Neoplasms

All Conditions

Carcinoma

Carcinoma, Squamous Cell

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Head and Neck Neoplasms

Pharmaceutical Solutions

All Drugs and Chemicals

Antineoplastic Agents

Cisplatin

In addition to Cisplatin and Radiotherapy, Debio 1143 in solution form will be administered orally or by feeding tube (while fasting) daily for 14 days every three weeks (on days 1-14, 22-35 and 43-56).

In addition to Cisplatin and Radiotherapy, matching placebo in solution form will be administered orally or by feeding tube (while fasting) daily for 14 days every three weeks (on days 1-14, 22-35 and 43-56).

A total of three cycles of cisplatin will be administered in a 1-hour IV infusion on days 2, 23 and 44. Cisplatin will be administered 0.5 hours after Debio 1143.

Standard fraction radiotherapy to the primary tumour will be delivered daily for 5 days per week over 7 weeks.

Radiotherapy

Debio 1143

Placebo

The use of multiple drugs in a single clinical trial or as a therapeutic strategy has become common, particularly in the treatment of cancer. Because traditional trials are designed to evaluate one agent at a time, the evaluation of therapies in combination requires specialized trial designs. In place of the traditional separate phase I and II trials, this trial uses a single phase I/II clinical trial to evaluate simultaneously the safety and efficacy of combination dose levels, and select the optimal combination dose.

Therefore, this is a two part trial of Debio 1143 combined with concurrent cisplatin and radiotherapy (CRT) in participants with previously untreated stage III, IVa or IVb head and neck cancer. The trial begins with an initial period of dose escalation (Phase I) to investigate the maximum tolerated dose (MTD) of Debio 1143 that can safely be given in combination with CRT.

Using the MTD determined in the Phase I portion, the randomized phase II trial in 94 participants compares Debio 1143 to placebo, both with concomitant CRT. The aim is to evaluate the efficacy and safety of Debio 1143.

Debio 1143-201 Dose-finding and Efficacy Phase I/II Trial

A Phase I/II Randomized Study to Determine the Maximum Tolerated Dose, Safety, Pharmacokinetics and Antitumor Activity of Debio 1143 Combined With Concurrent Chemo-Radiation Therapy in Patients With Locally Advanced Squamous Cell Carcinoma of the Head and Neck.

Categories will be based on severity graded according to NCI-CTCAE version 4 criteria

Categories: Treatment discontinuation, Treatment modification

Debiopharm International SA

Respiratory Tract (Lung and Bronchial) Diseases

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Antibodies

Avelumab

Immunoglobulins

Antineoplastic Agents, Immunological

Part A: Participants will receive Debio 1143 100 to 250 milligram (mg) capsule orally at an escalating dose levels for 10 days every 2 weeks along with avelumab 10 milligrams per kilogram (mg/kg) as an intravenous (IV) infusion every 2 weeks.

Part B: Participants will receive Debio 1143 capsules orally at a recommended phase 2 dose (RP2D) of 200 mg/day (days 1-10 and 15-24 every 28 days (\[q4w\]) in combination with avelumab IV infusion at the standard dose unless disease progression or unacceptable toxicity occurs, as judged by investigators up to 26 cycles (each cycle is of 28 days).

Debio 1143 100 to 250 mg, capsule orally for 10 days every 2 weeks.

Avelumab 10 mg/kg intravenous infusion every 2 weeks.

The study is primarily designed to assess the safety and tolerability of escalating oral doses of Debio 1143 and preliminary anti-tumour activity when combined with the standard dose of avelumab in participants with advanced solid malignancies.

A Dose-Finding Study of the Second Mitochondrial Activator of Caspases (SMAC) Mimetic Debio 1143 When Given in Combination With Avelumab to Participants With Advanced Solid Malignancies and to Participants With Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) After Platinum-Based Therapy

A Phase-Ib Dose-Finding Study of the SMAC Mimetic Debio 1143 When Given in Combination With the Anti-PD-L1 Antibody Avelumab to Patients With Advanced Solid Malignancies and, in an Expansion Cohort, to Patients With Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) After Platinum-Based Therapy

MTD:dose with estimated probability of dose limited toxicity(DLT) below 30%.DLT:any of following adverse events(AEs) during 1st treatment cycle if deemed related to treatment:grade (gr) 3/4 febrile neutropenia/any gr 4 neutropenia of \>5 days duration;gr 4 thrombocytopenia\[\<25000 per cubic millimetre(/mm\^3)\]/gr 3(\<50000/mm\^3),associated with medically concerning bleeding;gr ≥3 non-hematologic laboratory value;non-hematologic toxicity of gr 3/4,gr ≥2 uveitis/eye pain that does neither respond to topical therapy nor abate to gr 1within the avelumab re-treatment period/that required systemic treatment;gr ≥2 pneumonitis/interstitial lung disease that not resolve with dose delay and systemic steroids;toxicity related to study drug that requires dosing delay of \>2weeks,dose reduction,premature discontinuation of any of two;other drug related AE in the opinion of investigator is of potential clinical significance so that further dose-escalation would expose participants to unacceptable risk.

Objective response is defined as any partial response (PR) or complete response (CR) recorded from the start of study treatment until disease progression/recurrence is documented, a new systemic therapy is started or analysis cut-off, whichever occurs first. It is assessed by using Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1. RECIST v1.1 criteria- CR: disappearance of all target lesions, any pathological lymph nodes must have reduction in short axis to \<10 millimeter (mm). PR: At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameter.

An AE is any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. An SAE is any untoward medical occurrence at any dose that results in death; is life-threatening; requires hospitalization; results in persistent or significant disability or in congenital anomaly/birth defect. Severity will be graded by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.03.

Change in tumor size is the maximum reduction or, in case of no reduction, the minimum increase in tumor size from the start of study treatment until disease progression/recurrence, the start of a new systemic therapy or analysis cut-off, whichever occurs first.

Objective response is defined as any PR or CR recorded from the start of study treatment until disease progression/recurrence is documented, a new systemic therapy is started or analysis cut-off, whichever occurs first. It is assessed by using RECIST criteria. CR: disappearance of all target lesions, any pathological lymph nodes must have reduction in short axis to \<10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameter.

Best overall response (BOR) is defined as the best response (CR, PR, stable disease or disease progression) recorded from the start of study treatment until disease progression/recurrence is documented, a new systemic therapy is started or analysis cut-off, whichever occurs first. It is assessed by using RECIST criteria version 1.1. CR: disappearance of all target lesions, any pathological lymph nodes must have reduction in short axis to \<10 millimeter (mm). PR: At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameter. Disease progression: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). Stable Disease: Neither sufficient shrinkage to qualify for PR, nor sufficient increase to qualify for disease progression, taking as reference the smallest sum diameter while on study.

Duration of response is the time from documentation of tumor response to disease progression was observed in participants with CR or PR. RECIST v1.1 criteria- CR: disappearance of all target lesions, any pathological lymph nodes must have reduction in short axis to \<10 millimeter (mm). PR: At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameter. Disease progression: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study).

Disease control is derived as CR, PR or stable disease lasting at least 16 weeks reported during the study. RECIST v1.1 criteria- CR: Disappearance of all target lesions, any pathological lymph nodes must have reduction in short axis to \<10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameter.

PFS duration is defined as the time elapsed between treatment initiation and tumor progression or death from any cause, whichever occurs first. RECIST v1.1 criteria- CR: disappearance of all target lesions, any pathological lymph nodes must have reduction in short axis to \<10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameter. Disease progression: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study).

OS is defined as the time elapsed between treatment initiation and death from any cause.

Nivolumab

Immune Checkpoint Inhibitors

Participants received Debio 1143, 150 milligrams (mg) capsules, orally once on Days 1 to 10 and Days 15 to 24 of each 28-day treatment cycle along with nivolumab 240 mg, intravenous (IV) infusion on Days 1 and 15 of each 28-day treatment cycle allowed for a maximum of 26 cycles.

Participants received Debio 1143, 200 mg capsules, orally once on Days 1 to 10 and Days 15 to 24 of each 28-day treatment cycle along with nivolumab 240 mg, IV infusion on Days 1 and 15 of each 28-day treatment cycle allowed for a maximum of 26 cycles.

Participants with small-cell lung cancer (SCLC) received Debio 1143, 200 mg capsules, orally once on Days 1 to 28 in each 28-day treatment cycle along with nivolumab 240 mg, IV infusion on Days 1 and 15 of each 28-day treatment cycle allowed for a maximum of 26 cycles.

Participants with squamous cell carcinoma of the head and neck (SCCHN) received Debio 1143, 200 mg capsules, orally once on Days 1 to 28 in each 28-day treatment cycle along with nivolumab 240 mg, IV infusion on Days 1 and 15 of each 28-day treatment cycle allowed for a maximum of 26 cycles.

Participants with gastrointestinal (GI) cancers received Debio 1143, 200 mg capsules, orally once on Days 1 to 28 in each 28-day treatment cycle along with nivolumab 240 mg, IV infusion on Days 1 and 15 of each 28-day treatment cycle allowed for a maximum of 26 cycles.

Participants with gynecologic cancers received Debio 1143, 200 mg capsules, orally once on Days 1 to 28 in each 28-day treatment cycle along with nivolumab 240 mg, IV infusion on Days 1 and 15 of each 28-day treatment cycle allowed for a maximum of 26 cycles.

Part A (dose-optimization)- to determine the recommended phase 2 dose (RP2D) taking into account dose-limiting toxicity (DLT/s) in Cycle 1, overall safety/tolerability and pharmacokinetic (PK), by optimizing doses of Debio 1143 when combined with the standard dose of nivolumab, as well as treatment compliance in participants with advanced solid malignancies who failed prior systemic standard treatments.

Part B (basket trial)- to evaluate the preliminary anti-tumor activity of Debio 1143 at the RP2D in combination with nivolumab at the standard dose, overall and in each participant cohort (Cohort 1: small cell lung cancer \[SCLC\]; Cohort 2: squamous cell carcinoma of the head and neck \[SCCHN\]; Cohort 3: gastrointestinal (GI) cancers with known microsatellite instability-high/mismatch repair deficiency (MSI-H/MMRd) or other deoxyribonucleic acid (DNA) damage repair (DDR) abnormalities, including homologous recombination deficiency (HRD); Cohort 4: platinum-resistant epithelial ovarian cancer \[EOC\], endometrial cancer, primary peritoneal cancer (PPC) or cervical cancer, with known MSIH/MMRd, hereditary/somatic mutations of the breast cancer 1 (BRCA1) and BRCA2 genes or other DNA DDR abnormalities (incl. HRD).

Study to Assess Safety and Efficacy of the Second Mitochondrial-derived Activator of Caspases (SMAC) Mimetic Debio 1143

A Dose-optimization, Exploratory Phase Ib/II Study to Assess Safety and Efficacy of the Second Mitochondrial-derived Activator of Caspases (SMAC) Mimetic Debio 1143, When Given in Combination With the Anti-PD-1 Antibody Nivolumab in Patients With Specific Solid Tumors Who Have Progressed During or Immediately After Anti-PD-1/PD-L1 Treatment

DLT: any of following treatment-emergent adverse events (TEAEs) as per NCI CTCAE Grade V5.0 Criteria (Grades 1=mild, 2=moderate, 3=severe and 4 or 5= life-threatening/fatal outcomes) which are possibly, probably or definitely related to combination treatment and occurring in Cycle 1 (1 Cycle=28 days): Any Grade 4 or 5 hematologic toxicity, clinical or laboratory non-hematologic toxicity; febrile neutropenia any grade, Grade 3 thrombocytopenia if associated with bleeding or requiring platelet transfusion; Grade 2; Grade 3 and any other Grade 3 non-hematologic, treatment-related clinical toxicity lasting ≥3 days; delay of \>2 weeks due to drug-related toxicity in initiating Cycle 2; unable to complete at least 70% of the scheduled treatment (\>six Debio 1143 skipped doses in Cycle 1) due to treatment-related toxicity; required dose reduction in Cycle 1 or on Cycle 2 Day 1 or requirement for treatment withdrawal due to treatment-related toxicity (even if not meeting other DLT criteria).

ORR was determined per response evaluation criteria in solid tumors (RECIST) v1.1 and/or gynecologic cancer intergroup (GCIG) criteria (for Cohort 4). ORR was calculated as the percentage of participants with a confirmed objective response. A confirmed objective response is a confirmed best overall response of partial response (PR) or complete response (CR) recorded after the start of study treatment until disease progression/recurrence was documented, a new systemic anti-cancer therapy was started or analysis cut-off, whichever occurred first. CR is defined by the disappearance of all target lesions and reduction of any pathological lymph nodes in short axis to \<10 millimeters (mm). PR is defined by at least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameter.

An adverse event (AE) is any untoward medical occurrence in a clinical trial participant administered a medicinal product that does not necessarily have a causal relationship with this treatment. A TEAE is any new, related or non-related, undesirable medical occurrence or change of an existing condition in a participant that occurs during the treatment-emergent period, starting or worsening on or after the first study drug administration and up to 5 months after last nivolumab infusion, or the earliest date of new anticancer therapy - 1 day, whichever occurs first. An SAE is defined as any untoward medical occurrence that at any dose results in death; is life-threatening (i.e., puts the participant at immediate risk of death); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect, or is otherwise medically significant.

Vital sign parameters assessed comprise of systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate. Markedly abnormal criteria for vital signs include SBP \[millimeters of mercury (mmHg)\]: ≤ 90 mmHg OR change from baseline ≤ -20 mmHg, ≥ 140 mmHg OR change from baseline ≥ 20 mmHg; DBP (mmHg): ≤ 60 mmHg OR change from baseline ≤ -20 mmHg, ≥ 90 mmHg OR change from baseline ≥ 20 mmHg; Heart rate \[beats per minute (bpm)\]: ≤ 50 bpm OR change from baseline ≤ -20 bpm, ≥ 100 bpm OR change from baseline ≥ 20 bpm.

Change from baseline in temperature reported as TEAEs included pyrexia. A TEAE is any new, related or non-related, undesirable medical occurrence or change of an existing condition in a participant that occurs during the treatment-emergent period, starting or worsening on or after the first study drug administration and up to 5 months after last nivolumab infusion, or the earliest date of new anticancer therapy - 1 day, whichever occurs first.

ECG parameters comprised of PR Interval \[millisecond (msec)\], QRS Interval (msec), QT Interval (msec), QTcB Interval (msec), QTcF Interval (msec), heart rate (HR) (bpm), RR interval (msec), derived HR (msec), calculated as 60000/RR interval \[for data checking only: should be within 5% of HR\]. Marked abnormal criteria for ECG parameters included absolute values QRS interval: \< 50 msec, \> 110 msec; absolute values for QT interval, QTcB interval: \>450 msec, \> 480 msec, \> 500 msec, QTcF: \> 480 msec, \> 500 msec; change from baseline values for QTcB interval, and QTcF: \>30 msec increase from baseline, \>60 msec increase from baseline. Data for highest on-treatment change from baseline as per the markedly abnormal criteria for ECG parameters are reported. On-treatment is the period of time between the first and last administration of any study drug. Participants with at least one markedly abnormal change from baseline value in the above categories are reported.

The ECOG-PS was used to assess the effect of disease progression on participants' daily activities. ECOG-PS is graded as follows: Grade 0 - fully active, able to carry on all pre-disease performance without restriction; Grade 1 - restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature; Grade 2 - ambulatory and capable of all self-care, but unable to carry out any work activities, up and about more than 50% of waking hours; Grade 3 - capable of only limited self-care, confined to bed or chair for more than 50% of waking hours; Grade 4 - completely disabled, cannot carry on any self-care, totally confined to bed or chair; Grade 5 - dead. Shift values from baseline grade to worst on-treatment grade and missing values were reported.

ORR was determined per RECIST v1.1. ORR was calculated as the percentage of participants with a confirmed objective response. A confirmed objective response is a confirmed best overall response of PR or CR recorded after the start of study treatment until disease progression/recurrence was documented, a new systemic anti-cancer therapy was started or analysis cut-off, whichever occurred first. CR is defined by the disappearance of all target lesions and reduction of any pathological lymph nodes in short axis to \<10 mm. PR is defined by at least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameter.

uORR was calculated as the percentage of participants with unconfirmed objective response per RECIST v1.1. Unconfirmed objective response is an unconfirmed best overall response of PR or CR. Objective response was derived as any PR or CR recorded after the start of study treatment until disease progression/recurrence was documented, a new systemic anti-cancer therapy was started or analysis cut-off, whichever occurred first. CR is defined by the disappearance of all target lesions and reduction of any pathological lymph nodes in short axis to \<10 mm. PR is defined by at least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameter.

DCR was calculated as the percentage of participants with disease control. Disease control was derived as any CR, PR, or stable disease reported during the study. CR is defined by the disappearance of all target lesions and reduction of any pathological lymph nodes in short axis to \<10 mm. PR is defined by at least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameter.

DOR is defined as the time, in months, between date of the initial response (PR or CR) or date of first reduction of 50% in carbohydrate antigen 125 (CA-125), and date of the first documented disease progression or death due to any cause, whichever occurs first. CR is defined by the disappearance of all target lesions and reduction of any pathological lymph nodes in short axis to \<10 mm. PR is defined by at least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameter. Data is reported as Kaplan-Meier product-limit estimates.

PFS duration is defined as the time, in months, elapsed between treatment initiation and tumor progression or death from any cause, whichever occurs first.

PFS is defined as duration elapsed between treatment initiation and tumor progression or death from any cause, whichever occurs first. Data for PFS rate is reported as Kaplan-Meier product-limit estimates and includes Brookmeyer-Crowley confidence intervals.

OS is defined as the time elapsed, in months, between treatment initiation and death from any cause.

OS is defined as the time elapsed, in months, between treatment initiation and death from any cause. Data for OS rate is reported as Kaplan-Meier product-limit estimates and includes Brookmeyer-Crowley confidence intervals.

The average of the time taken in days for PR is reported. PR is defined by at least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameter.

Safety analysis set included all participants who were enrolled and received at least one dose of any study drug.

Participants received Debio 1143, 150 mg capsules, orally once on Days 1 to 10 and Days 15 to 24 of each 28-day treatment cycle along with nivolumab 240 mg, IV infusion on Days 1 and 15 of each 28-day treatment cycle allowed for a maximum of 26 cycles.

Part A - Debio 1143 150 mg + Nivolumab

Part A - Debio 1143 200 mg + Nivolumab

Participants with SCLC received Debio 1143, 200 mg capsules, orally once on Days 1 to 28 in each 28-day treatment cycle along with nivolumab 240 mg, IV infusion on Days 1 and 15 of each 28-day treatment cycle allowed for a maximum of 26 cycles.

Part B - Cohort 1 (SCLC): Debio 1143 200 mg + Nivolumab

Participants with SCCHN received Debio 1143, 200 mg capsules, orally once on Days 1 to 28 in each 28-day treatment cycle along with nivolumab 240 mg, IV infusion on Days 1 and 15 of each 28-day treatment cycle allowed for a maximum of 26 cycles.

Part B - Cohort 2 (SCCHN): Debio 1143 200 mg + Nivolumab

Participants with GI cancers received Debio 1143, 200 mg capsules, orally once on Days 1 to 28 in each 28-day treatment cycle along with nivolumab 240 mg, IV infusion on Days 1 and 15 of each 28-day treatment cycle allowed for a maximum of 26 cycles.

Part B - Cohort 3 (GI Cancers): Debio 1143 200 mg + Nivolumab

Part B - Cohort 4 (Gynecologic Cancers): Debio 1143 200 mg + Nivolumab

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race

Race/Ethnicity, Customized

Head Clinical Research & Development

Recommended phase 2 dose (RP2D) population included participants who received at least 70% of Debio 1143 (i.e., a maximum of 6 missed Debio 1143 doses) and at least one nivolumab dose as planned in Cycle 1.

Part A: Number of Participants With Dose-limiting Toxicities (DLTs)

Part B: Confirmed Objective Response Rate (ORR)

TEAEs

SAEs

Parts A and B: Number of Participants With Treatment-emergent Adverse Events (TEAEs) Including Laboratory Abnormalities Reported as TEAEs, and Serious Adverse Events (SAEs)

Safety analysis set included all participants who were enrolled and received at least one dose of any study drug. Overall number of participants analyzed indicates the number of participants with data available for analysis.

Parts A and B: Change From Baseline in Weight

Parts A and B: Number of Participants With Markedly Abnormal Change From Baseline in Vital Signs

Parts A and B: Number of Participants With Change From Baseline in Temperature Reported as TEAEs

QRS duration: >110 msec

QT Interval: >450 msec

QT Interval: >480 msec

QTcB Interval: >450 msec

QTcB Interval: >480 msec

QTcB Interval: >500 msec

QTcB Interval: >30 msec increase from baseline

QTcB Interval: >60 msec increase from baseline

QTcB Interval: >30 msec or >60 msec increase from baseline

QTcF Interval: >480 msec

QTcF Interval: >500 msec

QTcF Interval: >30 msec increase from baseline

QTcF Interval: >60 msec increase from baseline

Safety analysis set included all participants who were enrolled and received at least one dose of any study drug. Overall number of participants analyzed indicates the number of participants available for analysis.

Parts A and B: Number of Participants With Markedly Abnormal Change From Baseline in Electrocardiogram (ECG) Readings

Shift From Grade 0 to Grade 0

Shift From Grade 0 to Grade 1

Shift From Grade 0 to Grade 2

Shift From Grade 0 to Grade 3

Shift From Grade 1 to Grade 1

Shift From Grade 1 to Grade 2

Shift From Grade 1 to Grade 3

Missing

Parts A and B: Number of Participants With Shift From Baseline to Worst On-Treatment Value in Eastern Cooperative Oncology Group Performance Status (ECOG-PS)

TEAEs Leading to Discontinuation of Debio 1143

TEAEs Leading to Discontinuation of Nivolumab

TEAEs Leading to Dose Modification of Debio 1143

TEAEs Leading to Dose Modification of Nivolumab

Parts A and B: Number of Participants With TEAEs Including Laboratory Abnormalities Leading to Treatment Discontinuations and Dose Modifications

Part A: Confirmed Objective Response Rate (ORR)

Parts A and B: Unconfirmed Objective Response Rate (uORR)

Parts A and B: Disease Control Rate (DCR)

Safety analysis set included all participants who were enrolled and received at least one dose of any study drug. Overall number of participants analyzed indicates censored participants with at least a CR or PR.

Parts A and B: Median Duration of Response (DOR)

Parts A and B: Progression Free Survival (PFS)

Month 6

Month 12

Safety analysis set included all participants who were enrolled and received at least one dose of any study drug. Number analyzed indicates the number of participants analyzed at the given time points. No participants were analyzed at Month 12 in Part B.

Parts A and B: PFS Rate at Months 6 and 12

Parts A and B: Overall Survival (OS)

Month 18

Safety analysis set included all participants who were enrolled and received at least one dose of any study drug. Number analyzed indicates the number of participants analyzed at the given time points.

Parts A and B: OS Rate at Months 12 and 18

Debio 1143: Cycle 1 Day 1

Debio 1143: Cycle 1 Day 8

Debio 1143: Cycle 1 Day 15

Debio 1143: Cycle 1 Day 22

Debio 1143: Cycle 3 Day 1

Debio 1143: Cycle 3 Day 15

Debio 1143-MET1: Cycle 1 Day 1

Debio 1143-MET1: Cycle 1 Day 8

Debio 1143-MET1: Cycle 1 Day 15

Debio 1143-MET1: Cycle 1 Day 22

Debio 1143-MET1: Cycle 3 Day 1

Debio 1143-MET1: Cycle 3 Day 15

Safety analysis set included all participants who were enrolled and received at least one dose of any study drug. Number analyzed indicates the number of participants with available data for analysis at the given timepoint.

Part A: Area Under the Curve From Time 0 to 4 Hours (AUC0-4H) of Debio 1143 and Debio 1143-MET1

Safety analysis set included all participants who were enrolled and received at least one dose of any study drug. Overall number of participants analyzed indicates number of participants available for analysis. Number analyzed indicates the number of participants with available data for analysis at the given timepoint.

Part B: AUC0-4H of Debio 1143 and Debio 1143-MET1

Part A: Area Under the Curve From Time 0 to 8 Hours (AUC0-8H) of Debio 1143 and Debio 1143-MET1

Part A: Maximum Observed Concentration (Cmax) of Debio 1143 and Debio 1143-MET1

Part B: Cmax of Debio 1143 and Debio 1143-MET1

Debio 1143: Cycle 1 Day 3

Debio 1143: Cycle 1 Day 17

Debio 1143: Cycle 3 Day 3

Debio 1143: Cycle 3 Day 17

Debio 1143: Cycle 6 Day 1

Debio 1143-MET1: Cycle 1 Day 3

Debio 1143-MET1: Cycle 1 Day 17

Debio 1143-MET1: Cycle 3 Day 3

Debio 1143-MET1: Cycle 3 Day 17

Debio 1143-MET1: Cycle 6 Day 1

Part A: Trough Concentration (Cmin) of Debio 1143 and Debio 1143-MET1

Debio 1143-MET: Cycle 1 Day 8

Part B: Trough Concentration (Cmin) of Debio 1143 and Debio 1143-MET1

Cycle 1 Day 15

Cycle 3 Day 1

Cycle 3 Day 15

Part A: Serum Trough Concentration of Nivolumab

Cycle 6 Day 1

Part B: Serum Trough Concentration of Nivolumab

Safety analysis set included all participants who were enrolled and received at least one dose of any study drug. Overall number of participants analyzed indicates the number of participants with at least a CR or PR.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Debio 1143-201 Dose-finding and Efficacy Phase I/II Trial	NCT02022098	Squamous Cell C...	Cisplatin Radiotherapy Debio 1143 Placebo	18 Years - 75 Years	Debiopharm International SA
A Dose-Finding Study of the Second Mitochondrial Activator of Caspases (SMAC) Mimetic Debio 1143 When Given in Combination With Avelumab to Participants With Advanced Solid Malignancies and to Participants With Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) After Platinum-Based Therapy	NCT03270176	Carcinoma, Non-... Neoplasms	Debio 1143 Avelumab	18 Years -	Debiopharm International SA
Study to Assess Safety and Efficacy of the Second Mitochondrial-derived Activator of Caspases (SMAC) Mimetic Debio 1143	NCT04122625	Solid Tumor	Debio 1143 Nivolumab	18 Years -	Debiopharm International SA
Study to Assess Safety and Efficacy of the Second Mitochondrial-derived Activator of Caspases (SMAC) Mimetic Debio 1143	NCT04122625	Solid Tumor	Debio 1143 Nivolumab	18 Years -	Debiopharm International SA

Spots Global Cancer Trial Database for debio 1143

Every month we try and update this database with for debio 1143 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for debio 1143

Every month we try and update this database with for debio 1143 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for debio 1143 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.