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

• Sponsor: EMD Serono Research & Development Institute, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03770689
• Collaborator: Merck KGaA, Darmstadt, Germany (Industry)
• Enrollment: 19
• Locations: 14
• Arms: 4
• Actual Duration (Months): 35.1
• Patients Per Site: 1.4
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The main purpose of the study was to define maximum tolerated dose (MTD), recommended Phase II dose (RP2D) safety and tolerability of Peposertib in combination with capecitabine and radiotherapy (RT).

Condition or Disease	Intervention/Treatment	Phase
Locally Advanced Rectal Cancer	Drug: Peposertib 50 mg; Drug: Peposertib 100 mg; Drug: Peposertib 150 mg; Drug: Peposertib 250 mg; Drug: Capecitabine; Radiation: Radiotherapy (RT)	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 19 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multicenter Study With an Open-label Phase Ib Part Followed by a Randomized, Placebo-controlled, Double-blind, Phase II Part to Evaluate Efficacy, Safety, Tolerability, and Pharmacokinetics of the DNA-PK Inhibitor Peposertib (M3814) in Combination With Capecitabine and RT in Participants With Locally Advanced Rectal Cancer
• Actual Study Start Date: Mar 20, 2019
• Actual Primary Completion Date: Jun 21, 2021
• Actual Study Completion Date: Feb 21, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: Peposertib 50 mg; Participants received peposertib 50 milligram (mg) once daily 5 days per week up to 5.5 weeks.; Other Names: M3814 MSC2490484A ; Drug: Capecitabine; Participants received capecitabine at a dose of 825 milligram per square meter (mg/m^2) twice daily 5 days per week up to 5.5 weeks.; Radiation: Radiotherapy (RT); Participants received RT 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.
Experimental: 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.	Drug: Peposertib 100 mg; Participants received peposertib 100 mg once daily 5 days per week up to 5.5 weeks.; Drug: Capecitabine; Participants received capecitabine at a dose of 825 milligram per square meter (mg/m^2) twice daily 5 days per week up to 5.5 weeks.; Radiation: Radiotherapy (RT); Participants received RT 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.
Experimental: 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.	Drug: Peposertib 150 mg; Participants received peposertib 150 mg once daily 5 days per week up to 5.5 weeks.; Drug: Capecitabine; Participants received capecitabine at a dose of 825 milligram per square meter (mg/m^2) twice daily 5 days per week up to 5.5 weeks.; Radiation: Radiotherapy (RT); Participants received RT 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.
Experimental: 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.	Drug: Peposertib 250 mg; Participants received peposertib 250 mg once daily 5 days per week up to 5.5 weeks.; Drug: Capecitabine; Participants received capecitabine at a dose of 825 milligram per square meter (mg/m^2) twice daily 5 days per week up to 5.5 weeks.; Radiation: Radiotherapy (RT); Participants received RT 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.

Outcome Measures

Primary Outcome Measures

1. Number of Participants Who Experienced Dose Limiting Toxicity (DLT) Confirmed by Safety Monitoring Committee (SMC) [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)]

   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.

Secondary Outcome Measures

1. 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 [Time from first study intervention up to long term safety follow-up period (Up to approximately 1 year)]

   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.

2. Number of Participants With Abnormalities [Grade Greater Than or Equals to (>=) 3] in Laboratory Test Values [Time from first study intervention up to long term safety follow-up period (Up to approximately 1 year)]

   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.

3. Number of Participants With Markedly Abnormal Vital Sign Measurements [Time from first study intervention up to long term safety follow-up period (Up to approximately 1 year)]

   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.

4. Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Findings [Time from first study intervention up to long term safety follow-up period (Up to approximately 1 year)]

   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.

5. Percentage of Participants With Composite Pathological Complete Response (pCR)/ Clinical Complete Response (cCR) [At Week 15]

   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.

6. Disease-free Survival [Time from first study intervention up to approximately 24 months]

   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.

7. Percentage of Participants With Pathological Complete Response (pCR) [At Week 15]

   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.

8. Percentage of Participants With Clinical Complete Response (cCR) [At Week 15]

   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.

9. Time From Surgery to Local Recurrence [Time from surgery up to approximately 1 year]

   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.

10. Time From Surgery to Distant Metastasis [Time from surgery up to approximately 1 year]

    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.

11. Neoadjuvant Rectal (NAR) Score [At Week 15]

    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.

12. Maximum Observed Plasma Concentration (Cmax) of Peposertib [Pre-dose, 1, 2, 3, 4 and 6 hours post-dose on Fraction Day 1 and Fraction Day 9]

    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).

13. Area Under the Plasma Concentration-time Curve From Time Zero to Last Sampling Time (Tlast) (AUC0-t) of Peposertib [Pre-dose, 1, 2, 3, 4 and 6 hour post-dose on Fraction Day 1 and Fraction Day 9]

    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.

14. Time to Reach Maximum Plasma Concentration (Tmax) of Peposertib [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.

15. Total Body Clearance Following Oral Administration (CL/f) of Peposertib [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.

16. Apparent Volume of Distribution (Vz/f) of Peposertib [Pre-dose, 1, 2, 3, 4 and 6 hour post-dose on Fraction Day 1 and Fraction Day 9]

    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).

17. Apparent Terminal Half-life (t1/2) of Peposertib [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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Participants who have an Eastern Cooperative Oncology Group Performance Status less than or equals to (<=) 1

• Participants who have histologically confirmed and localized resectable rectal cancer (Stage 3)

• Participants who received induction chemotherapy are allowed to be enrolled to this study except this induction is resulting in clinical complete response (cCR) or tumor progression

• Participants who have lower edge of the tumor located in rectum

• Adequate hematological, hepatic and renal function as defined in the protocol

• Male participants if they agree to the following during the study intervention period and for at least 12 weeks after the last dose of study intervention

• Female participants are eligible if not pregnant or breastfeeding

• Other protocol defined inclusion criteria could apply

Exclusion Criteria:

• Participants with history of any other significant medical disease or psychiatric conditions that might in the assessment of the Investigator preclude safe participation in the study

• Participants with history of difficulty swallowing, malabsorption, or other chronic gastrointestinal disease or conditions that may hamper compliance and/or absorption of the study intervention

• Unstable cardiovascular function within 6 months prior to enrollment

• Hypertension uncontrolled by medication (ie, systolic blood pressure >= 150 millimeter of mercury (mmHg) and diastolic blood pressure >= 90 mmHg)

• Participants with history of other malignant disease within the past 5 years, other than successfully treated basal carcinoma of the skin or carcinoma in situ of the cervix

• Participants with known human immunodeficiency virus positivity, known active hepatitis (for example, hepatitis B virus or hepatitis C virus), current alcohol abuse, or cirrhosis

• Participants with ongoing active infection or treatment with a live attenuated vaccine within 4 weeks of dosing

• Participants with concomitant use of H2-blocker or proton pump inhibitors (PPIs) (or unable to stop at least 5 days prior to the first treatment). Note that calcium carbonate is acceptable

• Participation in any interventional clinical study within 28 days prior to Screening or during participation in this study

• Other protocol defined exclusion criteria could apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Colorado Cancer Center	Aurora	Colorado	United States	80045
2	Yale University - Pediatric Respiratory Medicine	New Haven	Connecticut	United States	06520
3	Montefiore Medical Center	Bronx	New York	United States	10461
4	Northwell Health, Inc	Great Neck	New York	United States	10042
5	Memorial Sloan-Kettering Cancer Center (MSKCC) - New York	New York	New York	United States	10065
6	Ohio State University Clinical Trials Management Office - Ohio State CTMO Parent	Columbus	Ohio	United States	43210
7	University of Toledo Medical Center - Hematology/Oncology	Toledo	Ohio	United States	43614
8	Med. Univ. of South Carolina	Charleston	South Carolina	United States	29425
9	Greenville Hospital System University Medical Center (ITOR)	Greenville	South Carolina	United States	29605
10	The University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030
11	Hospital Universitari Vall d'Hebron - Dept of Oncology	Barcelona		Spain
12	Hospital Universitario 12 de Octubre - Servicio de Oncologia	Madrid		Spain
13	Hospital Regional Universitario de Malaga	Málaga		Spain
14	Hospital Clinico Universitario de Valencia - Servicio de Hematologia y Oncologia Medica	Valencia		Spain

Sponsors and Collaborators

• EMD Serono Research & Development Institute, Inc.
• Merck KGaA, Darmstadt, Germany

Investigators

• Study Director: Medical Responsible, Merck KGaA, Darmstadt, Germany

Study Documents (Full-Text)

• Study Protocol - May 6, 2021
• Statistical Analysis Plan - Jul 7, 2021

More Information

Additional Information:

• Trial Awareness and Transparency website
• US Medical Information website, Medical Resources
• DDRiver website

Publications

None provided.

• Responsible Party: EMD Serono Research & Development Institute, Inc.
• ClinicalTrials.gov Identifier: NCT03770689
• Other Study ID Numbers: MS100036_0020; 2018-002275-18
• First Posted: Dec 10, 2018
• Last Update Posted: Jul 7, 2022
• Last Verified: Jun 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by EMD Serono Research & Development Institute, Inc.: DNA-PK inhibitor; Peposertib; capecitabine
• Additional relevant MeSH terms: Rectal Neoplasms; Capecitabine; Peposertib

Study Results

Participant Flow

Recruitment Details	First Participant First Visit (FPFV): 20 Mar 2019; Last Participant last Visit (LPLV): 21 June 2021
Pre-assignment Detail	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.

Arm/Group Title	Peposertib 50 mg + RT + Capecitabine:	Peposertib 100 mg + RT + Capecitabine:	Peposertib 150 mg + RT + Capecitabine:	Peposertib 250 mg + RT + Capecitabine:
Arm/Group Description	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.	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.	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.	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.
Period Title: Overall Study
STARTED	1	6	6	6
Pharmacokinetic Analysis Set	1	6	6	6
Full Analysis Set (FAS)	1	6	6	6
Safety Analysis Set (SAF)	1	6	6	6
COMPLETED	1	6	6	6
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	Peposertib 50 mg + RT + Capecitabine:	Peposertib 100 mg + RT + Capecitabine:	Peposertib 150 mg + RT + Capecitabine:	Peposertib 250 mg + RT + Capecitabine:	Total
Arm/Group Description	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.	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.	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.	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 of all reporting groups
Overall Participants	1	6	6	6	19
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	60	60 (15.0)	55 (8.9)	58 (11.2)	58 (11.1)
Sex: Female, Male (Count of Participants)
Female	0 0%	3 50%	2 33.3%	3 50%	8 42.1%
Male	1 100%	3 50%	4 66.7%	3 50%	11 57.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%	1 16.7%	1 5.3%
Not Hispanic or Latino	1 100%	6 100%	6 100%	5 83.3%	18 94.7%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%	0 0%
White	1 100%	6 100%	6 100%	6 100%	19 100%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Who Experienced Dose Limiting Toxicity (DLT) Confirmed by Safety Monitoring Committee (SMC)
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Peposertib 50 mg + RT + Capecitabine:	Peposertib 100 mg + RT + Capecitabine:	Peposertib 150 mg + RT + Capecitabine:	Peposertib 250 mg + RT + Capecitabine:
Arm/Group Description	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.	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.	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.	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.
Measure Participants	1	5	6	6
Count of Participants [Participants]	0 0%	1 16.7%	1 16.7%	3 50%

2. Secondary Outcome

Title	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
Description	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.
Time Frame	Time from first study intervention up to long term safety follow-up period (Up to approximately 1 year)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Peposertib 50 mg + RT + Capecitabine:	Peposertib 100 mg + RT + Capecitabine:	Peposertib 150 mg + RT + Capecitabine:	Peposertib 250 mg + RT + Capecitabine:
Arm/Group Description	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.	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.	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.	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.
Measure Participants	1	6	6	6
Participants with TEAEs	1 100%	6 100%	6 100%	6 100%
Participants with Treatment-Related TEAEs	1 100%	6 100%	6 100%	6 100%

3. Secondary Outcome

Title	Number of Participants With Abnormalities [Grade Greater Than or Equals to (>=) 3] in Laboratory Test Values
Description	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.
Time Frame	Time from first study intervention up to long term safety follow-up period (Up to approximately 1 year)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Peposertib 50 mg + RT + Capecitabine:	Peposertib 100 mg + RT + Capecitabine:	Peposertib 150 mg + RT + Capecitabine:	Peposertib 250 mg + RT + Capecitabine:
Arm/Group Description	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.	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.	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.	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.
Measure Participants	1	6	6	6
Count of Participants [Participants]	1 100%	6 100%	6 100%	6 100%

4. Secondary Outcome

Title	Number of Participants With Markedly Abnormal Vital Sign Measurements
Description	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.
Time Frame	Time from first study intervention up to long term safety follow-up period (Up to approximately 1 year)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Peposertib 50 mg + RT + Capecitabine:	Peposertib 100 mg + RT + Capecitabine:	Peposertib 150 mg + RT + Capecitabine:	Peposertib 250 mg + RT + Capecitabine:
Arm/Group Description	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.	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.	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.	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.
Measure Participants	1	6	6	6
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 0%

5. Secondary Outcome

Title	Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Findings
Description	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.
Time Frame	Time from first study intervention up to long term safety follow-up period (Up to approximately 1 year)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Peposertib 50 mg + RT + Capecitabine:	Peposertib 100 mg + RT + Capecitabine:	Peposertib 150 mg + RT + Capecitabine:	Peposertib 250 mg + RT + Capecitabine:
Arm/Group Description	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.	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.	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.	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.
Measure Participants	1	6	6	6
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 0%

6. Secondary Outcome

Title	Percentage of Participants With Composite Pathological Complete Response (pCR)/ Clinical Complete Response (cCR)
Description	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.
Time Frame	At Week 15

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Peposertib 50 mg + RT + Capecitabine:	Peposertib 100 mg + RT + Capecitabine:	Peposertib 150 mg + RT + Capecitabine:	Peposertib 250 mg + RT + Capecitabine:
Arm/Group Description	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.	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.	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.	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.
Measure Participants	1	6	6	6
Number (95% Confidence Interval) [percentage of participants]	0.0 0%	16.7 278.3%	0.0 0%	0.0 0%

7. Secondary Outcome

Title	Disease-free Survival
Description	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.
Time Frame	Time from first study intervention up to approximately 24 months

Outcome Measure Data

Analysis Population Description

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 (median survival time and survival rate estimates) including the corresponding 2-sided 95% Confidence Intervals (CIs) for this outcome measure.

Arm/Group Title	Overall Participants
Arm/Group Description	Participants received peposertib 50 mg, 100 mg, 150 mg and 250 mg in their respective cohort 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.
Measure Participants	19
Median (Full Range) [Months]	NA

8. Secondary Outcome

Title	Percentage of Participants With Pathological Complete Response (pCR)
Description	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.
Time Frame	At Week 15

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Peposertib 50 mg + RT + Capecitabine:	Peposertib 100 mg + RT + Capecitabine:	Peposertib 150 mg + RT + Capecitabine:	Peposertib 250 mg + RT + Capecitabine:
Arm/Group Description	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.	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.	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.	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.
Measure Participants	1	6	6	6
Number (95% Confidence Interval) [percentage of participants]	0.0 0%	0.0 0%	0.0 0%	0.0 0%

9. Secondary Outcome

Title	Percentage of Participants With Clinical Complete Response (cCR)
Description	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.
Time Frame	At Week 15

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Peposertib 50 mg + RT + Capecitabine:	Peposertib 100 mg + RT + Capecitabine:	Peposertib 150 mg + RT + Capecitabine:	Peposertib 250 mg + RT + Capecitabine:
Arm/Group Description	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.	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.	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.	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.
Measure Participants	1	6	6	6
Number (95% Confidence Interval) [percentage of participants]	0.0 0%	16.7 278.3%	16.7 278.3%	16.7 278.3%

10. Secondary Outcome

Title	Time From Surgery to Local Recurrence
Description	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.
Time Frame	Time from surgery up to approximately 1 year

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	All Participants
Arm/Group Description	Participants received peposertib 100 mg, 150 mg and 250 mg in their respective cohort 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.
Measure Participants	9
Median (Full Range) [months]	NA

11. Secondary Outcome

Title	Time From Surgery to Distant Metastasis
Description	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.
Time Frame	Time from surgery up to approximately 1 year

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	All Participants
Arm/Group Description	Participants received peposertib 100 mg, 150 mg and 250 mg in their respective cohort 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.
Measure Participants	9
Median (Full Range) [months]	NA

12. Secondary Outcome

Title	Neoadjuvant Rectal (NAR) Score
Description	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.
Time Frame	At Week 15

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Peposertib 50 mg + RT + Capecitabine:	Peposertib 100 mg + RT + Capecitabine:	Peposertib 150 mg + RT + Capecitabine:	Peposertib 250 mg + RT + Capecitabine:
Arm/Group Description	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.	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.	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.	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.
Measure Participants	0	2	2	5
Mean (Standard Deviation) [score on a scale]	9.4 (7.95)	13.8 (1.69)	21.2 (12.11)

13. Secondary Outcome

Title	Maximum Observed Plasma Concentration (Cmax) of Peposertib
Description	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).
Time Frame	Pre-dose, 1, 2, 3, 4 and 6 hours post-dose on Fraction Day 1 and Fraction Day 9

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Peposertib 50 mg + RT + Capecitabine:	Peposertib 100 mg + RT + Capecitabine:	Peposertib 150 mg + RT + Capecitabine:	Peposertib 250 mg + RT + Capecitabine:
Arm/Group Description	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.	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.	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.	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.
Measure Participants	2	5	6	6
Fraction Day 1	NA (NA)	593 (55.8)	728 (24.1)	1350 (55.5)
Fraction Day 9	NA (NA)	653 (50.4)	792 (41.8)	1760 (35.6)

14. Secondary Outcome

Title	Area Under the Plasma Concentration-time Curve From Time Zero to Last Sampling Time (Tlast) (AUC0-t) of Peposertib
Description	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.
Time Frame	Pre-dose, 1, 2, 3, 4 and 6 hour post-dose on Fraction Day 1 and Fraction Day 9

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Peposertib 50 mg + RT + Capecitabine:	Peposertib 100 mg + RT + Capecitabine:	Peposertib 150 mg + RT + Capecitabine:	Peposertib 250 mg + RT + Capecitabine:
Arm/Group Description	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.	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.	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.	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.
Measure Participants	2	5	6	6
Fraction Day 1	NA (NA)	2950 (69.8)	4000 (33.3)	7300 (71.7)
Fraction Day 9	NA (NA)	3450 (81.9)	5540 (51.0)	9450 (50.0)

15. Secondary Outcome

Title	Time to Reach Maximum Plasma Concentration (Tmax) of Peposertib
Description	Time to reach the maximum plasma concentration (Tmax) was obtained directly from the concentration versus time curve.
Time Frame	Pre-dose, 1, 2, 3, 4 and 6 hour post-dose on Fraction Day 1 and Fraction Day 9

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Peposertib 50 mg + RT + Capecitabine:	Peposertib 100 mg + RT + Capecitabine:	Peposertib 150 mg + RT + Capecitabine:	Peposertib 250 mg + RT + Capecitabine:
Arm/Group Description	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.	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.	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.	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.
Measure Participants	2	5	6	6
Fraction Day 1	NA	1.00	2.33	2.43
Fraction Day 9	NA	2.05	2.09	2.01

16. Secondary Outcome

Title	Total Body Clearance Following Oral Administration (CL/f) of Peposertib
Description	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.
Time Frame	Pre-dose, 1, 2, 3, 4 and 6 hour post-dose on Fraction Day 1

Outcome Measure Data

Analysis Population Description

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). Here, "Number of participants analyzed" signifies those participants who were evaluable for this outcome measure.

Arm/Group Title	Peposertib 50 mg + RT + Capecitabine:	Peposertib 100 mg + RT + Capecitabine:	Peposertib 150 mg + RT + Capecitabine:	Peposertib 250 mg + RT + Capecitabine:
Arm/Group Description	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.	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.	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.	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.
Measure Participants	0	5	6	5
Geometric Mean (Geometric Coefficient of Variation) [Liter per hour]	31.7 (74.5)	34.5 (41.1)	33.0 (87.6)

17. Secondary Outcome

Title	Apparent Volume of Distribution (Vz/f) of Peposertib
Description	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).
Time Frame	Pre-dose, 1, 2, 3, 4 and 6 hour post-dose on Fraction Day 1 and Fraction Day 9

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Peposertib 50 mg + RT + Capecitabine:	Peposertib 100 mg + RT + Capecitabine:	Peposertib 150 mg + RT + Capecitabine:	Peposertib 250 mg + RT + Capecitabine:
Arm/Group Description	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.	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.	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.	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.
Measure Participants	1	5	6	5
Fraction Day 1	256 (60.3)	274 (25.7)	245 (64.1)
Fraction Day 9	NA (NA)	261 (100.8)	217 (43.7)	234 (39.7)

18. Secondary Outcome

Title	Apparent Terminal Half-life (t1/2) of Peposertib
Description	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).
Time Frame	Pre-dose, 1, 2, 3, 4 and 6 hour post-dose on Fraction Day 1 and Fraction Day 9

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Peposertib 50 mg + RT + Capecitabine:	Peposertib 100 mg + RT + Capecitabine:	Peposertib 150 mg + RT + Capecitabine:	Peposertib 250 mg + RT + Capecitabine:
Arm/Group Description	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.	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.	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.	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.
Measure Participants	1	5	6	5
Fraction Day 1	5.60 (22.0)	5.51 (29.0)	5.14 (28.7)
Fraction Day 9	NA (NA)	6.28 (30.8)	5.04 (61.0)	6.12 (28.9)

Adverse Events

Time Frame	Baseline up to long term follow-up period (approximately up to 1 year)
Arm/Group Title	Peposertib 50 mg + RT + Capecitabine:		Peposertib 100 mg + RT + Capecitabine:		Peposertib 150 mg + RT + Capecitabine:		Peposertib 250 mg + RT + Capecitabine:
Arm/Group Description	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.		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.		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.		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.
All Cause Mortality
	Peposertib 50 mg + RT + Capecitabine:		Peposertib 100 mg + RT + Capecitabine:		Peposertib 150 mg + RT + Capecitabine:		Peposertib 250 mg + RT + Capecitabine:
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)
Serious Adverse Events
	Peposertib 50 mg + RT + Capecitabine:		Peposertib 100 mg + RT + Capecitabine:		Peposertib 150 mg + RT + Capecitabine:		Peposertib 250 mg + RT + Capecitabine:
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		3/6 (50%)		0/6 (0%)		4/6 (66.7%)
Gastrointestinal disorders
Diarrhoea	0/1 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)
Enterocolitis	0/1 (0%)		1/6 (16.7%)		0/6 (0%)		2/6 (33.3%)
Proctitis	0/1 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)
Small intestinal obstruction	0/1 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)
Infections and infestations
Pneumonia	0/1 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)
Sepsis	0/1 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)
Injury, poisoning and procedural complications
Accidental overdose	0/1 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)
Investigations
Alanine aminotransferase increased	0/1 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)
Aspartate aminotransferase increased	0/1 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)
Platelet count decreased	0/1 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)
Metabolism and nutrition disorders
Hypoalbuminaemia	0/1 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)
Other (Not Including Serious) Adverse Events
	Peposertib 50 mg + RT + Capecitabine:		Peposertib 100 mg + RT + Capecitabine:		Peposertib 150 mg + RT + Capecitabine:		Peposertib 250 mg + RT + Capecitabine:
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/1 (100%)		6/6 (100%)		6/6 (100%)		6/6 (100%)
Blood and lymphatic system disorders
Anaemia	0/1 (0%)		1/6 (16.7%)		1/6 (16.7%)		4/6 (66.7%)
Leukopenia	0/1 (0%)		0/6 (0%)		1/6 (16.7%)		2/6 (33.3%)
Lymphopenia	0/1 (0%)		1/6 (16.7%)		2/6 (33.3%)		1/6 (16.7%)
Neutropenia	0/1 (0%)		0/6 (0%)		1/6 (16.7%)		1/6 (16.7%)
Thrombocytopenia	0/1 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)
Eye disorders
Vision blurred	0/1 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)
Gastrointestinal disorders
Abdominal distension	0/1 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)
Abdominal pain	1/1 (100%)		0/6 (0%)		1/6 (16.7%)		1/6 (16.7%)
Abdominal pain lower	0/1 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)
Anal incontinence	0/1 (0%)		1/6 (16.7%)		2/6 (33.3%)		0/6 (0%)
Anal inflammation	0/1 (0%)		0/6 (0%)		1/6 (16.7%)		1/6 (16.7%)
Colitis	0/1 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)
Constipation	0/1 (0%)		0/6 (0%)		3/6 (50%)		1/6 (16.7%)
Diarrhoea	1/1 (100%)		5/6 (83.3%)		3/6 (50%)		5/6 (83.3%)
Dry mouth	0/1 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)
Dyschezia	1/1 (100%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
Flatulence	0/1 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)
Haematochezia	0/1 (0%)		1/6 (16.7%)		1/6 (16.7%)		0/6 (0%)
Nausea	1/1 (100%)		4/6 (66.7%)		2/6 (33.3%)		2/6 (33.3%)
Proctalgia	0/1 (0%)		3/6 (50%)		3/6 (50%)		1/6 (16.7%)
Proctitis	1/1 (100%)		2/6 (33.3%)		2/6 (33.3%)		3/6 (50%)
Rectal haemorrhage	0/1 (0%)		0/6 (0%)		2/6 (33.3%)		3/6 (50%)
Rectal tenesmus	0/1 (0%)		0/6 (0%)		2/6 (33.3%)		5/6 (83.3%)
Rectal ulcer	0/1 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)
Vomiting	0/1 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)
General disorders
Asthenia	0/1 (0%)		0/6 (0%)		1/6 (16.7%)		3/6 (50%)
Fatigue	1/1 (100%)		5/6 (83.3%)		3/6 (50%)		0/6 (0%)
Oedema peripheral	0/1 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)
Secretion discharge	0/1 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)
Infections and infestations
Bacteraemia	0/1 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)
Candida infection	0/1 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)
Urinary tract infection	0/1 (0%)		1/6 (16.7%)		0/6 (0%)		1/6 (16.7%)
Vaginal infection	0/1 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)
Injury, poisoning and procedural complications
Anal injury	0/1 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)
Radiation skin injury	1/1 (100%)		3/6 (50%)		2/6 (33.3%)		0/6 (0%)
Investigations
Alanine aminotransferase increased	0/1 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)
Aspartate aminotransferase increased	0/1 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)
Blood alkaline phosphatase increased	0/1 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)
Lymphocyte count decreased	0/1 (0%)		2/6 (33.3%)		2/6 (33.3%)		3/6 (50%)
Platelet count decreased	0/1 (0%)		1/6 (16.7%)		0/6 (0%)		1/6 (16.7%)
Weight decreased	0/1 (0%)		1/6 (16.7%)		2/6 (33.3%)		0/6 (0%)
White blood cell count decreased	0/1 (0%)		2/6 (33.3%)		0/6 (0%)		0/6 (0%)
Metabolism and nutrition disorders
Decreased appetite	0/1 (0%)		1/6 (16.7%)		3/6 (50%)		2/6 (33.3%)
Dehydration	0/1 (0%)		3/6 (50%)		0/6 (0%)		0/6 (0%)
Hyperglycaemia	0/1 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)
Hypoalbuminaemia	0/1 (0%)		1/6 (16.7%)		0/6 (0%)		1/6 (16.7%)
Hypocalcaemia	0/1 (0%)		1/6 (16.7%)		0/6 (0%)		1/6 (16.7%)
Hypokalaemia	0/1 (0%)		1/6 (16.7%)		0/6 (0%)		2/6 (33.3%)
Hyponatraemia	0/1 (0%)		1/6 (16.7%)		0/6 (0%)		1/6 (16.7%)
Nervous system disorders
Dizziness	0/1 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)
Dizziness postural	0/1 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)
Dysgeusia	0/1 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)
Sciatica	0/1 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)
Psychiatric disorders
Personality change	1/1 (100%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
Renal and urinary disorders
Bladder spasm	0/1 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)
Dysuria	0/1 (0%)		1/6 (16.7%)		1/6 (16.7%)		0/6 (0%)
Micturition urgency	0/1 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)
Haematuria	0/1 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)
Urinary hesitation	0/1 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)
Urinary incontinence	0/1 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)
Reproductive system and breast disorders
Pelvic pain	0/1 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	0/1 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)
Skin and subcutaneous tissue disorders
Dermatitis	0/1 (0%)		0/6 (0%)		1/6 (16.7%)		1/6 (16.7%)
Dry skin	0/1 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)
Erythema	0/1 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)
Palmar-plantar erythrodysaesthesia syndrome	0/1 (0%)		1/6 (16.7%)		2/6 (33.3%)		0/6 (0%)
Pruritus	1/1 (100%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
Rash maculo-papular	1/1 (100%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
Rash papular	0/1 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)
Skin reaction	0/1 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)
Skin ulcer	0/1 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)
Vascular disorders
Hypotension	0/1 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)
Peripheral embolism	0/1 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)

Limitations/Caveats

As decided by sponsor study was discontinued prior to the initiation of the Phase II part of the study; therefore, results only from the Phase Ib part of the study was reported.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.