Trial Outcomes & Findings for A Study Evaluating TAS-102 Plus Nivolumab in Patients With MSS CRC (NCT NCT02860546)
NCT ID: NCT02860546
Last Updated: 2024-09-03
Results Overview
irORR was defined as the percentage of participants achieving a complete response (irCR) or partial response (irPR) based on irRC criteria. Per irRC criteria, Complete Response (irCR) was defined as the disappearance of all tumor lesions (measurable or not, and no new lesions)., Partial Response (irPR) was defined as a decrease in the sum of the products of the two largest perpendicular diameters (SPD) by 50 percent (%) or greater by a consecutive assessment at least 4 weeks after first documentation, Stable Disease (irSD) was defined as the failure to meet criteria for irCR or irPR in absence of progressive disease (irPD), irPD was defined as at least 25% increase in SPD relative to nadir.
COMPLETED
PHASE2
18 participants
From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
2024-09-03
Participant Flow
The study was conducted at 3 centers in United States.
A total of 22 participants were screened out of which 18 participants passed the screening and were enrolled in the study. This study was planned to have 2 stages but only stage1 was completed. The study was halted following an interim analysis and no participants were enrolled in stage 2. Therefore, the data represented is for stage 1 only.
Participant milestones
| Measure |
TAS-102 + Nivolumab
Participants received a dose of 35 milligrams per meter square (mg/m\^2) of TAS-102 tablets orally twice per day (BID) within 1 hour after completion of morning and evening meals, in 4-week cycle. In each 4-week cycle, TAS-102 was administered for 2 weeks, as 5 days a week with 2 days rest, followed by a 14-day rest. Also participants received 3 milligrams per kilogram per dose (mg/kg/dose) Nivolumab intravenous (I.V) infusion over 60 minutes every 14 days (on Day 1 and Day 15 of each 4-week cycle).
|
|---|---|
|
Overall Study
STARTED
|
18
|
|
Overall Study
COMPLETED
|
0
|
|
Overall Study
NOT COMPLETED
|
18
|
Reasons for withdrawal
| Measure |
TAS-102 + Nivolumab
Participants received a dose of 35 milligrams per meter square (mg/m\^2) of TAS-102 tablets orally twice per day (BID) within 1 hour after completion of morning and evening meals, in 4-week cycle. In each 4-week cycle, TAS-102 was administered for 2 weeks, as 5 days a week with 2 days rest, followed by a 14-day rest. Also participants received 3 milligrams per kilogram per dose (mg/kg/dose) Nivolumab intravenous (I.V) infusion over 60 minutes every 14 days (on Day 1 and Day 15 of each 4-week cycle).
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|---|---|
|
Overall Study
Clinical Progression
|
6
|
|
Overall Study
Radiological Progression
|
12
|
Baseline Characteristics
A Study Evaluating TAS-102 Plus Nivolumab in Patients With MSS CRC
Baseline characteristics by cohort
| Measure |
TAS-102 + Nivolumab
n=18 Participants
Participants received a dose of 35 mg/m\^2 of TAS-102 tablets orally BID within 1 hour after completion of morning and evening meals, in 4-week cycle. In each 4-week cycle, TAS-102 was administered for 2 weeks, as 5 days a week with 2 days rest, followed by a 14-day rest. Also participants received 3 mg/kg/dose Nivolumab I.V infusion over 60 minutes every 14 days (on Day 1 and Day 15 of each 4-week cycle).
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|---|---|
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Age, Continuous
|
58.0 years
STANDARD_DEVIATION 7.32 • n=5 Participants
|
|
Sex: Female, Male
Female
|
9 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
9 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
4 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
12 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)Population: Efficacy population included all participants in the safety population (all participants who received at least 1 dose of study drug) who completed at least 6 months of tumor follow-up, unless the participant progressed or died before the 6-month follow-up.
irORR was defined as the percentage of participants achieving a complete response (irCR) or partial response (irPR) based on irRC criteria. Per irRC criteria, Complete Response (irCR) was defined as the disappearance of all tumor lesions (measurable or not, and no new lesions)., Partial Response (irPR) was defined as a decrease in the sum of the products of the two largest perpendicular diameters (SPD) by 50 percent (%) or greater by a consecutive assessment at least 4 weeks after first documentation, Stable Disease (irSD) was defined as the failure to meet criteria for irCR or irPR in absence of progressive disease (irPD), irPD was defined as at least 25% increase in SPD relative to nadir.
Outcome measures
| Measure |
TAS-102 + Nivolumab
n=18 Participants
Participants received a dose of 35 mg/m\^2 of TAS-102 tablets orally BID within 1 hour after completion of morning and evening meals, in 4-week cycle. In each 4-week cycle, TAS-102 was administered for 2 weeks, as 5 days a week with 2 days rest, followed by a 14-day rest. Also participants received 3 mg/kg/dose Nivolumab I.V infusion over 60 minutes every 14 days (on Day 1 and Day 15 of each 4-week cycle).
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|---|---|
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Immune-Related Overall Response Rate (irORR)
|
0 percentage of participants
|
SECONDARY outcome
Timeframe: Cycle 1 (each cycle is of 4 weeks)Population: DLT Evaluable (DLTE) population included all participants in the safety population in Stage 1, prior to confirming the recommended dose, who completed at least 1 cycle (28 days) of study treatment with at least 80% of the study treatment administered, unless the treatment was interrupted because of a DLT.
DLT: defined as occurrence of any of the following- Hematological toxicities: * Grade 4 neutropenia lasting greater than(\>)7 days * Grade 4 febrile neutropenia and fever greater than or equal to (\>=)38 degree celsius for over 1 hour * Grade 4 thrombocytopenia or grade 3 thrombocytopenia associated with bleeding or requiring transfusions Non-hematological toxicities: * Grade 3 or grade 4 non-hematologic toxicity (excluding alopecia, nausea, vomiting, diarrhea) * Grade 3 or grade 4 nausea/vomiting lasting \>48 hours and uncontrolled by aggressive anti-emetic therapy, including serotonin 5-HT3 receptor antagonists (e.g, ondansetron) * Grade 3 or grade 4 diarrhea lasting \> 48 hours and unresponsive to antidiarrheal medication Drug-related toxicities: * Any drug-related toxicity resulting in \> 2 weeks delay in initiation of Cycle 2 (i.e, cannot start Cycle 2 until Day 43 or later) * Any drug-related toxicity that prevents completion of 80% compliance for either drug in Cycle 1
Outcome measures
| Measure |
TAS-102 + Nivolumab
n=6 Participants
Participants received a dose of 35 mg/m\^2 of TAS-102 tablets orally BID within 1 hour after completion of morning and evening meals, in 4-week cycle. In each 4-week cycle, TAS-102 was administered for 2 weeks, as 5 days a week with 2 days rest, followed by a 14-day rest. Also participants received 3 mg/kg/dose Nivolumab I.V infusion over 60 minutes every 14 days (on Day 1 and Day 15 of each 4-week cycle).
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|---|---|
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Number of Participants With Dose Limiting Toxicities (DLTs)
|
0 Participants
|
SECONDARY outcome
Timeframe: Cycle 1 (each cycle is of 4 weeks)Population: DLTE population included all participants in the safety population in Stage 1, prior to confirming the recommended dose, who completed at least 1 cycle (4 weeks) of study treatment with at least 80% of the study treatment administered, unless the treatment was interrupted because of a DLT.
RP2D of TAS-102 was evaluated based on the safety and tolerability of the combination therapy of TAS-102 and Nivolumab.
Outcome measures
| Measure |
TAS-102 + Nivolumab
n=6 Participants
Participants received a dose of 35 mg/m\^2 of TAS-102 tablets orally BID within 1 hour after completion of morning and evening meals, in 4-week cycle. In each 4-week cycle, TAS-102 was administered for 2 weeks, as 5 days a week with 2 days rest, followed by a 14-day rest. Also participants received 3 mg/kg/dose Nivolumab I.V infusion over 60 minutes every 14 days (on Day 1 and Day 15 of each 4-week cycle).
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|---|---|
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Recommended Phase 2 Dose (RP2D)
|
35 mg/m^2
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SECONDARY outcome
Timeframe: From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)Population: Safety population included all participants who received at least 1 dose of study drug.
An adverse event (AE) was defined as any untoward medical condition that occurs in a participants while participating in a clinical study and does not necessarily have a causal relationship with the use of the study treatment. A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. TEAEs: AEs that developed or worsened during the on-treatment period which was defined as the period from the time of first dose of study treatment until 30 days after the last dose of study treatment.
Outcome measures
| Measure |
TAS-102 + Nivolumab
n=18 Participants
Participants received a dose of 35 mg/m\^2 of TAS-102 tablets orally BID within 1 hour after completion of morning and evening meals, in 4-week cycle. In each 4-week cycle, TAS-102 was administered for 2 weeks, as 5 days a week with 2 days rest, followed by a 14-day rest. Also participants received 3 mg/kg/dose Nivolumab I.V infusion over 60 minutes every 14 days (on Day 1 and Day 15 of each 4-week cycle).
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|---|---|
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Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
Participants with TEAEs
|
18 participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
Participants with TESAEs
|
6 participants
|
SECONDARY outcome
Timeframe: From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)Population: Safety population included all participants who received at least 1 dose of study drug.
Hematological and chemistry laboratory tests abnormalities were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03. as: Grade 1 (Mild, asymptomatic or mild symptoms); Grade 2 (Moderate, minimal, local or noninvasive intervention indicated); Grade 3 (Severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated); Grade 4 (Life-threatening consequences, urgent intervention indicated); Grade 5 (Death related to AE).
Outcome measures
| Measure |
TAS-102 + Nivolumab
n=18 Participants
Participants received a dose of 35 mg/m\^2 of TAS-102 tablets orally BID within 1 hour after completion of morning and evening meals, in 4-week cycle. In each 4-week cycle, TAS-102 was administered for 2 weeks, as 5 days a week with 2 days rest, followed by a 14-day rest. Also participants received 3 mg/kg/dose Nivolumab I.V infusion over 60 minutes every 14 days (on Day 1 and Day 15 of each 4-week cycle).
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|---|---|
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Number of Participants With Grade 3 or Higher Laboratory Tests Abnormalities
Grade 4: Neutropenia (neutrophils low)
|
3 participants
|
|
Number of Participants With Grade 3 or Higher Laboratory Tests Abnormalities
Grade 4: Anemia (hemoglobin low)
|
1 participants
|
|
Number of Participants With Grade 3 or Higher Laboratory Tests Abnormalities
Grade 4: Leukopenia (leukocytes low)
|
0 participants
|
|
Number of Participants With Grade 3 or Higher Laboratory Tests Abnormalities
Grade 4: Lymphopenia (lymphocytes low)
|
0 participants
|
|
Number of Participants With Grade 3 or Higher Laboratory Tests Abnormalities
Grade 4: Thrombocytopenia (platelets low)
|
0 participants
|
|
Number of Participants With Grade 3 or Higher Laboratory Tests Abnormalities
Grade 4: Bilirubin High
|
0 participants
|
|
Number of Participants With Grade 3 or Higher Laboratory Tests Abnormalities
Grade 4: Glucose High
|
0 participants
|
|
Number of Participants With Grade 3 or Higher Laboratory Tests Abnormalities
Grade 4: Sodium Low
|
0 participants
|
|
Number of Participants With Grade 3 or Higher Laboratory Tests Abnormalities
Grade 3: Neutropenia (neutrophils low)
|
3 participants
|
|
Number of Participants With Grade 3 or Higher Laboratory Tests Abnormalities
Grade 3: Anemia (hemoglobin low)
|
1 participants
|
|
Number of Participants With Grade 3 or Higher Laboratory Tests Abnormalities
Grade 3: Leukopenia (leukocytes low)
|
6 participants
|
|
Number of Participants With Grade 3 or Higher Laboratory Tests Abnormalities
Grade 3: Lymphopenia (lymphocytes low)
|
2 participants
|
|
Number of Participants With Grade 3 or Higher Laboratory Tests Abnormalities
Grade 3: Thrombocytopenia (platelets low)
|
1 participants
|
|
Number of Participants With Grade 3 or Higher Laboratory Tests Abnormalities
Grade 3: Bilirubin High
|
1 participants
|
|
Number of Participants With Grade 3 or Higher Laboratory Tests Abnormalities
Grade 3: Glucose High
|
1 participants
|
|
Number of Participants With Grade 3 or Higher Laboratory Tests Abnormalities
Grade 3: Sodium Low
|
1 participants
|
SECONDARY outcome
Timeframe: From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)Population: Efficacy population included all participants in the safety population who completed at least 6 months of tumor follow-up, unless the participant progressed or died before the 6-month follow-up.
ORR was defined as the percentage of participants with objective evidence of complete response (CR) or partial response (PR) per response evaluation criteria in solid tumors (RECIST) version 1.1.CR was defined as the disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to less than (\<)10 millimeters (mm). PR was defined as at least a 30 % decrease in the sum of diameters of the target lesions, taking as a reference the baseline sum diameters.
Outcome measures
| Measure |
TAS-102 + Nivolumab
n=18 Participants
Participants received a dose of 35 mg/m\^2 of TAS-102 tablets orally BID within 1 hour after completion of morning and evening meals, in 4-week cycle. In each 4-week cycle, TAS-102 was administered for 2 weeks, as 5 days a week with 2 days rest, followed by a 14-day rest. Also participants received 3 mg/kg/dose Nivolumab I.V infusion over 60 minutes every 14 days (on Day 1 and Day 15 of each 4-week cycle).
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|---|---|
|
Overall Response Rate (ORR)
|
0 percentage of participants
|
SECONDARY outcome
Timeframe: From the first dose of study treatment to disease progression or death (up to 53 weeks)Population: Efficacy population included all participants in the safety population who completed at least 6 months of tumor follow-up, unless the participant progressed or died before the 6-month follow-up.
Immune-related progression free survival was defined as the time (in months) from the date of first dose of study treatment until the date of the investigator-assessed radiological disease progression (based on irRC) or death due to any cause. Participants who were alive with no disease progression at the moment of the analysis cut-off date was censored at the date of the last tumor assessment. Per irRC criteria disease progression defined as at least 25% increase in SPD relative to nadir. Analysis was performed using Kaplan-Meier estimates.
Outcome measures
| Measure |
TAS-102 + Nivolumab
n=18 Participants
Participants received a dose of 35 mg/m\^2 of TAS-102 tablets orally BID within 1 hour after completion of morning and evening meals, in 4-week cycle. In each 4-week cycle, TAS-102 was administered for 2 weeks, as 5 days a week with 2 days rest, followed by a 14-day rest. Also participants received 3 mg/kg/dose Nivolumab I.V infusion over 60 minutes every 14 days (on Day 1 and Day 15 of each 4-week cycle).
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|---|---|
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Progression-Free Survival (PFS) Based on Immune Related Response-Criteria (irRC)
Radiologic progression of disease only
|
2.2 months
Interval 1.8 to 6.0
|
|
Progression-Free Survival (PFS) Based on Immune Related Response-Criteria (irRC)
Radiologic + clinical progression of disease
|
2.2 months
Interval 1.8 to 3.7
|
SECONDARY outcome
Timeframe: From the first dose of study treatment to disease progression or death (up to 53 weeks)Population: Efficacy population included all participants in the safety population who completed at least 6 months of tumor follow-up, unless the participant progressed or died before the 6-month follow-up.
Progression free survival was defined as the time (in months) from the date of first dose of study treatment until the date of the investigator-assessed radiological disease progression (based on RECIST 1.1) or death due to any cause. Per RECIST criteria disease progression defined as least 20% increase in the sum of diameters of the target lesions, taking as a reference the smallest sum on study, including the baseline sum. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Definitive new lesion presence also indicated progression.
Outcome measures
| Measure |
TAS-102 + Nivolumab
n=18 Participants
Participants received a dose of 35 mg/m\^2 of TAS-102 tablets orally BID within 1 hour after completion of morning and evening meals, in 4-week cycle. In each 4-week cycle, TAS-102 was administered for 2 weeks, as 5 days a week with 2 days rest, followed by a 14-day rest. Also participants received 3 mg/kg/dose Nivolumab I.V infusion over 60 minutes every 14 days (on Day 1 and Day 15 of each 4-week cycle).
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|---|---|
|
Progression-Free Survival (PFS) Based on RECIST Criteria
Radiologic progression of disease only
|
2.8 months
Interval 1.8 to 5.1
|
|
Progression-Free Survival (PFS) Based on RECIST Criteria
Radiologic + clinical progression of disease
|
2.5 months
Interval 1.8 to 3.7
|
SECONDARY outcome
Timeframe: From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)Population: Efficacy population included all participants in the safety population who completed at least 6 months of tumor follow-up, unless the participant progressed or died before the 6-month follow-up.
DCR was defined as the percentage of participants with objective evidence of radiologic complete response (CR), partial response (PR), or stable disease (SD) and was based on the overall best response from each participant as determined from investigator response assessments and following irRC criteria. Per irRC criteria, CR was defined as the disappearance of all tumor lesions (measurable or not, and no new lesions). PR was defined as a decrease in the sum of the products of the two largest perpendicular diameters by 50% or greater by a consecutive assessment at least 4 weeks after first documentation. SD was defined as the failure to meet criteria for irCR or irPR in absence of in absence of irPD.
Outcome measures
| Measure |
TAS-102 + Nivolumab
n=18 Participants
Participants received a dose of 35 mg/m\^2 of TAS-102 tablets orally BID within 1 hour after completion of morning and evening meals, in 4-week cycle. In each 4-week cycle, TAS-102 was administered for 2 weeks, as 5 days a week with 2 days rest, followed by a 14-day rest. Also participants received 3 mg/kg/dose Nivolumab I.V infusion over 60 minutes every 14 days (on Day 1 and Day 15 of each 4-week cycle).
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|---|---|
|
Disease Control Rate (DCR) Based on irRC Criteria
|
44.4 percentage of participants
Interval 21.5 to 69.2
|
SECONDARY outcome
Timeframe: From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)Population: Efficacy population included all participants in the safety population who completed at least 6 months of tumor follow-up, unless the participant progressed or died before the 6-month follow-up.
DCR was defined as the percentage of participants with objective evidence of radiologic CR, PR, or SD and was based on the overall best response from each participant as determined from investigator response assessments and following RECIST Criteria version 1.1. Per RECIST Criteria CR defined as disappearance of all target lesions. Reduction in any pathological lymph nodes in short axis to \<10 mm. PR defined as at least a 30% decrease in the sum of diameters of the target lesions, taking as a reference the baseline sum diameters. SD defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as a reference the smallest sum diameters during study.
Outcome measures
| Measure |
TAS-102 + Nivolumab
n=18 Participants
Participants received a dose of 35 mg/m\^2 of TAS-102 tablets orally BID within 1 hour after completion of morning and evening meals, in 4-week cycle. In each 4-week cycle, TAS-102 was administered for 2 weeks, as 5 days a week with 2 days rest, followed by a 14-day rest. Also participants received 3 mg/kg/dose Nivolumab I.V infusion over 60 minutes every 14 days (on Day 1 and Day 15 of each 4-week cycle).
|
|---|---|
|
Disease Control Rate (DCR) Based on RECIST Criteria
|
55.6 percentage of participants
Interval 30.8 to 78.5
|
SECONDARY outcome
Timeframe: From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)Population: Safety population included all participants who received at least 1 dose of study drug. Overall number of participants analyzed is 0 because data were not collected for the outcome measure at particular time point.
OS was defined as the time from the first dose of the study treatment to the death in the safety population. Participants alive at the time of the study discontinuation were censored. Analysis was performed using Kaplan-Meier estimates.
Outcome measures
Outcome data not reported
Adverse Events
TAS-102 + Nivolumab
Serious adverse events
| Measure |
TAS-102 + Nivolumab
n=18 participants at risk
Participants received a dose of 35 mg/m\^2 of TAS-102 tablets orally BID within 1 hour after completion of morning and evening meals, in 4-week cycle. In each 4-week cycle, TAS-102 was administered for 2 weeks, as 5 days a week with 2 days rest, followed by a 14-day rest. Also participants received 3 mg/kg/dose Nivolumab I.V infusion over 60 minutes every 14 days (on Day 1 and Day 15 of each 4-week cycle).
|
|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
11.1%
2/18 • Number of events 2 • From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
Analysis was performed on safety population.
|
|
Gastrointestinal disorders
Colitis
|
5.6%
1/18 • Number of events 1 • From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
Analysis was performed on safety population.
|
|
Gastrointestinal disorders
Diarrhoea
|
5.6%
1/18 • Number of events 1 • From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
Analysis was performed on safety population.
|
|
Gastrointestinal disorders
Nausea
|
11.1%
2/18 • Number of events 3 • From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
Analysis was performed on safety population.
|
|
Gastrointestinal disorders
Vomiting
|
5.6%
1/18 • Number of events 3 • From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
Analysis was performed on safety population.
|
|
General disorders
Pyrexia
|
5.6%
1/18 • Number of events 1 • From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
Analysis was performed on safety population.
|
|
Hepatobiliary disorders
Cholangitis
|
5.6%
1/18 • Number of events 1 • From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
Analysis was performed on safety population.
|
|
Infections and infestations
Urinary tract infection
|
5.6%
1/18 • Number of events 1 • From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
Analysis was performed on safety population.
|
|
Psychiatric disorders
Confusional state
|
5.6%
1/18 • Number of events 1 • From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
Analysis was performed on safety population.
|
|
Renal and urinary disorders
Obstructive uropathy
|
5.6%
1/18 • Number of events 1 • From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
Analysis was performed on safety population.
|
Other adverse events
| Measure |
TAS-102 + Nivolumab
n=18 participants at risk
Participants received a dose of 35 mg/m\^2 of TAS-102 tablets orally BID within 1 hour after completion of morning and evening meals, in 4-week cycle. In each 4-week cycle, TAS-102 was administered for 2 weeks, as 5 days a week with 2 days rest, followed by a 14-day rest. Also participants received 3 mg/kg/dose Nivolumab I.V infusion over 60 minutes every 14 days (on Day 1 and Day 15 of each 4-week cycle).
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
27.8%
5/18 • Number of events 11 • From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
Analysis was performed on safety population.
|
|
Blood and lymphatic system disorders
Lymphadenopathy
|
5.6%
1/18 • Number of events 1 • From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
Analysis was performed on safety population.
|
|
Blood and lymphatic system disorders
Neutropenia
|
16.7%
3/18 • Number of events 5 • From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
Analysis was performed on safety population.
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
11.1%
2/18 • Number of events 2 • From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
Analysis was performed on safety population.
|
|
Ear and labyrinth disorders
Tinnitus
|
5.6%
1/18 • Number of events 1 • From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
Analysis was performed on safety population.
|
|
Eye disorders
Lacrimation increased
|
5.6%
1/18 • Number of events 1 • From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
Analysis was performed on safety population.
|
|
Eye disorders
Photopsia
|
5.6%
1/18 • Number of events 1 • From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
Analysis was performed on safety population.
|
|
Gastrointestinal disorders
Abdominal distension
|
5.6%
1/18 • Number of events 1 • From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
Analysis was performed on safety population.
|
|
Gastrointestinal disorders
Abdominal pain
|
27.8%
5/18 • Number of events 6 • From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
Analysis was performed on safety population.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
11.1%
2/18 • Number of events 2 • From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
Analysis was performed on safety population.
|
|
Gastrointestinal disorders
Ascites
|
5.6%
1/18 • Number of events 1 • From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
Analysis was performed on safety population.
|
|
Gastrointestinal disorders
Constipation
|
22.2%
4/18 • Number of events 5 • From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
Analysis was performed on safety population.
|
|
Gastrointestinal disorders
Diarrhoea
|
61.1%
11/18 • Number of events 22 • From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
Analysis was performed on safety population.
|
|
Gastrointestinal disorders
Dyspepsia
|
5.6%
1/18 • Number of events 1 • From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
Analysis was performed on safety population.
|
|
Gastrointestinal disorders
Nausea
|
66.7%
12/18 • Number of events 25 • From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
Analysis was performed on safety population.
|
|
Gastrointestinal disorders
Proctalgia
|
5.6%
1/18 • Number of events 1 • From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
Analysis was performed on safety population.
|
|
Gastrointestinal disorders
Stomatitis
|
11.1%
2/18 • Number of events 2 • From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
Analysis was performed on safety population.
|
|
Gastrointestinal disorders
Vomiting
|
33.3%
6/18 • Number of events 9 • From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
Analysis was performed on safety population.
|
|
General disorders
Asthenia
|
11.1%
2/18 • Number of events 2 • From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
Analysis was performed on safety population.
|
|
General disorders
Fatigue
|
33.3%
6/18 • Number of events 14 • From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
Analysis was performed on safety population.
|
|
General disorders
Mucosal inflammation
|
11.1%
2/18 • Number of events 6 • From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
Analysis was performed on safety population.
|
|
General disorders
Oedema peripheral
|
5.6%
1/18 • Number of events 1 • From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
Analysis was performed on safety population.
|
|
General disorders
Pyrexia
|
11.1%
2/18 • Number of events 2 • From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
Analysis was performed on safety population.
|
|
Infections and infestations
Candida infection
|
5.6%
1/18 • Number of events 1 • From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
Analysis was performed on safety population.
|
|
Infections and infestations
Herpes zoster
|
5.6%
1/18 • Number of events 1 • From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
Analysis was performed on safety population.
|
|
Infections and infestations
Influenza
|
5.6%
1/18 • Number of events 1 • From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
Analysis was performed on safety population.
|
|
Infections and infestations
Oral herpes
|
5.6%
1/18 • Number of events 1 • From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
Analysis was performed on safety population.
|
|
Infections and infestations
Sinusitis
|
5.6%
1/18 • Number of events 1 • From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
Analysis was performed on safety population.
|
|
Infections and infestations
Upper respiratory tract infection
|
11.1%
2/18 • Number of events 2 • From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
Analysis was performed on safety population.
|
|
Infections and infestations
Urinary tract infection
|
11.1%
2/18 • Number of events 2 • From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
Analysis was performed on safety population.
|
|
Injury, poisoning and procedural complications
Medication error
|
5.6%
1/18 • Number of events 1 • From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
Analysis was performed on safety population.
|
|
Investigations
Alanine aminotransferase increased
|
5.6%
1/18 • Number of events 1 • From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
Analysis was performed on safety population.
|
|
Investigations
Blood bilirubin increased
|
11.1%
2/18 • Number of events 4 • From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
Analysis was performed on safety population.
|
|
Investigations
Neutrophil count decreased
|
33.3%
6/18 • Number of events 14 • From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
Analysis was performed on safety population.
|
|
Investigations
Platelet count decreased
|
5.6%
1/18 • Number of events 2 • From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
Analysis was performed on safety population.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
16.7%
3/18 • Number of events 3 • From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
Analysis was performed on safety population.
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
5.6%
1/18 • Number of events 1 • From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
Analysis was performed on safety population.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
5.6%
1/18 • Number of events 1 • From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
Analysis was performed on safety population.
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
5.6%
1/18 • Number of events 1 • From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
Analysis was performed on safety population.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
5.6%
1/18 • Number of events 1 • From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
Analysis was performed on safety population.
|
|
Nervous system disorders
Dizziness
|
5.6%
1/18 • Number of events 1 • From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
Analysis was performed on safety population.
|
|
Nervous system disorders
Sciatica
|
5.6%
1/18 • Number of events 2 • From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
Analysis was performed on safety population.
|
|
Psychiatric disorders
Insomnia
|
5.6%
1/18 • Number of events 1 • From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
Analysis was performed on safety population.
|
|
Renal and urinary disorders
Chromaturia
|
5.6%
1/18 • Number of events 1 • From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
Analysis was performed on safety population.
|
|
Renal and urinary disorders
Dysuria
|
11.1%
2/18 • Number of events 2 • From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
Analysis was performed on safety population.
|
|
Reproductive system and breast disorders
Vaginal discharge
|
5.6%
1/18 • Number of events 1 • From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
Analysis was performed on safety population.
|
|
Reproductive system and breast disorders
Vulvovaginal dryness
|
5.6%
1/18 • Number of events 1 • From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
Analysis was performed on safety population.
|
|
Reproductive system and breast disorders
Vulvovaginal pain
|
5.6%
1/18 • Number of events 1 • From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
Analysis was performed on safety population.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
5.6%
1/18 • Number of events 1 • From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
Analysis was performed on safety population.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
16.7%
3/18 • Number of events 3 • From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
Analysis was performed on safety population.
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
11.1%
2/18 • Number of events 2 • From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
Analysis was performed on safety population.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory tract congestion
|
5.6%
1/18 • Number of events 1 • From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
Analysis was performed on safety population.
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
11.1%
2/18 • Number of events 2 • From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
Analysis was performed on safety population.
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
5.6%
1/18 • Number of events 1 • From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
Analysis was performed on safety population.
|
|
Skin and subcutaneous tissue disorders
Erythema
|
5.6%
1/18 • Number of events 1 • From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
Analysis was performed on safety population.
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
5.6%
1/18 • Number of events 1 • From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
Analysis was performed on safety population.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
22.2%
4/18 • Number of events 4 • From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
Analysis was performed on safety population.
|
|
Skin and subcutaneous tissue disorders
Rash
|
5.6%
1/18 • Number of events 1 • From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
Analysis was performed on safety population.
|
|
Skin and subcutaneous tissue disorders
Rash follicular
|
11.1%
2/18 • Number of events 2 • From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
Analysis was performed on safety population.
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
11.1%
2/18 • Number of events 2 • From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
Analysis was performed on safety population.
|
|
Vascular disorders
Flushing
|
5.6%
1/18 • Number of events 1 • From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
Analysis was performed on safety population.
|
|
Vascular disorders
Hypertension
|
11.1%
2/18 • Number of events 2 • From first dose of study treatment up to 30 days after the last dose of study treatment (up to 53 weeks)
Analysis was performed on safety population.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place