Trial Outcomes & Findings for First-in-human Study of M4076 in Advanced Solid Tumors (DDRiver Solid Tumors 410) (NCT NCT04882917)

NCT ID: NCT04882917

Last Updated: 2025-03-07

Results Overview

A DLT was defined as the occurrence of any of following events that were judged by the study investigator, received at least 80% of the planned cumulative dose during the DLT period of each study intervention and completed the DLT period or additionally, participants who did not receive 80% of the planned total dose of study intervention, but at least 80% dosing of a different dose cohort and finished the DLT period are eligible for the DLT analysis set to be analyzed in the highest dose cohort for which they received 80% of dosing.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 22 participants
• Primary outcome timeframe: Day 1 to Day 21 of Cycle 1 (21-day cycle)
• Results posted on: 2025-03-07

Participant Flow

A total of 31 participants were screened, of which 22 participants received the study drug.

This study was to be conducted in 2 parts; Part 1A was the dose escalation phase and Part 1B was the expansion phase. However, the sponsor decided not to conduct the expansion phase (Part 2).

Participant milestones

Measure	Part 1A Dose Escalation: M4076 100 mg Participants received M4076 film coated tablets at a dose of 100 milligrams (mg), orally once daily in 21-day cycles, starting from Day 1 of each cycle disease progression, death, AE leading to discontinuation of study intervention(s), or withdrawal of consent, whichever occurred first, or End of Study	Part 1A Dose Escalation: M4076 200 mg Participants received M4076 film coated tablets at a dose of 200 mg, orally once daily in 21-day cycles, starting from Day 1 of each cycle disease progression, death, AE leading to discontinuation of study intervention(s), or withdrawal of consent, whichever occurred first, or End of Study.	Part 1A Dose Escalation: M4076 300 mg Participants received M4076 film coated tablets at a dose of 300 mg, orally once daily in 21-day cycles, starting from Day 1 of each cycle disease progression, death, AE leading to discontinuation of study intervention(s), or withdrawal of consent, whichever occurred first, or End of Study.	Part 1A Dose Escalation: M4076 400 mg Participants received M4076 film coated tablets at a dose of 400 mg, orally once daily in 21-day cycles, starting from Day 1 of each cycle disease progression, death, AE leading to discontinuation of study intervention(s), or withdrawal of consent, whichever occurred first, or End of Study.
Overall Study STARTED	2	7	9	4
Overall Study COMPLETED	0	6	5	1
Overall Study NOT COMPLETED	2	1	4	3

Reasons for withdrawal

Measure	Part 1A Dose Escalation: M4076 100 mg Participants received M4076 film coated tablets at a dose of 100 milligrams (mg), orally once daily in 21-day cycles, starting from Day 1 of each cycle disease progression, death, AE leading to discontinuation of study intervention(s), or withdrawal of consent, whichever occurred first, or End of Study	Part 1A Dose Escalation: M4076 200 mg Participants received M4076 film coated tablets at a dose of 200 mg, orally once daily in 21-day cycles, starting from Day 1 of each cycle disease progression, death, AE leading to discontinuation of study intervention(s), or withdrawal of consent, whichever occurred first, or End of Study.	Part 1A Dose Escalation: M4076 300 mg Participants received M4076 film coated tablets at a dose of 300 mg, orally once daily in 21-day cycles, starting from Day 1 of each cycle disease progression, death, AE leading to discontinuation of study intervention(s), or withdrawal of consent, whichever occurred first, or End of Study.	Part 1A Dose Escalation: M4076 400 mg Participants received M4076 film coated tablets at a dose of 400 mg, orally once daily in 21-day cycles, starting from Day 1 of each cycle disease progression, death, AE leading to discontinuation of study intervention(s), or withdrawal of consent, whichever occurred first, or End of Study.
Overall Study Adverse Event	0	1	2	2
Overall Study Withdrawal by Subject	1	0	2	1
Overall Study COVID-19-related and COVID-19-non-related	1	0	0	0

Baseline Characteristics

First-in-human Study of M4076 in Advanced Solid Tumors (DDRiver Solid Tumors 410)

Baseline characteristics by cohort

Measure	Part 1A Dose Escalation: M4076 100 mg n=2 Participants Participants received M4076 film coated tablets at a dose of 100 milligrams (mg), orally once daily in 21-day cycles, starting from Day 1 of each cycle disease progression, death, AE leading to discontinuation of study intervention(s), or withdrawal of consent, whichever occurred first, or End of Study	Part 1A Dose Escalation: M4076 200 mg n=7 Participants Participants received M4076 film coated tablets at a dose of 200 mg, orally once daily in 21-day cycles, starting from Day 1 of each cycle disease progression, death, AE leading to discontinuation of study intervention(s), or withdrawal of consent, whichever occurred first, or End of Study.	Part 1A Dose Escalation: M4076 300 mg n=9 Participants Participants received M4076 film coated tablets at a dose of 300 mg, orally once daily in 21-day cycles, starting from Day 1 of each cycle disease progression, death, AE leading to discontinuation of study intervention(s), or withdrawal of consent, whichever occurred first, or End of Study.	Part 1A Dose Escalation: M4076 400 mg n=4 Participants Participants received M4076 film coated tablets at a dose of 400 mg, orally once daily in 21-day cycles, starting from Day 1 of each cycle disease progression, death, AE leading to discontinuation of study intervention(s), or withdrawal of consent, whichever occurred first, or End of Study.	Total n=22 Participants Total of all reporting groups
Age, Continuous	74 Years STANDARD_DEVIATION 6.4 • n=5 Participants	53 Years STANDARD_DEVIATION 7.0 • n=7 Participants	60 Years STANDARD_DEVIATION 7.9 • n=5 Participants	57 Years STANDARD_DEVIATION 5.7 • n=4 Participants	58 Years STANDARD_DEVIATION 8.8 • n=21 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	5 Participants n=7 Participants	4 Participants n=5 Participants	3 Participants n=4 Participants	13 Participants n=21 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants	1 Participants n=4 Participants	9 Participants n=21 Participants
Race/Ethnicity, Customized Ethnicity-Hispanic or Latino	1 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	4 Participants n=21 Participants
Race/Ethnicity, Customized Ethnicity-Not Hispanic or Latino	1 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants	4 Participants n=4 Participants	18 Participants n=21 Participants
Race/Ethnicity, Customized Race-Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	2 Participants n=21 Participants
Race/Ethnicity, Customized Race-Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race/Ethnicity, Customized Race-Other	0 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants
Race/Ethnicity, Customized Race-White	2 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants	3 Participants n=4 Participants	17 Participants n=21 Participants

PRIMARY outcome

Timeframe: Day 1 to Day 21 of Cycle 1 (21-day cycle)

Population: Dose escalation set included all participants who received at least 80 percent (%) of the planned cumulative dose during the DLT period (Period 1) and have completed the DLT Period or experienced at least one DLT during the DLT period, regardless of administered number of doses of study intervention.

A DLT was defined as the occurrence of any of following events that were judged by the study investigator, received at least 80% of the planned cumulative dose during the DLT period of each study intervention and completed the DLT period or additionally, participants who did not receive 80% of the planned total dose of study intervention, but at least 80% dosing of a different dose cohort and finished the DLT period are eligible for the DLT analysis set to be analyzed in the highest dose cohort for which they received 80% of dosing.

Outcome measures

Measure	Part 1A Dose Escalation: M4076 100 mg n=2 Participants Participants received M4076 film coated tablets at a dose of 100 milligrams (mg), orally once daily in 21-day cycles, starting from Day 1 of each cycle disease progression, death, AE leading to discontinuation of study intervention(s), or withdrawal of consent, whichever occurred first, or End of Study	Part 1A Dose Escalation: M4076 200 mg n=5 Participants Participants received M4076 film coated tablets at a dose of 200 mg, orally once daily in 21-day cycles, starting from Day 1 of each cycle disease progression, death, AE leading to discontinuation of study intervention(s), or withdrawal of consent, whichever occurred first, or End of Study.	Part 1A Dose Escalation: M4076 300 mg n=7 Participants Participants received M4076 film coated tablets at a dose of 300 mg, orally once daily in 21-day cycles, starting from Day 1 of each cycle disease progression, death, AE leading to discontinuation of study intervention(s), or withdrawal of consent, whichever occurred first, or End of Study.	Part 1A Dose Escalation: M4076 400 mg n=4 Participants Participants received M4076 film coated tablets at a dose of 400 mg, orally once daily in 21-day cycles, starting from Day 1 of each cycle disease progression, death, AE leading to discontinuation of study intervention(s), or withdrawal of consent, whichever occurred first, or End of Study.
Number of Participants Who Experienced Dose Limiting Toxicities (DLTs) Assessed Using National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) Version 5.0	0 Participants	1 Participants	1 Participants	2 Participants

PRIMARY outcome

Timeframe: From the first dose of study drug administration until 30 days after the last dose of study drug administration (up to 603 days)

Population: Safety analysis set included all participants who were administered at least one dose of any study intervention.

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.

Outcome measures

Measure	Part 1A Dose Escalation: M4076 100 mg n=2 Participants Participants received M4076 film coated tablets at a dose of 100 milligrams (mg), orally once daily in 21-day cycles, starting from Day 1 of each cycle disease progression, death, AE leading to discontinuation of study intervention(s), or withdrawal of consent, whichever occurred first, or End of Study	Part 1A Dose Escalation: M4076 200 mg n=7 Participants Participants received M4076 film coated tablets at a dose of 200 mg, orally once daily in 21-day cycles, starting from Day 1 of each cycle disease progression, death, AE leading to discontinuation of study intervention(s), or withdrawal of consent, whichever occurred first, or End of Study.	Part 1A Dose Escalation: M4076 300 mg n=9 Participants Participants received M4076 film coated tablets at a dose of 300 mg, orally once daily in 21-day cycles, starting from Day 1 of each cycle disease progression, death, AE leading to discontinuation of study intervention(s), or withdrawal of consent, whichever occurred first, or End of Study.	Part 1A Dose Escalation: M4076 400 mg n=4 Participants Participants received M4076 film coated tablets at a dose of 400 mg, orally once daily in 21-day cycles, starting from Day 1 of each cycle disease progression, death, AE leading to discontinuation of study intervention(s), or withdrawal of consent, whichever occurred first, or End of Study.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment Related TEAEs TEAEs	2 Participants	7 Participants	9 Participants	4 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment Related TEAEs Treatment Related TEAEs	1 Participants	2 Participants	8 Participants	4 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1) up to 30 days after the last dose of study drug administration (up to 603 days)

Population: Safety analysis set included all participants who were administered at least one dose of any study intervention.

Vital sign assessments included assessments of heart rate, diastolic blood pressure, systolic blood pressure, weight, respiratory rate and temperature. Clinical significance was assessed by the investigator. Number of participants who with clinically significant changes from baseline in vital signs were reported.

Outcome measures

Measure	Part 1A Dose Escalation: M4076 100 mg n=2 Participants Participants received M4076 film coated tablets at a dose of 100 milligrams (mg), orally once daily in 21-day cycles, starting from Day 1 of each cycle disease progression, death, AE leading to discontinuation of study intervention(s), or withdrawal of consent, whichever occurred first, or End of Study	Part 1A Dose Escalation: M4076 200 mg n=7 Participants Participants received M4076 film coated tablets at a dose of 200 mg, orally once daily in 21-day cycles, starting from Day 1 of each cycle disease progression, death, AE leading to discontinuation of study intervention(s), or withdrawal of consent, whichever occurred first, or End of Study.	Part 1A Dose Escalation: M4076 300 mg n=9 Participants Participants received M4076 film coated tablets at a dose of 300 mg, orally once daily in 21-day cycles, starting from Day 1 of each cycle disease progression, death, AE leading to discontinuation of study intervention(s), or withdrawal of consent, whichever occurred first, or End of Study.	Part 1A Dose Escalation: M4076 400 mg n=4 Participants Participants received M4076 film coated tablets at a dose of 400 mg, orally once daily in 21-day cycles, starting from Day 1 of each cycle disease progression, death, AE leading to discontinuation of study intervention(s), or withdrawal of consent, whichever occurred first, or End of Study.
Number of Participants With Clinically Significant Changes From Baseline in Vital Signs	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1) up to 30 days after the last dose of study drug administration (up to 603 days)

Population: Safety analysis set included all participants who were administered at least one dose of any study intervention.

The laboratory measurements included hematology and biochemistry values were graded with National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 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 and biochemistry were reported.

Outcome measures

Measure	Part 1A Dose Escalation: M4076 100 mg n=2 Participants Participants received M4076 film coated tablets at a dose of 100 milligrams (mg), orally once daily in 21-day cycles, starting from Day 1 of each cycle disease progression, death, AE leading to discontinuation of study intervention(s), or withdrawal of consent, whichever occurred first, or End of Study	Part 1A Dose Escalation: M4076 200 mg n=7 Participants Participants received M4076 film coated tablets at a dose of 200 mg, orally once daily in 21-day cycles, starting from Day 1 of each cycle disease progression, death, AE leading to discontinuation of study intervention(s), or withdrawal of consent, whichever occurred first, or End of Study.	Part 1A Dose Escalation: M4076 300 mg n=9 Participants Participants received M4076 film coated tablets at a dose of 300 mg, orally once daily in 21-day cycles, starting from Day 1 of each cycle disease progression, death, AE leading to discontinuation of study intervention(s), or withdrawal of consent, whichever occurred first, or End of Study.	Part 1A Dose Escalation: M4076 400 mg n=4 Participants Participants received M4076 film coated tablets at a dose of 400 mg, orally once daily in 21-day cycles, starting from Day 1 of each cycle disease progression, death, AE leading to discontinuation of study intervention(s), or withdrawal of consent, whichever occurred first, or End of Study.
Number of Participants With Change From Baseline in Laboratory Test Abnormalities to Grade 3 or Higher Severity Based on NCI-CTCAE Version 5.0 Grade>=3 Bilirubin High	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Change From Baseline in Laboratory Test Abnormalities to Grade 3 or Higher Severity Based on NCI-CTCAE Version 5.0 Grade>=3 Alkaline Phosphatase High	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Change From Baseline in Laboratory Test Abnormalities to Grade 3 or Higher Severity Based on NCI-CTCAE Version 5.0 Grade>=3 Gamma Glutamyl Transferase High	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Change From Baseline in Laboratory Test Abnormalities to Grade 3 or Higher Severity Based on NCI-CTCAE Version 5.0 Grade>=3 Alanine Aminotransferase High	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Change From Baseline in Laboratory Test Abnormalities to Grade 3 or Higher Severity Based on NCI-CTCAE Version 5.0 Grade>=3 Aspartate Aminotransferase High	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Change From Baseline in Laboratory Test Abnormalities to Grade 3 or Higher Severity Based on NCI-CTCAE Version 5.0 Grade>=3 Lipase High	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Change From Baseline in Laboratory Test Abnormalities to Grade 3 or Higher Severity Based on NCI-CTCAE Version 5.0 Grade>=3 Sodium Low	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Change From Baseline in Laboratory Test Abnormalities to Grade 3 or Higher Severity Based on NCI-CTCAE Version 5.0 Grade>=3 Potassium High	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Change From Baseline in Laboratory Test Abnormalities to Grade 3 or Higher Severity Based on NCI-CTCAE Version 5.0 Grade>=3 Potassium Low	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Change From Baseline in Laboratory Test Abnormalities to Grade 3 or Higher Severity Based on NCI-CTCAE Version 5.0 Grade>=3 Calcium High	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Change From Baseline in Laboratory Test Abnormalities to Grade 3 or Higher Severity Based on NCI-CTCAE Version 5.0 Grade>=3 Hemoglobin Low	0 Participants	1 Participants	2 Participants	1 Participants
Number of Participants With Change From Baseline in Laboratory Test Abnormalities to Grade 3 or Higher Severity Based on NCI-CTCAE Version 5.0 Grade>=3 Lymphocytes Low	0 Participants	3 Participants	3 Participants	2 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1) up to 30 days after the last dose of study drug administration (up to 603 days)

Population: Safety analysis set included all participants who were administered at least one dose of any study intervention.

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 significant change from baseline in 12-lead ECG were reported.

Outcome measures

Measure	Part 1A Dose Escalation: M4076 100 mg n=2 Participants Participants received M4076 film coated tablets at a dose of 100 milligrams (mg), orally once daily in 21-day cycles, starting from Day 1 of each cycle disease progression, death, AE leading to discontinuation of study intervention(s), or withdrawal of consent, whichever occurred first, or End of Study	Part 1A Dose Escalation: M4076 200 mg n=7 Participants Participants received M4076 film coated tablets at a dose of 200 mg, orally once daily in 21-day cycles, starting from Day 1 of each cycle disease progression, death, AE leading to discontinuation of study intervention(s), or withdrawal of consent, whichever occurred first, or End of Study.	Part 1A Dose Escalation: M4076 300 mg n=9 Participants Participants received M4076 film coated tablets at a dose of 300 mg, orally once daily in 21-day cycles, starting from Day 1 of each cycle disease progression, death, AE leading to discontinuation of study intervention(s), or withdrawal of consent, whichever occurred first, or End of Study.	Part 1A Dose Escalation: M4076 400 mg n=4 Participants Participants received M4076 film coated tablets at a dose of 400 mg, orally once daily in 21-day cycles, starting from Day 1 of each cycle disease progression, death, AE leading to discontinuation of study intervention(s), or withdrawal of consent, whichever occurred first, or End of Study.
Number of Participants With Clinically Significant Changes From Baseline in Electrocardiogram (ECG) Values	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Time from first study treatment up to 603 days

Population: Full analysis set included all participants who were administered at least one dose of any study intervention.

Confirmed objective response was defined as the number of participants with a confirmed objective response of complete response (CR) or partial response (PR). CR: 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. Confirmed CR = at least 2 determinations of CR at least 4 weeks apart and before progression. Confirmed PR = at least 2 determinations of PR at least 4 weeks apart and before progression (and not qualifying for a CR).

Outcome measures

Measure	Part 1A Dose Escalation: M4076 100 mg n=2 Participants Participants received M4076 film coated tablets at a dose of 100 milligrams (mg), orally once daily in 21-day cycles, starting from Day 1 of each cycle disease progression, death, AE leading to discontinuation of study intervention(s), or withdrawal of consent, whichever occurred first, or End of Study	Part 1A Dose Escalation: M4076 200 mg n=7 Participants Participants received M4076 film coated tablets at a dose of 200 mg, orally once daily in 21-day cycles, starting from Day 1 of each cycle disease progression, death, AE leading to discontinuation of study intervention(s), or withdrawal of consent, whichever occurred first, or End of Study.	Part 1A Dose Escalation: M4076 300 mg n=9 Participants Participants received M4076 film coated tablets at a dose of 300 mg, orally once daily in 21-day cycles, starting from Day 1 of each cycle disease progression, death, AE leading to discontinuation of study intervention(s), or withdrawal of consent, whichever occurred first, or End of Study.	Part 1A Dose Escalation: M4076 400 mg n=4 Participants Participants received M4076 film coated tablets at a dose of 400 mg, orally once daily in 21-day cycles, starting from Day 1 of each cycle disease progression, death, AE leading to discontinuation of study intervention(s), or withdrawal of consent, whichever occurred first, or End of Study.
Number of Participants With Confirmed Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Investigator	0 Participants Interval 0.0 to 84.19	0 Participants Interval 0.0 to 40.96	0 Participants Interval 0.0 to 33.63	0 Participants Interval 0.0 to 15.44

SECONDARY outcome

Timeframe: Time from first documentation of objective response to the date of first documentation of PD or death due to any cause, assessed up to 603 days

Population: None of the participants showed objective response.

DOR was defined for participants with confirmed response, as the time from first documentation of objective response (Complete Response [CR] or Partial Response [PR]) to the date of first documentation of progression disease (PD) or death due to any cause, whichever occurred first. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the SLD of all lesions. PD: At least a 20 percent (%) increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Time from the first dose of study intervention until occurrence of PD, death due to any cause or last tumor assessment (assessed up to 603 days)

Population: Full analysis set included all participants who were administered at least one dose of any study intervention.

PFS is defined as the time (in months) from date of first administration of study intervention to the date of the first documentation of progressive disease (PD) or death due to any cause, whichever occurs first. PD is defined as at least a 20 percent (%) increase in the sum of the longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. PFS was to be estimated using Kaplan-Meier (KM) plots.

Outcome measures

Measure	Part 1A Dose Escalation: M4076 100 mg n=2 Participants Participants received M4076 film coated tablets at a dose of 100 milligrams (mg), orally once daily in 21-day cycles, starting from Day 1 of each cycle disease progression, death, AE leading to discontinuation of study intervention(s), or withdrawal of consent, whichever occurred first, or End of Study	Part 1A Dose Escalation: M4076 200 mg n=7 Participants Participants received M4076 film coated tablets at a dose of 200 mg, orally once daily in 21-day cycles, starting from Day 1 of each cycle disease progression, death, AE leading to discontinuation of study intervention(s), or withdrawal of consent, whichever occurred first, or End of Study.	Part 1A Dose Escalation: M4076 300 mg n=9 Participants Participants received M4076 film coated tablets at a dose of 300 mg, orally once daily in 21-day cycles, starting from Day 1 of each cycle disease progression, death, AE leading to discontinuation of study intervention(s), or withdrawal of consent, whichever occurred first, or End of Study.	Part 1A Dose Escalation: M4076 400 mg n=4 Participants Participants received M4076 film coated tablets at a dose of 400 mg, orally once daily in 21-day cycles, starting from Day 1 of each cycle disease progression, death, AE leading to discontinuation of study intervention(s), or withdrawal of consent, whichever occurred first, or End of Study.
Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by Investigators	NA months Median (and corresponding 95% CI) could not be estimated by KM estimates as there was no event of interest.	1.1 months Interval 0.2 to 1.58	1.3 months Interval 0.69 to 2.6	NA months Interval 1.22 to Median (and corresponding 95% CI) could not be estimated due to low number of events of interest (1 participant).

SECONDARY outcome

Timeframe: Day 1 and Day 8

Population: Pharmacokinetic Analysis Set included all participants who were administered at least one dose of study intervention. Here, "Number analyzed" signifies those participants who were evaluable for this outcome measure at specified timepoints.

Area under the plasma concentration vs time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLOQ). AUC0-tlast was to be calculated according to the mixed log-linear trapezoidal rule.

Outcome measures

Measure	Part 1A Dose Escalation: M4076 100 mg n=2 Participants Participants received M4076 film coated tablets at a dose of 100 milligrams (mg), orally once daily in 21-day cycles, starting from Day 1 of each cycle disease progression, death, AE leading to discontinuation of study intervention(s), or withdrawal of consent, whichever occurred first, or End of Study	Part 1A Dose Escalation: M4076 200 mg n=7 Participants Participants received M4076 film coated tablets at a dose of 200 mg, orally once daily in 21-day cycles, starting from Day 1 of each cycle disease progression, death, AE leading to discontinuation of study intervention(s), or withdrawal of consent, whichever occurred first, or End of Study.	Part 1A Dose Escalation: M4076 300 mg n=9 Participants Participants received M4076 film coated tablets at a dose of 300 mg, orally once daily in 21-day cycles, starting from Day 1 of each cycle disease progression, death, AE leading to discontinuation of study intervention(s), or withdrawal of consent, whichever occurred first, or End of Study.	Part 1A Dose Escalation: M4076 400 mg n=4 Participants Participants received M4076 film coated tablets at a dose of 400 mg, orally once daily in 21-day cycles, starting from Day 1 of each cycle disease progression, death, AE leading to discontinuation of study intervention(s), or withdrawal of consent, whichever occurred first, or End of Study.
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Sampling Time (AUClast) of M4076 Day 1	NA hour*nanograms per milliliter Geometric Coefficient of Variation NA Based on pre-specified criteria, statistical analysis was only performed if more than 2 participants have reportable parameter values.	37000 hour*nanograms per milliliter Geometric Coefficient of Variation 34.1	50500 hour*nanograms per milliliter Geometric Coefficient of Variation 45.1	76600 hour*nanograms per milliliter Geometric Coefficient of Variation 44.3
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Sampling Time (AUClast) of M4076 Day 8	NA hour*nanograms per milliliter Geometric Coefficient of Variation NA Based on pre-specified criteria, statistical analysis was only performed if more than 2 participants have reportable parameter values.	36500 hour*nanograms per milliliter Geometric Coefficient of Variation 109.2	56500 hour*nanograms per milliliter Geometric Coefficient of Variation 67.6	85900 hour*nanograms per milliliter Geometric Coefficient of Variation 40.8

SECONDARY outcome

Timeframe: Day 1 and Day 8

Population: Pharmacokinetic Analysis Set included all participants who were administered at least one dose of study intervention. Here, "Number of participants analyzed" signifies those participants who were evaluable for this outcome measure.

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. AUC0-inf = AUC0-tlast +Clast pred/ lambda z (single dose only)

Outcome measures

Measure	Part 1A Dose Escalation: M4076 100 mg n=2 Participants Participants received M4076 film coated tablets at a dose of 100 milligrams (mg), orally once daily in 21-day cycles, starting from Day 1 of each cycle disease progression, death, AE leading to discontinuation of study intervention(s), or withdrawal of consent, whichever occurred first, or End of Study	Part 1A Dose Escalation: M4076 200 mg n=6 Participants Participants received M4076 film coated tablets at a dose of 200 mg, orally once daily in 21-day cycles, starting from Day 1 of each cycle disease progression, death, AE leading to discontinuation of study intervention(s), or withdrawal of consent, whichever occurred first, or End of Study.	Part 1A Dose Escalation: M4076 300 mg n=6 Participants Participants received M4076 film coated tablets at a dose of 300 mg, orally once daily in 21-day cycles, starting from Day 1 of each cycle disease progression, death, AE leading to discontinuation of study intervention(s), or withdrawal of consent, whichever occurred first, or End of Study.	Part 1A Dose Escalation: M4076 400 mg n=3 Participants Participants received M4076 film coated tablets at a dose of 400 mg, orally once daily in 21-day cycles, starting from Day 1 of each cycle disease progression, death, AE leading to discontinuation of study intervention(s), or withdrawal of consent, whichever occurred first, or End of Study.
Area Under Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of M4076 Day 1	NA h*ng/mL Geometric Coefficient of Variation NA Based on pre-specified criteria, statistical analysis was only performed if more than 2 participants have reportable parameter values.	39200 h*ng/mL Geometric Coefficient of Variation 40.3	44900 h*ng/mL Geometric Coefficient of Variation 49.9	69800 h*ng/mL Geometric Coefficient of Variation 20.4

SECONDARY outcome

Timeframe: Day 1 and Day 8

Population: Pharmacokinetic Analysis Set included all participants who were administered at least one dose of study intervention, have no clinically important protocol deviations or important events affecting pharmacodynamics, and provide the baseline and at least one measurable pharmacodynamics endpoint post dose. Here, "Number of participants analyzed" signifies those participants who were evaluable for this outcome measure.

Cmax was obtained directly from the concentration versus time curve.

Outcome measures

Measure	Part 1A Dose Escalation: M4076 100 mg n=2 Participants Participants received M4076 film coated tablets at a dose of 100 milligrams (mg), orally once daily in 21-day cycles, starting from Day 1 of each cycle disease progression, death, AE leading to discontinuation of study intervention(s), or withdrawal of consent, whichever occurred first, or End of Study	Part 1A Dose Escalation: M4076 200 mg n=6 Participants Participants received M4076 film coated tablets at a dose of 200 mg, orally once daily in 21-day cycles, starting from Day 1 of each cycle disease progression, death, AE leading to discontinuation of study intervention(s), or withdrawal of consent, whichever occurred first, or End of Study.	Part 1A Dose Escalation: M4076 300 mg n=8 Participants Participants received M4076 film coated tablets at a dose of 300 mg, orally once daily in 21-day cycles, starting from Day 1 of each cycle disease progression, death, AE leading to discontinuation of study intervention(s), or withdrawal of consent, whichever occurred first, or End of Study.	Part 1A Dose Escalation: M4076 400 mg n=3 Participants Participants received M4076 film coated tablets at a dose of 400 mg, orally once daily in 21-day cycles, starting from Day 1 of each cycle disease progression, death, AE leading to discontinuation of study intervention(s), or withdrawal of consent, whichever occurred first, or End of Study.
Maximum Observed Plasma Concentration (Cmax) of M4076 Day 1	NA nanogram per milliliter (ng/mL) Geometric Coefficient of Variation NA Based on pre-specified criteria, statistical analysis was only performed if more than 2 participants have reportable parameter values	4080 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 26.5	6270 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 20.3	8510 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 30.1
Maximum Observed Plasma Concentration (Cmax) of M4076 Day 8	NA nanogram per milliliter (ng/mL) Geometric Coefficient of Variation NA Based on pre-specified criteria, statistical analysis was only performed if more than 2 participants have reportable parameter values.	4690 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 52.5	6730 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 26.3	9600 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 22.8

SECONDARY outcome

Timeframe: Baseline up to Day 23

Population: Data for p-ATM was not generated due to insufficient samples as all Peripheral Blood Mononuclear Cells (PBMC) samples were exhausted in gamma-H2AX analysis. Hence no data was collected.

Phosphorylated ataxia-telangiectasia mutated (p-ATM) is measured by flow cytometry and immunohistochemistry. Absolute change from baseline was to be reported.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline up to Day 23

Population: Data for p-CHK2 was not generated as no fresh tumor biopsies were collected. Hence no data was collected.

p-CHK2 is measured by flow cytometry and immunohistochemistry. Absolute change from baseline was to be reported.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline up to Day 23

Population: Data for p-ATM was not generated due to insufficient samples as all Peripheral Blood Mononuclear Cells (PBMC) samples were exhausted in gamma-H2AX analysis. Hence no data was collected.

Phosphorylated ataxia-telangiectasia mutated (p-ATM) is measured by flow cytometry and immunohistochemistry. Relative change from baseline was to be reported.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline up to Day 23

Population: Data for p-CHK2 was not generated as no fresh tumor biopsies were collected. Hence no data was collected.

p-CHK2 is measured by flow cytometry and immunohistochemistry. Relative change from baseline was to be reported.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline up to Day 23

Population: The pharmacodynamics (Pd) Analysis Set consisted of all participants, who received at least one dose of study intervention, had no clinically important protocol deviations or important events affecting Pd, and provide the baseline and at least one measurable Pd endpoint postdose. Participants will be analyzed per the actual study intervention they received.

gamma-H2AX is measured by flow cytometry and immunohistochemistry. Absolute values were reported for each participant as descriptive data for this outcome measure was not calculated. P= Part, D=Day, H=Hour in the below mentioned categories. Mean Fluorescent Intensity (MFI) is a number generated by the flow cytometer; an instrument that measures the fluorescent signal emitted by a sample. The stronger the fluorescent signal, the higher the MFI value detected by the instrument's acquisition software. The values displayed in the system represent each MFI measurement at different time points, with the MFI value for the blank sample subtracted.

Outcome measures

Measure	Part 1A Dose Escalation: M4076 100 mg n=21 Participants Participants received M4076 film coated tablets at a dose of 100 milligrams (mg), orally once daily in 21-day cycles, starting from Day 1 of each cycle disease progression, death, AE leading to discontinuation of study intervention(s), or withdrawal of consent, whichever occurred first, or End of Study	Part 1A Dose Escalation: M4076 200 mg Participants received M4076 film coated tablets at a dose of 200 mg, orally once daily in 21-day cycles, starting from Day 1 of each cycle disease progression, death, AE leading to discontinuation of study intervention(s), or withdrawal of consent, whichever occurred first, or End of Study.	Part 1A Dose Escalation: M4076 300 mg Participants received M4076 film coated tablets at a dose of 300 mg, orally once daily in 21-day cycles, starting from Day 1 of each cycle disease progression, death, AE leading to discontinuation of study intervention(s), or withdrawal of consent, whichever occurred first, or End of Study.	Part 1A Dose Escalation: M4076 400 mg Participants received M4076 film coated tablets at a dose of 400 mg, orally once daily in 21-day cycles, starting from Day 1 of each cycle disease progression, death, AE leading to discontinuation of study intervention(s), or withdrawal of consent, whichever occurred first, or End of Study.
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant1(P1AD1-2H Postdose)	1316 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant1(P1AD1-4H Postdose)	1037 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant1(P1AD1-6H Postdose)	3127 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant1(P1AD1-Predose)	1612 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant1(P1AD2-2-4H Postdose)	347 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant1(P1AD2-Predose)	1925 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant1(P1A/1BD22-2H Postdose	1030 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant1(P1A/1BD22-4H Postdose)	1023 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant1(P1A/1BD22-Predose)	1461 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant2(P1AD1-6H Postdose)	896 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant2(P1AD2-2-4H Postdose)	143 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant2(P1A/1BD22-2H Postdose)	753 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant2(P1A/1BD22-Predose)	1441 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant3(P1AD1-2H Postdose)	5555 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant3(P1AD1-4H Postdose)	4432 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant3(P1AD2-2H-4H Postdose)	1504 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant3(P1AD2-4H Predose)	2649 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant4(P1AD1-2H Postdose)	879 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant4(P1AD1-4H Potdose)	395 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant4(P1AD1-6H Postdose)	702 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant4(P1AD1-Predose)	-34 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant4(P1AD2-2H-4H Postdose)	1045 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant4(P1AD2-Predose)	1057 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant5(P1AD1-2H Postdose)	195 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant5(P1AD1-4H Postdose)	171 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant5(P1AD1-6H Postdose)	75 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant5(P1AD1-Predose)	144 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant5(P1AD2-2H-4H Postdose)	0 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant5(P1AD2-Predose)	22 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant6(P1AD1-2H Postdose)	57 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant6(P1AD1-4H Postdose)	138 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant6(P1AD1-6H Postdose)	116 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant6(P1AD1-4H Predose)	206 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant6(P1AD2-2H-4H Postdose)	1 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant6(P1AD2- Predose)	29 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant6(P1A/1BD22-2H Postdose)	994 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant6(P1A/1BD22-4H Postdose)	786 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant6(P1A/1BD22-Predose)	2371 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant7(P1A/1BD22-4H Postdose)	5397 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant7(P1A/1BD22-2H-4H Postdose)	770 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant7(P1AD2-Predose)	1103 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant8(P1AD1-2H Postdose)	1775 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant8(P1AD1-4H Postdose)	1504 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant8(P1AD1-6H Postdose)	854 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant8(P1AD1-Predose)	2294 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant8(P1AD1-2H-4H Postdose)	381 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant8(Part1AD2-Predose)	910 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant9(P1AD1-2H Postdose)	2836 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant9(P1AD1-4H Postdose)	1499 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant9(P1AD1-6H Postdose)	1901 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant9(P1AD1-Predose)	-4092 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant9(P1AD2-2H-4H Postdose)	2392 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant9(P1A/1BD22-2H Postdose)	2795 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant9(P1A/1BD22-4H Postdose)	3375 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant9(P1A/1BD22-Predose)	3412 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant10(P1A/1BD22-2H Postdose)	747 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant10(P1A/1BD22-4H Postdose)	1186 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant10(P1A/1BD22-Predose)	1608 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant10(P1AD1-2H Postdose)	2014 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant10(P1AD1-4H Postdose)	1522 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant10(P1AD1-2H-4H Postdose)	2363 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant10(P1AD2-Predose)	1018 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant11(P1AD1-2H Postdose)	2432 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant11(P1AD1-4H Postdose)	1282 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant11(P1A/1BD22-2H Postdose)	-802 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant11(P1A/1BD22- Predose)	-904 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant11(P1A/1BD22-4H Postdose)	-1708 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant12(P1AD1-2H Postdose)	3613 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant12(P1AD1-Predose)	5007 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant12(P1AD2-2H-4H Postdose)	4438 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant12(P1AD2-Predose)	4088 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant13(P1AD2-2H-4H Postdose)	2650 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant13(P1AD2-Predose)	2342 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant13(P1A/1BD22-2H Postdose)	1194 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant13(P1A/1BD22-4H Postdose)	-70 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant13(P1A/1BD22 Predose)	2532 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant14(P1AD1-2H Postdose)	329 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant14(P1AD1-4H Postdose)	139 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant14(P1AD1-6H Postdose)	194 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant14(P1AD1-Predose)	704 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant14(P1AD2-2H-4H Postdose)	208 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant14(P1AD2-Predose)	115 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant14(P1A/1BD22-Predose)	210 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant15(P1AD1-2H Postdose)	829 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant15(P1AD1-4H Postdose)	1006 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant15(P1AD1-6H Postdose)	596 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant15(P1AD1-Predose)	1808 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant15(P1AD2-2H-4H Postdose)	1742 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant15(P1AD2-2H Predose)	2074 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant16(P1AD1-2H Postdose)	562 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant16(P1AD1-4H Postdose)	416 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant16(P1AD1-6H Postdose)	554 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant16(P1AD1-Predose)	644 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant16(P1AD2-2H-4H Postdose)	704 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant17(P1AD1-2H Postdose)	2200 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant17(P1AD1-4H Postdose)	799 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant17(P1AD2-2H-4H Postdose)	729 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant17(P1AD2-Predose)	3157 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant18(P1AD1-6H Postdose)	845 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant18(P1AD1-Presdose)	1261 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant18(P1AD2-2H-4H Postdose)	2257 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant19(P1AD1-2H Postdose)	2182 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant19(P1AD1-4H Postdose)	1831 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant19(P1AD1-6H Postdose)	1871 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant19(P1AD1-Predose)	-2466 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant19(P1AD2-2H-4H Postdose)	1677 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant19(P1AD2-Predose)	4862 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant20(P1A/1BD22-2H Postdose)	11119 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant20(P1AD1-2H Postdose	1967 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant20(P1AD1-4H Postdose	-593 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant20(P1AD1-6H Postdose	2977 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant20(P1AD1-Predose)	262 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant20(P1AD2-2H-4H Postdose)	1860 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant20(P1AD2-Predose)	3150 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant21(P1AD1-2H Postdose)	660 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant21(P1AD1-4H Postdose)	1392 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant21(P1AD1-6H Postdose)	787 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant21(P1AD1 Predose)	2280 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant21(P1AD2-2H-4H Postdose)	-128 Mean fluorescence intensity	—	—	—
Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX Participant21(P1AD2 Predose)	1389 Mean fluorescence intensity	—	—	—

Adverse Events

Part 1A Dose Escalation: M4076 100 mg

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Part 1A Dose Escalation: M4076 200 mg

Serious events: 4 serious events

Other events: 7 other events

Deaths: 4 deaths

Part 1A Dose Escalation: M4076 300 mg

Serious events: 2 serious events

Other events: 9 other events

Deaths: 1 deaths

Part 1A Dose Escalation: M4076 400 mg

Serious events: 3 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Measure	Part 1A Dose Escalation: M4076 100 mg n=2 participants at risk Participants received M4076 film coated tablets at a dose of 100 milligrams (mg), orally once daily in 21-day cycles, starting from Day 1 of each cycle disease progression, death, AE leading to discontinuation of study intervention(s), or withdrawal of consent, whichever occurred first, or End of Study	Part 1A Dose Escalation: M4076 200 mg n=7 participants at risk Participants received M4076 film coated tablets at a dose of 200 mg, orally once daily in 21-day cycles, starting from Day 1 of each cycle disease progression, death, AE leading to discontinuation of study intervention(s), or withdrawal of consent, whichever occurred first, or End of Study.	Part 1A Dose Escalation: M4076 300 mg n=9 participants at risk Participants received M4076 film coated tablets at a dose of 300 mg, orally once daily in 21-day cycles, starting from Day 1 of each cycle disease progression, death, AE leading to discontinuation of study intervention(s), or withdrawal of consent, whichever occurred first, or End of Study.	Part 1A Dose Escalation: M4076 400 mg n=4 participants at risk Participants received M4076 film coated tablets at a dose of 400 mg, orally once daily in 21-day cycles, starting from Day 1 of each cycle disease progression, death, AE leading to discontinuation of study intervention(s), or withdrawal of consent, whichever occurred first, or End of Study.
Gastrointestinal disorders Abdominal pain	0.00% 0/2 • Up to 603 days	0.00% 0/7 • Up to 603 days	11.1% 1/9 • Number of events 1 • Up to 603 days	0.00% 0/4 • Up to 603 days
Gastrointestinal disorders Nausea	0.00% 0/2 • Up to 603 days	14.3% 1/7 • Number of events 1 • Up to 603 days	0.00% 0/9 • Up to 603 days	25.0% 1/4 • Number of events 1 • Up to 603 days
Gastrointestinal disorders Vomiting	0.00% 0/2 • Up to 603 days	14.3% 1/7 • Number of events 1 • Up to 603 days	0.00% 0/9 • Up to 603 days	0.00% 0/4 • Up to 603 days
General disorders Pyrexia	0.00% 0/2 • Up to 603 days	0.00% 0/7 • Up to 603 days	0.00% 0/9 • Up to 603 days	25.0% 1/4 • Number of events 1 • Up to 603 days
Immune system disorders Immune system disorder	0.00% 0/2 • Up to 603 days	0.00% 0/7 • Up to 603 days	0.00% 0/9 • Up to 603 days	25.0% 1/4 • Number of events 1 • Up to 603 days
Infections and infestations Enterocolitis infectious	0.00% 0/2 • Up to 603 days	0.00% 0/7 • Up to 603 days	0.00% 0/9 • Up to 603 days	25.0% 1/4 • Number of events 1 • Up to 603 days
Infections and infestations Liver abscess	0.00% 0/2 • Up to 603 days	0.00% 0/7 • Up to 603 days	0.00% 0/9 • Up to 603 days	25.0% 1/4 • Number of events 1 • Up to 603 days
Infections and infestations Pneumonia	0.00% 0/2 • Up to 603 days	14.3% 1/7 • Number of events 1 • Up to 603 days	0.00% 0/9 • Up to 603 days	0.00% 0/4 • Up to 603 days
Infections and infestations Sepsis	0.00% 0/2 • Up to 603 days	0.00% 0/7 • Up to 603 days	0.00% 0/9 • Up to 603 days	25.0% 1/4 • Number of events 1 • Up to 603 days
Infections and infestations Spontaneous bacterial peritonitis	0.00% 0/2 • Up to 603 days	0.00% 0/7 • Up to 603 days	11.1% 1/9 • Number of events 1 • Up to 603 days	0.00% 0/4 • Up to 603 days
Infections and infestations Urinary tract infection	0.00% 0/2 • Up to 603 days	14.3% 1/7 • Number of events 1 • Up to 603 days	0.00% 0/9 • Up to 603 days	0.00% 0/4 • Up to 603 days
Injury, poisoning and procedural complications Urinary tract stoma complication	0.00% 0/2 • Up to 603 days	0.00% 0/7 • Up to 603 days	11.1% 1/9 • Number of events 1 • Up to 603 days	0.00% 0/4 • Up to 603 days
Investigations Blood bilirubin increased	0.00% 0/2 • Up to 603 days	14.3% 1/7 • Number of events 1 • Up to 603 days	0.00% 0/9 • Up to 603 days	0.00% 0/4 • Up to 603 days
Investigations Lymphocyte count decreased	0.00% 0/2 • Up to 603 days	0.00% 0/7 • Up to 603 days	0.00% 0/9 • Up to 603 days	25.0% 1/4 • Number of events 1 • Up to 603 days
Metabolism and nutrition disorders Decreased appetite	0.00% 0/2 • Up to 603 days	14.3% 1/7 • Number of events 1 • Up to 603 days	0.00% 0/9 • Up to 603 days	0.00% 0/4 • Up to 603 days
Metabolism and nutrition disorders Dehydration	0.00% 0/2 • Up to 603 days	14.3% 1/7 • Number of events 1 • Up to 603 days	0.00% 0/9 • Up to 603 days	0.00% 0/4 • Up to 603 days
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/2 • Up to 603 days	14.3% 1/7 • Number of events 1 • Up to 603 days	0.00% 0/9 • Up to 603 days	0.00% 0/4 • Up to 603 days
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/2 • Up to 603 days	14.3% 1/7 • Number of events 1 • Up to 603 days	0.00% 0/9 • Up to 603 days	0.00% 0/4 • Up to 603 days
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/2 • Up to 603 days	0.00% 0/7 • Up to 603 days	0.00% 0/9 • Up to 603 days	50.0% 2/4 • Number of events 2 • Up to 603 days

Other adverse events

Measure	Part 1A Dose Escalation: M4076 100 mg n=2 participants at risk Participants received M4076 film coated tablets at a dose of 100 milligrams (mg), orally once daily in 21-day cycles, starting from Day 1 of each cycle disease progression, death, AE leading to discontinuation of study intervention(s), or withdrawal of consent, whichever occurred first, or End of Study	Part 1A Dose Escalation: M4076 200 mg n=7 participants at risk Participants received M4076 film coated tablets at a dose of 200 mg, orally once daily in 21-day cycles, starting from Day 1 of each cycle disease progression, death, AE leading to discontinuation of study intervention(s), or withdrawal of consent, whichever occurred first, or End of Study.	Part 1A Dose Escalation: M4076 300 mg n=9 participants at risk Participants received M4076 film coated tablets at a dose of 300 mg, orally once daily in 21-day cycles, starting from Day 1 of each cycle disease progression, death, AE leading to discontinuation of study intervention(s), or withdrawal of consent, whichever occurred first, or End of Study.	Part 1A Dose Escalation: M4076 400 mg n=4 participants at risk Participants received M4076 film coated tablets at a dose of 400 mg, orally once daily in 21-day cycles, starting from Day 1 of each cycle disease progression, death, AE leading to discontinuation of study intervention(s), or withdrawal of consent, whichever occurred first, or End of Study.
Blood and lymphatic system disorders Anaemia	0.00% 0/2 • Up to 603 days	14.3% 1/7 • Number of events 1 • Up to 603 days	22.2% 2/9 • Number of events 2 • Up to 603 days	25.0% 1/4 • Number of events 1 • Up to 603 days
Eye disorders Eye irritation	0.00% 0/2 • Up to 603 days	0.00% 0/7 • Up to 603 days	11.1% 1/9 • Number of events 1 • Up to 603 days	0.00% 0/4 • Up to 603 days
Gastrointestinal disorders Abdominal pain	0.00% 0/2 • Up to 603 days	42.9% 3/7 • Number of events 3 • Up to 603 days	11.1% 1/9 • Number of events 2 • Up to 603 days	0.00% 0/4 • Up to 603 days
Gastrointestinal disorders Constipation	0.00% 0/2 • Up to 603 days	0.00% 0/7 • Up to 603 days	11.1% 1/9 • Number of events 1 • Up to 603 days	25.0% 1/4 • Number of events 1 • Up to 603 days
Gastrointestinal disorders Diarrhoea	50.0% 1/2 • Number of events 1 • Up to 603 days	0.00% 0/7 • Up to 603 days	11.1% 1/9 • Number of events 1 • Up to 603 days	50.0% 2/4 • Number of events 2 • Up to 603 days
Gastrointestinal disorders Dyspepsia	0.00% 0/2 • Up to 603 days	14.3% 1/7 • Number of events 1 • Up to 603 days	0.00% 0/9 • Up to 603 days	0.00% 0/4 • Up to 603 days
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/2 • Up to 603 days	0.00% 0/7 • Up to 603 days	11.1% 1/9 • Number of events 1 • Up to 603 days	0.00% 0/4 • Up to 603 days
Gastrointestinal disorders Nausea	50.0% 1/2 • Number of events 1 • Up to 603 days	14.3% 1/7 • Number of events 1 • Up to 603 days	22.2% 2/9 • Number of events 2 • Up to 603 days	0.00% 0/4 • Up to 603 days
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/2 • Up to 603 days	0.00% 0/7 • Up to 603 days	0.00% 0/9 • Up to 603 days	25.0% 1/4 • Number of events 1 • Up to 603 days
Gastrointestinal disorders Vomiting	50.0% 1/2 • Number of events 1 • Up to 603 days	14.3% 1/7 • Number of events 1 • Up to 603 days	11.1% 1/9 • Number of events 1 • Up to 603 days	25.0% 1/4 • Number of events 1 • Up to 603 days
General disorders Fatigue	0.00% 0/2 • Up to 603 days	28.6% 2/7 • Number of events 2 • Up to 603 days	44.4% 4/9 • Number of events 4 • Up to 603 days	75.0% 3/4 • Number of events 3 • Up to 603 days
General disorders Gait disturbance	0.00% 0/2 • Up to 603 days	14.3% 1/7 • Number of events 1 • Up to 603 days	0.00% 0/9 • Up to 603 days	0.00% 0/4 • Up to 603 days
General disorders Oedema peripheral	0.00% 0/2 • Up to 603 days	0.00% 0/7 • Up to 603 days	11.1% 1/9 • Number of events 1 • Up to 603 days	25.0% 1/4 • Number of events 1 • Up to 603 days
General disorders Pyrexia	0.00% 0/2 • Up to 603 days	28.6% 2/7 • Number of events 3 • Up to 603 days	44.4% 4/9 • Number of events 4 • Up to 603 days	50.0% 2/4 • Number of events 3 • Up to 603 days
Infections and infestations COVID-19	0.00% 0/2 • Up to 603 days	0.00% 0/7 • Up to 603 days	11.1% 1/9 • Number of events 1 • Up to 603 days	0.00% 0/4 • Up to 603 days
Infections and infestations Cystitis	0.00% 0/2 • Up to 603 days	0.00% 0/7 • Up to 603 days	11.1% 1/9 • Number of events 1 • Up to 603 days	0.00% 0/4 • Up to 603 days
Infections and infestations Enterocolitis infectious	0.00% 0/2 • Up to 603 days	0.00% 0/7 • Up to 603 days	0.00% 0/9 • Up to 603 days	25.0% 1/4 • Number of events 1 • Up to 603 days
Infections and infestations Liver abscess	0.00% 0/2 • Up to 603 days	0.00% 0/7 • Up to 603 days	0.00% 0/9 • Up to 603 days	25.0% 1/4 • Number of events 1 • Up to 603 days
Infections and infestations Oral candidiasis	0.00% 0/2 • Up to 603 days	0.00% 0/7 • Up to 603 days	11.1% 1/9 • Number of events 1 • Up to 603 days	0.00% 0/4 • Up to 603 days
Infections and infestations Osteomyelitis	0.00% 0/2 • Up to 603 days	0.00% 0/7 • Up to 603 days	0.00% 0/9 • Up to 603 days	25.0% 1/4 • Number of events 1 • Up to 603 days
Infections and infestations Pneumonia	0.00% 0/2 • Up to 603 days	14.3% 1/7 • Number of events 1 • Up to 603 days	0.00% 0/9 • Up to 603 days	0.00% 0/4 • Up to 603 days
Infections and infestations Skin infection	0.00% 0/2 • Up to 603 days	0.00% 0/7 • Up to 603 days	0.00% 0/9 • Up to 603 days	25.0% 1/4 • Number of events 1 • Up to 603 days
Infections and infestations Spontaneous bacterial peritonitis	0.00% 0/2 • Up to 603 days	0.00% 0/7 • Up to 603 days	11.1% 1/9 • Number of events 1 • Up to 603 days	0.00% 0/4 • Up to 603 days
Infections and infestations Urinary tract infection	0.00% 0/2 • Up to 603 days	0.00% 0/7 • Up to 603 days	11.1% 1/9 • Number of events 1 • Up to 603 days	50.0% 2/4 • Number of events 2 • Up to 603 days
Investigations Alanine aminotransferase increased	0.00% 0/2 • Up to 603 days	14.3% 1/7 • Number of events 1 • Up to 603 days	22.2% 2/9 • Number of events 3 • Up to 603 days	25.0% 1/4 • Number of events 1 • Up to 603 days
Investigations Aspartate aminotransferase increased	0.00% 0/2 • Up to 603 days	28.6% 2/7 • Number of events 2 • Up to 603 days	11.1% 1/9 • Number of events 3 • Up to 603 days	25.0% 1/4 • Number of events 1 • Up to 603 days
Investigations Blood alkaline phosphatase increased	0.00% 0/2 • Up to 603 days	14.3% 1/7 • Number of events 1 • Up to 603 days	0.00% 0/9 • Up to 603 days	0.00% 0/4 • Up to 603 days
Investigations Blood bilirubin increased	0.00% 0/2 • Up to 603 days	28.6% 2/7 • Number of events 2 • Up to 603 days	0.00% 0/9 • Up to 603 days	0.00% 0/4 • Up to 603 days
Investigations Blood creatinine increased	0.00% 0/2 • Up to 603 days	14.3% 1/7 • Number of events 1 • Up to 603 days	22.2% 2/9 • Number of events 2 • Up to 603 days	75.0% 3/4 • Number of events 4 • Up to 603 days
Investigations Gamma-glutamyltransferase increased	0.00% 0/2 • Up to 603 days	14.3% 1/7 • Number of events 1 • Up to 603 days	0.00% 0/9 • Up to 603 days	0.00% 0/4 • Up to 603 days
Investigations Lymphocyte count decreased	0.00% 0/2 • Up to 603 days	14.3% 1/7 • Number of events 2 • Up to 603 days	11.1% 1/9 • Number of events 1 • Up to 603 days	0.00% 0/4 • Up to 603 days
Investigations Neutrophil count decreased	0.00% 0/2 • Up to 603 days	14.3% 1/7 • Number of events 1 • Up to 603 days	0.00% 0/9 • Up to 603 days	0.00% 0/4 • Up to 603 days
Investigations Platelet count decreased	0.00% 0/2 • Up to 603 days	14.3% 1/7 • Number of events 2 • Up to 603 days	0.00% 0/9 • Up to 603 days	0.00% 0/4 • Up to 603 days
Investigations White blood cell count increased	0.00% 0/2 • Up to 603 days	0.00% 0/7 • Up to 603 days	11.1% 1/9 • Number of events 1 • Up to 603 days	0.00% 0/4 • Up to 603 days
Metabolism and nutrition disorders Decreased appetite	0.00% 0/2 • Up to 603 days	14.3% 1/7 • Number of events 1 • Up to 603 days	11.1% 1/9 • Number of events 1 • Up to 603 days	0.00% 0/4 • Up to 603 days
Metabolism and nutrition disorders Dehydration	0.00% 0/2 • Up to 603 days	28.6% 2/7 • Number of events 2 • Up to 603 days	0.00% 0/9 • Up to 603 days	0.00% 0/4 • Up to 603 days
Metabolism and nutrition disorders Hypercalcaemia	0.00% 0/2 • Up to 603 days	14.3% 1/7 • Number of events 1 • Up to 603 days	0.00% 0/9 • Up to 603 days	0.00% 0/4 • Up to 603 days
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/2 • Up to 603 days	14.3% 1/7 • Number of events 1 • Up to 603 days	0.00% 0/9 • Up to 603 days	25.0% 1/4 • Number of events 1 • Up to 603 days
Metabolism and nutrition disorders Hypomagnesaemia	0.00% 0/2 • Up to 603 days	0.00% 0/7 • Up to 603 days	0.00% 0/9 • Up to 603 days	50.0% 2/4 • Number of events 4 • Up to 603 days
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/2 • Up to 603 days	14.3% 1/7 • Number of events 1 • Up to 603 days	0.00% 0/9 • Up to 603 days	0.00% 0/4 • Up to 603 days
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/2 • Up to 603 days	28.6% 2/7 • Number of events 2 • Up to 603 days	0.00% 0/9 • Up to 603 days	0.00% 0/4 • Up to 603 days
Musculoskeletal and connective tissue disorders Back pain	50.0% 1/2 • Number of events 1 • Up to 603 days	14.3% 1/7 • Number of events 1 • Up to 603 days	0.00% 0/9 • Up to 603 days	0.00% 0/4 • Up to 603 days
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/2 • Up to 603 days	14.3% 1/7 • Number of events 1 • Up to 603 days	0.00% 0/9 • Up to 603 days	0.00% 0/4 • Up to 603 days
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of skin	0.00% 0/2 • Up to 603 days	0.00% 0/7 • Up to 603 days	11.1% 1/9 • Number of events 1 • Up to 603 days	0.00% 0/4 • Up to 603 days
Nervous system disorders Dizziness	0.00% 0/2 • Up to 603 days	14.3% 1/7 • Number of events 1 • Up to 603 days	0.00% 0/9 • Up to 603 days	0.00% 0/4 • Up to 603 days
Nervous system disorders Headache	0.00% 0/2 • Up to 603 days	14.3% 1/7 • Number of events 1 • Up to 603 days	11.1% 1/9 • Number of events 1 • Up to 603 days	25.0% 1/4 • Number of events 1 • Up to 603 days
Nervous system disorders Paraesthesia	0.00% 0/2 • Up to 603 days	0.00% 0/7 • Up to 603 days	11.1% 1/9 • Number of events 1 • Up to 603 days	0.00% 0/4 • Up to 603 days
Nervous system disorders Peripheral sensory neuropathy	0.00% 0/2 • Up to 603 days	0.00% 0/7 • Up to 603 days	0.00% 0/9 • Up to 603 days	25.0% 1/4 • Number of events 1 • Up to 603 days
Nervous system disorders Syncope	50.0% 1/2 • Number of events 1 • Up to 603 days	0.00% 0/7 • Up to 603 days	0.00% 0/9 • Up to 603 days	0.00% 0/4 • Up to 603 days
Psychiatric disorders Confusional state	0.00% 0/2 • Up to 603 days	14.3% 1/7 • Number of events 1 • Up to 603 days	0.00% 0/9 • Up to 603 days	0.00% 0/4 • Up to 603 days
Renal and urinary disorders Dysuria	0.00% 0/2 • Up to 603 days	0.00% 0/7 • Up to 603 days	0.00% 0/9 • Up to 603 days	25.0% 1/4 • Number of events 1 • Up to 603 days
Renal and urinary disorders Urinary tract obstruction	0.00% 0/2 • Up to 603 days	0.00% 0/7 • Up to 603 days	0.00% 0/9 • Up to 603 days	25.0% 1/4 • Number of events 1 • Up to 603 days
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/2 • Up to 603 days	0.00% 0/7 • Up to 603 days	11.1% 1/9 • Number of events 1 • Up to 603 days	25.0% 1/4 • Number of events 1 • Up to 603 days
Respiratory, thoracic and mediastinal disorders Dyspnoea	50.0% 1/2 • Number of events 1 • Up to 603 days	0.00% 0/7 • Up to 603 days	0.00% 0/9 • Up to 603 days	25.0% 1/4 • Number of events 1 • Up to 603 days
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/2 • Up to 603 days	14.3% 1/7 • Number of events 1 • Up to 603 days	0.00% 0/9 • Up to 603 days	25.0% 1/4 • Number of events 1 • Up to 603 days
Skin and subcutaneous tissue disorders Dry skin	0.00% 0/2 • Up to 603 days	0.00% 0/7 • Up to 603 days	11.1% 1/9 • Number of events 1 • Up to 603 days	0.00% 0/4 • Up to 603 days
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/2 • Up to 603 days	0.00% 0/7 • Up to 603 days	11.1% 1/9 • Number of events 1 • Up to 603 days	0.00% 0/4 • Up to 603 days
Skin and subcutaneous tissue disorders Rash	0.00% 0/2 • Up to 603 days	0.00% 0/7 • Up to 603 days	11.1% 1/9 • Number of events 1 • Up to 603 days	0.00% 0/4 • Up to 603 days
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/2 • Up to 603 days	14.3% 1/7 • Number of events 1 • Up to 603 days	22.2% 2/9 • Number of events 2 • Up to 603 days	25.0% 1/4 • Number of events 1 • Up to 603 days
Vascular disorders Hypotension	0.00% 0/2 • Up to 603 days	14.3% 1/7 • Number of events 1 • Up to 603 days	11.1% 1/9 • Number of events 1 • Up to 603 days	0.00% 0/4 • Up to 603 days

Additional Information

Communication Center

Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Phone: +49-6151-72-5200

Email: service@emdgroup.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place