Trial Outcomes & Findings for Study of Peposertib in Combination With Capecitabine and RT in Rectal Cancer (NCT NCT03770689)

Last Updated: 2023-03-21

Results Overview

DLT is defined as any of following treatment emergent adverse events (TEAEs) considered possibly related to study treatment by Investigator and/or Sponsor up to completion of assigned chemoradiotherapy treatment. DLT were based on SMC: Adverse drug reaction that, in the opinion of SMC, is of potential clinical significance such that further dose escalation would expose participants to unacceptable risk; Any occurrence of drug-induced liver injury meeting the Hy's law criteria; Any Grade 3 toxicity excluding diarrhea, neutropenia lasting for ≤ 5 days, nausea \& vomiting, Grade 3 thrombocytopenia without bleeding; Grade ≥ 4 AEs at least possibly related to study drug, irrespective of duration, excluding: Isolated Grade 4 lymphocytopenia without clinical symptoms; Neutropenia lasting for ≤ 5 days and not associated with fever; Any toxicity related to study drug that causes participant to receive \> 80% of planned peposertib, capecitabine or RT dose.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

19 participants

Primary outcome timeframe

Time from first study intervention up to 19 weeks (including 5.5 weeks of treatment and 13.5 weeks of short term safety follow-up period)

Results posted on

2023-03-21

Participant Flow

The study was planned to be conducted in two phases: Phase Ib and Phase II. Phase II of the study was never initiated due to early discontinuation as per sponsor's decision.

Participant milestones

Participant milestones
Measure	Peposertib 50 mg + RT + Capecitabine: Participants received peposertib 50 milligram (mg) once daily in combination with capecitabine 825 milligram per square meter (mg/m\^2) twice daily 5 days per week and radiotherapy (RT) of 50 to 50.4 Gray (Gy) to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.	Peposertib 100 mg + RT + Capecitabine: Participants received peposertib 100 mg once daily in combination with capecitabine 825 mg/m\^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.	Peposertib 150 mg + RT + Capecitabine: Participants received peposertib 150 mg once daily in combination with capecitabine 825 mg/m\^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.	Peposertib 250 mg + RT + Capecitabine: Participants received peposertib 250 mg once daily in combination with capecitabine 825 mg/m\^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.
Overall Study STARTED	1	6	6	6
Overall Study Pharmacokinetic Analysis Set	1	6	6	6
Overall Study Full Analysis Set (FAS)	1	6	6	6
Overall Study Safety Analysis Set (SAF)	1	6	6	6
Overall Study COMPLETED	1	6	6	6
Overall Study NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Study of Peposertib in Combination With Capecitabine and RT in Rectal Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Peposertib 50 mg + RT + Capecitabine: n=1 Participants Participants received peposertib 50 milligram (mg) once daily in combination with capecitabine 825 milligram per square meter (mg/m\^2) twice daily 5 days per week and radiotherapy (RT) of 50 to 50.4 Gray (Gy) to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.	Peposertib 100 mg + RT + Capecitabine: n=6 Participants Participants received peposertib 100 mg once daily in combination with capecitabine 825 mg/m\^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.	Peposertib 150 mg + RT + Capecitabine: n=6 Participants Participants received peposertib 150 mg once daily in combination with capecitabine 825 mg/m\^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.	Peposertib 250 mg + RT + Capecitabine: n=6 Participants Participants received peposertib 250 mg once daily in combination with capecitabine 825 mg/m\^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.	Total n=19 Participants Total of all reporting groups
Age, Continuous	60 Years n=5 Participants	60 Years STANDARD_DEVIATION 15.0 • n=7 Participants	55 Years STANDARD_DEVIATION 8.9 • n=5 Participants	58 Years STANDARD_DEVIATION 11.2 • n=4 Participants	58 Years STANDARD_DEVIATION 11.1 • n=21 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants	8 Participants n=21 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants	3 Participants n=4 Participants	11 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	1 Participants n=5 Participants	6 Participants n=7 Participants	6 Participants n=5 Participants	5 Participants n=4 Participants	18 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	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) White	1 Participants n=5 Participants	6 Participants n=7 Participants	6 Participants n=5 Participants	6 Participants n=4 Participants	19 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: Time from first study intervention up to 19 weeks (including 5.5 weeks of treatment and 13.5 weeks of short term safety follow-up period)

Population: Dose escalation (DE) analysis set included all participants treated in dose escalation cohorts, who received at least 80% of peposertib, 50% of capecitabine, and 80% of RT planned dose and complete DLT period (5 or 5.5 weeks after start of treatment or for the entire duration of treatment). DE set also included participants treated in dose escalation cohorts who experience a DLT during DLT period regardless of the amount of each study intervention received/completion of the DLT period.

Outcome measures

Outcome measures
Measure	Peposertib 50 mg + RT + Capecitabine: n=1 Participants Participants received peposertib 50 milligram (mg) once daily in combination with capecitabine 825 milligram per square meter (mg/m\^2) twice daily 5 days per week and radiotherapy (RT) of 50 to 50.4 Gray (Gy) to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.	Peposertib 100 mg + RT + Capecitabine: n=5 Participants Participants received peposertib 100 mg once daily in combination with capecitabine 825 mg/m\^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.	Peposertib 150 mg + RT + Capecitabine: n=6 Participants Participants received peposertib 150 mg once daily in combination with capecitabine 825 mg/m\^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.	Peposertib 250 mg + RT + Capecitabine: n=6 Participants Participants received peposertib 250 mg once daily in combination with capecitabine 825 mg/m\^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.
Number of Participants Who Experienced Dose Limiting Toxicity (DLT) Confirmed by Safety Monitoring Committee (SMC)	0 Participants	1 Participants	1 Participants	3 Participants

SECONDARY outcome

Timeframe: Time from first study intervention up to long term safety follow-up period (Up to Month 35)

Population: SAF analysis set included all participants who received at least 1 dose of study intervention.

Adverse event (AE) is any untoward medical occurrence in participant administered pharmaceutical product, regardless of causal relationship with this treatment. Therefore, an AE can be any unfavorable \& unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, regardless if it is considered related to medicinal product. Serious AE: 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. TEAE: AE with onset after start of treatment or with onset date before the treatment start date but worsening after treatment start date. TEAEs included both serious and non-serious TEAEs. Treatment-related TEAEs: reasonably related to study intervention. Number of participants with TEAEs and treatment related TEAEs were reported.

Outcome measures

Outcome measures
Measure	Peposertib 50 mg + RT + Capecitabine: n=1 Participants Participants received peposertib 50 milligram (mg) once daily in combination with capecitabine 825 milligram per square meter (mg/m\^2) twice daily 5 days per week and radiotherapy (RT) of 50 to 50.4 Gray (Gy) to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.	Peposertib 100 mg + RT + Capecitabine: n=6 Participants Participants received peposertib 100 mg once daily in combination with capecitabine 825 mg/m\^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.	Peposertib 150 mg + RT + Capecitabine: n=6 Participants Participants received peposertib 150 mg once daily in combination with capecitabine 825 mg/m\^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.	Peposertib 250 mg + RT + Capecitabine: n=6 Participants Participants received peposertib 250 mg once daily in combination with capecitabine 825 mg/m\^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.
Number of Participants Wtih Treatment Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs According to National Cancer Institute Common Terminology Criteria of Adverse Events (NCI-CTCAE) Version 5.0 Participants with TEAEs	1 Participants	6 Participants	6 Participants	6 Participants
Number of Participants Wtih Treatment Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs According to National Cancer Institute Common Terminology Criteria of Adverse Events (NCI-CTCAE) Version 5.0 Participants with Treatment-Related TEAEs	1 Participants	6 Participants	6 Participants	6 Participants

SECONDARY outcome

Timeframe: Time from first study intervention up to long term safety follow-up period (Up to Month 35)

Population: SAF analysis set included all participants who received at least 1 dose of 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 abnormalities Grade \>= 3 in laboratory test values were reported.

Outcome measures

Outcome measures
Measure	Peposertib 50 mg + RT + Capecitabine: n=1 Participants Participants received peposertib 50 milligram (mg) once daily in combination with capecitabine 825 milligram per square meter (mg/m\^2) twice daily 5 days per week and radiotherapy (RT) of 50 to 50.4 Gray (Gy) to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.	Peposertib 100 mg + RT + Capecitabine: n=6 Participants Participants received peposertib 100 mg once daily in combination with capecitabine 825 mg/m\^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.	Peposertib 150 mg + RT + Capecitabine: n=6 Participants Participants received peposertib 150 mg once daily in combination with capecitabine 825 mg/m\^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.	Peposertib 250 mg + RT + Capecitabine: n=6 Participants Participants received peposertib 250 mg once daily in combination with capecitabine 825 mg/m\^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.
Number of Participants With Abnormalities [Grade Greater Than or Equals to (>=) 3] in Laboratory Test Values	1 Participants	6 Participants	6 Participants	6 Participants

SECONDARY outcome

Timeframe: Time from first study intervention up to long term safety follow-up period (Up to Month 35)

Population: SAF analysis set included all participants who received at least 1 dose of study intervention.

Vital sign assessments included assessments of heart rate, diastolic blood pressure, systolic blood pressure, respiratory rate and temperature. Number of participants with markedly abnormal vital sign measurements were reported.

Outcome measures

Outcome measures
Measure	Peposertib 50 mg + RT + Capecitabine: n=1 Participants Participants received peposertib 50 milligram (mg) once daily in combination with capecitabine 825 milligram per square meter (mg/m\^2) twice daily 5 days per week and radiotherapy (RT) of 50 to 50.4 Gray (Gy) to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.	Peposertib 100 mg + RT + Capecitabine: n=6 Participants Participants received peposertib 100 mg once daily in combination with capecitabine 825 mg/m\^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.	Peposertib 150 mg + RT + Capecitabine: n=6 Participants Participants received peposertib 150 mg once daily in combination with capecitabine 825 mg/m\^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.	Peposertib 250 mg + RT + Capecitabine: n=6 Participants Participants received peposertib 250 mg once daily in combination with capecitabine 825 mg/m\^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.
Number of Participants With Markedly Abnormal Vital Sign Measurements	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Time from first study intervention up to long term safety follow-up period (Up to Month 35)

Population: SAF analysis set included all participants who received at least 1 dose of study intervention.

Electrocardiograms (ECG) was obtained after the participant has been in a semi-supine position for at least 5 min. ECG parameters included heart rate, PQ/PR duration, QRS and QT duration, QT Interval. Clinical significance was determined by the investigator. Number of participants with clinically significant abnormalities in 12-lead ECG were reported.

Outcome measures

Outcome measures
Measure	Peposertib 50 mg + RT + Capecitabine: n=1 Participants Participants received peposertib 50 milligram (mg) once daily in combination with capecitabine 825 milligram per square meter (mg/m\^2) twice daily 5 days per week and radiotherapy (RT) of 50 to 50.4 Gray (Gy) to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.	Peposertib 100 mg + RT + Capecitabine: n=6 Participants Participants received peposertib 100 mg once daily in combination with capecitabine 825 mg/m\^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.	Peposertib 150 mg + RT + Capecitabine: n=6 Participants Participants received peposertib 150 mg once daily in combination with capecitabine 825 mg/m\^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.	Peposertib 250 mg + RT + Capecitabine: n=6 Participants Participants received peposertib 250 mg once daily in combination with capecitabine 825 mg/m\^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.
Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Findings	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: At Week 15

Population: Full analysis set (FAS) include all participants who are enrolled in the study and received at least 1 dose of study intervention.

pCR: It is defined as absence of viable tumor cells in the primary tumor and lymph nodes. Participants considered to have a pCR if they undergo surgery and no residual cancer is found on histological examination of removed specimen. cCR: Participants are considered to have a cCR if: 1) Absence of any residual tumor in primary site and draining lymph nodes on imaging with magnetic resonance imaging; 2) No visible lesion at endoscopy except a flat scar, telangiectasia, and/or whitening of mucosa; 3) Absence of any palpable tumor or irregularity on digital rectal examination (DRE) and endoscopic ultrasonography (EUS); 4) If a biopsy is taken, it must be negative. Participants are considered as responders to composite endpoint pCR/cCR if participant had surgery and had pCR; participant did not undergo surgery but had cCR. Number of participants with composite pathological complete response (pCR)/ clinical complete response (cCR) were reported.

Outcome measures

Outcome measures
Measure	Peposertib 50 mg + RT + Capecitabine: n=1 Participants Participants received peposertib 50 milligram (mg) once daily in combination with capecitabine 825 milligram per square meter (mg/m\^2) twice daily 5 days per week and radiotherapy (RT) of 50 to 50.4 Gray (Gy) to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.	Peposertib 100 mg + RT + Capecitabine: n=6 Participants Participants received peposertib 100 mg once daily in combination with capecitabine 825 mg/m\^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.	Peposertib 150 mg + RT + Capecitabine: n=6 Participants Participants received peposertib 150 mg once daily in combination with capecitabine 825 mg/m\^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.	Peposertib 250 mg + RT + Capecitabine: n=6 Participants Participants received peposertib 250 mg once daily in combination with capecitabine 825 mg/m\^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.
Percentage of Participants With Composite Pathological Complete Response (pCR)/ Clinical Complete Response (cCR)	0.0 percentage of participants Interval 0.0 to 97.5	16.7 percentage of participants Interval 0.4 to 64.1	0.0 percentage of participants Interval 0.0 to 45.9	0.0 percentage of participants Interval 0.0 to 45.9

SECONDARY outcome

Timeframe: Time from first study intervention up to approximately 35 months

Population: FAS include all participants who are enrolled in the study and received at least 1 dose of study intervention. As per the planned analysis, Kaplan-Meier estimates were planned to be presented as overall, together with a summary of associated statistics for this outcome measure.

Disease-free Survival time, defined as the time from first treatment day to the date of the first documentation of objective progressive disease or death due to any cause, whichever occurs first. Median disease-free survival time was estimated according to Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Peposertib 50 mg + RT + Capecitabine: n=19 Participants Participants received peposertib 50 milligram (mg) once daily in combination with capecitabine 825 milligram per square meter (mg/m\^2) twice daily 5 days per week and radiotherapy (RT) of 50 to 50.4 Gray (Gy) to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.	Peposertib 100 mg + RT + Capecitabine: Participants received peposertib 100 mg once daily in combination with capecitabine 825 mg/m\^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.	Peposertib 150 mg + RT + Capecitabine: Participants received peposertib 150 mg once daily in combination with capecitabine 825 mg/m\^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.	Peposertib 250 mg + RT + Capecitabine: Participants received peposertib 250 mg once daily in combination with capecitabine 825 mg/m\^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.
Disease-free Survival	21.2 Months Interval 0.0 to 23.5	—	—	—

SECONDARY outcome

Timeframe: At Week 15

Population: FAS include all participants who are enrolled in the study and received at least 1 dose of study intervention.

pCR is defined as the absence of viable tumor cells in the primary tumor and lymph nodes. Participants are considered to have a pCR if they undergo surgery and no residual cancer is found on histological examination of the removed specimen.

Outcome measures

Outcome measures
Measure	Peposertib 50 mg + RT + Capecitabine: n=1 Participants Participants received peposertib 50 milligram (mg) once daily in combination with capecitabine 825 milligram per square meter (mg/m\^2) twice daily 5 days per week and radiotherapy (RT) of 50 to 50.4 Gray (Gy) to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.	Peposertib 100 mg + RT + Capecitabine: n=6 Participants Participants received peposertib 100 mg once daily in combination with capecitabine 825 mg/m\^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.	Peposertib 150 mg + RT + Capecitabine: n=6 Participants Participants received peposertib 150 mg once daily in combination with capecitabine 825 mg/m\^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.	Peposertib 250 mg + RT + Capecitabine: n=6 Participants Participants received peposertib 250 mg once daily in combination with capecitabine 825 mg/m\^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.
Percentage of Participants With Pathological Complete Response (pCR)	0.0 percentage of participants Interval 0.0 to 97.5	0.0 percentage of participants Interval 0.0 to 45.9	0.0 percentage of participants Interval 0.0 to 45.9	0.0 percentage of participants Interval 0.0 to 45.9

SECONDARY outcome

Timeframe: At Week 15

Population: FAS include all participants who are enrolled in the study and received at least 1 dose of study intervention.

cCR: It is defined as participants considered to have a cCR if: 1) Absence of any residual tumor in the primary site and draining lymph nodes on imaging with magnetic resonance; 2) No visible lesion at endoscopy except a flat scar, telangiectasia, and/or whitening of the mucosa; 3) Absence of any palpable tumor or irregularity on digital rectal examination (DRE) and endoscopic ultrasonography (EUS); 4) If a biopsy is taken, it must be negative.

Outcome measures

Outcome measures
Measure	Peposertib 50 mg + RT + Capecitabine: n=1 Participants Participants received peposertib 50 milligram (mg) once daily in combination with capecitabine 825 milligram per square meter (mg/m\^2) twice daily 5 days per week and radiotherapy (RT) of 50 to 50.4 Gray (Gy) to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.	Peposertib 100 mg + RT + Capecitabine: n=6 Participants Participants received peposertib 100 mg once daily in combination with capecitabine 825 mg/m\^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.	Peposertib 150 mg + RT + Capecitabine: n=6 Participants Participants received peposertib 150 mg once daily in combination with capecitabine 825 mg/m\^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.	Peposertib 250 mg + RT + Capecitabine: n=6 Participants Participants received peposertib 250 mg once daily in combination with capecitabine 825 mg/m\^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.
Percentage of Participants With Clinical Complete Response (cCR)	0.0 percentage of participants Interval 0.0 to 97.5	16.7 percentage of participants Interval 0.4 to 64.1	16.7 percentage of participants Interval 0.4 to 64.1	16.7 percentage of participants Interval 0.4 to 64.1

SECONDARY outcome

Timeframe: Time from surgery up to 15 months

Population: FAS include all participants who are enrolled in the study and received at least 1 dose of study intervention. Here, number of participants analyzed signifies those participants who underwent rectal surgery. As per the planned analysis, Kaplan-Meier estimates were planned to be presented overall, together with a summary of associated statistics (median survival time and survival rate estimates) including the corresponding 2-sided 95% Confidence Intervals (CIs) for this outcome measure.

Time from surgery to local recurrence defined as time from day of surgery to the date of the first documentation of progression of disease, flagged as local recurrence. Median time from surgery to local recurrence was estimated according to Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Peposertib 50 mg + RT + Capecitabine: n=9 Participants Participants received peposertib 50 milligram (mg) once daily in combination with capecitabine 825 milligram per square meter (mg/m\^2) twice daily 5 days per week and radiotherapy (RT) of 50 to 50.4 Gray (Gy) to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.	Peposertib 100 mg + RT + Capecitabine: Participants received peposertib 100 mg once daily in combination with capecitabine 825 mg/m\^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.	Peposertib 150 mg + RT + Capecitabine: Participants received peposertib 150 mg once daily in combination with capecitabine 825 mg/m\^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.	Peposertib 250 mg + RT + Capecitabine: Participants received peposertib 250 mg once daily in combination with capecitabine 825 mg/m\^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.
Time From Surgery to Local Recurrence	NA months Interval 2.8 to 15.0 Due to small number of events, Median and CI could not be determined.	—	—	—

SECONDARY outcome

Timeframe: Time from surgery up to 15 months

Time from surgery to distant metastasis defined as time from day of surgery to the date of the first documentation of progression of disease, flagged as distant metastasis. Median time from surgery to distant metastasis was estimated according to Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Peposertib 50 mg + RT + Capecitabine: n=9 Participants Participants received peposertib 50 milligram (mg) once daily in combination with capecitabine 825 milligram per square meter (mg/m\^2) twice daily 5 days per week and radiotherapy (RT) of 50 to 50.4 Gray (Gy) to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.	Peposertib 100 mg + RT + Capecitabine: Participants received peposertib 100 mg once daily in combination with capecitabine 825 mg/m\^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.	Peposertib 150 mg + RT + Capecitabine: Participants received peposertib 150 mg once daily in combination with capecitabine 825 mg/m\^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.	Peposertib 250 mg + RT + Capecitabine: Participants received peposertib 250 mg once daily in combination with capecitabine 825 mg/m\^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.
Time From Surgery to Distant Metastasis	NA months Interval 2.8 to 15.0 Due to small number of events, Median and CI could not be determined.	—	—	—

SECONDARY outcome

Timeframe: At Week 15

Population: FAS include all participants who are enrolled in the study and received at least 1 dose of study intervention. Here, "Number of participants analyzed" signifies those participants who were evaluable for this outcome measure.

The NAR formula includes the clinical tumor (cT) stage, pathologic tumor (pT), and node (pN) stage according to the tumor, node, metastasis classification system for colorectal cancers. The NAR formula is as follows: \[5pN- 3 (cT- pT) + 12\]2 / 9.61 NAR score ranges from 0 to 100, whereas a score close to 100 is indicative of a poorer prognosis.

Outcome measures

Outcome measures
Measure	Peposertib 50 mg + RT + Capecitabine: Participants received peposertib 50 milligram (mg) once daily in combination with capecitabine 825 milligram per square meter (mg/m\^2) twice daily 5 days per week and radiotherapy (RT) of 50 to 50.4 Gray (Gy) to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.	Peposertib 100 mg + RT + Capecitabine: n=2 Participants Participants received peposertib 100 mg once daily in combination with capecitabine 825 mg/m\^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.	Peposertib 150 mg + RT + Capecitabine: n=2 Participants Participants received peposertib 150 mg once daily in combination with capecitabine 825 mg/m\^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.	Peposertib 250 mg + RT + Capecitabine: n=5 Participants Participants received peposertib 250 mg once daily in combination with capecitabine 825 mg/m\^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.
Neoadjuvant Rectal (NAR) Score	—	9.4 score on a scale Standard Deviation 7.95	13.8 score on a scale Standard Deviation 1.69	21.2 score on a scale Standard Deviation 12.11

SECONDARY outcome

Timeframe: Pre-dose, 1, 2, 3, 4 and 6 hours post-dose on Fraction Day 1 and Fraction Day 9

Population: Pharmacokinetic (PK) analysis set included participants who received at least 1 dose of peposertib and have sufficient peposertib plasma concentration data to enable the calculation of at least 1 PK parameter. Sufficient concentration data is defined as at least 3 valid, post dose, concentration points in the PK profile to obtain any PK parameter.

Cmax was obtained directly from the concentration versus time curve. One participant was assigned to receive peposertib 100 mg; however, this participant took peposertib 50 mg for FD 1 through FD 10 and then took peposertib 100 mg for remainder of study participation. PK results for this participant was summarized by actual dose received (50 mg) whereas non-PK results are summarized by planned dose (100 mg).

Outcome measures

Outcome measures
Measure	Peposertib 50 mg + RT + Capecitabine: n=2 Participants Participants received peposertib 50 milligram (mg) once daily in combination with capecitabine 825 milligram per square meter (mg/m\^2) twice daily 5 days per week and radiotherapy (RT) of 50 to 50.4 Gray (Gy) to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.	Peposertib 100 mg + RT + Capecitabine: n=5 Participants Participants received peposertib 100 mg once daily in combination with capecitabine 825 mg/m\^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.	Peposertib 150 mg + RT + Capecitabine: n=6 Participants Participants received peposertib 150 mg once daily in combination with capecitabine 825 mg/m\^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.	Peposertib 250 mg + RT + Capecitabine: n=6 Participants Participants received peposertib 250 mg once daily in combination with capecitabine 825 mg/m\^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.
Maximum Observed Plasma Concentration (Cmax) of Peposertib Fraction Day 1	NA nanogram per milliliter (ng/mL) Geometric Coefficient of Variation NA Geometric mean and Geometric coefficient of variation was not estimable, if evaluable subjects were less than 3 as per the planned decision because only 2 collected values were not sufficient to calculate a reliable estimation.	593 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 55.8	728 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 24.1	1350 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 55.5
Maximum Observed Plasma Concentration (Cmax) of Peposertib Fraction Day 9	NA nanogram per milliliter (ng/mL) Geometric Coefficient of Variation NA Geometric mean and Geometric coefficient of variation was not estimable, if evaluable subjects were less than 3 as per the planned decision because only 2 collected values were not sufficient to calculate a reliable estimation.	653 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 50.4	792 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 41.8	1760 nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 35.6

SECONDARY outcome

Timeframe: Pre-dose, 1, 2, 3, 4 and 6 hour post-dose on Fraction Day 1 and Fraction Day 9

Population: PK analysis set was used. One participant was assigned to receive peposertib 100 mg; however, this participant took peposertib 50 mg for FD 1 through FD 10 and then took peposertib 100 mg for remainder of study participation. PK results for this participant was summarized by actual dose received (50 mg) whereas non-PK results are summarized by planned dose (100 mg).

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 (LLQ). AUC0-t was to be calculated according to the mixed log-linear trapezoidal rule.

Outcome measures

Outcome measures
Measure	Peposertib 50 mg + RT + Capecitabine: n=2 Participants Participants received peposertib 50 milligram (mg) once daily in combination with capecitabine 825 milligram per square meter (mg/m\^2) twice daily 5 days per week and radiotherapy (RT) of 50 to 50.4 Gray (Gy) to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.	Peposertib 100 mg + RT + Capecitabine: n=5 Participants Participants received peposertib 100 mg once daily in combination with capecitabine 825 mg/m\^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.	Peposertib 150 mg + RT + Capecitabine: n=6 Participants Participants received peposertib 150 mg once daily in combination with capecitabine 825 mg/m\^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.	Peposertib 250 mg + RT + Capecitabine: n=6 Participants Participants received peposertib 250 mg once daily in combination with capecitabine 825 mg/m\^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.
Area Under the Plasma Concentration-time Curve From Time Zero to Last Sampling Time (Tlast) (AUC0-t) of Peposertib Fraction Day 1	NA hournanogram per milliliter (hng/mL) Geometric Coefficient of Variation NA Geometric mean and Geometric coefficient of variation was not estimable, if evaluable subjects were less than 3 as per the planned decision because only 2 collected values were not sufficient to calculate a reliable estimation.	2950 hournanogram per milliliter (hng/mL) Geometric Coefficient of Variation 69.8	4000 hournanogram per milliliter (hng/mL) Geometric Coefficient of Variation 33.3	7300 hournanogram per milliliter (hng/mL) Geometric Coefficient of Variation 71.7
Area Under the Plasma Concentration-time Curve From Time Zero to Last Sampling Time (Tlast) (AUC0-t) of Peposertib Fraction Day 9	NA hournanogram per milliliter (hng/mL) Geometric Coefficient of Variation NA Geometric mean and Geometric coefficient of variation was not estimable, if evaluable subjects were less than 3 as per the planned decision because only 2 collected values were not sufficient to calculate a reliable estimation.	3450 hournanogram per milliliter (hng/mL) Geometric Coefficient of Variation 81.9	5540 hournanogram per milliliter (hng/mL) Geometric Coefficient of Variation 51.0	9450 hournanogram per milliliter (hng/mL) Geometric Coefficient of Variation 50.0

SECONDARY outcome

Timeframe: Pre-dose, 1, 2, 3, 4 and 6 hour post-dose on Fraction Day 1 and Fraction Day 9

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

Outcome measures

Outcome measures
Measure	Peposertib 50 mg + RT + Capecitabine: n=2 Participants Participants received peposertib 50 milligram (mg) once daily in combination with capecitabine 825 milligram per square meter (mg/m\^2) twice daily 5 days per week and radiotherapy (RT) of 50 to 50.4 Gray (Gy) to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.	Peposertib 100 mg + RT + Capecitabine: n=5 Participants Participants received peposertib 100 mg once daily in combination with capecitabine 825 mg/m\^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.	Peposertib 150 mg + RT + Capecitabine: n=6 Participants Participants received peposertib 150 mg once daily in combination with capecitabine 825 mg/m\^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.	Peposertib 250 mg + RT + Capecitabine: n=6 Participants Participants received peposertib 250 mg once daily in combination with capecitabine 825 mg/m\^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.
Time to Reach Maximum Plasma Concentration (Tmax) of Peposertib Fraction Day 1	NA hours Interval 3.0 to 4.0 As per plan analysis, it was planned to report only minimum and maximum values if number of participants analyzed was less than or equal to 2 (n ≤ 2). Only the number of non-missing observations, the minimum and maximum values had to be reported.	1.00 hours Interval 0.83 to 2.0	2.33 hours Interval 1.07 to 2.97	2.43 hours Interval 0.85 to 4.0
Time to Reach Maximum Plasma Concentration (Tmax) of Peposertib Fraction Day 9	NA hours Interval 2.0 to 3.22 As per plan analysis, it was planned to report only minimum and maximum values if number of participants analyzed was less than or equal to 2 (n ≤ 2). Only the number of non-missing observations, the minimum and maximum values had to be reported.	2.05 hours Interval 0.83 to 2.25	2.09 hours Interval 1.07 to 3.82	2.01 hours Interval 0.92 to 7.33

SECONDARY outcome

Timeframe: Pre-dose, 1, 2, 3, 4 and 6 hour post-dose on Fraction Day 1

The apparent total body clearance of study intervention following extravascular administration on FD1, taking into account the fraction of dose absorbed. CL/f = Dose oral (p.o.)/AUC0-inf. The predicted AUC0-inf should be used.

Outcome measures

Outcome measures
Measure	Peposertib 50 mg + RT + Capecitabine: Participants received peposertib 50 milligram (mg) once daily in combination with capecitabine 825 milligram per square meter (mg/m\^2) twice daily 5 days per week and radiotherapy (RT) of 50 to 50.4 Gray (Gy) to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.	Peposertib 100 mg + RT + Capecitabine: n=5 Participants Participants received peposertib 100 mg once daily in combination with capecitabine 825 mg/m\^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.	Peposertib 150 mg + RT + Capecitabine: n=6 Participants Participants received peposertib 150 mg once daily in combination with capecitabine 825 mg/m\^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.	Peposertib 250 mg + RT + Capecitabine: n=5 Participants Participants received peposertib 250 mg once daily in combination with capecitabine 825 mg/m\^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.
Total Body Clearance Following Oral Administration (CL/f) of Peposertib	—	31.7 Liter per hour Geometric Coefficient of Variation 74.5	34.5 Liter per hour Geometric Coefficient of Variation 41.1	33.0 Liter per hour Geometric Coefficient of Variation 87.6

SECONDARY outcome

Timeframe: Pre-dose, 1, 2, 3, 4 and 6 hour post-dose on Fraction Day 1 and Fraction Day 9

Population: PK analysis set was used. Here, "Number of participants" analyzed signifies those participants who were evaluable for this outcome measure. Here, "Number Analyzed" signified those participants who were evaluable at specified timepoint.

The apparent volume of distribution during the terminal phase following extravascular administration, based on the fraction of dose absorbed. Vz/f = Dose/(AUC0-inf multiplied by Lambda z) following single dose. Vz/f= Dose/(AUCtau\*Lambda z) following multiple dose. One participant was assigned to receive peposertib 100 mg; however, this participant took peposertib 50 mg for FD 1 through FD 10 and then took peposertib 100 mg for remainder of study participation. PK results for this participant was summarized by actual dose received (50 mg) whereas non-PK results are summarized by planned dose (100 mg).

Outcome measures

Outcome measures
Measure	Peposertib 50 mg + RT + Capecitabine: n=1 Participants Participants received peposertib 50 milligram (mg) once daily in combination with capecitabine 825 milligram per square meter (mg/m\^2) twice daily 5 days per week and radiotherapy (RT) of 50 to 50.4 Gray (Gy) to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.	Peposertib 100 mg + RT + Capecitabine: n=5 Participants Participants received peposertib 100 mg once daily in combination with capecitabine 825 mg/m\^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.	Peposertib 150 mg + RT + Capecitabine: n=6 Participants Participants received peposertib 150 mg once daily in combination with capecitabine 825 mg/m\^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.	Peposertib 250 mg + RT + Capecitabine: n=5 Participants Participants received peposertib 250 mg once daily in combination with capecitabine 825 mg/m\^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.
Apparent Volume of Distribution (Vz/f) of Peposertib Fraction Day 1	—	256 Liter Geometric Coefficient of Variation 60.3	274 Liter Geometric Coefficient of Variation 25.7	245 Liter Geometric Coefficient of Variation 64.1
Apparent Volume of Distribution (Vz/f) of Peposertib Fraction Day 9	NA Liter Geometric Coefficient of Variation NA Geometric mean and Geometric coefficient of variation was not estimable if evaluable subjects were less than 3 as per the planned decision because only 2 collected values were not sufficient to calculate a reliable estimation.	261 Liter Geometric Coefficient of Variation 100.8	217 Liter Geometric Coefficient of Variation 43.7	234 Liter Geometric Coefficient of Variation 39.7

SECONDARY outcome

Timeframe: Pre-dose, 1, 2, 3, 4 and 6 hour post-dose on Fraction Day 1 and Fraction Day 9

Terminal half-life is the time measured for the concentration to decrease by one half. Terminal half-life calculated by natural log 2 divided by lambda z. One participant was assigned to receive peposertib 100 mg; however, this participant took peposertib 50 mg for FD 1 through FD 10 and then took peposertib 100 mg for remainder of study participation. PK results for this participant was summarized by actual dose received (50 mg) whereas non-PK results are summarized by planned dose (100 mg).

Outcome measures

Outcome measures
Measure	Peposertib 50 mg + RT + Capecitabine: n=1 Participants Participants received peposertib 50 milligram (mg) once daily in combination with capecitabine 825 milligram per square meter (mg/m\^2) twice daily 5 days per week and radiotherapy (RT) of 50 to 50.4 Gray (Gy) to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.	Peposertib 100 mg + RT + Capecitabine: n=5 Participants Participants received peposertib 100 mg once daily in combination with capecitabine 825 mg/m\^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.	Peposertib 150 mg + RT + Capecitabine: n=6 Participants Participants received peposertib 150 mg once daily in combination with capecitabine 825 mg/m\^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.	Peposertib 250 mg + RT + Capecitabine: n=5 Participants Participants received peposertib 250 mg once daily in combination with capecitabine 825 mg/m\^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.
Apparent Terminal Half-life (t1/2) of Peposertib Fraction Day 1	—	5.60 hours Geometric Coefficient of Variation 22.0	5.51 hours Geometric Coefficient of Variation 29.0	5.14 hours Geometric Coefficient of Variation 28.7
Apparent Terminal Half-life (t1/2) of Peposertib Fraction Day 9	NA hours Geometric Coefficient of Variation NA Geometric mean and Geometric coefficient of variation was not estimable, if evaluable subjects were less than 3 as per the planned decision because only 2 collected values were not sufficient to calculate a reliable estimation.	6.28 hours Geometric Coefficient of Variation 30.8	5.04 hours Geometric Coefficient of Variation 61.0	6.12 hours Geometric Coefficient of Variation 28.9

Adverse Events

Peposertib 50 mg + RT + Capecitabine:

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Peposertib 100 mg + RT + Capecitabine:

Serious events: 3 serious events

Other events: 5 other events

Deaths: 1 deaths

Peposertib 150 mg + RT + Capecitabine:

Serious events: 0 serious events

Other events: 6 other events

Deaths: 1 deaths

Peposertib 250 mg + RT + Capecitabine:

Serious events: 4 serious events

Other events: 6 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Peposertib 50 mg + RT + Capecitabine: n=1 participants at risk Participants received peposertib 50 milligram (mg) once daily in combination with capecitabine 825 milligram per square meter (mg/m\^2) twice daily 5 days per week and radiotherapy (RT) of 50 to 50.4 Gray (Gy) to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.	Peposertib 100 mg + RT + Capecitabine: n=6 participants at risk Participants received peposertib 100 mg once daily in combination with capecitabine 825 mg/m\^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.	Peposertib 150 mg + RT + Capecitabine: n=6 participants at risk Participants received peposertib 150 mg once daily in combination with capecitabine 825 mg/m\^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.	Peposertib 250 mg + RT + Capecitabine: n=6 participants at risk Participants received peposertib 250 mg once daily in combination with capecitabine 825 mg/m\^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.
Gastrointestinal disorders Diarrhoea	0.00% 0/1 • Baseline up to long term follow-up period (approximately Month 35)	16.7% 1/6 • Baseline up to long term follow-up period (approximately Month 35)	0.00% 0/6 • Baseline up to long term follow-up period (approximately Month 35)	0.00% 0/6 • Baseline up to long term follow-up period (approximately Month 35)
Gastrointestinal disorders Enterocolitis	0.00% 0/1 • Baseline up to long term follow-up period (approximately Month 35)	16.7% 1/6 • Baseline up to long term follow-up period (approximately Month 35)	0.00% 0/6 • Baseline up to long term follow-up period (approximately Month 35)	33.3% 2/6 • Baseline up to long term follow-up period (approximately Month 35)
Gastrointestinal disorders Proctitis	0.00% 0/1 • Baseline up to long term follow-up period (approximately Month 35)	0.00% 0/6 • Baseline up to long term follow-up period (approximately Month 35)	0.00% 0/6 • Baseline up to long term follow-up period (approximately Month 35)	16.7% 1/6 • Baseline up to long term follow-up period (approximately Month 35)
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/1 • Baseline up to long term follow-up period (approximately Month 35)	16.7% 1/6 • Baseline up to long term follow-up period (approximately Month 35)	0.00% 0/6 • Baseline up to long term follow-up period (approximately Month 35)	0.00% 0/6 • Baseline up to long term follow-up period (approximately Month 35)
Infections and infestations Pneumonia	0.00% 0/1 • Baseline up to long term follow-up period (approximately Month 35)	16.7% 1/6 • Baseline up to long term follow-up period (approximately Month 35)	0.00% 0/6 • Baseline up to long term follow-up period (approximately Month 35)	0.00% 0/6 • Baseline up to long term follow-up period (approximately Month 35)
Infections and infestations Sepsis	0.00% 0/1 • Baseline up to long term follow-up period (approximately Month 35)	16.7% 1/6 • Baseline up to long term follow-up period (approximately Month 35)	0.00% 0/6 • Baseline up to long term follow-up period (approximately Month 35)	0.00% 0/6 • Baseline up to long term follow-up period (approximately Month 35)
Injury, poisoning and procedural complications Accidental overdose	0.00% 0/1 • Baseline up to long term follow-up period (approximately Month 35)	0.00% 0/6 • Baseline up to long term follow-up period (approximately Month 35)	0.00% 0/6 • Baseline up to long term follow-up period (approximately Month 35)	16.7% 1/6 • Baseline up to long term follow-up period (approximately Month 35)
Investigations Alanine aminotransferase increased	0.00% 0/1 • Baseline up to long term follow-up period (approximately Month 35)	16.7% 1/6 • Baseline up to long term follow-up period (approximately Month 35)	0.00% 0/6 • Baseline up to long term follow-up period (approximately Month 35)	0.00% 0/6 • Baseline up to long term follow-up period (approximately Month 35)
Investigations Aspartate aminotransferase increased	0.00% 0/1 • Baseline up to long term follow-up period (approximately Month 35)	16.7% 1/6 • Baseline up to long term follow-up period (approximately Month 35)	0.00% 0/6 • Baseline up to long term follow-up period (approximately Month 35)	0.00% 0/6 • Baseline up to long term follow-up period (approximately Month 35)
Investigations Platelet count decreased	0.00% 0/1 • Baseline up to long term follow-up period (approximately Month 35)	16.7% 1/6 • Baseline up to long term follow-up period (approximately Month 35)	0.00% 0/6 • Baseline up to long term follow-up period (approximately Month 35)	0.00% 0/6 • Baseline up to long term follow-up period (approximately Month 35)
Metabolism and nutrition disorders Hypoalbuminaemia	0.00% 0/1 • Baseline up to long term follow-up period (approximately Month 35)	16.7% 1/6 • Baseline up to long term follow-up period (approximately Month 35)	0.00% 0/6 • Baseline up to long term follow-up period (approximately Month 35)	0.00% 0/6 • Baseline up to long term follow-up period (approximately Month 35)

Other adverse events

Additional Information

Communication Center

Merck KGaA, Darmstadt, Germany

Phone: +49-6151-72-5200

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Peposertib 50 mg + RT + Capecitabine: n=2 Participants Participants received peposertib 50 milligram (mg) once daily in combination with capecitabine 825 milligram per square meter (mg/m\^2) twice daily 5 days per week and radiotherapy (RT) of 50 to 50.4 Gray (Gy) to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.	Peposertib 100 mg + RT + Capecitabine: n=5 Participants Participants received peposertib 100 mg once daily in combination with capecitabine 825 mg/m\^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.	Peposertib 150 mg + RT + Capecitabine: n=6 Participants Participants received peposertib 150 mg once daily in combination with capecitabine 825 mg/m\^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.	Peposertib 250 mg + RT + Capecitabine: n=6 Participants Participants received peposertib 250 mg once daily in combination with capecitabine 825 mg/m\^2 twice daily 5 days per week and RT of 50 to 50.4 Gy to the tumor area and 45 Gy to the electively irradiated tissues in 25 to 28 fractions up to 5.5 weeks treatment period.
Area Under the Plasma Concentration-time Curve From Time Zero to Last Sampling Time (Tlast) (AUC0-t) of Peposertib Fraction Day 1	NA hournanogram per milliliter (hng/mL) Geometric Coefficient of Variation NA Geometric mean and Geometric coefficient of variation was not estimable, if evaluable subjects were less than 3 as per the planned decision because only 2 collected values were not sufficient to calculate a reliable estimation.	2950 hournanogram per milliliter (hng/mL) Geometric Coefficient of Variation 69.8	4000 hournanogram per milliliter (hng/mL) Geometric Coefficient of Variation 33.3	7300 hournanogram per milliliter (hng/mL) Geometric Coefficient of Variation 71.7
Area Under the Plasma Concentration-time Curve From Time Zero to Last Sampling Time (Tlast) (AUC0-t) of Peposertib Fraction Day 9	NA hournanogram per milliliter (hng/mL) Geometric Coefficient of Variation NA Geometric mean and Geometric coefficient of variation was not estimable, if evaluable subjects were less than 3 as per the planned decision because only 2 collected values were not sufficient to calculate a reliable estimation.	3450 hournanogram per milliliter (hng/mL) Geometric Coefficient of Variation 81.9	5540 hournanogram per milliliter (hng/mL) Geometric Coefficient of Variation 51.0	9450 hournanogram per milliliter (hng/mL) Geometric Coefficient of Variation 50.0