Squamous Cell Carcinoma of the Head and Neck
Conditions
Keywords
TrilynX
Brief summary
The primary objective of the study was to demonstrate superior efficacy of Xevinapant (Debio 1143) vs placebo when added to chemoradiotherapy (CRT) in locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN).
Interventions
Xevinapant (Debio 1143) administrated as oral solution from Day 1 to 14, every 21-day cycle.
DRUGCisplatin
Cisplatin administered as an IV infusion every 3 weeks (Q3W).
RADIATIONIntensity Modulation Radiation Therapy (IMRT)
70 Gy given in 35 fractions over 7 weeks.
DRUGPlacebo
Matched placebo administrated as oral solution from Day 1 to 14, every 21-day cycle.
Sponsors
GORTEC (Head and Neck Oncology and Radiotherapy Group)
Merck KGaA, Darmstadt, Germany
EMD Serono Research & Development Institute, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1 * Histologically confirmed diagnosis of previously untreated Locally Advanced Squamous Cell Carcinoma of the Head and Neck (LA-SCCHN) participant (stage III, IVa or IVb according to the American Joint Committee on Cancer(AJCC))/Classification of malignant tumors: T=size of the primary tumor, N=regional lymph node involvement, M=distant metastasis (TNM) Staging System, 8th Edition.) suitable for definitive ChemoRadiotherapy (CRT), of at least one of the following sites: oropharynx, hypopharynx and larynx * For OroPharyngeal Cancer (OPC) participants, primary tumors must be human papillomavirus (HPV)-negative as determined by p16 expression using immunohistochemistry * Evaluable tumor burden (measurable and/or non-measurable tumor lesions) assessed by computed tomography scan (CT-scan) or magnetic resonance imaging (MRI), based on Response evaluation criteria in solid tumors (RECIST) version 1.1 * Peripheral neuropathy less than (\<) grade 2 * Adequate hematologic, renal and hepatic function * Other protocol defined inclusion criteria may apply
Exclusion criteria
* Primary tumor of nasopharynx, paranasal sinuses, nasal or oral cavity, salivary, thyroid or parathyroid gland pathologies, skin or unknown primary site * Metastatic disease (stage IVc as per AJCC/TNM, 8th Ed.) * Prior definitive or adjuvant Radiotherapy (RT) and/or radical surgery to the head and neck region which may jeopardize the primary tumor irradiation plan, or any other prior SCCHN systemic treatment, including investigational agents * Documented weight loss of \>10% during the last 4 weeks prior to randomization (unless adequate measures are undertaken for nutritional support), OR plasmatic albumin \< 3.0 g/dL. No albumin transfusions are allowed within 2 weeks before randomization * Known allergy to Xevinapant (Debio 1143), cisplatin, carboplatin, other platinum-based agent or any excipient known to be present in any of these products or in the placebo formulation * other protocol defined
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Event-Free Survival (EFS) as Assessed by Blinded Independent Review Committee (BIRC) | From randomization to the earliest between any EFS event or End of Study (EOS) (up to 188 weeks and 5 days) | Event-Free Survival (EFS) as assessed by BIRC is the time from randomization to the first of: (1) Death from any cause; (2) Progression: either radiological (per RECIST v1.1) or clinical (with/without radiologic proof, assessed endoscopically); (3) Primary treatment failure prior to complete response (CR): requirement for radical salvage surgery at primary tumor site with viable tumor confirmed histologically, even without RECIST progression; (4) Relapse after CR (locoregional): including radical salvage surgery or elective neck dissection/biopsy more than equal to (\>=) 22 weeks post-randomization showing viable tumor cells regardless of radiologic status; (5) Second cancers, unless histology excludes squamous origin. Calculated via Kaplan Meier method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as Assessed by Blinded Independent Review Committee (BIRC) | From randomization to the first occurrence of progression (radiological or clinical, as assessed by the BIRC) or death from any cause or EOS (up to 188 weeks and 5 days ) | PFS according to RECIST v1.1 defined as the time from randomization to the first occurrence of progression (radiological or clinical, as assessed by the BIRC) or death from any cause. According to RECIST 1.1, progressive disease (PD) was defined as a 20% relative increase in the sum of diameters (SOD) of target lesions, taking as reference the nadir SOD and an absolute increase of \>5 millimeter (mm) in the SOD, or the appearance of new lesions. Calculated via Kaplan Meier method. |
| Locoregional Control (LRC) Time | From randomization to the first occurrence of progression at the site of the primary tumor or the locoregional lymph nodes or End Of Study (EOS) (188 weeks and 5 days) | LRC time is defined as the time from randomization to the first occurrence of progression at the site of the primary tumor or the locoregional lymph nodes, either according to RECIST v1.1 or based on clinical assessment (radiological or clinical, as assessed by the Investigator). According to RECIST 1.1, progressive disease (PD) was defined as a 20% relative increase in the sum of diameters (SOD) of target lesions, taking as reference the nadir SOD and an absolute increase of \>5 millimeter (mm) in the SOD, or the appearance of new lesions. Calculated via Kaplan Meier method. |
| Objective Response Rate (ORR) as Assessed by BIRC | At 9 and 12 months post randomization | Objective response rate was defined as percentage of participants with either a confirmed complete response (CR) or partial response (PR). CR: Disappearance of all target and non-target lesions. PR: At least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum of their diameters, and no unequivocal progression of non-target lesions. Progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on the study, or unequivocal progression of non-target lesions, or appearance of any new lesion. |
| Complete Response Rate (CRR) | At 9 and 12 months post randomization | CRR defined as the number of participants with Complete Response by RECIST v1.1, as assessed by the BIRC. Complete response is defined as disappearance of all target and non-target lesions. |
| Duration of Response (DOR) | Time from first evidence of response to the first occurrence of progression or death from any cause, assessed up to 24 months | Duration of response (DoR) defined as the time from the first evidence of response (partial or complete, as assessed by the BIRC according to RECIST v1.1) to the first occurrence of progression (radiological or clinical, as assessed by the BIRC) or death from any cause. Kaplan Meier method was used for calculation. |
| Number of Participants With Radical Salvage Surgery | At 9, 12, 24 and 36 months post randomization | Number of Participants with Radical Salvage Surgery (excluding elective neck dissection without anatomopathological evidence of residual malignant cells) was reported. |
| Time to Subsequent Systemic Cancer Treatments | Up to 188 weeks and 5 days post randomization | Time to new subsequent systemic cancer treatment (in months) was derived as (date of event/censoring - randomization date +1) / 30.4375. Calculated via kaplan meier method. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Adverse Events (AEs) of Special Interest | From signed informed consent to EOS (up to 188 weeks and 5 days) | An AE is any unfavorable/unintended sign (e.g., abnormal lab result), symptom or disease temporally linked to study drug, whether or not related. A serious AE leads to death, is life-threatening, causes significant/persistent disability, hospitalization, congenital anomaly, or is medically important. TEAEs include both serious and non-serious AEs after treatment. AESIs are events of clinical interest needing close monitoring. In this study, AESIs include: infusion reactions including hypersensitivity, immune-related AEs, aspartate aminotransferase/alanine transaminase increases, lipase/amylase elevation, acute renal failure, QTcF more than 30 milliseconds above baseline, and ≥Grade 2 inflammatory cutaneous AEs. |
| Number of Participants With Severity of Grade Greater or Equal to 3 TEAEs | From signed informed consent to EOS (up to 188 weeks and 5 days) | Severity of TEAEs were evaluated using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version. The grade are as follows: grade 1 : mild grade 2 : moderate grade 3 : severe or medically significant but not immediately life-threatening grade 4 : life threatening or disabling grade 5 : death related to AE. |
| Change From Baseline in Laboratory Parameters: Basophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | At Baseline, Cycle 3 Day 1 (C3D1) (combination period), EOT (15 days after last study treatment administration) and baseline upto event free survival (EFS) follow up Month 18 after EOT (max on treatment change) | Change from Baseline in Laboratory Parameters: Basophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets was reported. |
| Percent Change From Baseline in Laboratory Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes | At Cycle 3 Day 1 (C3D1) (combination period), EOT (15 days after last study treatment administration) and baseline upto event free survival (EFS) follow up Month 18 after EOT (max on treatment change) | Change from Baseline in Laboratory Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes was reported. |
| Change From Baseline in Laboratory Parameters: Erythrocytes | At Baseline, Cycle 3 Day 1 (C3D1) (combination period), EOT (15 days after last study treatment administration) and baseline upto event free survival (EFS) follow up Month 18 after EOT (max on treatment change) | Change from Baseline in Laboratory Parameters: Erythrocytes was reported. |
| Change From Baseline in Laboratory Parameters: Hemoglobin, Albumin, Protein | At Baseline, Cycle 3 Day 1 (C3D1) (combination period), EOT (15 days after last study treatment administration) and baseline upto event free survival (EFS) follow up Month 18 after EOT (max on treatment change) | Change from Baseline in Laboratory Parameters: Hemoglobin, Albumin, Protein was reported. |
| Change From Baseline in Laboratory Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Lipase | At Baseline, Cycle 3 Day 1 (C3D1) (combination period), EOT (15 days after last study treatment administration) and baseline upto event free survival (EFS) follow up Month 18 after EOT (max on treatment change) | Change from Baseline in Laboratory Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Lipase was reported. |
| Change From Baseline in Laboratory Parameters: Bilirubin, Creatinine, Direct Bilirubin, Urate | At Baseline, Cycle 3 Day 1 (C3D1) (combination period), EOT (15 days after last study treatment administration) and baseline upto event free survival (EFS) follow up Month 18 after EOT (max on treatment change) | Change from Baseline in Laboratory Parameters: Bilirubin, Creatinine, Direct Bilirubin, Urate was reported. |
| Change From Baseline in Laboratory Parameters: C Reactive Protein | At Baseline, Cycle 3 Day 1 (C3D1) (combination period), EOT (15 days after last study treatment administration) and baseline upto event free survival (EFS) follow up Month 18 after EOT (max on treatment change) | Change from Baseline in Laboratory Parameters: C Reactive Protein was reported. |
| Change From Baseline in Laboratory Parameters: Calcium, Magnesium, Potassium, Sodium, Urea | At Baseline, Cycle 3 Day 1 (C3D1) (combination period), EOT (15 days after last study treatment administration) and baseline upto event free survival (EFS) follow up Month 18 after EOT (max on treatment change) | Change from Baseline in Laboratory Parameters: Calcium, Magnesium, Potassium, Sodium, Urea was reported. |
| Change From Baseline in Estimated Glomerular Filtration Rate | At Baseline, Cycle 3 Day 1 (C3D1) (combination period), EOT (15 days after last study treatment administration) and baseline upto event free survival (EFS) follow up Month 18 after EOT (max on treatment change) | Change from baseline in biochemistry parameter eGFR was reported. The Glomerular Filtration Rate was measured as milliliter per minute per 1.73 square meter (mL/min/1.73m\^2). |
| Change From Baseline in Activated Partial Thromboplastin Time (PTT)/ Standard and Prothrombin Time | At Baseline, Cycle 3 Day 1 (C3D1) (combination period), EOT (15 days after last study treatment administration) and baseline upto event free survival (EFS) follow up Month 18 after EOT (max on treatment change) | Change from Baseline in coagulation parameter activated PTT/standard and prothrombin Time was reported. |
| Overall Survival (OS) | From randomization to the earliest between death or EOS (up to 188 weeks and 5 days) | Overall survival is defined as the time from randomization to the date of death. Calculated via Kaplan Meier method. |
| Change From Baseline in Prothrombin International Normalized Ratio | At Baseline, Cycle 3 Day 1 (C3D1) (combination period), EOT (15 days after last study treatment administration) and baseline upto event free survival (EFS) follow up Month 18 after EOT (max on treatment change) | Change from baseline in coagulation parameters prothrombin international normalized ratio was reported. |
| Change From Baseline in Vital Signs: Systolic Blood Pressure, Diastolic Blood Pressure | At Baseline, Cycle 3 Day 1 (C3D1) (combination period), EOT (15 days after last study treatment administration) and baseline upto event free survival (EFS) follow up Month 18 after EOT (max on treatment increase & decrease) | Change from Baseline in Vital Signs: Systolic Blood Pressure, Diastolic Blood Pressure was reported. |
| Change From Baseline in Vital Signs: Heart Rate | At Baseline, Cycle 3 Day 1 (C3D1) (combination period), EOT (15 days after last study treatment administration) and baseline upto event free survival (EFS) follow up Month 18 after EOT (max on treatment increase & decrease) | Change from Baseline in Vital Signs: Heart Rate was reported. |
| Change From Baseline in Vital Signs: Respiratory Rate | At Baseline, Cycle 3 Day 1 (C3D1) (combination period), EOT (15 days after last study treatment administration) and baseline upto event free survival (EFS) follow up Month 18 after EOT (max on treatment increase & decrease) | Change from Baseline in Vital Signs: Respiratory Rate was reported. |
| Change From Baseline in Vital Signs: Body Temperature | At Baseline, Cycle 3 Day 1 (C3D1) (combination period), EOT (15 days after last study treatment administration) and baseline upto event free survival (EFS) follow up Month 18 after EOT (max on treatment increase) | Change from Baseline in Vital Signs: Body Temperature was reported. |
| Change From Baseline in Vital Signs: Body Weight | At Baseline, C3D1 (combination period), EOT (15 days after last study treatment administration) and baseline upto event free survival (EFS) follow up Month 18 after EOT (max on treatment increase & decrease) | Change from Baseline in Vital Signs: Body Weight was reported. |
| Change From Baseline in ECG Parameters | At Baseline, and upto event free survival (EFS) follow up Month 18 after EOT (max on treatment increase) | The 12-lead ECGs were recorded after the participants have rested for at least 5 minutes in supine position. The parameters included Respiratory Rate (RR), Pulse Rate (PR), QRS, QT and QTcF calculated by the Bazett formula. |
| Treatment Duration | Up to end of study (up to 188weeks and 5 days) | Treatment duration is calculated by study treatment component as (last dose date minus first dose date plus x)/7, where x=8 for xevinapant/matched placebo, x=21 for cisplatin/carboplatin, x=3 for IMRT. |
| Number of Participants Who Completed Cycle 1, 2, 3, 4, 5 and 6 | Cycle 1, 2, 3, 4, 5 and 6 (each cycle is of 3 weeks) | Number of participants who completed cycle 1, 2, 3, 4, 5 or 6 of xevinapant/matched placebo were reported. |
| Total Cumulative Dose of Xevinapant/ Matched Placebo | Up to end of treatment (Day 134) | Total cumulative dose of Xevinapant/ Matched Placebo was reported in form of mean and standard deviation. |
| Total Cumulative Dose of Cisplatin | Up to end of treatment (Day 134) | Total cumulative dose of cisplatin was reported. |
| Total Cumulative Dose of Carboplatin | Up to end of treatment (Day 134) | Total cumulative dose of carboplatin was reported as mean and standard deviation. |
| Total Cumulative Dose of Intensity-Modulated Radiation Therapy (IMRT) | Up to end of treatment (Day 134) | Total cumulative dose of IMRT were reported in form of mean and standard deviation. |
| Overall Dose Intensity of Xevinapant/Matched Placebo | Cycle 1, 2, 3, 4 5, 6 (each cycle is of 3 weeks) or End of Treatment (Day 134) | Overall dose intensity of Xevinapant/ matched placebo is calculated as the mean of the dose intensities of the individual cycles. |
| Overall Dose Intensity of Cisplatin | Cycle 1, 2, 3, 4 5, 6 (each cycle is of 3 weeks) or End of Treatment (Day 134) | Overall dose intensity of Cisplatin is calculated as the mean of the dose intensities of the individual cycles. This was reported with the unit of measure milligrams per meter square per week (mg/m2/week). |
| Overall Dose Intensity of Carboplatin | Cycle 1, 2, 3, 4 5, 6 (each cycle is of 3 weeks) or End of Treatment (Day 134) | Overall dose intensity of Carboplatin is calculated as the mean of the dose intensities of the individual cycles. This was reported with unit of measure Milligrams per minute per milliliter per week (mg min/mL/week). |
| Relative Dose Intensity | Up to 50 months | Relative dose intensity (RDI) represents the percentage of the amount of a drug actually delivered \[actual dose intensity (DI)\] to the amount planned (planned DI). The purpose of calculating RDI is to evaluate whether the planned DI of an anti-cancer treatment was actually achieved which may suggest the feasibility of planned treatment regimen. |
| Number of Participants With Treatment Interruption, Treatment Reduction and Treatment Discontinuation for Xevinapant/ Matched Placebo | Up to end of treatment (Day 134) | Number of participants with Treatment Interruption, Treatment Reduction and Treatment Discontinuation was reported. |
| Change From Baseline in Fibrinogen | At Baseline, Cycle 3 Day 1 (C3D1) (combination period), EOT (15 days after last study treatment administration) and baseline upto event free survival (EFS) follow up Month 18 after EOT (max on treatment change) | Change from Baseline in coagulation parameter fibrinogen was reported. |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, China, Czechia, France, Georgia, Germany, Greece, Hungary, Israel, Italy, Japan, Poland, Portugal, Russia, South Korea, Spain, Switzerland, Taiwan, Ukraine, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sequence 1: Debio 1143 + CRT Participants received a combination of Debio 1143 along with Chemoradiotherapy (CRT): Radiotherapy +Cisplatin + Xevinapant (Debio 1143). Participants received 6 cycles of oral solution of Xevinapant at a dose of 200 milligrams per day (mg/day) once daily from Day 1 to 14, per 3-week cycle in combination with 70 Gray (Gy) of intensity modulated radiation therapy (IMRT) in 35 fractions, 2 Gy/fraction, over 7 weeks, and High-dose cisplatin (100 mg/m2) on Day 2 of a 3-week cycle per 3 cycles (combination therapy period). If high-dose cisplatin 100 mg/m2 was not tolerated after the first dose, participants could be switched to carboplatin (10mg/mL, iv infusion), followed by 3 cycles of monotherapy of Xevinapant at a dose of 200 mg/day from Day 1 to 14, per 3-week cycle (monotherapy period). | 364 |
| Sequence 2: Placebo + CRT Participants received a combination of placebo matched to Debio 1143 along with Chemoradiotherapy(CRT): Radiotherapy +Cisplatin+ placebo matched to Xevinapant (Debio 1143). Participants received 6 cycles of oral solution of placebo matched to Xevinapant once daily from Day 1 to 14, per 3-week cycle in combination with 70 Gray (Gy) of intensity modulated radiation therapy (IMRT) in 35 fractions, 2 Gy/fraction, over 7 weeks, and High-dose cisplatin (100 mg/m2) on Day 2 of a 3-week cycle per 3 cycles(combination therapy period).If high-dose cisplatin 100 mg/m2 was not tolerated after the first dose, participants could be switched to carboplatin (10mg/mL, iv infusion), followed by 3 cycles of monotherapy of placebo matched to Xevinapant from Day 1 to 14, per 3-week cycle (monotherapy period). | 366 |
| Total | 730 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 3 |
| Overall Study | Death | 111 | 93 |
| Overall Study | Lost to Follow-up | 10 | 9 |
| Overall Study | Other Reasons | 4 | 5 |
| Overall Study | PROTOCOL DEVIATION | 0 | 1 |
| Overall Study | RANDOMIZED BY MISTAKE | 0 | 1 |
| Overall Study | STUDY TERMINATED BY SPONSOR | 214 | 232 |
| Overall Study | Withdrawal by Subject | 22 | 22 |
Baseline characteristics
| Characteristic | Sequence 1: Debio 1143 + CRT | Sequence 2: Placebo + CRT | Total |
|---|---|---|---|
| Age, Continuous | 60 Years STANDARD_DEVIATION 8.01 | 60 Years STANDARD_DEVIATION 8.53 | 60 Years STANDARD_DEVIATION 8.27 |
| Race/Ethnicity, Customized Ethnicity-Hispanic or Latino | 41 Participants | 46 Participants | 87 Participants |
| Race/Ethnicity, Customized Ethnicity-Not Hispanic or Latino | 264 Participants | 273 Participants | 537 Participants |
| Race/Ethnicity, Customized Ethnicity-Unknown or Not Reported | 59 Participants | 47 Participants | 106 Participants |
| Race/Ethnicity, Customized Race-Asian | 59 Participants | 60 Participants | 119 Participants |
| Race/Ethnicity, Customized Race-Black or African American | 5 Participants | 6 Participants | 11 Participants |
| Race/Ethnicity, Customized Race-Other | 5 Participants | 9 Participants | 14 Participants |
| Race/Ethnicity, Customized Race-Unknown or Not Reported | 42 Participants | 35 Participants | 77 Participants |
| Race/Ethnicity, Customized Race-White | 253 Participants | 256 Participants | 509 Participants |
| Sex: Female, Male Female | 64 Participants | 57 Participants | 121 Participants |
| Sex: Female, Male Male | 300 Participants | 309 Participants | 609 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 111 / 364 | 93 / 366 |
| other Total, other adverse events | 360 / 364 | 350 / 356 |
| serious Total, serious adverse events | 194 / 364 | 129 / 356 |
Outcome results
Primary
Event-Free Survival (EFS) as Assessed by Blinded Independent Review Committee (BIRC)
Event-Free Survival (EFS) as assessed by BIRC is the time from randomization to the first of: (1) Death from any cause; (2) Progression: either radiological (per RECIST v1.1) or clinical (with/without radiologic proof, assessed endoscopically); (3) Primary treatment failure prior to complete response (CR): requirement for radical salvage surgery at primary tumor site with viable tumor confirmed histologically, even without RECIST progression; (4) Relapse after CR (locoregional): including radical salvage surgery or elective neck dissection/biopsy more than equal to (\>=) 22 weeks post-randomization showing viable tumor cells regardless of radiologic status; (5) Second cancers, unless histology excludes squamous origin. Calculated via Kaplan Meier method.
Time frame: From randomization to the earliest between any EFS event or End of Study (EOS) (up to 188 weeks and 5 days)
Population: The Intention To Treat (ITT) set included all randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sequence 1: Debio 1143 + CRT | Event-Free Survival (EFS) as Assessed by Blinded Independent Review Committee (BIRC) | 19.4 months |
| Sequence 2: Placebo + CRT | Event-Free Survival (EFS) as Assessed by Blinded Independent Review Committee (BIRC) | 33.1 months |
Secondary
Change From Baseline in Activated Partial Thromboplastin Time (PTT)/ Standard and Prothrombin Time
Change from Baseline in coagulation parameter activated PTT/standard and prothrombin Time was reported.
Time frame: At Baseline, Cycle 3 Day 1 (C3D1) (combination period), EOT (15 days after last study treatment administration) and baseline upto event free survival (EFS) follow up Month 18 after EOT (max on treatment change)
Population: The SAF set included all participants who received any dose of any of the study intervention (xevinapant/matched placebo, cisplatin/carboplatin, IMRT). Here overall number of participants analyzed signified participants who were evaluable for this outcome measure and number analyzed signifies participants who were evaluable at specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Activated Partial Thromboplastin Time (PTT)/ Standard and Prothrombin Time | Activated PTT/Standard: Baseline | 26.15 seconds (Sec) | Standard Deviation 2.349 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Activated Partial Thromboplastin Time (PTT)/ Standard and Prothrombin Time | Activated PTT/Standard: C3D1 | -0.80 seconds (Sec) | Standard Deviation 3.132 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Activated Partial Thromboplastin Time (PTT)/ Standard and Prothrombin Time | Activated PTT/Standard: EOT | -0.29 seconds (Sec) | Standard Deviation 2.812 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Activated Partial Thromboplastin Time (PTT)/ Standard and Prothrombin Time | Activated PTT/Standard: Max on-treatment change | -1.01 seconds (Sec) | Standard Deviation 4.165 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Activated Partial Thromboplastin Time (PTT)/ Standard and Prothrombin Time | Prothrombin Time: Baseline | 10.50 seconds (Sec) | Standard Deviation 0.73 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Activated Partial Thromboplastin Time (PTT)/ Standard and Prothrombin Time | Prothrombin Time: C3D1 | 0.11 seconds (Sec) | Standard Deviation 1.73 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Activated Partial Thromboplastin Time (PTT)/ Standard and Prothrombin Time | Prothrombin Time: EOT | 0.17 seconds (Sec) | Standard Deviation 1.757 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Activated Partial Thromboplastin Time (PTT)/ Standard and Prothrombin Time | Prothrombin Time: Max on-treatment change | 0.35 seconds (Sec) | Standard Deviation 2.364 |
| Sequence 2: Placebo + CRT | Change From Baseline in Activated Partial Thromboplastin Time (PTT)/ Standard and Prothrombin Time | Prothrombin Time: Max on-treatment change | -0.01 seconds (Sec) | Standard Deviation 1.838 |
| Sequence 2: Placebo + CRT | Change From Baseline in Activated Partial Thromboplastin Time (PTT)/ Standard and Prothrombin Time | Activated PTT/Standard: Baseline | 26.25 seconds (Sec) | Standard Deviation 2.54 |
| Sequence 2: Placebo + CRT | Change From Baseline in Activated Partial Thromboplastin Time (PTT)/ Standard and Prothrombin Time | Prothrombin Time: Baseline | 10.73 seconds (Sec) | Standard Deviation 1.696 |
| Sequence 2: Placebo + CRT | Change From Baseline in Activated Partial Thromboplastin Time (PTT)/ Standard and Prothrombin Time | Activated PTT/Standard: C3D1 | -0.91 seconds (Sec) | Standard Deviation 2.324 |
| Sequence 2: Placebo + CRT | Change From Baseline in Activated Partial Thromboplastin Time (PTT)/ Standard and Prothrombin Time | Prothrombin Time: EOT | -0.04 seconds (Sec) | Standard Deviation 1.697 |
| Sequence 2: Placebo + CRT | Change From Baseline in Activated Partial Thromboplastin Time (PTT)/ Standard and Prothrombin Time | Activated PTT/Standard: EOT | -0.09 seconds (Sec) | Standard Deviation 2.419 |
| Sequence 2: Placebo + CRT | Change From Baseline in Activated Partial Thromboplastin Time (PTT)/ Standard and Prothrombin Time | Prothrombin Time: C3D1 | -0.17 seconds (Sec) | Standard Deviation 1.543 |
| Sequence 2: Placebo + CRT | Change From Baseline in Activated Partial Thromboplastin Time (PTT)/ Standard and Prothrombin Time | Activated PTT/Standard: Max on-treatment change | -0.87 seconds (Sec) | Standard Deviation 3.509 |
Secondary
Change From Baseline in ECG Parameters
The 12-lead ECGs were recorded after the participants have rested for at least 5 minutes in supine position. The parameters included Respiratory Rate (RR), Pulse Rate (PR), QRS, QT and QTcF calculated by the Bazett formula.
Time frame: At Baseline, and upto event free survival (EFS) follow up Month 18 after EOT (max on treatment increase)
Population: The SAF set included all participants who received any dose of any of the study intervention (xevinapant/matched placebo, cisplatin/carboplatin, IMRT). Here number analyzed signifies participants who were evaluable at specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sequence 1: Debio 1143 + CRT | Change From Baseline in ECG Parameters | QRS Duration: Baseline | 90.4 millisecond | Standard Deviation 14.78 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in ECG Parameters | QT Interval: Max on-treatment increase | 33.3 millisecond | Standard Deviation 26.91 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in ECG Parameters | PR Interval: Max on-treatment increase | 15.2 millisecond | Standard Deviation 16.48 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in ECG Parameters | RR Interval: Baseline | 824.5 millisecond | Standard Deviation 163.43 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in ECG Parameters | RR Interval: Max on-treatment increase | 139.5 millisecond | Standard Deviation 125.19 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in ECG Parameters | QRS Duration: Max on-treatment increase | 9.8 millisecond | Standard Deviation 9.87 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in ECG Parameters | QTcF Interval: Baseline | 406.3 millisecond | Standard Deviation 22.78 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in ECG Parameters | PR Interval: Baseline | 154.6 millisecond | Standard Deviation 28.05 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in ECG Parameters | QTcF Interval: Max on-treatment increase | 24.9 millisecond | Standard Deviation 21.27 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in ECG Parameters | QT Interval: Baseline | 381.9 millisecond | Standard Deviation 30.29 |
| Sequence 2: Placebo + CRT | Change From Baseline in ECG Parameters | QTcF Interval: Max on-treatment increase | 19.7 millisecond | Standard Deviation 19.17 |
| Sequence 2: Placebo + CRT | Change From Baseline in ECG Parameters | PR Interval: Baseline | 159.2 millisecond | Standard Deviation 29.85 |
| Sequence 2: Placebo + CRT | Change From Baseline in ECG Parameters | PR Interval: Max on-treatment increase | 15.8 millisecond | Standard Deviation 19.9 |
| Sequence 2: Placebo + CRT | Change From Baseline in ECG Parameters | QRS Duration: Baseline | 91.9 millisecond | Standard Deviation 14.48 |
| Sequence 2: Placebo + CRT | Change From Baseline in ECG Parameters | QRS Duration: Max on-treatment increase | 9.8 millisecond | Standard Deviation 21.97 |
| Sequence 2: Placebo + CRT | Change From Baseline in ECG Parameters | QT Interval: Baseline | 385.7 millisecond | Standard Deviation 33.47 |
| Sequence 2: Placebo + CRT | Change From Baseline in ECG Parameters | QT Interval: Max on-treatment increase | 26.9 millisecond | Standard Deviation 21.78 |
| Sequence 2: Placebo + CRT | Change From Baseline in ECG Parameters | RR Interval: Max on-treatment increase | 117.2 millisecond | Standard Deviation 87.11 |
| Sequence 2: Placebo + CRT | Change From Baseline in ECG Parameters | QTcF Interval: Baseline | 406.6 millisecond | Standard Deviation 25.06 |
| Sequence 2: Placebo + CRT | Change From Baseline in ECG Parameters | RR Interval: Baseline | 858.0 millisecond | Standard Deviation 153.3 |
Secondary
Change From Baseline in Estimated Glomerular Filtration Rate
Change from baseline in biochemistry parameter eGFR was reported. The Glomerular Filtration Rate was measured as milliliter per minute per 1.73 square meter (mL/min/1.73m\^2).
Time frame: At Baseline, Cycle 3 Day 1 (C3D1) (combination period), EOT (15 days after last study treatment administration) and baseline upto event free survival (EFS) follow up Month 18 after EOT (max on treatment change)
Population: The SAF set included all participants who received any dose of any of the study intervention (xevinapant/matched placebo, cisplatin/carboplatin, IMRT). Here overall number of participants analyzed signified participants who were evaluable for this outcome measure and number analyzed signifies participants who were evaluable at specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Estimated Glomerular Filtration Rate | Baseline | 96.956 mL/min/1.73m*2 | Standard Deviation 14.2212 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Estimated Glomerular Filtration Rate | C3D1 | -8.799 mL/min/1.73m*2 | Standard Deviation 19.0295 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Estimated Glomerular Filtration Rate | EOT | -11.385 mL/min/1.73m*2 | Standard Deviation 20.6015 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Estimated Glomerular Filtration Rate | Max on-treatment change | -19.439 mL/min/1.73m*2 | Standard Deviation 27.3672 |
| Sequence 2: Placebo + CRT | Change From Baseline in Estimated Glomerular Filtration Rate | Max on-treatment change | -19.528 mL/min/1.73m*2 | Standard Deviation 25.7099 |
| Sequence 2: Placebo + CRT | Change From Baseline in Estimated Glomerular Filtration Rate | Baseline | 95.244 mL/min/1.73m*2 | Standard Deviation 14.129 |
| Sequence 2: Placebo + CRT | Change From Baseline in Estimated Glomerular Filtration Rate | EOT | -12.594 mL/min/1.73m*2 | Standard Deviation 18.0053 |
| Sequence 2: Placebo + CRT | Change From Baseline in Estimated Glomerular Filtration Rate | C3D1 | -9.205 mL/min/1.73m*2 | Standard Deviation 18.5178 |
Secondary
Change From Baseline in Fibrinogen
Change from Baseline in coagulation parameter fibrinogen was reported.
Time frame: At Baseline, Cycle 3 Day 1 (C3D1) (combination period), EOT (15 days after last study treatment administration) and baseline upto event free survival (EFS) follow up Month 18 after EOT (max on treatment change)
Population: The SAF set included all participants who received any dose of any of the study intervention (xevinapant/matched placebo, cisplatin/carboplatin, IMRT). Here overall number of participants analyzed signified participants who were evaluable for this outcome measure and number analyzed signifies participants who were evaluable at specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Fibrinogen | Baseline | 486.9 milligrams per deciliter (mg/dl) | Standard Deviation 140.35 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Fibrinogen | C3D1 | 121.3 milligrams per deciliter (mg/dl) | Standard Deviation 164.05 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Fibrinogen | EOT | 17.8 milligrams per deciliter (mg/dl) | Standard Deviation 150.78 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Fibrinogen | Max on-treatment change | 112.6 milligrams per deciliter (mg/dl) | Standard Deviation 212.46 |
| Sequence 2: Placebo + CRT | Change From Baseline in Fibrinogen | Max on-treatment change | 122.4 milligrams per deciliter (mg/dl) | Standard Deviation 207.11 |
| Sequence 2: Placebo + CRT | Change From Baseline in Fibrinogen | Baseline | 467.7 milligrams per deciliter (mg/dl) | Standard Deviation 119.14 |
| Sequence 2: Placebo + CRT | Change From Baseline in Fibrinogen | EOT | 1.0 milligrams per deciliter (mg/dl) | Standard Deviation 138.69 |
| Sequence 2: Placebo + CRT | Change From Baseline in Fibrinogen | C3D1 | 109.8 milligrams per deciliter (mg/dl) | Standard Deviation 157.03 |
Secondary
Change From Baseline in Laboratory Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Lipase
Change from Baseline in Laboratory Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Lipase was reported.
Time frame: At Baseline, Cycle 3 Day 1 (C3D1) (combination period), EOT (15 days after last study treatment administration) and baseline upto event free survival (EFS) follow up Month 18 after EOT (max on treatment change)
Population: The SAF set included all participants who received any dose of any of the study intervention (xevinapant/matched placebo, cisplatin/carboplatin, IMRT). Here number analyzed signifies participants who were evaluable at specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Lipase | Alanine Aminotransferase: Baseline | 18.9 microgram per liter (mcg/L) | Standard Deviation 12.1 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Lipase | Alanine Aminotransferase: C3D1 | 0.5 microgram per liter (mcg/L) | Standard Deviation 16.77 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Lipase | Alanine Aminotransferase: EOT | -2.0 microgram per liter (mcg/L) | Standard Deviation 18.25 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Lipase | Alanine Aminotransferase: Max on-treatment change | 55.8 microgram per liter (mcg/L) | Standard Deviation 70.73 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Lipase | Alkaline Phosphatase: Baseline | 79.3 microgram per liter (mcg/L) | Standard Deviation 24.48 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Lipase | Alkaline Phosphatase: C3D1 | -0.8 microgram per liter (mcg/L) | Standard Deviation 19.94 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Lipase | Alkaline Phosphatase: EOT | -2.2 microgram per liter (mcg/L) | Standard Deviation 28.14 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Lipase | Alkaline Phosphatase: Max on-treatment change | 12.7 microgram per liter (mcg/L) | Standard Deviation 47.38 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Lipase | Amylase: Baseline | 70.0 microgram per liter (mcg/L) | Standard Deviation 42.81 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Lipase | Amylase: C3D1 | -14.0 microgram per liter (mcg/L) | Standard Deviation 38.07 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Lipase | Amylase: EOT | -13.5 microgram per liter (mcg/L) | Standard Deviation 40.51 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Lipase | Amylase: Max on-treatment change | 125.8 microgram per liter (mcg/L) | Standard Deviation 205.22 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Lipase | Aspartate Aminotransferase: Baseline | 19.8 microgram per liter (mcg/L) | Standard Deviation 11.1 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Lipase | Aspartate Aminotransferase: C3D1 | -2.4 microgram per liter (mcg/L) | Standard Deviation 12.3 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Lipase | Aspartate Aminotransferase: EOT | 0.4 microgram per liter (mcg/L) | Standard Deviation 19.01 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Lipase | Aspartate Aminotransferase: Max on-treatment change | 20.0 microgram per liter (mcg/L) | Standard Deviation 37.35 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Lipase | Lipase: Baseline | 35.4 microgram per liter (mcg/L) | Standard Deviation 48.01 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Lipase | Lipase: C3D1 | -4.0 microgram per liter (mcg/L) | Standard Deviation 39.69 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Lipase | Lipase: EOT | -1.8 microgram per liter (mcg/L) | Standard Deviation 47.38 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Lipase | Lipase: Max on-treatment change | 87.3 microgram per liter (mcg/L) | Standard Deviation 196.87 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Lipase | Lipase: C3D1 | -4.0 microgram per liter (mcg/L) | Standard Deviation 23.64 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Lipase | Alanine Aminotransferase: Baseline | 19.4 microgram per liter (mcg/L) | Standard Deviation 12.66 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Lipase | Amylase: EOT | -13.5 microgram per liter (mcg/L) | Standard Deviation 33.79 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Lipase | Alanine Aminotransferase: C3D1 | -4.6 microgram per liter (mcg/L) | Standard Deviation 13.53 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Lipase | Aspartate Aminotransferase: Max on-treatment change | 9.7 microgram per liter (mcg/L) | Standard Deviation 25.02 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Lipase | Alanine Aminotransferase: EOT | -3.4 microgram per liter (mcg/L) | Standard Deviation 15.87 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Lipase | Amylase: Max on-treatment change | 60.4 microgram per liter (mcg/L) | Standard Deviation 119.29 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Lipase | Alanine Aminotransferase: Max on-treatment change | 26.5 microgram per liter (mcg/L) | Standard Deviation 45.39 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Lipase | Lipase: Max on-treatment change | 25.0 microgram per liter (mcg/L) | Standard Deviation 60.54 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Lipase | Alkaline Phosphatase: Baseline | 78.0 microgram per liter (mcg/L) | Standard Deviation 23.2 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Lipase | Aspartate Aminotransferase: Baseline | 19.8 microgram per liter (mcg/L) | Standard Deviation 8.31 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Lipase | Alkaline Phosphatase: C3D1 | -1.0 microgram per liter (mcg/L) | Standard Deviation 21.89 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Lipase | Lipase: Baseline | 29.8 microgram per liter (mcg/L) | Standard Deviation 19.37 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Lipase | Alkaline Phosphatase: EOT | -5.6 microgram per liter (mcg/L) | Standard Deviation 18.79 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Lipase | Aspartate Aminotransferase: C3D1 | -3.5 microgram per liter (mcg/L) | Standard Deviation 8.63 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Lipase | Alkaline Phosphatase: Max on-treatment change | 5.6 microgram per liter (mcg/L) | Standard Deviation 49.27 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Lipase | Lipase: EOT | -1.0 microgram per liter (mcg/L) | Standard Deviation 21.69 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Lipase | Amylase: Baseline | 67.8 microgram per liter (mcg/L) | Standard Deviation 61.61 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Lipase | Aspartate Aminotransferase: EOT | 0.9 microgram per liter (mcg/L) | Standard Deviation 18.8 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Lipase | Amylase: C3D1 | -14.0 microgram per liter (mcg/L) | Standard Deviation 32.85 |
Secondary
Change From Baseline in Laboratory Parameters: Basophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets
Change from Baseline in Laboratory Parameters: Basophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets was reported.
Time frame: At Baseline, Cycle 3 Day 1 (C3D1) (combination period), EOT (15 days after last study treatment administration) and baseline upto event free survival (EFS) follow up Month 18 after EOT (max on treatment change)
Population: The SAF set included all participants who received any dose of any of the study intervention (xevinapant/matched placebo, cisplatin/carboplatin, IMRT). Here overall number of participants analyzed signified participants who were evaluable for this outcome measure and number analyzed signifies participants who were evaluable at specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Basophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Leukocytes: EOT | -2.129 10^9 cells per liter | Standard Deviation 3.2074 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Basophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Basophils: C3D1 | -0.032 10^9 cells per liter | Standard Deviation 0.0367 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Basophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Basophils: EOT | -0.021 10^9 cells per liter | Standard Deviation 0.0367 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Basophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Basophil: Max on-treatment change | -0.022 10^9 cells per liter | Standard Deviation 0.0673 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Basophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Leukocytes: Baseline | 8.175 10^9 cells per liter | Standard Deviation 2.9656 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Basophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Leukocytes: C3D1 | -4.065 10^9 cells per liter | Standard Deviation 3.1244 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Basophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Basophils: Baseline | 0.052 10^9 cells per liter | Standard Deviation 0.0343 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Basophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Leukocytes: Max on-treatment change | -3.045 10^9 cells per liter | Standard Deviation 7.5455 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Basophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Lymphocytes: Baseline | 1.753 10^9 cells per liter | Standard Deviation 0.5734 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Basophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Lymphocytes: C3D1 | -1.168 10^9 cells per liter | Standard Deviation 0.5804 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Basophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Lymphocytes: EOT | -0.884 10^9 cells per liter | Standard Deviation 0.5485 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Basophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Lymphocyte: Max on-treatment change | -1.382 10^9 cells per liter | Standard Deviation 0.6359 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Basophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Monocytes: Baseline | 0.518 10^9 cells per liter | Standard Deviation 0.2156 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Basophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Monocytes: C3D1 | -0.139 10^9 cells per liter | Standard Deviation 0.2389 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Basophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Monocytes: EOT | -0.114 10^9 cells per liter | Standard Deviation 0.1991 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Basophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Monocyte: Max on-treatment change | -0.175 10^9 cells per liter | Standard Deviation 0.405 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Basophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Neutrophils: Baseline | 5.669 10^9 cells per liter | Standard Deviation 2.6589 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Basophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Neutrophils: C3D1 | -2.646 10^9 cells per liter | Standard Deviation 2.8532 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Basophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Neutrophils: EOT | -1.081 10^9 cells per liter | Standard Deviation 2.9287 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Basophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Neutrophils: Max on-treatment change | -0.528 10^9 cells per liter | Standard Deviation 7.2775 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Basophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Platelets: Baseline | 292.6 10^9 cells per liter | Standard Deviation 104.86 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Basophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Platelets: C3D1 | -48.2 10^9 cells per liter | Standard Deviation 112.13 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Basophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Platelets: EOT | -24.8 10^9 cells per liter | Standard Deviation 94.59 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Basophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Platelets: Max on-treatment change | -63.2 10^9 cells per liter | Standard Deviation 203.4 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Basophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Platelets: EOT | -38.6 10^9 cells per liter | Standard Deviation 87.16 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Basophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Basophils: Baseline | 0.054 10^9 cells per liter | Standard Deviation 0.0367 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Basophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Monocytes: Baseline | 0.506 10^9 cells per liter | Standard Deviation 0.2072 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Basophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Basophils: C3D1 | -0.041 10^9 cells per liter | Standard Deviation 0.0362 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Basophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Neutrophils: EOT | -1.275 10^9 cells per liter | Standard Deviation 2.2696 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Basophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Basophils: EOT | -0.023 10^9 cells per liter | Standard Deviation 0.0312 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Basophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Monocytes: C3D1 | -0.169 10^9 cells per liter | Standard Deviation 0.2063 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Basophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Basophil: Max on-treatment change | -0.031 10^9 cells per liter | Standard Deviation 0.0618 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Basophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Platelets: C3D1 | -56.5 10^9 cells per liter | Standard Deviation 109.52 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Basophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Leukocytes: Baseline | 8.105 10^9 cells per liter | Standard Deviation 2.6725 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Basophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Monocytes: EOT | -0.100 10^9 cells per liter | Standard Deviation 0.1683 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Basophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Leukocytes: C3D1 | -4.597 10^9 cells per liter | Standard Deviation 2.9352 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Basophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Neutrophils: Max on-treatment change | -1.095 10^9 cells per liter | Standard Deviation 6.3143 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Basophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Leukocytes: EOT | -2.354 10^9 cells per liter | Standard Deviation 2.4137 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Basophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Monocyte: Max on-treatment change | -0.152 10^9 cells per liter | Standard Deviation 0.387 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Basophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Leukocytes: Max on-treatment change | -3.444 10^9 cells per liter | Standard Deviation 6.7059 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Basophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Platelets: Max on-treatment change | -88.7 10^9 cells per liter | Standard Deviation 171.61 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Basophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Lymphocytes: Baseline | 1.753 10^9 cells per liter | Standard Deviation 0.6367 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Basophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Neutrophils: Baseline | 5.610 10^9 cells per liter | Standard Deviation 2.3663 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Basophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Lymphocytes: C3D1 | -1.251 10^9 cells per liter | Standard Deviation 0.5742 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Basophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Platelets: Baseline | 287.7 10^9 cells per liter | Standard Deviation 107.38 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Basophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Lymphocytes: EOT | -0.901 10^9 cells per liter | Standard Deviation 0.5536 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Basophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Neutrophils: C3D1 | -3.018 10^9 cells per liter | Standard Deviation 2.6744 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Basophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Lymphocyte: Max on-treatment change | -1.356 10^9 cells per liter | Standard Deviation 0.615 |
Secondary
Change From Baseline in Laboratory Parameters: Bilirubin, Creatinine, Direct Bilirubin, Urate
Change from Baseline in Laboratory Parameters: Bilirubin, Creatinine, Direct Bilirubin, Urate was reported.
Time frame: At Baseline, Cycle 3 Day 1 (C3D1) (combination period), EOT (15 days after last study treatment administration) and baseline upto event free survival (EFS) follow up Month 18 after EOT (max on treatment change)
Population: The SAF set included all participants who received any dose of any of the study intervention (xevinapant/matched placebo, cisplatin/carboplatin, IMRT). Here number analyzed signifies participants who were evaluable at specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Bilirubin, Creatinine, Direct Bilirubin, Urate | Direct Bilirubin: Baseline | 4.8 micromole per liter (mcmol/L) | Standard Deviation 0.75 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Bilirubin, Creatinine, Direct Bilirubin, Urate | Bilirubin: C3D1 | -1.8 micromole per liter (mcmol/L) | Standard Deviation 3.74 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Bilirubin, Creatinine, Direct Bilirubin, Urate | Creatinine: C3D1 | 11.771 micromole per liter (mcmol/L) | Standard Deviation 27.4012 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Bilirubin, Creatinine, Direct Bilirubin, Urate | Bilirubin: Max on-treatment change | 1.1 micromole per liter (mcmol/L) | Standard Deviation 7.49 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Bilirubin, Creatinine, Direct Bilirubin, Urate | Direct Bilirubin: Max on-treatment change | 2.5 micromole per liter (mcmol/L) | Standard Deviation 2.12 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Bilirubin, Creatinine, Direct Bilirubin, Urate | Creatinine: EOT | 17.660 micromole per liter (mcmol/L) | Standard Deviation 49.3934 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Bilirubin, Creatinine, Direct Bilirubin, Urate | Urate: Baseline | 303.1 micromole per liter (mcmol/L) | Standard Deviation 79.62 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Bilirubin, Creatinine, Direct Bilirubin, Urate | Bilirubin: EOT | -2.0 micromole per liter (mcmol/L) | Standard Deviation 3.85 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Bilirubin, Creatinine, Direct Bilirubin, Urate | Urate: C3D1 | -25.4 micromole per liter (mcmol/L) | Standard Deviation 90.93 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Bilirubin, Creatinine, Direct Bilirubin, Urate | Creatinine: Max on-treatment change | 292.808 micromole per liter (mcmol/L) | Standard Deviation 4199.9623 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Bilirubin, Creatinine, Direct Bilirubin, Urate | Urate: EOT | 25.9 micromole per liter (mcmol/L) | Standard Deviation 85.01 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Bilirubin, Creatinine, Direct Bilirubin, Urate | Creatinine: Baseline | 67.884 micromole per liter (mcmol/L) | Standard Deviation 15.1427 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Bilirubin, Creatinine, Direct Bilirubin, Urate | Urate: Max on-treatment change | 1.2 micromole per liter (mcmol/L) | Standard Deviation 140.44 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Bilirubin, Creatinine, Direct Bilirubin, Urate | Bilirubin: Baseline | 7.4 micromole per liter (mcmol/L) | Standard Deviation 4.03 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Bilirubin, Creatinine, Direct Bilirubin, Urate | Urate: C3D1 | -21.5 micromole per liter (mcmol/L) | Standard Deviation 91.07 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Bilirubin, Creatinine, Direct Bilirubin, Urate | Urate: EOT | 33.1 micromole per liter (mcmol/L) | Standard Deviation 80.07 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Bilirubin, Creatinine, Direct Bilirubin, Urate | Urate: Max on-treatment change | 12.7 micromole per liter (mcmol/L) | Standard Deviation 137.74 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Bilirubin, Creatinine, Direct Bilirubin, Urate | Bilirubin: Baseline | 7.8 micromole per liter (mcmol/L) | Standard Deviation 4.06 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Bilirubin, Creatinine, Direct Bilirubin, Urate | Bilirubin: C3D1 | -1.5 micromole per liter (mcmol/L) | Standard Deviation 3.68 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Bilirubin, Creatinine, Direct Bilirubin, Urate | Bilirubin: EOT | -1.3 micromole per liter (mcmol/L) | Standard Deviation 3.52 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Bilirubin, Creatinine, Direct Bilirubin, Urate | Bilirubin: Max on-treatment change | 0.1 micromole per liter (mcmol/L) | Standard Deviation 6.83 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Bilirubin, Creatinine, Direct Bilirubin, Urate | Creatinine: Baseline | 70.612 micromole per liter (mcmol/L) | Standard Deviation 15.3405 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Bilirubin, Creatinine, Direct Bilirubin, Urate | Creatinine: C3D1 | 11.740 micromole per liter (mcmol/L) | Standard Deviation 26.2545 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Bilirubin, Creatinine, Direct Bilirubin, Urate | Creatinine: EOT | 16.243 micromole per liter (mcmol/L) | Standard Deviation 32.1216 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Bilirubin, Creatinine, Direct Bilirubin, Urate | Creatinine: Max on-treatment change | 360.521 micromole per liter (mcmol/L) | Standard Deviation 5664.5213 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Bilirubin, Creatinine, Direct Bilirubin, Urate | Direct Bilirubin: Baseline | 5.6 micromole per liter (mcmol/L) | Standard Deviation 1.33 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Bilirubin, Creatinine, Direct Bilirubin, Urate | Direct Bilirubin: C3D1 | 3.0 micromole per liter (mcmol/L) | — |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Bilirubin, Creatinine, Direct Bilirubin, Urate | Direct Bilirubin: EOT | 0.0 micromole per liter (mcmol/L) | Standard Deviation 1.41 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Bilirubin, Creatinine, Direct Bilirubin, Urate | Direct Bilirubin: Max on-treatment change | 1.0 micromole per liter (mcmol/L) | Standard Deviation 2.14 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Bilirubin, Creatinine, Direct Bilirubin, Urate | Urate: Baseline | 305.9 micromole per liter (mcmol/L) | Standard Deviation 82.79 |
Secondary
Change From Baseline in Laboratory Parameters: Calcium, Magnesium, Potassium, Sodium, Urea
Change from Baseline in Laboratory Parameters: Calcium, Magnesium, Potassium, Sodium, Urea was reported.
Time frame: At Baseline, Cycle 3 Day 1 (C3D1) (combination period), EOT (15 days after last study treatment administration) and baseline upto event free survival (EFS) follow up Month 18 after EOT (max on treatment change)
Population: The SAF set included all participants who received any dose of any of the study intervention (xevinapant/matched placebo, cisplatin/carboplatin, IMRT). Here number analyzed signifies participants who were evaluable at specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Calcium, Magnesium, Potassium, Sodium, Urea | Calcium: Baseline | 2.4065 millimoles per liter (mmol/L) | Standard Deviation 0.1405 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Calcium, Magnesium, Potassium, Sodium, Urea | Calcium: C3D1 | -0.1054 millimoles per liter (mmol/L) | Standard Deviation 0.1683 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Calcium, Magnesium, Potassium, Sodium, Urea | Calcium: EOT | 0.0006 millimoles per liter (mmol/L) | Standard Deviation 0.15586 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Calcium, Magnesium, Potassium, Sodium, Urea | Calcium: Max on-treatment change | -0.1182 millimoles per liter (mmol/L) | Standard Deviation 0.64226 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Calcium, Magnesium, Potassium, Sodium, Urea | Magnesium: Baseline | 0.8731 millimoles per liter (mmol/L) | Standard Deviation 0.08816 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Calcium, Magnesium, Potassium, Sodium, Urea | Magnesium: C3D1 | -0.0871 millimoles per liter (mmol/L) | Standard Deviation 0.11743 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Calcium, Magnesium, Potassium, Sodium, Urea | Magnesium: EOT | -0.0588 millimoles per liter (mmol/L) | Standard Deviation 0.10612 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Calcium, Magnesium, Potassium, Sodium, Urea | Magnesium: Max on-treatment change | -0.1231 millimoles per liter (mmol/L) | Standard Deviation 0.21711 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Calcium, Magnesium, Potassium, Sodium, Urea | Potassium: Baseline | 4.4270 millimoles per liter (mmol/L) | Standard Deviation 0.4161 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Calcium, Magnesium, Potassium, Sodium, Urea | Potassium: C3D1 | -0.1226 millimoles per liter (mmol/L) | Standard Deviation 0.60007 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Calcium, Magnesium, Potassium, Sodium, Urea | Potassium: EOT | -0.0374 millimoles per liter (mmol/L) | Standard Deviation 0.52898 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Calcium, Magnesium, Potassium, Sodium, Urea | Potassium: Max on-treatment change | -0.2845 millimoles per liter (mmol/L) | Standard Deviation 1.13356 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Calcium, Magnesium, Potassium, Sodium, Urea | Sodium: Baseline | 139.3333 millimoles per liter (mmol/L) | Standard Deviation 2.72935 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Calcium, Magnesium, Potassium, Sodium, Urea | Sodium: C3D1 | -2.0828 millimoles per liter (mmol/L) | Standard Deviation 3.96368 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Calcium, Magnesium, Potassium, Sodium, Urea | Sodium: EOT | -0.9510 millimoles per liter (mmol/L) | Standard Deviation 3.53728 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Calcium, Magnesium, Potassium, Sodium, Urea | Sodium: Max on-treatment change | -4.7482 millimoles per liter (mmol/L) | Standard Deviation 9.86512 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Calcium, Magnesium, Potassium, Sodium, Urea | Urea: Baseline | 5.22 millimoles per liter (mmol/L) | Standard Deviation 1.885 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Calcium, Magnesium, Potassium, Sodium, Urea | Urea: C3D1 | 1.89 millimoles per liter (mmol/L) | Standard Deviation 3.302 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Calcium, Magnesium, Potassium, Sodium, Urea | Urea: EOT | 1.73 millimoles per liter (mmol/L) | Standard Deviation 3.266 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Calcium, Magnesium, Potassium, Sodium, Urea | Urea: Max on-treatment change | 8.51 millimoles per liter (mmol/L) | Standard Deviation 7.226 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Calcium, Magnesium, Potassium, Sodium, Urea | Urea: C3D1 | 1.87 millimoles per liter (mmol/L) | Standard Deviation 3.961 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Calcium, Magnesium, Potassium, Sodium, Urea | Calcium: Baseline | 2.4043 millimoles per liter (mmol/L) | Standard Deviation 0.11777 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Calcium, Magnesium, Potassium, Sodium, Urea | Potassium: EOT | 0.0170 millimoles per liter (mmol/L) | Standard Deviation 0.58221 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Calcium, Magnesium, Potassium, Sodium, Urea | Calcium: C3D1 | -0.0574 millimoles per liter (mmol/L) | Standard Deviation 0.12989 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Calcium, Magnesium, Potassium, Sodium, Urea | Sodium: Max on-treatment change | -4.6627 millimoles per liter (mmol/L) | Standard Deviation 14.14911 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Calcium, Magnesium, Potassium, Sodium, Urea | Calcium: EOT | 0.0136 millimoles per liter (mmol/L) | Standard Deviation 0.12258 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Calcium, Magnesium, Potassium, Sodium, Urea | Potassium: Max on-treatment change | -0.2551 millimoles per liter (mmol/L) | Standard Deviation 1.14282 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Calcium, Magnesium, Potassium, Sodium, Urea | Calcium: Max on-treatment change | -0.0575 millimoles per liter (mmol/L) | Standard Deviation 0.63941 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Calcium, Magnesium, Potassium, Sodium, Urea | Urea: Max on-treatment change | 6.18 millimoles per liter (mmol/L) | Standard Deviation 6.11 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Calcium, Magnesium, Potassium, Sodium, Urea | Magnesium: Baseline | 0.8718 millimoles per liter (mmol/L) | Standard Deviation 0.088 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Calcium, Magnesium, Potassium, Sodium, Urea | Sodium: Baseline | 139.1798 millimoles per liter (mmol/L) | Standard Deviation 3.19705 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Calcium, Magnesium, Potassium, Sodium, Urea | Magnesium: C3D1 | -0.0719 millimoles per liter (mmol/L) | Standard Deviation 0.11889 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Calcium, Magnesium, Potassium, Sodium, Urea | Urea: Baseline | 5.23 millimoles per liter (mmol/L) | Standard Deviation 2.068 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Calcium, Magnesium, Potassium, Sodium, Urea | Magnesium: EOT | -0.0372 millimoles per liter (mmol/L) | Standard Deviation 0.08725 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Calcium, Magnesium, Potassium, Sodium, Urea | Sodium: C3D1 | -1.5527 millimoles per liter (mmol/L) | Standard Deviation 3.7311 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Calcium, Magnesium, Potassium, Sodium, Urea | Magnesium: Max on-treatment change | -0.0860 millimoles per liter (mmol/L) | Standard Deviation 0.21948 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Calcium, Magnesium, Potassium, Sodium, Urea | Urea: EOT | 1.40 millimoles per liter (mmol/L) | Standard Deviation 2.922 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Calcium, Magnesium, Potassium, Sodium, Urea | Potassium: Baseline | 4.4534 millimoles per liter (mmol/L) | Standard Deviation 0.44584 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Calcium, Magnesium, Potassium, Sodium, Urea | Sodium: EOT | -0.9521 millimoles per liter (mmol/L) | Standard Deviation 3.71944 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Calcium, Magnesium, Potassium, Sodium, Urea | Potassium: C3D1 | -0.0877 millimoles per liter (mmol/L) | Standard Deviation 0.58424 |
Secondary
Change From Baseline in Laboratory Parameters: C Reactive Protein
Change from Baseline in Laboratory Parameters: C Reactive Protein was reported.
Time frame: At Baseline, Cycle 3 Day 1 (C3D1) (combination period), EOT (15 days after last study treatment administration) and baseline upto event free survival (EFS) follow up Month 18 after EOT (max on treatment change)
Population: The SAF set included all participants who received any dose of any of the study intervention (xevinapant/matched placebo, cisplatin/carboplatin, IMRT). Here number analyzed signifies participants who were evaluable at specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: C Reactive Protein | Baseline | 15.80 milligrams per liter (mg/L) | Standard Deviation 24.655 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: C Reactive Protein | C3D1 | 25.30 milligrams per liter (mg/L) | Standard Deviation 50.259 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: C Reactive Protein | EOT | 1.26 milligrams per liter (mg/L) | Standard Deviation 31.784 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: C Reactive Protein | Max on-treatment change | 43.91 milligrams per liter (mg/L) | Standard Deviation 66.024 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: C Reactive Protein | Max on-treatment change | 27.90 milligrams per liter (mg/L) | Standard Deviation 56.262 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: C Reactive Protein | Baseline | 13.78 milligrams per liter (mg/L) | Standard Deviation 21.78 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: C Reactive Protein | EOT | 1.22 milligrams per liter (mg/L) | Standard Deviation 27.72 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: C Reactive Protein | C3D1 | 11.66 milligrams per liter (mg/L) | Standard Deviation 36.791 |
Secondary
Change From Baseline in Laboratory Parameters: Erythrocytes
Change from Baseline in Laboratory Parameters: Erythrocytes was reported.
Time frame: At Baseline, Cycle 3 Day 1 (C3D1) (combination period), EOT (15 days after last study treatment administration) and baseline upto event free survival (EFS) follow up Month 18 after EOT (max on treatment change)
Population: The SAF set included all participants who received any dose of any of the study intervention (xevinapant/matched placebo, cisplatin/carboplatin, IMRT). Here overall number of participants analyzed signified participants who were evaluable for this outcome measure and number analyzed signifies participants who were evaluable at specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Erythrocytes | EOT | -0.70 10^12 cells per liter | Standard Deviation 0.575 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Erythrocytes | C3D1 | -0.81 10^12 cells per liter | Standard Deviation 0.456 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Erythrocytes | Max on-treatment change | -1.14 10^12 cells per liter | Standard Deviation 0.636 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Erythrocytes | Baseline | 4.27 10^12 cells per liter | Standard Deviation 0.507 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Erythrocytes | Max on-treatment change | -1.19 10^12 cells per liter | Standard Deviation 0.605 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Erythrocytes | C3D1 | -0.82 10^12 cells per liter | Standard Deviation 0.433 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Erythrocytes | EOT | -0.59 10^12 cells per liter | Standard Deviation 0.464 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Erythrocytes | Baseline | 4.37 10^12 cells per liter | Standard Deviation 0.477 |
Secondary
Change From Baseline in Laboratory Parameters: Hemoglobin, Albumin, Protein
Change from Baseline in Laboratory Parameters: Hemoglobin, Albumin, Protein was reported.
Time frame: At Baseline, Cycle 3 Day 1 (C3D1) (combination period), EOT (15 days after last study treatment administration) and baseline upto event free survival (EFS) follow up Month 18 after EOT (max on treatment change)
Population: The SAF set included all participants who received any dose of any of the study intervention (xevinapant/matched placebo, cisplatin/carboplatin, IMRT). Here overall number of participants analyzed signified participants who were evaluable for this outcome measure and number analyzed signifies participants who were evaluable at specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Hemoglobin, Albumin, Protein | Hemoglobin: Baseline | 132.9 grams per liters (g/L) | Standard Deviation 15.08 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Hemoglobin, Albumin, Protein | Hemoglobin: C3D1 | -25.7 grams per liters (g/L) | Standard Deviation 14.24 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Hemoglobin, Albumin, Protein | Hemoglobin: EOT | -19.1 grams per liters (g/L) | Standard Deviation 17.73 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Hemoglobin, Albumin, Protein | Hemoglobin: Max on-treatment change | -34.8 grams per liters (g/L) | Standard Deviation 19.83 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Hemoglobin, Albumin, Protein | Albumin: Baseline | 43.2 grams per liters (g/L) | Standard Deviation 3.95 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Hemoglobin, Albumin, Protein | Albumin: C3D1 | -4.0 grams per liters (g/L) | Standard Deviation 4.33 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Hemoglobin, Albumin, Protein | Albumin: EOT | -1.1 grams per liters (g/L) | Standard Deviation 4.43 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Hemoglobin, Albumin, Protein | Albumin: Max on-treatment change | -4.8 grams per liters (g/L) | Standard Deviation 6.38 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Hemoglobin, Albumin, Protein | Protein: Baseline | 70.1 grams per liters (g/L) | Standard Deviation 5.11 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Hemoglobin, Albumin, Protein | Protein: C3D1 | -4.5 grams per liters (g/L) | Standard Deviation 5.73 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Hemoglobin, Albumin, Protein | Protein: EOT | -0.3 grams per liters (g/L) | Standard Deviation 6.1 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Laboratory Parameters: Hemoglobin, Albumin, Protein | Protein: Max on-treatment change | -4.7 grams per liters (g/L) | Standard Deviation 9.12 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Hemoglobin, Albumin, Protein | Protein: EOT | -0.7 grams per liters (g/L) | Standard Deviation 5.32 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Hemoglobin, Albumin, Protein | Hemoglobin: Baseline | 135.4 grams per liters (g/L) | Standard Deviation 14.34 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Hemoglobin, Albumin, Protein | Albumin: EOT | 0.4 grams per liters (g/L) | Standard Deviation 4.02 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Hemoglobin, Albumin, Protein | Hemoglobin: C3D1 | -25.2 grams per liters (g/L) | Standard Deviation 13.75 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Hemoglobin, Albumin, Protein | Protein: C3D1 | -4.3 grams per liters (g/L) | Standard Deviation 5.24 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Hemoglobin, Albumin, Protein | Hemoglobin: EOT | -14.4 grams per liters (g/L) | Standard Deviation 14.44 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Hemoglobin, Albumin, Protein | Albumin: Max on-treatment change | -2.6 grams per liters (g/L) | Standard Deviation 5.9 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Hemoglobin, Albumin, Protein | Hemoglobin: Max on-treatment change | -35.8 grams per liters (g/L) | Standard Deviation 18.82 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Hemoglobin, Albumin, Protein | Protein: Max on-treatment change | -5.0 grams per liters (g/L) | Standard Deviation 8.03 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Hemoglobin, Albumin, Protein | Albumin: Baseline | 43.6 grams per liters (g/L) | Standard Deviation 3.55 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Hemoglobin, Albumin, Protein | Protein: Baseline | 70.5 grams per liters (g/L) | Standard Deviation 4.78 |
| Sequence 2: Placebo + CRT | Change From Baseline in Laboratory Parameters: Hemoglobin, Albumin, Protein | Albumin: C3D1 | -2.6 grams per liters (g/L) | Standard Deviation 3.61 |
Secondary
Change From Baseline in Prothrombin International Normalized Ratio
Change from baseline in coagulation parameters prothrombin international normalized ratio was reported.
Time frame: At Baseline, Cycle 3 Day 1 (C3D1) (combination period), EOT (15 days after last study treatment administration) and baseline upto event free survival (EFS) follow up Month 18 after EOT (max on treatment change)
Population: The SAF set included all participants who received any dose of any of the study intervention (xevinapant/matched placebo, cisplatin/carboplatin, IMRT). Here overall number of participants analyzed signified participants who were evaluable for this outcome measure and number analyzed signifies participants who were evaluable at specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Prothrombin International Normalized Ratio | Baseline | 0.96 ratio | Standard Deviation 0.09 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Prothrombin International Normalized Ratio | C3D1 | 0.01 ratio | Standard Deviation 0.195 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Prothrombin International Normalized Ratio | EOT | 0.02 ratio | Standard Deviation 0.197 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Prothrombin International Normalized Ratio | Max on-treatment change | 0.04 ratio | Standard Deviation 0.265 |
| Sequence 2: Placebo + CRT | Change From Baseline in Prothrombin International Normalized Ratio | Max on-treatment change | 0.00 ratio | Standard Deviation 0.212 |
| Sequence 2: Placebo + CRT | Change From Baseline in Prothrombin International Normalized Ratio | Baseline | 0.99 ratio | Standard Deviation 0.188 |
| Sequence 2: Placebo + CRT | Change From Baseline in Prothrombin International Normalized Ratio | EOT | 0.00 ratio | Standard Deviation 0.195 |
| Sequence 2: Placebo + CRT | Change From Baseline in Prothrombin International Normalized Ratio | C3D1 | -0.02 ratio | Standard Deviation 0.175 |
Secondary
Change From Baseline in Vital Signs: Body Temperature
Change from Baseline in Vital Signs: Body Temperature was reported.
Time frame: At Baseline, Cycle 3 Day 1 (C3D1) (combination period), EOT (15 days after last study treatment administration) and baseline upto event free survival (EFS) follow up Month 18 after EOT (max on treatment increase)
Population: The SAF set included all participants who received any dose of any of the study intervention (xevinapant/matched placebo, cisplatin/carboplatin, IMRT). Here overall number of participants analyzed signified participants who were evaluable for this outcome measure and number analyzed signifies participants who were evaluable at specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Vital Signs: Body Temperature | Baseline | 36.44 degree Celsius | Standard Deviation 0.443 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Vital Signs: Body Temperature | C3D1 | 0.10 degree Celsius | Standard Deviation 36.49 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Vital Signs: Body Temperature | EOT | 0.00 degree Celsius | Standard Deviation 0.463 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Vital Signs: Body Temperature | Max on-treatment increase | 0.57 degree Celsius | Standard Deviation 0.445 |
| Sequence 2: Placebo + CRT | Change From Baseline in Vital Signs: Body Temperature | Max on-treatment increase | 0.51 degree Celsius | Standard Deviation 0.413 |
| Sequence 2: Placebo + CRT | Change From Baseline in Vital Signs: Body Temperature | Baseline | 36.41 degree Celsius | Standard Deviation 0.432 |
| Sequence 2: Placebo + CRT | Change From Baseline in Vital Signs: Body Temperature | EOT | 0.00 degree Celsius | Standard Deviation 0.453 |
| Sequence 2: Placebo + CRT | Change From Baseline in Vital Signs: Body Temperature | C3D1 | 0.07 degree Celsius | Standard Deviation 0.476 |
Secondary
Change From Baseline in Vital Signs: Body Weight
Change from Baseline in Vital Signs: Body Weight was reported.
Time frame: At Baseline, C3D1 (combination period), EOT (15 days after last study treatment administration) and baseline upto event free survival (EFS) follow up Month 18 after EOT (max on treatment increase & decrease)
Population: The SAF set included all participants who received any dose of any of the study intervention (xevinapant/matched placebo, cisplatin/carboplatin, IMRT). Here number analyzed signifies participants who were evaluable at specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Vital Signs: Body Weight | C3D1 | -4.762 kilograms (kg) | Standard Deviation 3.9129 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Vital Signs: Body Weight | Max on-treatment increase | 2.497 kilograms (kg) | Standard Deviation 2.1157 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Vital Signs: Body Weight | EOT | -6.282 kilograms (kg) | Standard Deviation 6.116 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Vital Signs: Body Weight | Max on-treatment decrease | -8.182 kilograms (kg) | Standard Deviation 5.1605 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Vital Signs: Body Weight | Baseline | 69.552 kilograms (kg) | Standard Deviation 16.8493 |
| Sequence 2: Placebo + CRT | Change From Baseline in Vital Signs: Body Weight | Max on-treatment decrease | -7.379 kilograms (kg) | Standard Deviation 4.8001 |
| Sequence 2: Placebo + CRT | Change From Baseline in Vital Signs: Body Weight | Baseline | 70.261 kilograms (kg) | Standard Deviation 15.2793 |
| Sequence 2: Placebo + CRT | Change From Baseline in Vital Signs: Body Weight | C3D1 | -4.331 kilograms (kg) | Standard Deviation 3.6001 |
| Sequence 2: Placebo + CRT | Change From Baseline in Vital Signs: Body Weight | EOT | -4.819 kilograms (kg) | Standard Deviation 5.9718 |
| Sequence 2: Placebo + CRT | Change From Baseline in Vital Signs: Body Weight | Max on-treatment increase | 2.549 kilograms (kg) | Standard Deviation 2.7503 |
Secondary
Change From Baseline in Vital Signs: Heart Rate
Change from Baseline in Vital Signs: Heart Rate was reported.
Time frame: At Baseline, Cycle 3 Day 1 (C3D1) (combination period), EOT (15 days after last study treatment administration) and baseline upto event free survival (EFS) follow up Month 18 after EOT (max on treatment increase & decrease)
Population: The SAF set included all participants who received any dose of any of the study intervention (xevinapant/matched placebo, cisplatin/carboplatin, IMRT). Here number analyzed signifies participants who were evaluable at specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Vital Signs: Heart Rate | Heart Rate: C3D1 | 5.2 beats/minute | Standard Deviation 13.71 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Vital Signs: Heart Rate | Heart Rate: Max on-treatment increase | 17.8 beats/minute | Standard Deviation 12.3 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Vital Signs: Heart Rate | Heart Rate: EOT | 2.8 beats/minute | Standard Deviation 14.33 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Vital Signs: Heart Rate | Heart Rate: Max on-treatment decrease | -11.7 beats/minute | Standard Deviation 9 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Vital Signs: Heart Rate | Heart Rate: Baseline | 77.6 beats/minute | Standard Deviation 12.35 |
| Sequence 2: Placebo + CRT | Change From Baseline in Vital Signs: Heart Rate | Heart Rate: Max on-treatment decrease | -12.2 beats/minute | Standard Deviation 9.13 |
| Sequence 2: Placebo + CRT | Change From Baseline in Vital Signs: Heart Rate | Heart Rate: Baseline | 76.1 beats/minute | Standard Deviation 12.6 |
| Sequence 2: Placebo + CRT | Change From Baseline in Vital Signs: Heart Rate | Heart Rate: C3D1 | 3.4 beats/minute | Standard Deviation 13.92 |
| Sequence 2: Placebo + CRT | Change From Baseline in Vital Signs: Heart Rate | Heart Rate: EOT | 2.2 beats/minute | Standard Deviation 13.51 |
| Sequence 2: Placebo + CRT | Change From Baseline in Vital Signs: Heart Rate | Heart Rate: Max on-treatment increase | 16.7 beats/minute | Standard Deviation 10.97 |
Secondary
Change From Baseline in Vital Signs: Respiratory Rate
Change from Baseline in Vital Signs: Respiratory Rate was reported.
Time frame: At Baseline, Cycle 3 Day 1 (C3D1) (combination period), EOT (15 days after last study treatment administration) and baseline upto event free survival (EFS) follow up Month 18 after EOT (max on treatment increase & decrease)
Population: The SAF set included all participants who received any dose of any of the study intervention (xevinapant/matched placebo, cisplatin/carboplatin, IMRT). Here number analyzed signifies participants who were evaluable at specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Vital Signs: Respiratory Rate | Respiratory Rate: C3D1 | -0.1 breaths/minute | Standard Deviation 2.65 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Vital Signs: Respiratory Rate | Respiratory Rate: Max on-treatment increase | 3.2 breaths/minute | Standard Deviation 2.66 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Vital Signs: Respiratory Rate | Respiratory Rate: EOT | -0.1 breaths/minute | Standard Deviation 2.83 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Vital Signs: Respiratory Rate | Respiratory Rate: Max on-treatment decrease | -3.1 breaths/minute | Standard Deviation 2.52 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Vital Signs: Respiratory Rate | Respiratory Rate: Baseline | 16.8 breaths/minute | Standard Deviation 2.38 |
| Sequence 2: Placebo + CRT | Change From Baseline in Vital Signs: Respiratory Rate | Respiratory Rate: Max on-treatment decrease | -2.7 breaths/minute | Standard Deviation 2.88 |
| Sequence 2: Placebo + CRT | Change From Baseline in Vital Signs: Respiratory Rate | Respiratory Rate: Baseline | 16.7 breaths/minute | Standard Deviation 2.98 |
| Sequence 2: Placebo + CRT | Change From Baseline in Vital Signs: Respiratory Rate | Respiratory Rate: C3D1 | 0.0 breaths/minute | Standard Deviation 2.76 |
| Sequence 2: Placebo + CRT | Change From Baseline in Vital Signs: Respiratory Rate | Respiratory Rate: EOT | -0.1 breaths/minute | Standard Deviation 3.01 |
| Sequence 2: Placebo + CRT | Change From Baseline in Vital Signs: Respiratory Rate | Respiratory Rate: Max on-treatment increase | 2.7 breaths/minute | Standard Deviation 2.13 |
Secondary
Change From Baseline in Vital Signs: Systolic Blood Pressure, Diastolic Blood Pressure
Change from Baseline in Vital Signs: Systolic Blood Pressure, Diastolic Blood Pressure was reported.
Time frame: At Baseline, Cycle 3 Day 1 (C3D1) (combination period), EOT (15 days after last study treatment administration) and baseline upto event free survival (EFS) follow up Month 18 after EOT (max on treatment increase & decrease)
Population: The SAF set included all participants who received any dose of any of the study intervention (xevinapant/matched placebo, cisplatin/carboplatin, IMRT). Here number analyzed signifies participants who were evaluable at specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Vital Signs: Systolic Blood Pressure, Diastolic Blood Pressure | Systolic Blood Pressure: Baseline | 128.0 millimeters of mercury (mmHg) | Standard Deviation 18.08 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Vital Signs: Systolic Blood Pressure, Diastolic Blood Pressure | Systolic Blood Pressure: C3D1 | -10.1 millimeters of mercury (mmHg) | Standard Deviation 19.36 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Vital Signs: Systolic Blood Pressure, Diastolic Blood Pressure | Systolic Blood Pressure: EOT | -5.8 millimeters of mercury (mmHg) | Standard Deviation 20.47 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Vital Signs: Systolic Blood Pressure, Diastolic Blood Pressure | Systolic BP: Max on-treatment increase | 15.6 millimeters of mercury (mmHg) | Standard Deviation 12.89 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Vital Signs: Systolic Blood Pressure, Diastolic Blood Pressure | Systolic BP: Max on-treatment decrease | -24.7 millimeters of mercury (mmHg) | Standard Deviation 15.85 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Vital Signs: Systolic Blood Pressure, Diastolic Blood Pressure | Diastolic Blood Pressure: Baseline | 77.4 millimeters of mercury (mmHg) | Standard Deviation 10.6 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Vital Signs: Systolic Blood Pressure, Diastolic Blood Pressure | Diastolic Blood Pressure: C3D1 | -5.6 millimeters of mercury (mmHg) | Standard Deviation 12.04 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Vital Signs: Systolic Blood Pressure, Diastolic Blood Pressure | Diastolic Blood Pressure: EOT | -1.8 millimeters of mercury (mmHg) | Standard Deviation 12.02 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Vital Signs: Systolic Blood Pressure, Diastolic Blood Pressure | Diastolic BP: Max on-treatment increase | 11.1 millimeters of mercury (mmHg) | Standard Deviation 7.54 |
| Sequence 1: Debio 1143 + CRT | Change From Baseline in Vital Signs: Systolic Blood Pressure, Diastolic Blood Pressure | Diastolic BP: Max on-treatment decrease | -15.2 millimeters of mercury (mmHg) | Standard Deviation 9.43 |
| Sequence 2: Placebo + CRT | Change From Baseline in Vital Signs: Systolic Blood Pressure, Diastolic Blood Pressure | Diastolic Blood Pressure: EOT | -1.2 millimeters of mercury (mmHg) | Standard Deviation 11.55 |
| Sequence 2: Placebo + CRT | Change From Baseline in Vital Signs: Systolic Blood Pressure, Diastolic Blood Pressure | Systolic Blood Pressure: Baseline | 128.2 millimeters of mercury (mmHg) | Standard Deviation 16.96 |
| Sequence 2: Placebo + CRT | Change From Baseline in Vital Signs: Systolic Blood Pressure, Diastolic Blood Pressure | Diastolic Blood Pressure: Baseline | 77.5 millimeters of mercury (mmHg) | Standard Deviation 9.75 |
| Sequence 2: Placebo + CRT | Change From Baseline in Vital Signs: Systolic Blood Pressure, Diastolic Blood Pressure | Systolic Blood Pressure: C3D1 | -7.9 millimeters of mercury (mmHg) | Standard Deviation 17.53 |
| Sequence 2: Placebo + CRT | Change From Baseline in Vital Signs: Systolic Blood Pressure, Diastolic Blood Pressure | Diastolic BP: Max on-treatment decrease | -13.2 millimeters of mercury (mmHg) | Standard Deviation 8.42 |
| Sequence 2: Placebo + CRT | Change From Baseline in Vital Signs: Systolic Blood Pressure, Diastolic Blood Pressure | Systolic Blood Pressure: EOT | -3.4 millimeters of mercury (mmHg) | Standard Deviation 20.03 |
| Sequence 2: Placebo + CRT | Change From Baseline in Vital Signs: Systolic Blood Pressure, Diastolic Blood Pressure | Diastolic Blood Pressure: C3D1 | -4.0 millimeters of mercury (mmHg) | Standard Deviation 10.65 |
| Sequence 2: Placebo + CRT | Change From Baseline in Vital Signs: Systolic Blood Pressure, Diastolic Blood Pressure | Systolic BP: Max on-treatment increase | 16.5 millimeters of mercury (mmHg) | Standard Deviation 12.43 |
| Sequence 2: Placebo + CRT | Change From Baseline in Vital Signs: Systolic Blood Pressure, Diastolic Blood Pressure | Diastolic BP: Max on-treatment increase | 11.2 millimeters of mercury (mmHg) | Standard Deviation 8.09 |
| Sequence 2: Placebo + CRT | Change From Baseline in Vital Signs: Systolic Blood Pressure, Diastolic Blood Pressure | Systolic BP: Max on-treatment decrease | -21.9 millimeters of mercury (mmHg) | Standard Deviation 14.48 |
Secondary
Complete Response Rate (CRR)
CRR defined as the number of participants with Complete Response by RECIST v1.1, as assessed by the BIRC. Complete response is defined as disappearance of all target and non-target lesions.
Time frame: At 9 and 12 months post randomization
Population: The ITT set included all randomized participants. Participants were analyzed according to the randomized treatment (assigned arm) assignment following the intention-to-treat principle.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Sequence 1: Debio 1143 + CRT | Complete Response Rate (CRR) | 9 Months Post Randomization | 187 Participants |
| Sequence 1: Debio 1143 + CRT | Complete Response Rate (CRR) | 12 Months Post Randomization | 194 Participants |
| Sequence 2: Placebo + CRT | Complete Response Rate (CRR) | 9 Months Post Randomization | 212 Participants |
| Sequence 2: Placebo + CRT | Complete Response Rate (CRR) | 12 Months Post Randomization | 222 Participants |
Secondary
Duration of Response (DOR)
Duration of response (DoR) defined as the time from the first evidence of response (partial or complete, as assessed by the BIRC according to RECIST v1.1) to the first occurrence of progression (radiological or clinical, as assessed by the BIRC) or death from any cause. Kaplan Meier method was used for calculation.
Time frame: Time from first evidence of response to the first occurrence of progression or death from any cause, assessed up to 24 months
Population: The ITT set included all randomized participants. Participants were analyzed according to the randomized treatment (assigned arm) assignment following the intention-to-treat principle. Number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sequence 1: Debio 1143 + CRT | Duration of Response (DOR) | NA months |
| Sequence 2: Placebo + CRT | Duration of Response (DOR) | NA months |
Secondary
Locoregional Control (LRC) Time
LRC time is defined as the time from randomization to the first occurrence of progression at the site of the primary tumor or the locoregional lymph nodes, either according to RECIST v1.1 or based on clinical assessment (radiological or clinical, as assessed by the Investigator). According to RECIST 1.1, progressive disease (PD) was defined as a 20% relative increase in the sum of diameters (SOD) of target lesions, taking as reference the nadir SOD and an absolute increase of \>5 millimeter (mm) in the SOD, or the appearance of new lesions. Calculated via Kaplan Meier method.
Time frame: From randomization to the first occurrence of progression at the site of the primary tumor or the locoregional lymph nodes or End Of Study (EOS) (188 weeks and 5 days)
Population: The ITT set included all randomized participants. Participants were analyzed according to the randomized treatment (assigned arm) assignment following the intention-to-treat principle.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sequence 1: Debio 1143 + CRT | Locoregional Control (LRC) Time | NA months |
| Sequence 2: Placebo + CRT | Locoregional Control (LRC) Time | NA months |
Secondary
Number of Participants Who Completed Cycle 1, 2, 3, 4, 5 and 6
Number of participants who completed cycle 1, 2, 3, 4, 5 or 6 of xevinapant/matched placebo were reported.
Time frame: Cycle 1, 2, 3, 4, 5 and 6 (each cycle is of 3 weeks)
Population: The SAF set included all participants who received any dose of any of the study intervention (xevinapant/matched placebo, cisplatin/carboplatin, IMRT).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sequence 1: Debio 1143 + CRT | Number of Participants Who Completed Cycle 1, 2, 3, 4, 5 and 6 | Cycle 1 | 363 count of participants |
| Sequence 1: Debio 1143 + CRT | Number of Participants Who Completed Cycle 1, 2, 3, 4, 5 and 6 | Cycle 2 | 325 count of participants |
| Sequence 1: Debio 1143 + CRT | Number of Participants Who Completed Cycle 1, 2, 3, 4, 5 and 6 | Cycle 3 | 290 count of participants |
| Sequence 1: Debio 1143 + CRT | Number of Participants Who Completed Cycle 1, 2, 3, 4, 5 and 6 | Cycle 4 | 266 count of participants |
| Sequence 1: Debio 1143 + CRT | Number of Participants Who Completed Cycle 1, 2, 3, 4, 5 and 6 | Cycle 5 | 263 count of participants |
| Sequence 1: Debio 1143 + CRT | Number of Participants Who Completed Cycle 1, 2, 3, 4, 5 and 6 | Cycle 6 | 246 count of participants |
| Sequence 2: Placebo + CRT | Number of Participants Who Completed Cycle 1, 2, 3, 4, 5 and 6 | Cycle 5 | 307 count of participants |
| Sequence 2: Placebo + CRT | Number of Participants Who Completed Cycle 1, 2, 3, 4, 5 and 6 | Cycle 1 | 355 count of participants |
| Sequence 2: Placebo + CRT | Number of Participants Who Completed Cycle 1, 2, 3, 4, 5 and 6 | Cycle 4 | 210 count of participants |
| Sequence 2: Placebo + CRT | Number of Participants Who Completed Cycle 1, 2, 3, 4, 5 and 6 | Cycle 2 | 335 count of participants |
| Sequence 2: Placebo + CRT | Number of Participants Who Completed Cycle 1, 2, 3, 4, 5 and 6 | Cycle 6 | 297 count of participants |
| Sequence 2: Placebo + CRT | Number of Participants Who Completed Cycle 1, 2, 3, 4, 5 and 6 | Cycle 3 | 314 count of participants |
Secondary
Number of Participants With Radical Salvage Surgery
Number of Participants with Radical Salvage Surgery (excluding elective neck dissection without anatomopathological evidence of residual malignant cells) was reported.
Time frame: At 9, 12, 24 and 36 months post randomization
Population: The ITT set included all randomized participants. Participants were analyzed according to the randomized treatment (assigned arm) assignment following the intention-to-treat principle.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Sequence 1: Debio 1143 + CRT | Number of Participants With Radical Salvage Surgery | Month 9 | 10 Participants |
| Sequence 1: Debio 1143 + CRT | Number of Participants With Radical Salvage Surgery | Month 12 | 19 Participants |
| Sequence 1: Debio 1143 + CRT | Number of Participants With Radical Salvage Surgery | Month 24 | 23 Participants |
| Sequence 1: Debio 1143 + CRT | Number of Participants With Radical Salvage Surgery | Month 36 | 23 Participants |
| Sequence 2: Placebo + CRT | Number of Participants With Radical Salvage Surgery | Month 36 | 9 Participants |
| Sequence 2: Placebo + CRT | Number of Participants With Radical Salvage Surgery | Month 9 | 3 Participants |
| Sequence 2: Placebo + CRT | Number of Participants With Radical Salvage Surgery | Month 24 | 9 Participants |
| Sequence 2: Placebo + CRT | Number of Participants With Radical Salvage Surgery | Month 12 | 5 Participants |
Secondary
Number of Participants With Severity of Grade Greater or Equal to 3 TEAEs
Severity of TEAEs were evaluated using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version. The grade are as follows: grade 1 : mild grade 2 : moderate grade 3 : severe or medically significant but not immediately life-threatening grade 4 : life threatening or disabling grade 5 : death related to AE.
Time frame: From signed informed consent to EOS (up to 188 weeks and 5 days)
Population: The SAF set included all participants who received any dose of any of the study intervention (xevinapant/matched placebo, cisplatin/carboplatin, IMRT).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sequence 1: Debio 1143 + CRT | Number of Participants With Severity of Grade Greater or Equal to 3 TEAEs | 320 Participants |
| Sequence 2: Placebo + CRT | Number of Participants With Severity of Grade Greater or Equal to 3 TEAEs | 286 Participants |
Secondary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Adverse Events (AEs) of Special Interest
An AE is any unfavorable/unintended sign (e.g., abnormal lab result), symptom or disease temporally linked to study drug, whether or not related. A serious AE leads to death, is life-threatening, causes significant/persistent disability, hospitalization, congenital anomaly, or is medically important. TEAEs include both serious and non-serious AEs after treatment. AESIs are events of clinical interest needing close monitoring. In this study, AESIs include: infusion reactions including hypersensitivity, immune-related AEs, aspartate aminotransferase/alanine transaminase increases, lipase/amylase elevation, acute renal failure, QTcF more than 30 milliseconds above baseline, and ≥Grade 2 inflammatory cutaneous AEs.
Time frame: From signed informed consent to EOS (up to 188 weeks and 5 days)
Population: The safety analysis set (SAF set) included all participants who received any dose of any of the study intervention (xevinapant/matched placebo, cisplatin/carboplatin, IMRT).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Sequence 1: Debio 1143 + CRT | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Adverse Events (AEs) of Special Interest | TEAEs | 362 Participants |
| Sequence 1: Debio 1143 + CRT | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Adverse Events (AEs) of Special Interest | Serious TEAEs | 194 Participants |
| Sequence 1: Debio 1143 + CRT | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Adverse Events (AEs) of Special Interest | AESI | 357 Participants |
| Sequence 2: Placebo + CRT | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Adverse Events (AEs) of Special Interest | TEAEs | 351 Participants |
| Sequence 2: Placebo + CRT | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Adverse Events (AEs) of Special Interest | Serious TEAEs | 129 Participants |
| Sequence 2: Placebo + CRT | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Adverse Events (AEs) of Special Interest | AESI | 342 Participants |
Secondary
Number of Participants With Treatment Interruption, Treatment Reduction and Treatment Discontinuation for Xevinapant/ Matched Placebo
Number of participants with Treatment Interruption, Treatment Reduction and Treatment Discontinuation was reported.
Time frame: Up to end of treatment (Day 134)
Population: The SAF set included all participants who received any dose of any of the study intervention (xevinapant/matched placebo, cisplatin/carboplatin, IMRT). Here number analyzed signifies participants who were evaluable for each specific category.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Sequence 1: Debio 1143 + CRT | Number of Participants With Treatment Interruption, Treatment Reduction and Treatment Discontinuation for Xevinapant/ Matched Placebo | Treatment Interruption of xevinapant/ matched placebo | 206 Participants |
| Sequence 1: Debio 1143 + CRT | Number of Participants With Treatment Interruption, Treatment Reduction and Treatment Discontinuation for Xevinapant/ Matched Placebo | Treatment Reduction of xevinapant/ matched placebo | 34 Participants |
| Sequence 1: Debio 1143 + CRT | Number of Participants With Treatment Interruption, Treatment Reduction and Treatment Discontinuation for Xevinapant/ Matched Placebo | Treatment Discontinuation of xevinapant/ matched placebo | 71 Participants |
| Sequence 2: Placebo + CRT | Number of Participants With Treatment Interruption, Treatment Reduction and Treatment Discontinuation for Xevinapant/ Matched Placebo | Treatment Interruption of xevinapant/ matched placebo | 147 Participants |
| Sequence 2: Placebo + CRT | Number of Participants With Treatment Interruption, Treatment Reduction and Treatment Discontinuation for Xevinapant/ Matched Placebo | Treatment Reduction of xevinapant/ matched placebo | 17 Participants |
| Sequence 2: Placebo + CRT | Number of Participants With Treatment Interruption, Treatment Reduction and Treatment Discontinuation for Xevinapant/ Matched Placebo | Treatment Discontinuation of xevinapant/ matched placebo | 30 Participants |
Secondary
Objective Response Rate (ORR) as Assessed by BIRC
Objective response rate was defined as percentage of participants with either a confirmed complete response (CR) or partial response (PR). CR: Disappearance of all target and non-target lesions. PR: At least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum of their diameters, and no unequivocal progression of non-target lesions. Progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on the study, or unequivocal progression of non-target lesions, or appearance of any new lesion.
Time frame: At 9 and 12 months post randomization
Population: The ITT set included all randomized participants. Participants were analyzed according to the randomized treatment (assigned arm) assignment following the intention-to-treat principle.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sequence 1: Debio 1143 + CRT | Objective Response Rate (ORR) as Assessed by BIRC | 9 Months Post Randomization | 73.4 percentage of participants |
| Sequence 1: Debio 1143 + CRT | Objective Response Rate (ORR) as Assessed by BIRC | 12 Months Post Randomization | 73.6 percentage of participants |
| Sequence 2: Placebo + CRT | Objective Response Rate (ORR) as Assessed by BIRC | 9 Months Post Randomization | 77.3 percentage of participants |
| Sequence 2: Placebo + CRT | Objective Response Rate (ORR) as Assessed by BIRC | 12 Months Post Randomization | 77.9 percentage of participants |
Secondary
Overall Dose Intensity of Carboplatin
Overall dose intensity of Carboplatin is calculated as the mean of the dose intensities of the individual cycles. This was reported with unit of measure Milligrams per minute per milliliter per week (mg min/mL/week).
Time frame: Cycle 1, 2, 3, 4 5, 6 (each cycle is of 3 weeks) or End of Treatment (Day 134)
Population: The SAF set included all participants who received any dose of any of the study intervention (xevinapant/matched placebo, cisplatin/carboplatin, IMRT).Here overall number of participants analyzed signified participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sequence 1: Debio 1143 + CRT | Overall Dose Intensity of Carboplatin | 1.59 mg min/mL/week | Standard Deviation 0.136 |
| Sequence 2: Placebo + CRT | Overall Dose Intensity of Carboplatin | 1.60 mg min/mL/week | Standard Deviation 0.123 |
Secondary
Overall Dose Intensity of Cisplatin
Overall dose intensity of Cisplatin is calculated as the mean of the dose intensities of the individual cycles. This was reported with the unit of measure milligrams per meter square per week (mg/m2/week).
Time frame: Cycle 1, 2, 3, 4 5, 6 (each cycle is of 3 weeks) or End of Treatment (Day 134)
Population: The SAF set included all participants who received any dose of any of the study intervention (xevinapant/matched placebo, cisplatin/carboplatin, IMRT). Here overall number of participants analyzed signified participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sequence 1: Debio 1143 + CRT | Overall Dose Intensity of Cisplatin | 32.33 mg/m2/week | Standard Deviation 3.053 |
| Sequence 2: Placebo + CRT | Overall Dose Intensity of Cisplatin | 32.55 mg/m2/week | Standard Deviation 2.301 |
Secondary
Overall Dose Intensity of Xevinapant/Matched Placebo
Overall dose intensity of Xevinapant/ matched placebo is calculated as the mean of the dose intensities of the individual cycles.
Time frame: Cycle 1, 2, 3, 4 5, 6 (each cycle is of 3 weeks) or End of Treatment (Day 134)
Population: The SAF set included all participants who received any dose of any of the study intervention (xevinapant/matched placebo, cisplatin/carboplatin, IMRT).Here overall number of participants analyzed signified participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sequence 1: Debio 1143 + CRT | Overall Dose Intensity of Xevinapant/Matched Placebo | 122.72 milligrams per day (mg/day) | Standard Deviation 18.274 |
| Sequence 2: Placebo + CRT | Overall Dose Intensity of Xevinapant/Matched Placebo | 126.56 milligrams per day (mg/day) | Standard Deviation 16.495 |
Secondary
Overall Survival (OS)
Overall survival is defined as the time from randomization to the date of death. Calculated via Kaplan Meier method.
Time frame: From randomization to the earliest between death or EOS (up to 188 weeks and 5 days)
Population: The ITT set included all randomized participants. Participants were analyzed according to the randomized treatment (assigned arm) assignment following the intention-to-treat principle.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sequence 1: Debio 1143 + CRT | Overall Survival (OS) | NA months |
| Sequence 2: Placebo + CRT | Overall Survival (OS) | NA months |
Secondary
Percent Change From Baseline in Laboratory Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes
Change from Baseline in Laboratory Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes was reported.
Time frame: At Cycle 3 Day 1 (C3D1) (combination period), EOT (15 days after last study treatment administration) and baseline upto event free survival (EFS) follow up Month 18 after EOT (max on treatment change)
Population: The SAF set included all participants who received any dose of any of the study intervention (xevinapant/matched placebo, cisplatin/carboplatin, IMRT). Here overall number of participants analyzed signified participants who were evaluable for this outcome measure and number analyzed signifies participants who were evaluable at specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sequence 1: Debio 1143 + CRT | Percent Change From Baseline in Laboratory Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes | C3D1: Basophils/Leukocytes | -0.21 percent change | Standard Deviation 0.551 |
| Sequence 1: Debio 1143 + CRT | Percent Change From Baseline in Laboratory Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes | Max on-treatment change: Lymphocytes/Leukocytes | -11.39 percent change | Standard Deviation 15.553 |
| Sequence 1: Debio 1143 + CRT | Percent Change From Baseline in Laboratory Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes | EOT: Eosinophils/Leukocytes | 0.60 percent change | Standard Deviation 3.435 |
| Sequence 1: Debio 1143 + CRT | Percent Change From Baseline in Laboratory Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes | C3D1: Monocytes/Leukocytes | 3.65 percent change | Standard Deviation 4.502 |
| Sequence 1: Debio 1143 + CRT | Percent Change From Baseline in Laboratory Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes | Max on-treatment change: Basophils/Leukocytes | 0.03 percent change | Standard Deviation 0.985 |
| Sequence 1: Debio 1143 + CRT | Percent Change From Baseline in Laboratory Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes | EOT: Monocytes/Leukocytes | 0.64 percent change | Standard Deviation 2.666 |
| Sequence 1: Debio 1143 + CRT | Percent Change From Baseline in Laboratory Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes | Max on-treatment change: Eosinophils/Leukocytes | 1.32 percent change | Standard Deviation 5.005 |
| Sequence 1: Debio 1143 + CRT | Percent Change From Baseline in Laboratory Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes | Max on-treatment change: Monocytes/Leukocytes | 5.87 percent change | Standard Deviation 6.06 |
| Sequence 1: Debio 1143 + CRT | Percent Change From Baseline in Laboratory Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes | EOT: Basophils/Leukocytes | -0.14 percent change | Standard Deviation 0.502 |
| Sequence 1: Debio 1143 + CRT | Percent Change From Baseline in Laboratory Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes | C3D1: Neutrophils/Leukocytes | 2.67 percent change | Standard Deviation 14.064 |
| Sequence 1: Debio 1143 + CRT | Percent Change From Baseline in Laboratory Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes | C3D1: Lymphocytes/Leukocytes | -6.89 percent change | Standard Deviation 10.604 |
| Sequence 1: Debio 1143 + CRT | Percent Change From Baseline in Laboratory Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes | EOT: Neutrophils/Leukocytes | 5.75 percent change | Standard Deviation 10.651 |
| Sequence 1: Debio 1143 + CRT | Percent Change From Baseline in Laboratory Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes | C3D1: Eosinophils/Leukocytes | -0.04 percent change | Standard Deviation 2.874 |
| Sequence 1: Debio 1143 + CRT | Percent Change From Baseline in Laboratory Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes | Max on-treatment change: Neutrophils/Leukocytes | 6.80 percent change | Standard Deviation 24.388 |
| Sequence 1: Debio 1143 + CRT | Percent Change From Baseline in Laboratory Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes | EOT: Lymphocytes/Leukocytes | -6.85 percent change | Standard Deviation 8.855 |
| Sequence 2: Placebo + CRT | Percent Change From Baseline in Laboratory Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes | Max on-treatment change: Neutrophils/Leukocytes | 7.45 percent change | Standard Deviation 21.764 |
| Sequence 2: Placebo + CRT | Percent Change From Baseline in Laboratory Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes | C3D1: Basophils/Leukocytes | -0.29 percent change | Standard Deviation 0.527 |
| Sequence 2: Placebo + CRT | Percent Change From Baseline in Laboratory Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes | EOT: Basophils/Leukocytes | -0.13 percent change | Standard Deviation 0.483 |
| Sequence 2: Placebo + CRT | Percent Change From Baseline in Laboratory Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes | Max on-treatment change: Basophils/Leukocytes | 0.00 percent change | Standard Deviation 1.032 |
| Sequence 2: Placebo + CRT | Percent Change From Baseline in Laboratory Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes | C3D1: Eosinophils/Leukocytes | -0.39 percent change | Standard Deviation 2.147 |
| Sequence 2: Placebo + CRT | Percent Change From Baseline in Laboratory Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes | EOT: Eosinophils/Leukocytes | 0.07 percent change | Standard Deviation 1.878 |
| Sequence 2: Placebo + CRT | Percent Change From Baseline in Laboratory Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes | Max on-treatment change: Eosinophils/Leukocytes | 0.04 percent change | Standard Deviation 3.308 |
| Sequence 2: Placebo + CRT | Percent Change From Baseline in Laboratory Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes | C3D1: Lymphocytes/Leukocytes | -5.80 percent change | Standard Deviation 10.086 |
| Sequence 2: Placebo + CRT | Percent Change From Baseline in Laboratory Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes | EOT: Lymphocytes/Leukocytes | -6.91 percent change | Standard Deviation 7.85 |
| Sequence 2: Placebo + CRT | Percent Change From Baseline in Laboratory Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes | Max on-treatment change: Lymphocytes/Leukocytes | -10.07 percent change | Standard Deviation 15.985 |
| Sequence 2: Placebo + CRT | Percent Change From Baseline in Laboratory Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes | C3D1: Monocytes/Leukocytes | 3.90 percent change | Standard Deviation 3.84 |
| Sequence 2: Placebo + CRT | Percent Change From Baseline in Laboratory Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes | EOT: Monocytes/Leukocytes | 0.89 percent change | Standard Deviation 2.454 |
| Sequence 2: Placebo + CRT | Percent Change From Baseline in Laboratory Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes | Max on-treatment change: Monocytes/Leukocytes | 6.26 percent change | Standard Deviation 5.631 |
| Sequence 2: Placebo + CRT | Percent Change From Baseline in Laboratory Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes | C3D1: Neutrophils/Leukocytes | 2.33 percent change | Standard Deviation 12.467 |
| Sequence 2: Placebo + CRT | Percent Change From Baseline in Laboratory Parameters: Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes | EOT: Neutrophils/Leukocytes | 6.08 percent change | Standard Deviation 9.086 |
Secondary
Progression Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as Assessed by Blinded Independent Review Committee (BIRC)
PFS according to RECIST v1.1 defined as the time from randomization to the first occurrence of progression (radiological or clinical, as assessed by the BIRC) or death from any cause. According to RECIST 1.1, progressive disease (PD) was defined as a 20% relative increase in the sum of diameters (SOD) of target lesions, taking as reference the nadir SOD and an absolute increase of \>5 millimeter (mm) in the SOD, or the appearance of new lesions. Calculated via Kaplan Meier method.
Time frame: From randomization to the first occurrence of progression (radiological or clinical, as assessed by the BIRC) or death from any cause or EOS (up to 188 weeks and 5 days )
Population: The ITT set included all randomized participants. Participants were analyzed according to the randomized treatment (assigned arm) assignment following the intention-to-treat principle.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sequence 1: Debio 1143 + CRT | Progression Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as Assessed by Blinded Independent Review Committee (BIRC) | 26.8 months |
| Sequence 2: Placebo + CRT | Progression Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as Assessed by Blinded Independent Review Committee (BIRC) | 33.1 months |
Secondary
Relative Dose Intensity
Relative dose intensity (RDI) represents the percentage of the amount of a drug actually delivered \[actual dose intensity (DI)\] to the amount planned (planned DI). The purpose of calculating RDI is to evaluate whether the planned DI of an anti-cancer treatment was actually achieved which may suggest the feasibility of planned treatment regimen.
Time frame: Up to 50 months
Population: The SAF set included all participants who received any dose of any of the study intervention (xevinapant/matched placebo, cisplatin/carboplatin, IMRT). Here number analyzed signifies participants who were evaluable for each specific category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sequence 1: Debio 1143 + CRT | Relative Dose Intensity | Xevinapant/matched placebo | 92.04 percentage (%) of dose intensity | Standard Deviation 13.706 |
| Sequence 1: Debio 1143 + CRT | Relative Dose Intensity | Cisplatin | 96.98 percentage (%) of dose intensity | Standard Deviation 9.159 |
| Sequence 1: Debio 1143 + CRT | Relative Dose Intensity | Carboplatin | 95.19 percentage (%) of dose intensity | Standard Deviation 8.182 |
| Sequence 2: Placebo + CRT | Relative Dose Intensity | Xevinapant/matched placebo | 94.92 percentage (%) of dose intensity | Standard Deviation 12.372 |
| Sequence 2: Placebo + CRT | Relative Dose Intensity | Cisplatin | 97.65 percentage (%) of dose intensity | Standard Deviation 6.904 |
| Sequence 2: Placebo + CRT | Relative Dose Intensity | Carboplatin | 96.17 percentage (%) of dose intensity | Standard Deviation 7.386 |
Secondary
Time to Subsequent Systemic Cancer Treatments
Time to new subsequent systemic cancer treatment (in months) was derived as (date of event/censoring - randomization date +1) / 30.4375. Calculated via kaplan meier method.
Time frame: Up to 188 weeks and 5 days post randomization
Population: The ITT set included all randomized participants. Participants were analyzed according to the randomized treatment (assigned arm) assignment following the intention-to-treat principle.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sequence 1: Debio 1143 + CRT | Time to Subsequent Systemic Cancer Treatments | NA months |
| Sequence 2: Placebo + CRT | Time to Subsequent Systemic Cancer Treatments | NA months |
Secondary
Total Cumulative Dose of Carboplatin
Total cumulative dose of carboplatin was reported as mean and standard deviation.
Time frame: Up to end of treatment (Day 134)
Population: The SAF set included all participants who received any dose of any of the study intervention (xevinapant/matched placebo, cisplatin/carboplatin, IMRT). Here overall number of participants analyzed signified participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sequence 1: Debio 1143 + CRT | Total Cumulative Dose of Carboplatin | 6.9 mg*min/mL | Standard Deviation 2.37 |
| Sequence 2: Placebo + CRT | Total Cumulative Dose of Carboplatin | 6.6 mg*min/mL | Standard Deviation 2.26 |
Secondary
Total Cumulative Dose of Cisplatin
Total cumulative dose of cisplatin was reported.
Time frame: Up to end of treatment (Day 134)
Population: The SAF set included all participants who received any dose of any of the study intervention (xevinapant/matched placebo, cisplatin/carboplatin, IMRT). Here overall number of participants analyzed signified participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sequence 1: Debio 1143 + CRT | Total Cumulative Dose of Cisplatin | 223.3 milligrams per square meter (mg/m^2) | Standard Deviation 76.26 |
| Sequence 2: Placebo + CRT | Total Cumulative Dose of Cisplatin | 236.3 milligrams per square meter (mg/m^2) | Standard Deviation 73.14 |
Secondary
Total Cumulative Dose of Intensity-Modulated Radiation Therapy (IMRT)
Total cumulative dose of IMRT were reported in form of mean and standard deviation.
Time frame: Up to end of treatment (Day 134)
Population: The SAF set included all participants who received any dose of any of the study intervention (xevinapant/matched placebo, cisplatin/carboplatin, IMRT). Here overall number of participants analyzed signified participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sequence 1: Debio 1143 + CRT | Total Cumulative Dose of Intensity-Modulated Radiation Therapy (IMRT) | 66.4 Gray (Gy) | Standard Deviation 12.32 |
| Sequence 2: Placebo + CRT | Total Cumulative Dose of Intensity-Modulated Radiation Therapy (IMRT) | 67.9 Gray (Gy) | Standard Deviation 9.74 |
Secondary
Total Cumulative Dose of Xevinapant/ Matched Placebo
Total cumulative dose of Xevinapant/ Matched Placebo was reported in form of mean and standard deviation.
Time frame: Up to end of treatment (Day 134)
Population: The SAF set included all participants who received any dose of any of the study intervention (xevinapant/matched placebo, cisplatin/carboplatin, IMRT). Here overall number of participants analyzed signified participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sequence 1: Debio 1143 + CRT | Total Cumulative Dose of Xevinapant/ Matched Placebo | 12383.6 milligrams (mg) | Standard Deviation 5375.66 |
| Sequence 2: Placebo + CRT | Total Cumulative Dose of Xevinapant/ Matched Placebo | 14417.0 milligrams (mg) | Standard Deviation 4288.55 |
Secondary
Treatment Duration
Treatment duration is calculated by study treatment component as (last dose date minus first dose date plus x)/7, where x=8 for xevinapant/matched placebo, x=21 for cisplatin/carboplatin, x=3 for IMRT.
Time frame: Up to end of study (up to 188weeks and 5 days)
Population: The SAF set included all participants who received any dose of any of the study intervention (xevinapant/matched placebo, cisplatin/carboplatin, IMRT). Here number analyzed signifies participants who were evaluable for each specific category.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Sequence 1: Debio 1143 + CRT | Treatment Duration | Xevinapant/matched placebo | 18.00 weeks |
| Sequence 1: Debio 1143 + CRT | Treatment Duration | Cisplatin | 8.86 weeks |
| Sequence 1: Debio 1143 + CRT | Treatment Duration | Carboplatin | 3.00 weeks |
| Sequence 1: Debio 1143 + CRT | Treatment Duration | IMRT | 7.43 weeks |
| Sequence 2: Placebo + CRT | Treatment Duration | IMRT | 7.43 weeks |
| Sequence 2: Placebo + CRT | Treatment Duration | Xevinapant/matched placebo | 18.00 weeks |
| Sequence 2: Placebo + CRT | Treatment Duration | Carboplatin | 3.00 weeks |
| Sequence 2: Placebo + CRT | Treatment Duration | Cisplatin | 9.00 weeks |