Trial Outcomes & Findings for M3541 in Combination With Radiotherapy in Solid Tumors (NCT NCT03225105)

NCT ID: NCT03225105

Last Updated: 2023-11-22

Results Overview

DLT is classified per the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 and defined as any of the following events occurring after first dose of study intervention and judged not to be related to underlying disease or any previous or concomitant medication. Grade (Gr) \>=3 non-hematologic toxicity with exception of Nausea, vomiting and diarrhea lasting =\<3 days in once per FD; Worsening of preexisting tumor pain associated with tumor lesions for which participant was irradiated in context of this study; Evidence of treatment-related hepatocellular injury for \>3 days in the once per FD; Any occurrence of Hy's law; Gr 4 neutropenia lasting for \>5 days, Gr 4 thrombocytopenia or Gr 4 anemia that was unexplained by underlying disease; Any toxicity related to study treatment that caused participant to interrupt treatment for not to be able to be treated within 24 hours of the scheduled treatment time.

Recruitment status

TERMINATED

Study phase

PHASE1

Target enrollment

15 participants

Primary outcome timeframe

Baseline up to 5 weeks (including 2 weeks of treatment and 3 weeks of follow-up period)

Results posted on

2023-11-22

Participant Flow

This dose-escalation study was planned to be conducted as per 3 dosing schedules for M3541 including M3541 once per Fraction Day daily, M3541 twice and thrice weekly in combination with fractionated RT given in 10 fractions. However, due to early termination of the study, 2 intermittent schedules (thrice weekly and twice weekly) were never opened and did not enroll any participants.

Participant milestones

Participant milestones
Measure
M3541 50 mg + RT
Participants received 50 milligrams (mg) M3541 orally once per fraction day (FD) in combination with palliative radiotherapy (RT) administered in fraction of 30 Gray (Gy) given in 10 fractions of 3 Gy/FD on FD 1 to FD 10, for 2 consecutive calendar weeks (ie, Monday through Friday, with the intervening Saturday and Sunday as M3541 / RT holidays).
M3541 100 mg + RT
Participants received 100 mg M3541 orally once per FD in combination with palliative RT administered in fraction of 30 Gray (Gy) given in 10 fractions of 3 Gy/FD on FD 1 to FD 10 for 2 consecutive calendar weeks (ie, Monday through Friday, with the intervening Saturday and Sunday as M3541 / RT holidays).
M3541 200 mg + RT
Participants received 200 mg M3541 orally once per FD in combination with palliative RT administered in fraction of 30 Gray (Gy) given in 10 fractions of 3 Gy/FD on FD 1 to FD 10 for 2 consecutive calendar weeks (ie, Monday through Friday, with the intervening Saturday and Sunday as M3541 / RT holidays).
M3541 300 mg + RT
Participants received 300 mg M3541 orally once per FD in combination with palliative RT administered in fraction of 30 Gray (Gy) given in 10 fractions of 3 Gy/FD on FD 1 to FD 10 for 2 consecutive calendar weeks (ie, Monday through Friday, with the intervening Saturday and Sunday as M3541 / RT holidays).
Overall Study
STARTED
3
4
5
3
Overall Study
COMPLETED
0
0
0
0
Overall Study
NOT COMPLETED
3
4
5
3

Reasons for withdrawal

Reasons for withdrawal
Measure
M3541 50 mg + RT
Participants received 50 milligrams (mg) M3541 orally once per fraction day (FD) in combination with palliative radiotherapy (RT) administered in fraction of 30 Gray (Gy) given in 10 fractions of 3 Gy/FD on FD 1 to FD 10, for 2 consecutive calendar weeks (ie, Monday through Friday, with the intervening Saturday and Sunday as M3541 / RT holidays).
M3541 100 mg + RT
Participants received 100 mg M3541 orally once per FD in combination with palliative RT administered in fraction of 30 Gray (Gy) given in 10 fractions of 3 Gy/FD on FD 1 to FD 10 for 2 consecutive calendar weeks (ie, Monday through Friday, with the intervening Saturday and Sunday as M3541 / RT holidays).
M3541 200 mg + RT
Participants received 200 mg M3541 orally once per FD in combination with palliative RT administered in fraction of 30 Gray (Gy) given in 10 fractions of 3 Gy/FD on FD 1 to FD 10 for 2 consecutive calendar weeks (ie, Monday through Friday, with the intervening Saturday and Sunday as M3541 / RT holidays).
M3541 300 mg + RT
Participants received 300 mg M3541 orally once per FD in combination with palliative RT administered in fraction of 30 Gray (Gy) given in 10 fractions of 3 Gy/FD on FD 1 to FD 10 for 2 consecutive calendar weeks (ie, Monday through Friday, with the intervening Saturday and Sunday as M3541 / RT holidays).
Overall Study
Withdrawal by Subject
1
0
0
0
Overall Study
Death
0
4
2
0
Overall Study
Study termination per Sponsor Decision
2
0
3
3

Baseline Characteristics

M3541 in Combination With Radiotherapy in Solid Tumors

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
M3541 50 mg + RT
n=3 Participants
Participants received 50 milligrams (mg) M3541 orally once per fraction day (FD) in combination with palliative radiotherapy (RT) administered in fraction of 30 Gray (Gy) given in 10 fractions of 3 Gy/FD on FD 1 to FD 10, for 2 consecutive calendar weeks (ie, Monday through Friday, with the intervening Saturday and Sunday as M3541 / RT holidays).
M3541 100 mg + RT
n=4 Participants
Participants received 100 mg M3541 orally once per FD in combination with palliative RT administered in fraction of 30 Gray (Gy) given in 10 fractions of 3 Gy/FD on FD 1 to FD 10 for 2 consecutive calendar weeks (ie, Monday through Friday, with the intervening Saturday and Sunday as M3541 / RT holidays).
M3541 200 mg + RT
n=5 Participants
Participants received 200 mg M3541 orally once per FD in combination with palliative RT administered in fraction of 30 Gray (Gy) given in 10 fractions of 3 Gy/FD on FD 1 to FD 10 for 2 consecutive calendar weeks (ie, Monday through Friday, with the intervening Saturday and Sunday as M3541 / RT holidays).
M3541 300 mg + RT
n=3 Participants
Participants received 300 mg M3541 orally once per FD in combination with palliative RT administered in fraction of 30 Gray (Gy) given in 10 fractions of 3 Gy/FD on FD 1 to FD 10 for 2 consecutive calendar weeks (ie, Monday through Friday, with the intervening Saturday and Sunday as M3541 / RT holidays).
Total
n=15 Participants
Total of all reporting groups
Age, Continuous
61 Years
STANDARD_DEVIATION 3.8 • n=5 Participants
67 Years
STANDARD_DEVIATION 6.3 • n=7 Participants
66 Years
STANDARD_DEVIATION 7.4 • n=5 Participants
47 Years
STANDARD_DEVIATION 10.1 • n=4 Participants
62 Years
STANDARD_DEVIATION 10.1 • n=21 Participants
Sex: Female, Male
Female
0 Participants
n=5 Participants
3 Participants
n=7 Participants
3 Participants
n=5 Participants
2 Participants
n=4 Participants
8 Participants
n=21 Participants
Sex: Female, Male
Male
3 Participants
n=5 Participants
1 Participants
n=7 Participants
2 Participants
n=5 Participants
1 Participants
n=4 Participants
7 Participants
n=21 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
1 Participants
n=4 Participants
1 Participants
n=21 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
3 Participants
n=5 Participants
4 Participants
n=7 Participants
5 Participants
n=5 Participants
2 Participants
n=4 Participants
14 Participants
n=21 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
0 Participants
n=21 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
0 Participants
n=21 Participants
Race (NIH/OMB)
Asian
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
0 Participants
n=21 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
0 Participants
n=21 Participants
Race (NIH/OMB)
Black or African American
0 Participants
n=5 Participants
1 Participants
n=7 Participants
2 Participants
n=5 Participants
1 Participants
n=4 Participants
4 Participants
n=21 Participants
Race (NIH/OMB)
White
3 Participants
n=5 Participants
3 Participants
n=7 Participants
3 Participants
n=5 Participants
2 Participants
n=4 Participants
11 Participants
n=21 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
0 Participants
n=21 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
0 Participants
n=21 Participants

PRIMARY outcome

Timeframe: Baseline up to 5 weeks (including 2 weeks of treatment and 3 weeks of follow-up period)

Population: DLT analysis set included participants who received at least 1 dose of M3541and met at least one of the following criteria: Experienced at least 1 DLT during the DLT evaluation period, regardless of the number of doses of M3541 administered or received at least 80% of planned dose of each treatment, that is, 8 fractions of RT and 8 of 10 M3541 administrations during the treatment period

DLT is classified per the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 and defined as any of the following events occurring after first dose of study intervention and judged not to be related to underlying disease or any previous or concomitant medication. Grade (Gr) \>=3 non-hematologic toxicity with exception of Nausea, vomiting and diarrhea lasting =\<3 days in once per FD; Worsening of preexisting tumor pain associated with tumor lesions for which participant was irradiated in context of this study; Evidence of treatment-related hepatocellular injury for \>3 days in the once per FD; Any occurrence of Hy's law; Gr 4 neutropenia lasting for \>5 days, Gr 4 thrombocytopenia or Gr 4 anemia that was unexplained by underlying disease; Any toxicity related to study treatment that caused participant to interrupt treatment for not to be able to be treated within 24 hours of the scheduled treatment time.

Outcome measures

Outcome measures
Measure
M3541 50 mg + RT
n=3 Participants
Participants received 50 milligrams (mg) M3541 orally once per fraction day (FD) in combination with palliative radiotherapy (RT) administered in fraction of 30 Gray (Gy) given in 10 fractions of 3 Gy/FD on FD 1 to FD 10, for 2 consecutive calendar weeks (ie, Monday through Friday, with the intervening Saturday and Sunday as M3541 / RT holidays).
M3541 100 mg + RT
n=4 Participants
Participants received 100 mg M3541 orally once per FD in combination with palliative RT administered in fraction of 30 Gray (Gy) given in 10 fractions of 3 Gy/FD on FD 1 to FD 10 for 2 consecutive calendar weeks (ie, Monday through Friday, with the intervening Saturday and Sunday as M3541 / RT holidays).
M3541 200 mg + RT
n=5 Participants
Participants received 200 mg M3541 orally once per FD in combination with palliative RT administered in fraction of 30 Gray (Gy) given in 10 fractions of 3 Gy/FD on FD 1 to FD 10 for 2 consecutive calendar weeks (ie, Monday through Friday, with the intervening Saturday and Sunday as M3541 / RT holidays).
M3541 300 mg + RT
Participants received 300 mg M3541 orally once per FD in combination with palliative RT administered in fraction of 30 Gray (Gy) given in 10 fractions of 3 Gy/FD on FD 1 to FD 10 for 2 consecutive calendar weeks (ie, Monday through Friday, with the intervening Saturday and Sunday as M3541 / RT holidays).
M3541 50 mg + 100 mg + 200 mg + RT: Number of Participants With Dose Limiting Toxicities (DLTs)
0 Participants
0 Participants
1 Participants

PRIMARY outcome

Timeframe: Baseline up to 4 weeks (including 2 weeks of treatment and 2 weeks of the follow-up period)

Population: DLT analysis set included participants who received at least 1 dose of M3541and met at least one of the following criteria: Experienced at least 1 DLT during the DLT evaluation period, regardless of the number of doses of M3541 administered or received at least 80% of planned dose of each treatment, that is, 8 fractions of RT and 8 of 10 M3541 administrations during the treatment period

DLT is classified per the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 and defined as any of the following events occurring after first dose of study intervention and judged not to be related to underlying disease or any previous or concomitant medication. Grade (Gr) \>=3 non-hematologic toxicity with exception of Nausea, vomiting and diarrhea lasting =\<3 days in once per FD; Worsening of preexisting tumor pain associated with tumor lesions for which participant was irradiated in context of this study; Evidence of treatment-related hepatocellular injury for \>3 days in the once per FD; Any occurrence of Hy's law; Gr 4 neutropenia lasting for \>5 days, Gr 4 thrombocytopenia or Gr 4 anemia that was unexplained by underlying disease; Any toxicity related to study treatment that caused participant to interrupt treatment for not to be able to be treated within 24 hours of the scheduled treatment time.

Outcome measures

Outcome measures
Measure
M3541 50 mg + RT
n=3 Participants
Participants received 50 milligrams (mg) M3541 orally once per fraction day (FD) in combination with palliative radiotherapy (RT) administered in fraction of 30 Gray (Gy) given in 10 fractions of 3 Gy/FD on FD 1 to FD 10, for 2 consecutive calendar weeks (ie, Monday through Friday, with the intervening Saturday and Sunday as M3541 / RT holidays).
M3541 100 mg + RT
Participants received 100 mg M3541 orally once per FD in combination with palliative RT administered in fraction of 30 Gray (Gy) given in 10 fractions of 3 Gy/FD on FD 1 to FD 10 for 2 consecutive calendar weeks (ie, Monday through Friday, with the intervening Saturday and Sunday as M3541 / RT holidays).
M3541 200 mg + RT
Participants received 200 mg M3541 orally once per FD in combination with palliative RT administered in fraction of 30 Gray (Gy) given in 10 fractions of 3 Gy/FD on FD 1 to FD 10 for 2 consecutive calendar weeks (ie, Monday through Friday, with the intervening Saturday and Sunday as M3541 / RT holidays).
M3541 300 mg + RT
Participants received 300 mg M3541 orally once per FD in combination with palliative RT administered in fraction of 30 Gray (Gy) given in 10 fractions of 3 Gy/FD on FD 1 to FD 10 for 2 consecutive calendar weeks (ie, Monday through Friday, with the intervening Saturday and Sunday as M3541 / RT holidays).
M3541 300 mg + RT: Number of Participants With Dose Limiting Toxicities (DLTs)
0 Participants

SECONDARY outcome

Timeframe: Baseline up to 749 days

Population: Safety analysis set included all participants who received at least 1 dose of M3541.

An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A serious AE 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. TEAEs are events with start date on or after the date of first dose of study treatment and up to and including 30 days after the last dose of study treatment, or events with start date prior to the date of first dose of study treatment, and worsened in severity or become serious during treatment. TEAEs include both Serious TEAEs and non-serious TEAEs.

Outcome measures

Outcome measures
Measure
M3541 50 mg + RT
n=3 Participants
Participants received 50 milligrams (mg) M3541 orally once per fraction day (FD) in combination with palliative radiotherapy (RT) administered in fraction of 30 Gray (Gy) given in 10 fractions of 3 Gy/FD on FD 1 to FD 10, for 2 consecutive calendar weeks (ie, Monday through Friday, with the intervening Saturday and Sunday as M3541 / RT holidays).
M3541 100 mg + RT
n=4 Participants
Participants received 100 mg M3541 orally once per FD in combination with palliative RT administered in fraction of 30 Gray (Gy) given in 10 fractions of 3 Gy/FD on FD 1 to FD 10 for 2 consecutive calendar weeks (ie, Monday through Friday, with the intervening Saturday and Sunday as M3541 / RT holidays).
M3541 200 mg + RT
n=5 Participants
Participants received 200 mg M3541 orally once per FD in combination with palliative RT administered in fraction of 30 Gray (Gy) given in 10 fractions of 3 Gy/FD on FD 1 to FD 10 for 2 consecutive calendar weeks (ie, Monday through Friday, with the intervening Saturday and Sunday as M3541 / RT holidays).
M3541 300 mg + RT
n=3 Participants
Participants received 300 mg M3541 orally once per FD in combination with palliative RT administered in fraction of 30 Gray (Gy) given in 10 fractions of 3 Gy/FD on FD 1 to FD 10 for 2 consecutive calendar weeks (ie, Monday through Friday, with the intervening Saturday and Sunday as M3541 / RT holidays).
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Grade >=3 Adverse Events (AEs), Serious TEAEs and Deaths According to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events, Version 4.03 (CTCAE V4.03)
Participants with TEAEs
3 Participants
4 Participants
5 Participants
3 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Grade >=3 Adverse Events (AEs), Serious TEAEs and Deaths According to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events, Version 4.03 (CTCAE V4.03)
Participants with Grade >=3 AEs
1 Participants
1 Participants
1 Participants
1 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Grade >=3 Adverse Events (AEs), Serious TEAEs and Deaths According to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events, Version 4.03 (CTCAE V4.03)
Participants with Serious TEAEs
0 Participants
1 Participants
1 Participants
0 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Grade >=3 Adverse Events (AEs), Serious TEAEs and Deaths According to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events, Version 4.03 (CTCAE V4.03)
Participants with Death
0 Participants
4 Participants
2 Participants
0 Participants

SECONDARY outcome

Timeframe: Baseline up to Day 44

Population: Safety analysis set included all participants who received at least 1 dose of M3541.

The laboratory assessment included measurements hematology and biochemistry parameters. It had been graded according to NCI-CTCAE version 4.03 into Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (Life-threatening) and Grade 5 = death. Participants with grade 3 or higher were reported.

Outcome measures

Outcome measures
Measure
M3541 50 mg + RT
n=3 Participants
Participants received 50 milligrams (mg) M3541 orally once per fraction day (FD) in combination with palliative radiotherapy (RT) administered in fraction of 30 Gray (Gy) given in 10 fractions of 3 Gy/FD on FD 1 to FD 10, for 2 consecutive calendar weeks (ie, Monday through Friday, with the intervening Saturday and Sunday as M3541 / RT holidays).
M3541 100 mg + RT
n=4 Participants
Participants received 100 mg M3541 orally once per FD in combination with palliative RT administered in fraction of 30 Gray (Gy) given in 10 fractions of 3 Gy/FD on FD 1 to FD 10 for 2 consecutive calendar weeks (ie, Monday through Friday, with the intervening Saturday and Sunday as M3541 / RT holidays).
M3541 200 mg + RT
n=5 Participants
Participants received 200 mg M3541 orally once per FD in combination with palliative RT administered in fraction of 30 Gray (Gy) given in 10 fractions of 3 Gy/FD on FD 1 to FD 10 for 2 consecutive calendar weeks (ie, Monday through Friday, with the intervening Saturday and Sunday as M3541 / RT holidays).
M3541 300 mg + RT
n=3 Participants
Participants received 300 mg M3541 orally once per FD in combination with palliative RT administered in fraction of 30 Gray (Gy) given in 10 fractions of 3 Gy/FD on FD 1 to FD 10 for 2 consecutive calendar weeks (ie, Monday through Friday, with the intervening Saturday and Sunday as M3541 / RT holidays).
Number of Participants With Grade 3 or Higher Laboratory Abnormalities Based on National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE)
Hematology
1 Participants
1 Participants
2 Participants
0 Participants
Number of Participants With Grade 3 or Higher Laboratory Abnormalities Based on National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE)
Biochemistry
1 Participants
2 Participants
3 Participants
0 Participants

SECONDARY outcome

Timeframe: Baseline up to 379 days

Population: Safety analysis set included all participants who received at least 1 dose of M3541.

Vital signs assessment included blood pressure, pulse rate, body temperature, respiratory rate, and body weight. Notably abnormal vital signs were: Blood pressure: systolic blood pressure \>= 140 millimeter of mercury (mmHg) \& diastolic blood pressure \>=90 mmHg on treatment; Pulse rate \>100 beats/min; Body temperature \>= 38 degree Celsius (°C) on treatment; Respiratory rate \>= 20 breaths/min; Weight (kilogram) \> +/-20% from baseline. Number of Participants with abnormalities in vital signs were reported.

Outcome measures

Outcome measures
Measure
M3541 50 mg + RT
n=3 Participants
Participants received 50 milligrams (mg) M3541 orally once per fraction day (FD) in combination with palliative radiotherapy (RT) administered in fraction of 30 Gray (Gy) given in 10 fractions of 3 Gy/FD on FD 1 to FD 10, for 2 consecutive calendar weeks (ie, Monday through Friday, with the intervening Saturday and Sunday as M3541 / RT holidays).
M3541 100 mg + RT
n=4 Participants
Participants received 100 mg M3541 orally once per FD in combination with palliative RT administered in fraction of 30 Gray (Gy) given in 10 fractions of 3 Gy/FD on FD 1 to FD 10 for 2 consecutive calendar weeks (ie, Monday through Friday, with the intervening Saturday and Sunday as M3541 / RT holidays).
M3541 200 mg + RT
n=5 Participants
Participants received 200 mg M3541 orally once per FD in combination with palliative RT administered in fraction of 30 Gray (Gy) given in 10 fractions of 3 Gy/FD on FD 1 to FD 10 for 2 consecutive calendar weeks (ie, Monday through Friday, with the intervening Saturday and Sunday as M3541 / RT holidays).
M3541 300 mg + RT
n=3 Participants
Participants received 300 mg M3541 orally once per FD in combination with palliative RT administered in fraction of 30 Gray (Gy) given in 10 fractions of 3 Gy/FD on FD 1 to FD 10 for 2 consecutive calendar weeks (ie, Monday through Friday, with the intervening Saturday and Sunday as M3541 / RT holidays).
Number of Participants With Abnormalities in Vital Signs
Blood Pressure
1 Participants
2 Participants
0 Participants
0 Participants
Number of Participants With Abnormalities in Vital Signs
Pulse rate
2 Participants
2 Participants
4 Participants
2 Participants
Number of Participants With Abnormalities in Vital Signs
Body temperature
0 Participants
0 Participants
2 Participants
0 Participants
Number of Participants With Abnormalities in Vital Signs
Respiratory rate
1 Participants
1 Participants
1 Participants
1 Participants
Number of Participants With Abnormalities in Vital Signs
Weight
0 Participants
0 Participants
0 Participants
0 Participants

SECONDARY outcome

Timeframe: Baseline up to 379 days

Population: Safety analysis set included all participants who received at least 1 dose of M3541.

Number of participants with any clinically significant abnormalities in physical examination reported as adverse events with National Cancer Institute Common Terminology Criteria (NCI-CTC) Grade \>=3 were presented.

Outcome measures

Outcome measures
Measure
M3541 50 mg + RT
n=3 Participants
Participants received 50 milligrams (mg) M3541 orally once per fraction day (FD) in combination with palliative radiotherapy (RT) administered in fraction of 30 Gray (Gy) given in 10 fractions of 3 Gy/FD on FD 1 to FD 10, for 2 consecutive calendar weeks (ie, Monday through Friday, with the intervening Saturday and Sunday as M3541 / RT holidays).
M3541 100 mg + RT
n=4 Participants
Participants received 100 mg M3541 orally once per FD in combination with palliative RT administered in fraction of 30 Gray (Gy) given in 10 fractions of 3 Gy/FD on FD 1 to FD 10 for 2 consecutive calendar weeks (ie, Monday through Friday, with the intervening Saturday and Sunday as M3541 / RT holidays).
M3541 200 mg + RT
n=5 Participants
Participants received 200 mg M3541 orally once per FD in combination with palliative RT administered in fraction of 30 Gray (Gy) given in 10 fractions of 3 Gy/FD on FD 1 to FD 10 for 2 consecutive calendar weeks (ie, Monday through Friday, with the intervening Saturday and Sunday as M3541 / RT holidays).
M3541 300 mg + RT
n=3 Participants
Participants received 300 mg M3541 orally once per FD in combination with palliative RT administered in fraction of 30 Gray (Gy) given in 10 fractions of 3 Gy/FD on FD 1 to FD 10 for 2 consecutive calendar weeks (ie, Monday through Friday, with the intervening Saturday and Sunday as M3541 / RT holidays).
Number of Participants With Abnormalities in Physical Examination Reported as Adverse Events (AEs)
0 Participants
0 Participants
1 Participants
0 Participants

SECONDARY outcome

Timeframe: Baseline up to 15 days

Population: Safety analysis set included all participants who received at least 1 dose of M3541. Here "Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure with normal ECG at baseline.

The 12-lead ECG was recorded after the participant was in semi-supine position for at least 5 minutes. The ECG was obtained using a Holter recorder. Number of Participants with abnormal change from baseline in ECG were reported.

Outcome measures

Outcome measures
Measure
M3541 50 mg + RT
Participants received 50 milligrams (mg) M3541 orally once per fraction day (FD) in combination with palliative radiotherapy (RT) administered in fraction of 30 Gray (Gy) given in 10 fractions of 3 Gy/FD on FD 1 to FD 10, for 2 consecutive calendar weeks (ie, Monday through Friday, with the intervening Saturday and Sunday as M3541 / RT holidays).
M3541 100 mg + RT
n=3 Participants
Participants received 100 mg M3541 orally once per FD in combination with palliative RT administered in fraction of 30 Gray (Gy) given in 10 fractions of 3 Gy/FD on FD 1 to FD 10 for 2 consecutive calendar weeks (ie, Monday through Friday, with the intervening Saturday and Sunday as M3541 / RT holidays).
M3541 200 mg + RT
Participants received 200 mg M3541 orally once per FD in combination with palliative RT administered in fraction of 30 Gray (Gy) given in 10 fractions of 3 Gy/FD on FD 1 to FD 10 for 2 consecutive calendar weeks (ie, Monday through Friday, with the intervening Saturday and Sunday as M3541 / RT holidays).
M3541 300 mg + RT
n=1 Participants
Participants received 300 mg M3541 orally once per FD in combination with palliative RT administered in fraction of 30 Gray (Gy) given in 10 fractions of 3 Gy/FD on FD 1 to FD 10 for 2 consecutive calendar weeks (ie, Monday through Friday, with the intervening Saturday and Sunday as M3541 / RT holidays).
Number of Participants With Abnormal Change From Baseline in Electrocardiogram (ECG)
2 Participants
1 Participants

SECONDARY outcome

Timeframe: Time from randomization to 964 days

Population: Safety analysis set included all participants who received at least 1 dose of M3541.

BOR was determined according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). BOR is defined as the best response of any of the complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) recorded from the date of randomization until disease progression or recurrence (taking the smallest measurement recorded since the start of treatment as reference). 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. SD=Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR. PD is defined as 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 measures
Measure
M3541 50 mg + RT
n=3 Participants
Participants received 50 milligrams (mg) M3541 orally once per fraction day (FD) in combination with palliative radiotherapy (RT) administered in fraction of 30 Gray (Gy) given in 10 fractions of 3 Gy/FD on FD 1 to FD 10, for 2 consecutive calendar weeks (ie, Monday through Friday, with the intervening Saturday and Sunday as M3541 / RT holidays).
M3541 100 mg + RT
n=4 Participants
Participants received 100 mg M3541 orally once per FD in combination with palliative RT administered in fraction of 30 Gray (Gy) given in 10 fractions of 3 Gy/FD on FD 1 to FD 10 for 2 consecutive calendar weeks (ie, Monday through Friday, with the intervening Saturday and Sunday as M3541 / RT holidays).
M3541 200 mg + RT
n=5 Participants
Participants received 200 mg M3541 orally once per FD in combination with palliative RT administered in fraction of 30 Gray (Gy) given in 10 fractions of 3 Gy/FD on FD 1 to FD 10 for 2 consecutive calendar weeks (ie, Monday through Friday, with the intervening Saturday and Sunday as M3541 / RT holidays).
M3541 300 mg + RT
n=3 Participants
Participants received 300 mg M3541 orally once per FD in combination with palliative RT administered in fraction of 30 Gray (Gy) given in 10 fractions of 3 Gy/FD on FD 1 to FD 10 for 2 consecutive calendar weeks (ie, Monday through Friday, with the intervening Saturday and Sunday as M3541 / RT holidays).
Number of Participants With Best Overall Response (BOR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Complete Response
0 Participants
0 Participants
0 Participants
0 Participants
Number of Participants With Best Overall Response (BOR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Partial Response
1 Participants
0 Participants
2 Participants
0 Participants
Number of Participants With Best Overall Response (BOR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Stable Disease
1 Participants
2 Participants
3 Participants
3 Participants
Number of Participants With Best Overall Response (BOR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Progressive Disease
1 Participants
2 Participants
0 Participants
0 Participants

SECONDARY outcome

Timeframe: From first dose of study drug to disease progression or death from any cause, assessed up to 964 days

Population: Safety analysis set included all participants who received at least 1 dose of M3541. The summarized data was not available for this outcome measure, therefore individual data was presented. "Number Analyzed" signifies participants evaluable in respective arm.

PFS is defined as the time (in months) from first administration of M3541 until the first date of progressive disease (PD) or death due to any cause. PFS was assessed as per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). PD was defined as at least a 20% 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 and unequivocal progression of non-target lesions. Participants with neither disease progression nor death were censored at the last date of the last tumor assessment that confirmed that their disease had not progressed. Participant wise data reported for this outcome measure.

Outcome measures

Outcome measures
Measure
M3541 50 mg + RT
n=3 Participants
Participants received 50 milligrams (mg) M3541 orally once per fraction day (FD) in combination with palliative radiotherapy (RT) administered in fraction of 30 Gray (Gy) given in 10 fractions of 3 Gy/FD on FD 1 to FD 10, for 2 consecutive calendar weeks (ie, Monday through Friday, with the intervening Saturday and Sunday as M3541 / RT holidays).
M3541 100 mg + RT
n=4 Participants
Participants received 100 mg M3541 orally once per FD in combination with palliative RT administered in fraction of 30 Gray (Gy) given in 10 fractions of 3 Gy/FD on FD 1 to FD 10 for 2 consecutive calendar weeks (ie, Monday through Friday, with the intervening Saturday and Sunday as M3541 / RT holidays).
M3541 200 mg + RT
n=5 Participants
Participants received 200 mg M3541 orally once per FD in combination with palliative RT administered in fraction of 30 Gray (Gy) given in 10 fractions of 3 Gy/FD on FD 1 to FD 10 for 2 consecutive calendar weeks (ie, Monday through Friday, with the intervening Saturday and Sunday as M3541 / RT holidays).
M3541 300 mg + RT
n=3 Participants
Participants received 300 mg M3541 orally once per FD in combination with palliative RT administered in fraction of 30 Gray (Gy) given in 10 fractions of 3 Gy/FD on FD 1 to FD 10 for 2 consecutive calendar weeks (ie, Monday through Friday, with the intervening Saturday and Sunday as M3541 / RT holidays).
Progression-Free Survival (PFS) Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Investigator
Participant-1
2.92 Months
Progression-Free Survival (PFS) Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Investigator
Participant-2
11.04 Months
Progression-Free Survival (PFS) Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Investigator
Participant-3
1.41 Months
Progression-Free Survival (PFS) Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Investigator
Participant-4
1.25 Months
Progression-Free Survival (PFS) Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Investigator
Participant-5
1.54 Months
Progression-Free Survival (PFS) Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Investigator
Participant-6
1.87 Months
Progression-Free Survival (PFS) Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Investigator
Participant-7
1.41 Months
Progression-Free Survival (PFS) Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Investigator
Participant-8
3.55 Months
Progression-Free Survival (PFS) Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Investigator
Participant-9
1.97 Months
Progression-Free Survival (PFS) Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Investigator
Participant-10
3.55 Months
Progression-Free Survival (PFS) Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Investigator
Participant-11
1.84 Months
Progression-Free Survival (PFS) Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Investigator
Participant-12
3.15 Months
Progression-Free Survival (PFS) Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Investigator
Participant-13
2.14 Months
Progression-Free Survival (PFS) Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Investigator
Participant-14
1.94 Months
Progression-Free Survival (PFS) Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Investigator
Participant-15
1.74 Months

SECONDARY outcome

Timeframe: Pre-dose, 0.5, 1, 1.5, 2.25, 3, 4, 6 hours post-dose on Fraction Day 1; Pre-dose, 2.25 hours post-dose on Fraction Day 2, 5, 6 and 7; Pre-dose, 0.5, 1, 1.5, 2.25, 3, 4, and 6 hours post-dose on Fraction Day 10

Population: As per changes in planned analysis, the outcome measure related to pharmacokinetic parameters was not assessed.

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Pre-dose, 0.5, 1, 1.5, 2.25, 3, 4, 6 hours post-dose on Fraction Day 1; Pre-dose, 2.25 hours post-dose on Fraction Day 2, 5, 6 and 7; Pre-dose, 0.5, 1, 1.5, 2.25, 3, 4, and 6 hours post-dose on Fraction Day 10

Population: As per changes in planned analysis, the outcome measure related to pharmacokinetic parameters was not assessed.

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Pre-dose, 0.5, 1, 1.5, 2.25, 3, 4, 6 hours post-dose on Fraction Day 1; Pre-dose, 2.25 hours post-dose on Fraction Day 2, 5, 6 and 7; Pre-dose, 0.5, 1, 1.5, 2.25, 3, 4, and 6 hours post-dose on Fraction Day 10

Population: As per changes in planned analysis, the outcome measure related to pharmacokinetic parameters was not assessed.

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Pre-dose, 0.5, 1, 1.5, 2.25, 3, 4, 6 hours post-dose on Fraction Day 1; Pre-dose, 2.25 hours post-dose on Fraction Day 2, 5, 6 and 7; Pre-dose, 0.5, 1, 1.5, 2.25, 3, 4, and 6 hours post-dose on Fraction Day 10

Population: As per changes in planned analysis, the outcome measure related to pharmacokinetic parameters was not assessed.

Apparent terminal half-life was defined as the time required for the plasma concentration of drug to decrease 50 percent in the final stage of its elimination.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Pre-dose, 0.5, 1, 1.5, 2.25, 3, 4, 6 hours post-dose on Fraction Day 1; Pre-dose, 2.25 hours post-dose on Fraction Day 2, 5, 6 and 7; Pre-dose, 0.5, 1, 1.5, 2.25, 3, 4, and 6 hours post-dose on Fraction Day 10

Population: As per changes in planned analysis, the outcome measure related to pharmacokinetic parameters was not assessed.

AUC(0-last) is defined as the area under the concentration-time curve from dosing (time 0) to the time of the last measured concentration. AUC(0-last) will be estimated using the Linear Up Log Down calculation method.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Pre-dose, 0.5, 1, 1.5, 2.25, 3, 4, 6 hours post-dose on Fraction Day 1; Pre-dose, 2.25 hours post-dose on Fraction Day 2, 5, 6 and 7; Pre-dose, 0.5, 1, 1.5, 2.25, 3, 4, and 6 hours post-dose on Fraction Day 10

Population: As per changes in planned analysis, the outcome measure related to pharmacokinetic parameters was not assessed.

The Dose normalized AUC from time zero to the last sampling time (0-last) at which the concentration is at or above the lower limit of quantification. Normalized using the actual dose, using the formula AUC0-last/Dose.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Pre-dose, 0.5, 1, 1.5, 2.25, 3, 4, 6 hours post-dose on Fraction Day 1; Pre-dose, 2.25 hours post-dose on Fraction Day 2, 5, 6 and 7; Pre-dose, 0.5, 1, 1.5, 2.25, 3, 4, and 6 hours post-dose on Fraction Day 10

Population: As per changes in planned analysis, the outcome measure related to pharmacokinetic parameters was not assessed.

Area under the drug concentration-time curve from 0 to 6 hour post dosing for M3541. AUC0-6 was calculated according to the mixed log-linear trapezoidal rule.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Pre-dose, 0.5, 1, 1.5, 2.25, 3, 4, 6 hours post-dose on Fraction Day 1; Pre-dose, 2.25 hours post-dose on Fraction Day 2, 5, 6 and 7; Pre-dose, 0.5, 1, 1.5, 2.25, 3, 4, and 6 hours post-dose on Fraction Day 10

Population: As per changes in planned analysis, the outcome measure related to pharmacokinetic parameters was not assessed.

AUC0-inf is the area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Pre-dose, 0.5, 1, 1.5, 2.25, 3, 4, 6 hours post-dose on Fraction Day 1; Pre-dose, 2.25 hours post-dose on Fraction Day 2, 5, 6 and 7; Pre-dose, 0.5, 1, 1.5, 2.25, 3, 4, and 6 hours post-dose on Fraction Day 10

Population: As per changes in planned analysis, the outcome measure related to pharmacokinetic parameters was not assessed.

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Pre-dose, 0.5, 1, 1.5, 2.25, 3, 4, 6 hours post-dose on Fraction Day 1; Pre-dose, 2.25 hours post-dose on Fraction Day 2, 5, 6 and 7; Pre-dose, 0.5, 1, 1.5, 2.25, 3, 4, and 6 hours post-dose on Fraction Day 10

Population: As per changes in planned analysis, the outcome measure related to pharmacokinetic parameters was not assessed.

Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. CL/f = Dose /AUC0-inf. Predicted AUC0-inf should be used.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Pre-dose, 0.5, 1, 1.5, 2.25, 3, 4, 6 hours post-dose on Fraction Day 1; Pre-dose, 2.25 hours post-dose on Fraction Day 2, 5, 6 and 7; Pre-dose, 0.5, 1, 1.5, 2.25, 3, 4, and 6 hours post-dose on Fraction Day 10

Population: As per changes in planned analysis, the outcome measure related to pharmacokinetic parameters was not assessed.

Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Pre-dose, 0.5, 1, 1.5, 2.25, 3, 4, 6 hours post-dose on Fraction Day 1; Pre-dose, 2.25 hours post-dose on Fraction Day 2, 5, 6 and 7; Pre-dose, 0.5, 1, 1.5, 2.25, 3, 4, and 6 hours post-dose on Fraction Day 10

Population: As per changes in planned analysis, the outcome measure related to pharmacokinetic parameters was not assessed.

The Vz/f was defined as the theoretical volume in which the total amount of required to uniformly distribute to produce the desired plasma concentration. Apparent volume of distribution after oral dose (Vz/F) was influenced by the fraction absorbed. The Vz/f was calculated by dividing the dose with area under the concentration time curve from time zero to infinity multiplied with terminal elimination rate constant Lambda(z). Vz/f=Dose/AUC(0-inf)\* Lambda(z).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Pre-dose, 0.5, 1, 1.5, 2.25, 3, 4, 6 hours post-dose on Fraction Day 1; Pre-dose, 2.25 hours post-dose on Fraction Day 2, 5, 6 and 7; Pre-dose, 0.5, 1, 1.5, 2.25, 3, 4, and 6 hours post-dose on Fraction Day 10

Population: As per changes in planned analysis, the outcome measure related to pharmacokinetic parameters was not assessed.

Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vss/f after oral dose was influenced by the fraction absorbed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Pre-dose, 0.5, 1, 1.5, 2.25, 3, 4, 6 hours post-dose on Fraction Day 1; Pre-dose, 2.25 hours post-dose on Fraction Day 2, 5, 6 and 7; Pre-dose, 0.5, 1, 1.5, 2.25, 3, 4, and 6 hours post-dose on Fraction Day 10

Population: As per changes in planned analysis, the outcome measure related to pharmacokinetic parameters was not assessed.

The accumulation ratio to assess the increase in exposure via AUC0-6h. Racc(AUC0-6h)= (AUC0-6h after multiple dose) / (AUC0-6h after single dose).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Pre-dose, 0.5, 1, 1.5, 2.25, 3, 4, 6 hours post-dose on Fraction Day 1; Pre-dose, 2.25 hours post-dose on Fraction Day 2, 5, 6 and 7; Pre-dose, 0.5, 1, 1.5, 2.25, 3, 4, and 6 hours post-dose on Fraction Day 10

Population: As per changes in planned analysis, the outcome measure related to pharmacokinetic parameters was not assessed.

The accumulation ratio is to assess the increase in maximum concentration with multiple dosing. Racc(Cmax) = (Cmax after multiple dose)/ (Cmax after single dose).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Pre-dose, 0.5, 1, 1.5, 2.25, 3, 4, 6 hours post-dose on Fraction Day 1; Pre-dose, 2.25 hours post-dose on Fraction Day 2, 5, 6 and 7; Pre-dose, 0.5, 1, 1.5, 2.25, 3, 4, and 6 hours post-dose on Fraction Day 10

Population: As per changes in planned analysis, the outcome measure related to pharmacokinetic parameters was not assessed.

Ctrough is the concentration prior to study drug administration.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Pre-dose, 0.5, 1, 1.5, 2.25, 3, 4, 6 hours post-dose on Fraction Day 1; Pre-dose, 2.25 hours post-dose on Fraction Day 2, 5, 6 and 7; Pre-dose, 0.5, 1, 1.5, 2.25, 3, 4, and 6 hours post-dose on Fraction Day 10

Population: As per changes in planned analysis, the outcome measure related to pharmacokinetic parameters was not assessed.

Cmin is minimum observed plasma concentration obtained directly from the concentration versus time curve.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Pre-dose, 0.5, 1, 1.5, 2.25, 3, 4, 6 hours post-dose on Fraction Day 1; Pre-dose, 2.25 hours post-dose on Fraction Day 2, 5, 6 and 7; Pre-dose, 0.5, 1, 1.5, 2.25, 3, 4, and 6 hours post-dose on Fraction Day 10

Population: As per changes in planned analysis, the outcome measure related to pharmacokinetic parameters was not assessed.

Cavg was defined as average plasma concentration.

Outcome measures

Outcome data not reported

Adverse Events

M3541 50 mg + RT

Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths

M3541 100 mg + RT

Serious events: 1 serious events
Other events: 4 other events
Deaths: 4 deaths

M3541 200 mg + RT

Serious events: 1 serious events
Other events: 5 other events
Deaths: 2 deaths

M3541 300 mg + RT

Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
M3541 50 mg + RT
n=3 participants at risk
Participants received 50 milligrams (mg) M3541 orally once per fraction day (FD) in combination with palliative radiotherapy (RT) administered in fraction of 30 Gray (Gy) given in 10 fractions of 3 Gy/FD on FD 1 to FD 10, for 2 consecutive calendar weeks (ie, Monday through Friday, with the intervening Saturday and Sunday as M3541 / RT holidays).
M3541 100 mg + RT
n=4 participants at risk
Participants received 100 mg M3541 orally once per FD in combination with palliative RT administered in fraction of 30 Gray (Gy) given in 10 fractions of 3 Gy/FD on FD 1 to FD 10 for 2 consecutive calendar weeks (ie, Monday through Friday, with the intervening Saturday and Sunday as M3541 / RT holidays).
M3541 200 mg + RT
n=5 participants at risk
Participants received 200 mg M3541 orally once per FD in combination with palliative RT administered in fraction of 30 Gray (Gy) given in 10 fractions of 3 Gy/FD on FD 1 to FD 10 for 2 consecutive calendar weeks (ie, Monday through Friday, with the intervening Saturday and Sunday as M3541 / RT holidays).
M3541 300 mg + RT
n=3 participants at risk
Participants received 300 mg M3541 orally once per FD in combination with palliative RT administered in fraction of 30 Gray (Gy) given in 10 fractions of 3 Gy/FD on FD 1 to FD 10 for 2 consecutive calendar weeks (ie, Monday through Friday, with the intervening Saturday and Sunday as M3541 / RT holidays).
Infections and infestations
Urinary tract infection
0.00%
0/3 • Baseline up to 749 days
25.0%
1/4 • Baseline up to 749 days
20.0%
1/5 • Baseline up to 749 days
0.00%
0/3 • Baseline up to 749 days
Investigations
Blood creatinine increased
0.00%
0/3 • Baseline up to 749 days
0.00%
0/4 • Baseline up to 749 days
20.0%
1/5 • Baseline up to 749 days
0.00%
0/3 • Baseline up to 749 days
Metabolism and nutrition disorders
Dehydration
0.00%
0/3 • Baseline up to 749 days
0.00%
0/4 • Baseline up to 749 days
20.0%
1/5 • Baseline up to 749 days
0.00%
0/3 • Baseline up to 749 days
Metabolism and nutrition disorders
Hyponatraemia
0.00%
0/3 • Baseline up to 749 days
0.00%
0/4 • Baseline up to 749 days
20.0%
1/5 • Baseline up to 749 days
0.00%
0/3 • Baseline up to 749 days

Other adverse events

Other adverse events
Measure
M3541 50 mg + RT
n=3 participants at risk
Participants received 50 milligrams (mg) M3541 orally once per fraction day (FD) in combination with palliative radiotherapy (RT) administered in fraction of 30 Gray (Gy) given in 10 fractions of 3 Gy/FD on FD 1 to FD 10, for 2 consecutive calendar weeks (ie, Monday through Friday, with the intervening Saturday and Sunday as M3541 / RT holidays).
M3541 100 mg + RT
n=4 participants at risk
Participants received 100 mg M3541 orally once per FD in combination with palliative RT administered in fraction of 30 Gray (Gy) given in 10 fractions of 3 Gy/FD on FD 1 to FD 10 for 2 consecutive calendar weeks (ie, Monday through Friday, with the intervening Saturday and Sunday as M3541 / RT holidays).
M3541 200 mg + RT
n=5 participants at risk
Participants received 200 mg M3541 orally once per FD in combination with palliative RT administered in fraction of 30 Gray (Gy) given in 10 fractions of 3 Gy/FD on FD 1 to FD 10 for 2 consecutive calendar weeks (ie, Monday through Friday, with the intervening Saturday and Sunday as M3541 / RT holidays).
M3541 300 mg + RT
n=3 participants at risk
Participants received 300 mg M3541 orally once per FD in combination with palliative RT administered in fraction of 30 Gray (Gy) given in 10 fractions of 3 Gy/FD on FD 1 to FD 10 for 2 consecutive calendar weeks (ie, Monday through Friday, with the intervening Saturday and Sunday as M3541 / RT holidays).
Blood and lymphatic system disorders
Anaemia
0.00%
0/3 • Baseline up to 749 days
0.00%
0/4 • Baseline up to 749 days
20.0%
1/5 • Baseline up to 749 days
0.00%
0/3 • Baseline up to 749 days
Blood and lymphatic system disorders
Febrile neutropenia
0.00%
0/3 • Baseline up to 749 days
0.00%
0/4 • Baseline up to 749 days
20.0%
1/5 • Baseline up to 749 days
0.00%
0/3 • Baseline up to 749 days
Cardiac disorders
Tachycardia
33.3%
1/3 • Baseline up to 749 days
0.00%
0/4 • Baseline up to 749 days
0.00%
0/5 • Baseline up to 749 days
0.00%
0/3 • Baseline up to 749 days
Eye disorders
Visual impairment
0.00%
0/3 • Baseline up to 749 days
25.0%
1/4 • Baseline up to 749 days
0.00%
0/5 • Baseline up to 749 days
0.00%
0/3 • Baseline up to 749 days
Gastrointestinal disorders
Abdominal pain
0.00%
0/3 • Baseline up to 749 days
0.00%
0/4 • Baseline up to 749 days
20.0%
1/5 • Baseline up to 749 days
0.00%
0/3 • Baseline up to 749 days
Gastrointestinal disorders
Abdominal pain lower
0.00%
0/3 • Baseline up to 749 days
0.00%
0/4 • Baseline up to 749 days
0.00%
0/5 • Baseline up to 749 days
33.3%
1/3 • Baseline up to 749 days
Gastrointestinal disorders
Colitis
0.00%
0/3 • Baseline up to 749 days
0.00%
0/4 • Baseline up to 749 days
0.00%
0/5 • Baseline up to 749 days
33.3%
1/3 • Baseline up to 749 days
Gastrointestinal disorders
Diarrhoea
0.00%
0/3 • Baseline up to 749 days
25.0%
1/4 • Baseline up to 749 days
60.0%
3/5 • Baseline up to 749 days
33.3%
1/3 • Baseline up to 749 days
Gastrointestinal disorders
Dyspepsia
66.7%
2/3 • Baseline up to 749 days
0.00%
0/4 • Baseline up to 749 days
0.00%
0/5 • Baseline up to 749 days
0.00%
0/3 • Baseline up to 749 days
Gastrointestinal disorders
Dysphagia
33.3%
1/3 • Baseline up to 749 days
0.00%
0/4 • Baseline up to 749 days
0.00%
0/5 • Baseline up to 749 days
0.00%
0/3 • Baseline up to 749 days
Gastrointestinal disorders
Enterocolitis
0.00%
0/3 • Baseline up to 749 days
0.00%
0/4 • Baseline up to 749 days
20.0%
1/5 • Baseline up to 749 days
0.00%
0/3 • Baseline up to 749 days
Gastrointestinal disorders
Nausea
33.3%
1/3 • Baseline up to 749 days
0.00%
0/4 • Baseline up to 749 days
40.0%
2/5 • Baseline up to 749 days
0.00%
0/3 • Baseline up to 749 days
Gastrointestinal disorders
Odynophagia
33.3%
1/3 • Baseline up to 749 days
0.00%
0/4 • Baseline up to 749 days
0.00%
0/5 • Baseline up to 749 days
0.00%
0/3 • Baseline up to 749 days
Gastrointestinal disorders
Proctitis
0.00%
0/3 • Baseline up to 749 days
0.00%
0/4 • Baseline up to 749 days
0.00%
0/5 • Baseline up to 749 days
33.3%
1/3 • Baseline up to 749 days
Gastrointestinal disorders
Stomatitis
33.3%
1/3 • Baseline up to 749 days
0.00%
0/4 • Baseline up to 749 days
0.00%
0/5 • Baseline up to 749 days
0.00%
0/3 • Baseline up to 749 days
Gastrointestinal disorders
Vomiting
0.00%
0/3 • Baseline up to 749 days
0.00%
0/4 • Baseline up to 749 days
40.0%
2/5 • Baseline up to 749 days
0.00%
0/3 • Baseline up to 749 days
General disorders
Face oedema
33.3%
1/3 • Baseline up to 749 days
0.00%
0/4 • Baseline up to 749 days
0.00%
0/5 • Baseline up to 749 days
0.00%
0/3 • Baseline up to 749 days
General disorders
Facial pain
0.00%
0/3 • Baseline up to 749 days
25.0%
1/4 • Baseline up to 749 days
0.00%
0/5 • Baseline up to 749 days
0.00%
0/3 • Baseline up to 749 days
General disorders
Fatigue
66.7%
2/3 • Baseline up to 749 days
0.00%
0/4 • Baseline up to 749 days
40.0%
2/5 • Baseline up to 749 days
33.3%
1/3 • Baseline up to 749 days
General disorders
Influenza like illness
0.00%
0/3 • Baseline up to 749 days
25.0%
1/4 • Baseline up to 749 days
0.00%
0/5 • Baseline up to 749 days
0.00%
0/3 • Baseline up to 749 days
General disorders
Non-cardiac chest pain
33.3%
1/3 • Baseline up to 749 days
0.00%
0/4 • Baseline up to 749 days
0.00%
0/5 • Baseline up to 749 days
0.00%
0/3 • Baseline up to 749 days
General disorders
Oedema peripheral
33.3%
1/3 • Baseline up to 749 days
0.00%
0/4 • Baseline up to 749 days
0.00%
0/5 • Baseline up to 749 days
0.00%
0/3 • Baseline up to 749 days
General disorders
Pain
33.3%
1/3 • Baseline up to 749 days
0.00%
0/4 • Baseline up to 749 days
0.00%
0/5 • Baseline up to 749 days
0.00%
0/3 • Baseline up to 749 days
General disorders
Pyrexia
0.00%
0/3 • Baseline up to 749 days
25.0%
1/4 • Baseline up to 749 days
20.0%
1/5 • Baseline up to 749 days
0.00%
0/3 • Baseline up to 749 days
General disorders
Swelling face
0.00%
0/3 • Baseline up to 749 days
25.0%
1/4 • Baseline up to 749 days
0.00%
0/5 • Baseline up to 749 days
0.00%
0/3 • Baseline up to 749 days
Infections and infestations
Candida infection
0.00%
0/3 • Baseline up to 749 days
0.00%
0/4 • Baseline up to 749 days
20.0%
1/5 • Baseline up to 749 days
0.00%
0/3 • Baseline up to 749 days
Infections and infestations
Upper respiratory tract infection
33.3%
1/3 • Baseline up to 749 days
0.00%
0/4 • Baseline up to 749 days
0.00%
0/5 • Baseline up to 749 days
0.00%
0/3 • Baseline up to 749 days
Infections and infestations
Urinary tract infection
0.00%
0/3 • Baseline up to 749 days
25.0%
1/4 • Baseline up to 749 days
40.0%
2/5 • Baseline up to 749 days
0.00%
0/3 • Baseline up to 749 days
Injury, poisoning and procedural complications
Contusion
0.00%
0/3 • Baseline up to 749 days
0.00%
0/4 • Baseline up to 749 days
20.0%
1/5 • Baseline up to 749 days
0.00%
0/3 • Baseline up to 749 days
Injury, poisoning and procedural complications
Eye contusion
0.00%
0/3 • Baseline up to 749 days
25.0%
1/4 • Baseline up to 749 days
0.00%
0/5 • Baseline up to 749 days
0.00%
0/3 • Baseline up to 749 days
Injury, poisoning and procedural complications
Fall
0.00%
0/3 • Baseline up to 749 days
25.0%
1/4 • Baseline up to 749 days
0.00%
0/5 • Baseline up to 749 days
0.00%
0/3 • Baseline up to 749 days
Injury, poisoning and procedural complications
Radiation skin injury
0.00%
0/3 • Baseline up to 749 days
0.00%
0/4 • Baseline up to 749 days
0.00%
0/5 • Baseline up to 749 days
33.3%
1/3 • Baseline up to 749 days
Investigations
Activated partial thromboplastin time prolonged
0.00%
0/3 • Baseline up to 749 days
25.0%
1/4 • Baseline up to 749 days
0.00%
0/5 • Baseline up to 749 days
0.00%
0/3 • Baseline up to 749 days
Investigations
Alanine aminotransferase increased
0.00%
0/3 • Baseline up to 749 days
0.00%
0/4 • Baseline up to 749 days
20.0%
1/5 • Baseline up to 749 days
0.00%
0/3 • Baseline up to 749 days
Investigations
Aspartate aminotransferase increased
0.00%
0/3 • Baseline up to 749 days
0.00%
0/4 • Baseline up to 749 days
20.0%
1/5 • Baseline up to 749 days
0.00%
0/3 • Baseline up to 749 days
Investigations
Blood creatinine increased
0.00%
0/3 • Baseline up to 749 days
25.0%
1/4 • Baseline up to 749 days
20.0%
1/5 • Baseline up to 749 days
0.00%
0/3 • Baseline up to 749 days
Investigations
International normalised ratio increased
0.00%
0/3 • Baseline up to 749 days
25.0%
1/4 • Baseline up to 749 days
0.00%
0/5 • Baseline up to 749 days
0.00%
0/3 • Baseline up to 749 days
Investigations
Neutrophil count decreased
0.00%
0/3 • Baseline up to 749 days
0.00%
0/4 • Baseline up to 749 days
20.0%
1/5 • Baseline up to 749 days
0.00%
0/3 • Baseline up to 749 days
Investigations
Platelet count decreased
0.00%
0/3 • Baseline up to 749 days
0.00%
0/4 • Baseline up to 749 days
20.0%
1/5 • Baseline up to 749 days
0.00%
0/3 • Baseline up to 749 days
Metabolism and nutrition disorders
Decreased appetite
33.3%
1/3 • Baseline up to 749 days
0.00%
0/4 • Baseline up to 749 days
0.00%
0/5 • Baseline up to 749 days
0.00%
0/3 • Baseline up to 749 days
Metabolism and nutrition disorders
Dehydration
33.3%
1/3 • Baseline up to 749 days
0.00%
0/4 • Baseline up to 749 days
0.00%
0/5 • Baseline up to 749 days
0.00%
0/3 • Baseline up to 749 days
Metabolism and nutrition disorders
Gout
0.00%
0/3 • Baseline up to 749 days
0.00%
0/4 • Baseline up to 749 days
20.0%
1/5 • Baseline up to 749 days
0.00%
0/3 • Baseline up to 749 days
Metabolism and nutrition disorders
Hyperkalaemia
0.00%
0/3 • Baseline up to 749 days
0.00%
0/4 • Baseline up to 749 days
20.0%
1/5 • Baseline up to 749 days
0.00%
0/3 • Baseline up to 749 days
Metabolism and nutrition disorders
Hypomagnesaemia
0.00%
0/3 • Baseline up to 749 days
25.0%
1/4 • Baseline up to 749 days
0.00%
0/5 • Baseline up to 749 days
0.00%
0/3 • Baseline up to 749 days
Metabolism and nutrition disorders
Hyponatraemia
33.3%
1/3 • Baseline up to 749 days
0.00%
0/4 • Baseline up to 749 days
20.0%
1/5 • Baseline up to 749 days
0.00%
0/3 • Baseline up to 749 days
Musculoskeletal and connective tissue disorders
Arthralgia
0.00%
0/3 • Baseline up to 749 days
25.0%
1/4 • Baseline up to 749 days
0.00%
0/5 • Baseline up to 749 days
0.00%
0/3 • Baseline up to 749 days
Musculoskeletal and connective tissue disorders
Back pain
33.3%
1/3 • Baseline up to 749 days
0.00%
0/4 • Baseline up to 749 days
0.00%
0/5 • Baseline up to 749 days
0.00%
0/3 • Baseline up to 749 days
Musculoskeletal and connective tissue disorders
Flank pain
0.00%
0/3 • Baseline up to 749 days
0.00%
0/4 • Baseline up to 749 days
0.00%
0/5 • Baseline up to 749 days
33.3%
1/3 • Baseline up to 749 days
Musculoskeletal and connective tissue disorders
Muscular weakness
0.00%
0/3 • Baseline up to 749 days
50.0%
2/4 • Baseline up to 749 days
20.0%
1/5 • Baseline up to 749 days
0.00%
0/3 • Baseline up to 749 days
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
33.3%
1/3 • Baseline up to 749 days
0.00%
0/4 • Baseline up to 749 days
0.00%
0/5 • Baseline up to 749 days
0.00%
0/3 • Baseline up to 749 days
Musculoskeletal and connective tissue disorders
Myalgia
0.00%
0/3 • Baseline up to 749 days
0.00%
0/4 • Baseline up to 749 days
20.0%
1/5 • Baseline up to 749 days
0.00%
0/3 • Baseline up to 749 days
Musculoskeletal and connective tissue disorders
Neck pain
0.00%
0/3 • Baseline up to 749 days
25.0%
1/4 • Baseline up to 749 days
0.00%
0/5 • Baseline up to 749 days
0.00%
0/3 • Baseline up to 749 days
Musculoskeletal and connective tissue disorders
Pain in extremity
0.00%
0/3 • Baseline up to 749 days
25.0%
1/4 • Baseline up to 749 days
0.00%
0/5 • Baseline up to 749 days
0.00%
0/3 • Baseline up to 749 days
Nervous system disorders
Dizziness
33.3%
1/3 • Baseline up to 749 days
0.00%
0/4 • Baseline up to 749 days
0.00%
0/5 • Baseline up to 749 days
0.00%
0/3 • Baseline up to 749 days
Nervous system disorders
Headache
33.3%
1/3 • Baseline up to 749 days
25.0%
1/4 • Baseline up to 749 days
0.00%
0/5 • Baseline up to 749 days
0.00%
0/3 • Baseline up to 749 days
Nervous system disorders
Hypoaesthesia
0.00%
0/3 • Baseline up to 749 days
0.00%
0/4 • Baseline up to 749 days
20.0%
1/5 • Baseline up to 749 days
0.00%
0/3 • Baseline up to 749 days
Nervous system disorders
Peripheral sensory neuropathy
0.00%
0/3 • Baseline up to 749 days
0.00%
0/4 • Baseline up to 749 days
0.00%
0/5 • Baseline up to 749 days
33.3%
1/3 • Baseline up to 749 days
Psychiatric disorders
Insomnia
0.00%
0/3 • Baseline up to 749 days
0.00%
0/4 • Baseline up to 749 days
0.00%
0/5 • Baseline up to 749 days
33.3%
1/3 • Baseline up to 749 days
Reproductive system and breast disorders
Dyspareunia
0.00%
0/3 • Baseline up to 749 days
0.00%
0/4 • Baseline up to 749 days
0.00%
0/5 • Baseline up to 749 days
33.3%
1/3 • Baseline up to 749 days
Respiratory, thoracic and mediastinal disorders
Dysphonia
0.00%
0/3 • Baseline up to 749 days
0.00%
0/4 • Baseline up to 749 days
20.0%
1/5 • Baseline up to 749 days
0.00%
0/3 • Baseline up to 749 days
Respiratory, thoracic and mediastinal disorders
Haemoptysis
33.3%
1/3 • Baseline up to 749 days
0.00%
0/4 • Baseline up to 749 days
0.00%
0/5 • Baseline up to 749 days
0.00%
0/3 • Baseline up to 749 days
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
33.3%
1/3 • Baseline up to 749 days
25.0%
1/4 • Baseline up to 749 days
20.0%
1/5 • Baseline up to 749 days
0.00%
0/3 • Baseline up to 749 days
Respiratory, thoracic and mediastinal disorders
Productive cough
0.00%
0/3 • Baseline up to 749 days
0.00%
0/4 • Baseline up to 749 days
20.0%
1/5 • Baseline up to 749 days
33.3%
1/3 • Baseline up to 749 days
Respiratory, thoracic and mediastinal disorders
Wheezing
0.00%
0/3 • Baseline up to 749 days
0.00%
0/4 • Baseline up to 749 days
0.00%
0/5 • Baseline up to 749 days
33.3%
1/3 • Baseline up to 749 days
Skin and subcutaneous tissue disorders
Blister
0.00%
0/3 • Baseline up to 749 days
0.00%
0/4 • Baseline up to 749 days
20.0%
1/5 • Baseline up to 749 days
0.00%
0/3 • Baseline up to 749 days
Skin and subcutaneous tissue disorders
Dry skin
0.00%
0/3 • Baseline up to 749 days
25.0%
1/4 • Baseline up to 749 days
20.0%
1/5 • Baseline up to 749 days
33.3%
1/3 • Baseline up to 749 days
Skin and subcutaneous tissue disorders
Erythema
0.00%
0/3 • Baseline up to 749 days
0.00%
0/4 • Baseline up to 749 days
0.00%
0/5 • Baseline up to 749 days
33.3%
1/3 • Baseline up to 749 days
Skin and subcutaneous tissue disorders
Pruritus
0.00%
0/3 • Baseline up to 749 days
25.0%
1/4 • Baseline up to 749 days
20.0%
1/5 • Baseline up to 749 days
66.7%
2/3 • Baseline up to 749 days
Skin and subcutaneous tissue disorders
Rash
0.00%
0/3 • Baseline up to 749 days
0.00%
0/4 • Baseline up to 749 days
20.0%
1/5 • Baseline up to 749 days
0.00%
0/3 • Baseline up to 749 days
Skin and subcutaneous tissue disorders
Rash erythematous
0.00%
0/3 • Baseline up to 749 days
0.00%
0/4 • Baseline up to 749 days
20.0%
1/5 • Baseline up to 749 days
0.00%
0/3 • Baseline up to 749 days
Skin and subcutaneous tissue disorders
Rash maculo-papular
0.00%
0/3 • Baseline up to 749 days
25.0%
1/4 • Baseline up to 749 days
0.00%
0/5 • Baseline up to 749 days
33.3%
1/3 • Baseline up to 749 days
Skin and subcutaneous tissue disorders
Urticaria
0.00%
0/3 • Baseline up to 749 days
0.00%
0/4 • Baseline up to 749 days
20.0%
1/5 • Baseline up to 749 days
0.00%
0/3 • Baseline up to 749 days

Additional Information

Communication Center

Merck KGaA, Darmstadt, Germany

Phone: +49-6151-72-5200

Results disclosure agreements

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