	BG0001 BG0010 BG0021 BG0030 BG004
White	BG0002 BG0013 BG0022 BG0033 BG004
More than one race	BG0000 BG0010 BG0020 BG0030 BG004
Unknown or Not Reported	BG0000 BG0010 BG0020 BG0030 BG004

ID	Title	Description
OG000	Part 1A Dose Escalation: M4112 100 mg	Participants received an oral dose of 100 milligrams (mg) M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG001	Part 1A Dose Escalation: M4112 200 mg	Participants received an oral dose of 200 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG002	Part 1A Dose Escalation: M4112 400 mg	Participants received an oral dose of 400 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG003	Part 1A Dose Escalation: M4112 600 mg	Participants received an oral dose of 600 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG004	Part 1A Dose Escalation: M4112 800 mg	Participants received an oral dose of 800 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).

Primary

Part 1A Dose Escalation: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Who Experienced a Treatment Related Adverse Events (TRAE) According to National Cancer Institute Common Toxicity Criteria for Adverse Events Version 4.03

An adverse event (AE) was defined as any untoward medical occurrence in participant which does not necessarily have casual relationship with treatment was any unfavorable and unintended sign(including abnormal laboratory finding), symptom/disease temporally associated with use of medicinal product, whether/not considered related to medicinal product. A serious adverse event(SAE) was AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Term TEAE is defined as AEs starting/worsening after first intake of the study drug. TEAEs included both Serious TEAEs and non-serious TEAEs. Treatment related AE was defined as having a "Possible" or "Related" relationship to study treatment, as assessed by the Investigator.

The safety analysis set included all participants who had received at least 1 dose of the study treatment.

Posted

Count of Participants

Participants

Baseline up to safety follow-up visit, assessed up to 15.4 months

ID	Title	Description
OG000	Part 1A Dose Escalation: M4112 100 mg	Participants received an oral dose of 100 milligrams (mg) M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG001	Part 1A Dose Escalation: M4112 200 mg	Participants received an oral dose of 200 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG002	Part 1A Dose Escalation: M4112 400 mg	Participants received an oral dose of 400 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG003	Part 1A Dose Escalation: M4112 600 mg	Participants received an oral dose of 600 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG004	Part 1A Dose Escalation: M4112 800 mg	Participants received an oral dose of 800 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).

Units	Counts
Participants	OG0003 OG0013 OG0023 OG003

Title

Denominators

Categories

Any TEAE

Title	Measurements
	OG0003 OG0013 OG0023 OG003

Primary

Part 1A Dose Escalation: Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters

The laboratory measurements included hematology, biochemistry and hormonal tests. Number of participants with any clinically significant abnormalities in laboratory measurements were reported. Clinical significance was determined by the investigator.

The safety analysis set included all participants who had received at least 1 dose of the study treatment.

Posted

Count of Participants

Participants

Baseline up to safety follow-up visit, assessed up to 15.4 months

ID	Title	Description
OG000	Part 1A Dose Escalation: M4112 100 mg	Participants received an oral dose of 100 milligrams (mg) M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG001	Part 1A Dose Escalation: M4112 200 mg	Participants received an oral dose of 200 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG002	Part 1A Dose Escalation: M4112 400 mg	Participants received an oral dose of 400 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG003	Part 1A Dose Escalation: M4112 600 mg	Participants received an oral dose of 600 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG004	Part 1A Dose Escalation: M4112 800 mg	Participants received an oral dose of 800 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).

Units	Counts
Participants	OG0003 OG0013 OG0023 OG003

Title

Denominators

Categories

Title	Measurements
	OG0001 OG0010 OG0020 OG003

Primary

Part 1A Dose Escalation: Number of Participants With Clinically Significant Abnormalities in Vital Signs

Vital signs assessment included blood pressure, pulse rate and body temperature. Number of Participants with any clinically significant abnormalities in vital signs were reported. Clinical significance was determined by the investigator.

The safety analysis set included all participants who had received at least 1 dose of the study treatment.

Posted

Count of Participants

Participants

Baseline up to safety follow-up visit, assessed up to 15.4 months

ID	Title	Description
OG000	Part 1A Dose Escalation: M4112 100 mg	Participants received an oral dose of 100 milligrams (mg) M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG001	Part 1A Dose Escalation: M4112 200 mg	Participants received an oral dose of 200 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG002	Part 1A Dose Escalation: M4112 400 mg	Participants received an oral dose of 400 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG003	Part 1A Dose Escalation: M4112 600 mg	Participants received an oral dose of 600 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG004	Part 1A Dose Escalation: M4112 800 mg	Participants received an oral dose of 800 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).

Units	Counts
Participants	OG0003 OG0013 OG0023 OG003

Title

Denominators

Categories

Title	Measurements
	OG0002 OG0010 OG0021 OG003

Primary

Part 1A Dose Escalation: Number of Participants With On-Treatment Shift in Eastern Cooperative Oncology Performance Status (ECOG PS) Score From 0 to 1

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 4, 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. Number of participants with on-treatment shift in ECOG PS Score from 0 to 1 were reported.

The safety analysis set included all participants who had received at least 1 dose of the study treatment.

Posted

Count of Participants

Participants

Baseline up to safety follow-up visit, assessed up to 15.4 months

ID	Title	Description
OG000	Part 1A Dose Escalation: M4112 100 mg	Participants received an oral dose of 100 milligrams (mg) M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG001	Part 1A Dose Escalation: M4112 200 mg	Participants received an oral dose of 200 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG002	Part 1A Dose Escalation: M4112 400 mg	Participants received an oral dose of 400 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG003	Part 1A Dose Escalation: M4112 600 mg	Participants received an oral dose of 600 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG004	Part 1A Dose Escalation: M4112 800 mg	Participants received an oral dose of 800 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).

Units	Counts
Participants	OG0003 OG0013 OG0023 OG003

Title

Denominators

Categories

Title	Measurements
	OG0001 OG0010 OG0021 OG003

Primary

Part 1A Dose Escalation: Number of Participants With Clinically Significant Change From Baseline in Physical Examination Abnormalities

A complete physical examination (including, general appearance, skin, pulmonary, cardiovascular, gastrointestinal, external genitourinary only as medically relevant, lymphatic, neurologic and musculoskeletal systems, head/neck, extremities, eyes, ears, nose, throat, and cognitive status) was performed. Number of participants with clinical significant change from baseline in physical examination abnormalities were reported. Clinical significance was determined by the investigator.

The safety analysis set included all participants who had received at least 1 dose of the study treatment.

Posted

Count of Participants

Participants

Baseline up to safety follow-up visit, assessed up to 15.4 months

ID	Title	Description
OG000	Part 1A Dose Escalation: M4112 100 mg	Participants received an oral dose of 100 milligrams (mg) M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG001	Part 1A Dose Escalation: M4112 200 mg	Participants received an oral dose of 200 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG002	Part 1A Dose Escalation: M4112 400 mg	Participants received an oral dose of 400 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG003	Part 1A Dose Escalation: M4112 600 mg	Participants received an oral dose of 600 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG004	Part 1A Dose Escalation: M4112 800 mg	Participants received an oral dose of 800 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).

Units	Counts
Participants	OG0003 OG0013 OG0023 OG003

Title

Denominators

Categories

Title	Measurements
	OG0000 OG0010 OG0020 OG003

Secondary

Part 1A Dose Escalation: Area Under the Plasma Concentration Curve From Time Zero to 8 Hours Post Dose AUC(0-8h) of M4112

Area under the drug concentration-time curve from 0 to 8 h post dosing for M4112. AUC0-8 was calculated according to the mixed log-linear trapezoidal rule.

Pharmacokinetic (PK) analysis set included all participants who received M4112 and for whom at least 1 dose of M4112 and must have sufficient M4112 plasma concentration data to enable the calculation of at least 1 PK parameter. Here "number analyzed" signifies those participants who were evaluable for this outcome measure at given time points.

Posted

Geometric Mean

Geometric Coefficient of Variation

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

Pre-dose, 0.5, 1, 2, 3, 4, 6 and 8 h post-dose on Day 1 and 15 of Cycle 1 (Each Cycle is for 28 days)

ID	Title	Description
OG000	Part 1A Dose Escalation: M4112 100 mg	Participants received an oral dose of 100 milligrams (mg) M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG001	Part 1A Dose Escalation: M4112 200 mg	Participants received an oral dose of 200 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG002	Part 1A Dose Escalation: M4112 400 mg	Participants received an oral dose of 400 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG003	Part 1A Dose Escalation: M4112 600 mg	Participants received an oral dose of 600 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG004	Part 1A Dose Escalation: M4112 800 mg	Participants received an oral dose of 800 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).

Units	Counts
Participants	OG0003 OG0013 OG0023 OG003

Title	Denominators	Categories
Cycle 1 Day 1	ParticipantsOG0003 ParticipantsOG0013 ParticipantsOG0023 ParticipantsOG003

Secondary

Part 1A Dose Escalation: Maximum Observed Plasma Concentration (Cmax) of M4112

Pharmacokinetic PK parameter Cmax was obtained directly from the plasma concentration versus time curve.

PK analysis set included all participants who received M4112 and for whom at least 1 dose of M4112 and must have sufficient M4112 plasma concentration data to enable the calculation of at least 1 PK parameter. Here "number analyzed" signifies those participants who were evaluable for this outcome measure at given time points.

Posted

Geometric Mean

Geometric Coefficient of Variation

nanogram per milliliter (ng/mL)

Pre-dose, 0.5, 1, 2, 3, 4, 6 and 8 h post-dose on Day 1 and 15 of Cycle 1 (Each Cycle is for 28 days)

ID	Title	Description
OG000	Part 1A Dose Escalation: M4112 100 mg	Participants received an oral dose of 100 milligrams (mg) M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG001	Part 1A Dose Escalation: M4112 200 mg	Participants received an oral dose of 200 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG002	Part 1A Dose Escalation: M4112 400 mg	Participants received an oral dose of 400 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG003	Part 1A Dose Escalation: M4112 600 mg	Participants received an oral dose of 600 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG004	Part 1A Dose Escalation: M4112 800 mg	Participants received an oral dose of 800 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).

Units	Counts
Participants	OG0003 OG0013 OG0023 OG003

Title	Denominators	Categories
Cycle 1 Day 1	ParticipantsOG0003 ParticipantsOG0013 ParticipantsOG0023 ParticipantsOG003

Secondary

Part 1A Dose Escalation: Time to Reach Maximum Plasma Concentration (Tmax) of M4112

Time to reach the maximum plasma concentration (Tmax) was obtained directly from the concentration versus time curve.

Posted

Median

Full Range

Hours

Pre-dose, 0.5, 1, 2, 3, 4, 6 and 8 h post-dose on Day 1 and 15 of Cycle 1 (Each Cycle is for 28 days)

ID	Title	Description
OG000	Part 1A Dose Escalation: M4112 100 mg	Participants received an oral dose of 100 milligrams (mg) M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG001	Part 1A Dose Escalation: M4112 200 mg	Participants received an oral dose of 200 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG002	Part 1A Dose Escalation: M4112 400 mg	Participants received an oral dose of 400 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG003	Part 1A Dose Escalation: M4112 600 mg	Participants received an oral dose of 600 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG004	Part 1A Dose Escalation: M4112 800 mg	Participants received an oral dose of 800 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).

Units	Counts
Participants	OG0003 OG0013 OG0023 OG003

Title	Denominators	Categories
Cycle 1 Day 1	ParticipantsOG0003 ParticipantsOG0013 ParticipantsOG0023 ParticipantsOG003

Secondary

Part 1A Dose Escalation: Dose Normalized Area Under the Plasma Concentration-Time Curve From Time Zero to 8 Hour Post-dose (AUC0-8/Dose) of M4112

Dose normalized was calculated as area under the plasma concentration-time curve from time zero to 8 h postdose divided by dose.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng*h/mL/mg

Pre-dose, 0.5, 1, 2, 3, 4, 6 and 8 h post-dose on Day 1 and 15 of Cycle 1 (Each Cycle is for 28 days)

ID	Title	Description
OG000	Part 1A Dose Escalation: M4112 100 mg	Participants received an oral dose of 100 milligrams (mg) M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG001	Part 1A Dose Escalation: M4112 200 mg	Participants received an oral dose of 200 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG002	Part 1A Dose Escalation: M4112 400 mg	Participants received an oral dose of 400 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG003	Part 1A Dose Escalation: M4112 600 mg	Participants received an oral dose of 600 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG004	Part 1A Dose Escalation: M4112 800 mg	Participants received an oral dose of 800 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).

Units	Counts
Participants	OG0003 OG0013 OG0023 OG003

Title	Denominators	Categories
Cycle 1 Day 1	ParticipantsOG0003 ParticipantsOG0013 ParticipantsOG0023 ParticipantsOG003

Secondary

Part 1A Dose Escalation: Dose Normalized Maximum Observed Plasma Concentration (Cmax/Dose) of M4112

Dose normalized was calculated as Cmax obtained directly from the concentration versus time curve divided by dose.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL/mg

Pre-dose, 0.5, 1, 2, 3, 4, 6 and 8 h post-dose on Day 1 and 15 of Cycle 1 (Each Cycle is for 28 days)

ID	Title	Description
OG000	Part 1A Dose Escalation: M4112 100 mg	Participants received an oral dose of 100 milligrams (mg) M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG001	Part 1A Dose Escalation: M4112 200 mg	Participants received an oral dose of 200 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG002	Part 1A Dose Escalation: M4112 400 mg	Participants received an oral dose of 400 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG003	Part 1A Dose Escalation: M4112 600 mg	Participants received an oral dose of 600 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG004	Part 1A Dose Escalation: M4112 800 mg	Participants received an oral dose of 800 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).

Units	Counts
Participants	OG0003 OG0013 OG0023 OG003

Title	Denominators	Categories
Cycle 1 Day 1	ParticipantsOG0003 ParticipantsOG0013 ParticipantsOG0023 ParticipantsOG003

Secondary

Part 1A Dose Escalation: Accumulation Ratio for Area Under the Plasma Concentration-Time Curve From Time Zero to 8 Hour Post-dose (Racc[AUC0-8h]) of M4112

Accumulation ratio for Area Under the Plasma Concentration-Time Curve From Time Zero to 8 hours After Administration (Racc[AUC0-8h]) of M4112 was reported. Racc(AUC0-8h) calculated as AUC0-8h, on Cycle 1 Day 15 divided by AUC0-8h on Cycle 1 Day 1.

PK analysis set included all participants who received M4112 and for whom at least 1 dose of M4112 and must have sufficient M4112 plasma concentration data to enable the calculation of at least 1 PK parameter. Here "Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.

Posted

Geometric Mean

Geometric Coefficient of Variation

Ratio

Pre-dose, 0.5, 1, 2, 3, 4, 6 and 8 h post-dose on Day 1 and 15 of Cycle 1 (Each Cycle is for 28 days)

ID	Title	Description
OG000	Part 1A Dose Escalation: M4112 100 mg	Participants received an oral dose of 100 milligrams (mg) M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG001	Part 1A Dose Escalation: M4112 200 mg	Participants received an oral dose of 200 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG002	Part 1A Dose Escalation: M4112 400 mg	Participants received an oral dose of 400 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG003	Part 1A Dose Escalation: M4112 600 mg	Participants received an oral dose of 600 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG004	Part 1A Dose Escalation: M4112 800 mg	Participants received an oral dose of 800 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).

Units	Counts
Participants	OG0003 OG0013 OG0023 OG003

Title

Denominators

Categories

Title	Measurements
	OG0001.35± 11.4 OG0010.868± 15.3 OG0021.14± 50.1 OG003

Secondary

Part IA Dose Escalation: Accumulation Ratio for Maximum Observed Plasma Concentration (Racc [Cmax]) of M4112

Accumulation ratio for Cmax was calculated as Cmax, Cycle 1 Day 15 divided by Cmax, Cycle 1 Day 1.

PK analysis set included all participants who received M4112 and for whom at least 1 dose of M4112 and must have sufficient M4112 plasma concentration data to enable the calculation of at least 1 PK parameter. Here "Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.

Posted

Geometric Mean

Geometric Coefficient of Variation

Ratio

Pre-dose, 0.5, 1, 2, 3, 4, 6 and 8 h post-dose on Day 1 and 15 of Cycle 1 (Each Cycle is for 28 days)

ID	Title	Description
OG000	Part 1A Dose Escalation: M4112 100 mg	Participants received an oral dose of 100 milligrams (mg) M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG001	Part 1A Dose Escalation: M4112 200 mg	Participants received an oral dose of 200 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG002	Part 1A Dose Escalation: M4112 400 mg	Participants received an oral dose of 400 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG003	Part 1A Dose Escalation: M4112 600 mg	Participants received an oral dose of 600 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG004	Part 1A Dose Escalation: M4112 800 mg	Participants received an oral dose of 800 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).

Units	Counts
Participants	OG0003 OG0013 OG0023 OG003

Title

Denominators

Categories

Title	Measurements
	OG0001.21± 24.8 OG0010.815± 7.0 OG0020.856± 66.8 OG003

Secondary

Part 1A Dose Escalation: Pre-dose Observed Plasma Concentration (Cpre) of M4112

Maximum pre-dose observed plasma concentration was reported.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Pre-dose on Days 8, 15 (Cycle 1) and Day 1 (Cycle 2) (Each Cycle is 28 days)

ID	Title	Description
OG000	Part 1A Dose Escalation: M4112 100 mg	Participants received an oral dose of 100 milligrams (mg) M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG001	Part 1A Dose Escalation: M4112 200 mg	Participants received an oral dose of 200 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG002	Part 1A Dose Escalation: M4112 400 mg	Participants received an oral dose of 400 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG003	Part 1A Dose Escalation: M4112 600 mg	Participants received an oral dose of 600 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG004	Part 1A Dose Escalation: M4112 800 mg	Participants received an oral dose of 800 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).

Units	Counts
Participants	OG0003 OG0013 OG0023 OG003

Title	Denominators	Categories
Cycle 1 Day 8	ParticipantsOG0003 ParticipantsOG0013 ParticipantsOG0023 ParticipantsOG003

Secondary

Part 1A Dose Escalation: Dose Normalized Pre-dose Observed Plasma Concentration (Cpre/Dose) of M4112

Dose normalized pre-dose observed plasma concentration (Cpre/dose) of M4112 was reported.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL/mg

Pre-dose on Days 8, 15 (Cycle 1) and Day 1 (Cycle 2) (Each Cycle is 28 days)

ID	Title	Description
OG000	Part 1A Dose Escalation: M4112 100 mg	Participants received an oral dose of 100 milligrams (mg) M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG001	Part 1A Dose Escalation: M4112 200 mg	Participants received an oral dose of 200 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG002	Part 1A Dose Escalation: M4112 400 mg	Participants received an oral dose of 400 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG003	Part 1A Dose Escalation: M4112 600 mg	Participants received an oral dose of 600 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG004	Part 1A Dose Escalation: M4112 800 mg	Participants received an oral dose of 800 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).

Units	Counts
Participants	OG0003 OG0013 OG0023 OG003

Title	Denominators	Categories
Cycle 1 Day 8	ParticipantsOG0003 ParticipantsOG0013 ParticipantsOG0023 ParticipantsOG003

Secondary

Part 1A Dose Escalation: Slope of Concentration-QTc (cQTc) Regression of M4112

Time-matched, replicate ECGs and PK samples collected in the dose-escalation phase and planned to analyze QTC response using slope analysis of exposure/response.

Data was not collected as the study was prematurely terminated due to lackluster pharmacodynamic data.

Posted

Baseline up to safety follow-up visit, assessed up to 15.4 months

ID	Title	Description
OG000	Part 1A Dose Escalation: M4112 100 mg	Participants received an oral dose of 100 milligrams (mg) M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG001	Part 1A Dose Escalation: M4112 200 mg	Participants received an oral dose of 200 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG002	Part 1A Dose Escalation: M4112 400 mg	Participants received an oral dose of 400 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG003	Part 1A Dose Escalation: M4112 600 mg	Participants received an oral dose of 600 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG004	Part 1A Dose Escalation: M4112 800 mg	Participants received an oral dose of 800 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).

Units	Counts
Participants	OG0000 OG0010 OG0020 OG003

Secondary

Part 1A Dose Escalation: Number of Participants With Best Overall Response (BOR)

BOR was determined according to Response Evaluation Criteria in Solid Tumors version1.1(RECIST 1.1).Best response obtained among all tumor assessment visits after the date of first study drug administration until documented disease progression. BOR rate is defined as the number of participants with BOR was either confirmed complete response (CR) partial response (PR), stable disease (SD) and progressive disease (PD) relative to the number of participants belonging to the study of interest. CR:Disappearance of all target lesions; PR:At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD; PD:At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; SD:Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.

The safety analysis set included all participants who had received at least 1 dose of the study treatment. Here "Number of participants analyzed" signifies those participants who were evaluable for this outcome measure.

Posted

Count of Participants

Participants

From first dose of study drug administration until PD, assessed up to 15.4 months

ID	Title	Description
OG000	Part 1A Dose Escalation: M4112 100 mg	Participants received an oral dose of 100 milligrams (mg) M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG001	Part 1A Dose Escalation: M4112 200 mg	Participants received an oral dose of 200 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG002	Part 1A Dose Escalation: M4112 400 mg	Participants received an oral dose of 400 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG003	Part 1A Dose Escalation: M4112 600 mg	Participants received an oral dose of 600 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG004	Part 1A Dose Escalation: M4112 800 mg	Participants received an oral dose of 800 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).

Units	Counts
Participants	OG0003 OG0013 OG0023 OG003

Title

Denominators

Categories

Complete Response

Title	Measurements
	OG0000 OG0010 OG0020 OG003

Secondary

Part 1A Dose Escalation: Duration of Response

Duration of response defined as time from first documentation of objective response complete response (CR) or partial response (PR) whichever is first recorded) to date of first documentation of objective progression of disease or death due to any cause whichever occurs first. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of longest diameter (SLD) of all lesions.

Data was not collected as the study was prematurely terminated due to lackluster pharmacodynamic data.

Posted

From first dose of study drug administration until PD, assessed up to 15.4 months

ID	Title	Description
OG000	Part 1A Dose Escalation: M4112 100 mg	Participants received an oral dose of 100 milligrams (mg) M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG001	Part 1A Dose Escalation: M4112 200 mg	Participants received an oral dose of 200 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG002	Part 1A Dose Escalation: M4112 400 mg	Participants received an oral dose of 400 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG003	Part 1A Dose Escalation: M4112 600 mg	Participants received an oral dose of 600 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG004	Part 1A Dose Escalation: M4112 800 mg	Participants received an oral dose of 800 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).

Units	Counts
Participants	OG0000 OG0010 OG0020 OG003

Secondary

Part 1A Dose Escalation: Disease Control Rate

Disease control was defined as percentage of participants with complete response (CR), partial response (PR), or stable disease (SD) as the best overall response according to radiological assessments as adjudicated by the IRC from randomization until the first occurrence of PD. CR defined as disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR defined as at least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters. PD was defined as an increase of at least 20% in the sum of the diameters of target lesions, taking as reference the smallest sum of the diameters of target lesions recorded since treatment started. Percentage of participants with disease control were reported.

The safety analysis set included all participants who had received at least 1 dose of the study treatment.

Posted

Number

95% Confidence Interval

Percentage of Participants

From first dose of study drug administration until PD, assessed up to 15.4 months

ID	Title	Description
OG000	Part 1A Dose Escalation: M4112 100 mg	Participants received an oral dose of 100 milligrams (mg) M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG001	Part 1A Dose Escalation: M4112 200 mg	Participants received an oral dose of 200 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG002	Part 1A Dose Escalation: M4112 400 mg	Participants received an oral dose of 400 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG003	Part 1A Dose Escalation: M4112 600 mg	Participants received an oral dose of 600 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG004	Part 1A Dose Escalation: M4112 800 mg	Participants received an oral dose of 800 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).

Units	Counts
Participants	OG0003 OG0013 OG0023 OG003

Title

Denominators

Categories

Title	Measurements
	OG00066.7(9.4 to 99.2) OG001100(29.2 to 100.0) OG002100(29.2 to 100.0) OG003

Secondary

Part 1A Dose Escalation: Time to Tumor Response

Tumor response was defined as the presence of at least 1 confirmed complete response (CR) or confirmed partial response (PR) as judged by RECIST version 1.1. CR was defined for target lesions (TLs) as the disappearance of all lesions, and for non-target lesions (NTLs) as the disappearance of all non-target non-measurable lesions and/or normalization of serum levels of tumor markers. PR was defined for TLs as at least a 30 percent (%) decrease from baseline (BL) in the sum of longest diameter (SLD) of TLs.

Data was not collected as the study was prematurely terminated due to lackluster pharmacodynamic data.

Posted

From first dose of study drug administration until PD, assessed up to 15.4 months

ID	Title	Description
OG000	Part 1A Dose Escalation: M4112 100 mg	Participants received an oral dose of 100 milligrams (mg) M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG001	Part 1A Dose Escalation: M4112 200 mg	Participants received an oral dose of 200 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG002	Part 1A Dose Escalation: M4112 400 mg	Participants received an oral dose of 400 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG003	Part 1A Dose Escalation: M4112 600 mg	Participants received an oral dose of 600 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG004	Part 1A Dose Escalation: M4112 800 mg	Participants received an oral dose of 800 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).

Units	Counts
Participants	OG0000 OG0010 OG0020 OG003

Secondary

Part 1A Dose Escalation: Progression Free Survival Time (PFS)

Progression free survival time defined as time from start date to the date of the first documentation of objective progression of disease or death due to any cause, whichever occurs first. PD was defined as at least a 20 percent (%) increase in the sum of longest diameter (SLD), 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.

The safety analysis set included all participants who had received at least 1 dose of the study treatment.

Posted

Median

Full Range

Months

From first dose of study drug administration until PD, assessed up to 15.4 months

ID	Title	Description
OG000	Part 1A Dose Escalation: M4112 100 mg	Participants received an oral dose of 100 milligrams (mg) M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG001	Part 1A Dose Escalation: M4112 200 mg	Participants received an oral dose of 200 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG002	Part 1A Dose Escalation: M4112 400 mg	Participants received an oral dose of 400 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG003	Part 1A Dose Escalation: M4112 600 mg	Participants received an oral dose of 600 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).
OG004	Part 1A Dose Escalation: M4112 800 mg	Participants received an oral dose of 800 mg M4112 twice daily in 28-day cycles, starting from Day 1 of each cycle until confirmed disease progression or unacceptable toxicity (up to 15 Months).

Units	Counts
Participants	OG0003 OG0013 OG0023 OG003

Title

Denominators

Categories

Title	Measurements
	OG0003.7(1.9 to 8.1) OG0015.5(3.9 to 5.5) OG002NA(2.1 to 10.2)The Median was not reached due to higher number (\>50%) of censored participants.

Cycle 2 Day 1

- ParticipantsOG0003
- ParticipantsOG0012
- ParticipantsOG0023
- ParticipantsOG0032
- ParticipantsOG0041

Title	Measurements
	OG000128± 67.7 OG001NA± NAGeometric Mean and Geometric Coefficient of Variation were not calculated as it was pre-specified not to calculate the Descriptive statistics if less than 3 number of participants. Individual values were 83.3 and 85.2 ng/mL. OG002957± 72.1 OG003

Cycle 2 Day 1

- ParticipantsOG0003
- ParticipantsOG0012
- ParticipantsOG0023
- ParticipantsOG0032
- ParticipantsOG0041

Title	Measurements
	OG0001.28± 67.7 OG001NA± NAGeometric Mean and Geometric Coefficient of Variation were not calculated as it was pre-specified not to calculate the Descriptive statistics if less than 3 number of participants. Individual values were 0.417 and 0.426 ng/mL/mg. OG0022.39± 72.1 OG003